充血Congestion 淋巴结其他
描述（中文）
在啮齿类动物的淋巴结中可见血管（如毛细血管或微静脉）充血（congestion），尤其与血管扩张（angiectasis）相关（Figure 1、Figure 2，箭头）。充血的特征是血管内血液过度积聚，其原因或为流入增加，或为回流受阻。充血的血管可能扩张（血管扩张性），也可能不扩张。在淋巴结中，充血应与窦性红细胞增多（sinus erythrocytosis）、出血（hemorrhage）、血管瘤（hemangioma）及血管肉瘤（hemangiosarcoma）相鉴别。充血与窦性红细胞增多的区别在于，血液积聚于血管腔内而非淋巴窦内。充血与出血的区别在于，红细胞及其他血液成分位于血管内而非外渗。充血可伴随血管瘤或血管肉瘤出现；但该病变为继发性，且通常由正常的血液成分构成。充血时可伴有外渗的红细胞，但在无坏死或其他病变的情况下，这些外渗红细胞应归因于剖检技术，并被视为解剖所致的人工假象。
诊断建议
当认为淋巴结充血与受试物相关时，应予以诊断并分级。若淋巴结充血继发于其他病变（如血管扩张或肿瘤），或认为系安乐死、剖检或动物死亡方式所致，则不应诊断，但可在病理学描述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Congestion of blood vessels (e.g., capillaries or venules) may be seen in lymph nodes of rodents, particularly associated with angiectasis ( Figure 1 and Figure 2 , arrows). Congestion is characterized by excessive accumulation of blood within a vessel, due either to increased afflux or to obstruction of return flow. Congested vessels may or may not be dilated (angiectatic). In the lymph node, congestion should be distinguished from sinus erythrocytosis, hemorrhage, hemangioma, and hemangiosarcoma. Congestion differs from sinus erythrocytosis in that the accumulation of blood is within blood vessel lumens and not lymphatic sinuses. Congestion differs from hemorrhage in that erythrocytes and other blood components are intravascular and not extravasated. Congestion may accompany a hemangioma or hemangiosarcoma; however, the lesion is secondary and typically consists of normal blood components. Extravasated erythrocytes may be present with congestion, but in the absence of necrosis or other lesions, they are attributed to necropsy technique and considered to be a dissection-induced artifact.
Recommendation
When lymph node congestion is believed to be associated with treatment, it should be diagnosed and graded. If lymph node congestion is secondary to another lesion (e.g., angiectasis or neoplasia) or believed to be the result of euthanasia, necropsy, or the manner in which the animal died, it should not be diagnosed but may be described in the pathology narrative.
坏死Necrosis 淋巴结坏死
描述（中文）
淋巴结坏死（necrosis of the lymph nodes）在啮齿类动物中是一种不常见的病变；然而，它可由血流阻塞（梗死）、肿瘤形成、感染因子（如真菌、细菌）或异物（如受试物）所诱发。该病变的特征是细胞肿胀伴染色质聚集、核碎裂或核溶解，导致细胞核溶解、细胞裂解以及大量颗粒状嗜酸性物质积聚（Figure 1、Figure 2，箭头）。淋巴结坏死通常伴有炎症（Figure 2，箭头head），并且根据严重程度和慢性程度，还可伴有纤维化、出血和/或矿化。坏死应与淋巴细胞凋亡相鉴别，后者的特征是细胞皱缩、核固缩以及淋巴细胞碎裂为膜结合的（凋亡）小体，随后被巨噬细胞（可染小体巨噬细胞）吞噬。
诊断建议
淋巴结坏死应予以诊断并赋予严重程度分级。如果淋巴结坏死继发于其他病变（如肿瘤形成、炎症），除非严重程度足以支持，否则不应诊断，但应在病理学描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Necrosis of the lymph nodes is an uncommon lesion in rodents; however, it may be induced by obstruction of blood flow (infarction), neoplasia, an infectious agent (e.g., fungi, bacteria), or foreign body (e.g., test article). This lesion is characterized by cellular swelling with chromatin clumping, karyorrhexis, or karyolysis, leading to dissolution of nuclei, cell lysis, and accumulation of abundant granular eosinophilic material ( Figure 1 and Figure 2 , arrows). Lymph node necrosis is generally accompanied by inflammation ( Figure 2 , arrowhead) and can also be accompanied by fibrosis, hemorrhage, and/or mineralization, depending on severity and chronicity. Necrosis should be differentiated from lymphocyte apoptosis, which is characterized by cell shrinkage, nuclear pyknosis, and fragmentation of lymphocytes into membrane-bound (apoptotic) bodies that are subsequently phagocytized by macrophages (tingible-body macrophages).
Recommendation
Necrosis of the lymph node should be diagnosed and assigned a severity grade. If lymph node necrosis is present secondary to another lesion (e.g., neoplasia, inflammation), it should not be diagnosed unless warranted by severity, but should be described in the pathology narrative.
浆细胞增生Hyperplasia Plasma Cell 淋巴结增生
描述（中文）
浆细胞增生（plasma cell hyperplasia）是啮齿类动物淋巴结中的常见病变，尤其多见于下颌淋巴结（mandibular lymph nodes）（Figure 1、Figure 2），最常见的原因是接触饮食性抗原后的反应。如果不是背景病变，则浆细胞增生可能与受试物相关，或与其他器官的炎性、感染性或肿瘤性病变相关。浆细胞及其前体细胞正常情况下存在于髓索（medullary cords）中；因此，髓索是浆细胞增生的主要部位（Figure 1）。浆细胞通常因需要产生抗体的抗原刺激而增多，因此通常B细胞（淋巴样）增生伴有浆细胞增生。髓系增生（myeloid hyperplasia）也可能存在。成熟浆细胞胞质呈嗜碱性至嗜酸性，细胞核偏位，可见高尔基体透明区（Golgi clear zone），染色质呈车轮状（cartwheel chromatin pattern）（Figure 2，箭头）。根据抗原刺激的程度和慢性程度，可能出现一些含有拉塞尔小体（Russell bodies）的莫特细胞（Mott cells）。在显著（marked）浆细胞增生时，淋巴结可显著增大，主要由浆细胞构成，并可能表现为正常淋巴结结构的部分消失。显著浆细胞增生可通过后者（浆细胞肿瘤）中存在浆细胞前体细胞、非典型浆细胞、被膜浸润和转移而与浆细胞肿瘤相鉴别。
诊断建议
淋巴结中的浆细胞增生应当被诊断并给出严重程度分级。然而，如果该病变伴随淋巴细胞增生和/或肿瘤性病变，则不应单独诊断，而应在叙述性描述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Plasma cell hyperplasia is a common finding in the lymph nodes of rodents, particularly in the mandibular lymph nodes ( Figure 1 and Figure 2 ), most often in response to exposure to dietary antigens. If not a background lesion, then plasma cell hyperplasia may be treatment related or associated with inflammatory, infectious, or neoplastic lesions in other organs. Plasma cells and their precursors are normally present in the medullary cords; therefore, these cords are the primary site of plasma cell hyperplasia ( Figure 1 ). Plasma cells usually increase in response to antigenic stimulation requiring antibody production, so typically B-cell (lymphoid) hyperplasia is accompanied by plasma cell hyperplasia. Myeloid hyperplasia may also be present. Mature plasma cells have basophilic to eosinophilic cytoplasm, eccentrically located nuclei, a Golgi clear zone, and a cartwheel chromatin pattern ( Figure 2 , arrows). Depending on the degree and chronicity of antigenic stimulation, some Mott cells with Russell bodies may be present. With marked plasma cell hyperplasia, the lymph node may be greatly enlarged and composed mostly of plasma cells and may exhibit partial effacement of normal nodal architecture. Marked plasma cell hyperplasia may be differentiated from plasma cell neoplasia by the presence of plasma cell precursors, atypical plasma cells, capsular infiltration, and metastases in the latter.
Recommendation
Plasma cell hyperplasia in lymph nodes should be diagnosed and given a severity grade. However, if this lesion accompanies lymphocyte hyperplasia and/or neoplasia, it should not be diagnosed separately but should be described in the narrative.
淋巴窦扩张Lymphatic Sinus Ectasia 淋巴结扩张
描述（中文）
淋巴窦扩张（lymphatic sinus ectasia）可累及大鼠和小鼠淋巴结的被膜下窦（Figure 1，箭头）、副皮质窦或髓窦（Figure 2，箭头）。窦相对于淋巴结体积增大，衬覆淋巴内皮，可充满淡嗜酸性/双染性物质（推测为淋巴液）。腔内可见少量淋巴细胞、巨噬细胞和/或红细胞。淋巴窦扩张可能与处理或剂量相关；然而，该病变也可见于对照和老龄啮齿类动物，尤其是肠系膜或纵隔淋巴结。弥漫性窦扩张也可能与淋巴组织萎缩相关。淋巴窦扩张应与淋巴结内血管扩张（blood vessel angiectasis）相鉴别，后者的特征为皮质、髓质、被膜、门部或周围结缔组织内薄壁静脉的扩张和充血。淋巴窦扩张既往使用的术语有“淋巴管扩张（lymphangiectasia）”、“淋巴囊肿（lymphatic cysts）”、“囊性淋巴管扩张（cystic lymphatic ectasia）”和“窦扩张（sinus dilatation）”。
诊断建议
淋巴窦扩张应予以诊断并赋予严重程度分级。如果该病变作为淋巴组织萎缩的组成部分存在，则应诊断萎缩，并在叙述中描述淋巴窦扩张及任何其他相关病变。
参考切片图（2 张）
查看英文原文
Comment
Lymphatic sinus ectasia can involve the subcapsular ( Figure 1 , arrow), paracortical, or medullary ( Figure 2 , arrow) sinuses of lymph nodes in rats and mice. Sinuses are enlarged relative to the size of the lymph node, are lined by lymphatic endothelium, and may be filled with pale eosinophilic/amphophilic material (presumably lymph). Few intraluminal lymphocytes, macrophages, and/or erythrocytes may be present. Lymphatic sinus ectasia may be related to treatment or dose; however, this lesion can also be seen in control and aging rodents, particularly in the mesenteric or mediastinal lymph nodes. Diffuse sinus ectasia may also be associated with lymphoid atrophy. Lymphatic sinus ectasia should be differentiated from blood vessel angiectasis in the lymph node, which is characterized by the dilatation and congestion of thin veins within the cortex, medulla, capsule, hilus, or surrounding connective tissue. Previous terms for lymphatic sinus ectasia are "lymphangiectasia," "lymphatic cysts," "cystic lymphatic ectasia," and "sinus dilatation."
Recommendation
Lymphatic sinus ectasia should be diagnosed and assigned a severity grade. If this lesion is present as a component of lymphoid atrophy, atrophy should be diagnosed, and the lymphatic sinus ectasia and any other associated lesions should be described in the narrative.
淋巴细胞凋亡Apoptosis Lymphocyte 淋巴结凋亡
描述（中文）
淋巴细胞凋亡（lymphocyte apoptosis）的特征是细胞皱缩、核固缩，以及淋巴细胞碎裂成膜结合的（凋亡）小体，随后被巨噬细胞（可染体巨噬细胞）吞噬（Figure 1、Figure 2，箭头）。这种类型的细胞死亡通常发生于次级滤泡生发中心内的B细胞，在那里它是一种重要的稳态机制。Figure 1、Figure 2展示了副皮质区T细胞中的该病变。淋巴细胞凋亡在淋巴结中可以是正常的，在免疫缺陷小鼠的淋巴结中可增多，或由各种损伤性刺激诱导。某些损伤性刺激在低剂量时诱导淋巴细胞凋亡，而在较高剂量时该刺激导致坏死。此类刺激的例子包括热、辐射、缺氧和细胞毒性抗癌药物（如环磷酰胺）。地塞米松也可引发淋巴细胞凋亡；然而，胸腺和脾对该效应的敏感性高于淋巴结。如果足够严重，淋巴细胞凋亡可导致淋巴结萎缩。历史上，淋巴细胞凋亡曾被称为“淋巴细胞坏死”，但该病变的正确术语是“淋巴细胞凋亡”。淋巴细胞的单细胞坏死此前尚未在淋巴结中被描述。淋巴细胞凋亡必须与坏死相鉴别，尽管两者可同时发生。坏死通常成组细胞发生，其特征是细胞肿胀、核浓缩、碎裂和溶解、细胞溶解，以及嗜酸性胞质和核碎裂碎屑的积聚。炎症通常伴随坏死，因为细胞溶解将细胞内容物（包括促炎介质）释放到间质间隙中。
诊断建议
淋巴结中的淋巴细胞凋亡可以是正常的。如果与同期对照相比增多，则应诊断淋巴细胞凋亡并赋予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Lymphocyte apoptosis is characterized by cell shrinkage, nuclear pyknosis, and fragmentation of lymphocytes into membrane-bound (apoptotic) bodies that are subsequently phagocytized by macrophages (tingible-body macrophages) ( Figure 1 and Figure 2 , arrowheads). This type of cell death normally occurs in B cells within the germinal centers of secondary follicles, where it is an important homeostatic mechanism. Figure 1 and Figure 2 demonstrate the lesion in T cells in the paracortex. Lymphocyte apoptosis may be normal in lymph nodes, increased in nodes of immunodeficient mice, or induced by various injurious stimuli. Some injurious stimuli induce lymphocyte apoptosis at low doses, whereas at higher doses the stimulus leads to necrosis. Examples of such stimuli include heat, irradiation, hypoxia, and cytotoxic cancer drugs (e.g., cyclophosphamide). Dexamethasone can also incite lymphocyte apoptosis; however, the thymus and spleen are more sensitive to this effect than is the lymph node. If severe enough, lymphocyte apoptosis may lead to lymph node atrophy. Historically, lymphocytes apoptosis has been called "lymphocyte necrosis," but the correct terminology for this lesion is "lymphocyte apoptosis." Single-cell necrosis of lymphocytes has not previously been described in the lymph node. Lymphocyte apoptosis must be differentiated from necrosis, although both can occur together. Necrosis generally occurs in groups of cells and is characterized by cell swelling, condensation, fragmentation and dissolution of the nucleus, cell lysis, and accumulation of eosinophilic cytoplasmic and karyorrhectic nuclear debris. Inflammation generally accompanies necrosis because cell lysis releases cellular contents, including proinflammatory mediators, into the interstitial space.
Recommendation
Lymphocyte apoptosis in the lymph node can be normal. If increased compared with concurrent controls, lymphocyte apoptosis should be diagnosed and assigned a severity grade.
淋巴细胞增生Hyperplasia Lymphocyte 淋巴结增生
描述（中文）
在啮齿类动物中，淋巴细胞增生（lymphocyte hyperplasia）可能累及淋巴结的多个解剖区域，包括富含B细胞的滤泡（滤泡性）、富含T细胞的副皮质区（副皮质性）、髓索，或三者全部受累。滤泡性增生（follicular hyperplasia）表现为初级滤泡数量和体积增加，有时还包括刺激形成次级滤泡（生发中心）。受刺激的生发中心含有大的淋巴母细胞（中心母细胞），并伴有淋巴细胞凋亡增加及可染体巨噬细胞。副皮质区淋巴细胞增生（paracortical lymphocyte hyperplasia）表现为细胞密度增加，偶伴面积增大（Figure 1、Figure 2，箭头）。淋巴细胞增生可伴有血管内淋巴细胞数量增加（淋巴细胞运输）（Figure 2，箭头头）。淋巴细胞增生在正常啮齿类动物中可呈现不同程度，取决于部位（如肠系膜或下颌淋巴结）、年龄、动物健康状态及切面。该病变通常被认为是反应性或免疫反应，而非肿瘤前病变。淋巴细胞增生应与淋巴瘤相鉴别。增生时，淋巴细胞成熟、小、形态正常，并存在于各自相应的区域；而淋巴瘤通常以肿瘤性淋巴细胞呈单一形态群体、淋巴结结构破坏、淋巴结体积增大及侵犯邻近组织为特征。
诊断建议
淋巴结淋巴细胞增生无论何时出现，均应作出诊断、标明部位（如滤泡、副皮质区）并分级。由于淋巴结存在变异性，淋巴细胞增生仅应在仔细评估并与同期对照比较后作出诊断。诊断该病变时必须考虑切片的充分性（即浅表或切向切片）。对于某些淋巴结（如腘淋巴结），可能难以获得充分的切片。
参考切片图（2 张）
查看英文原文
Comment
In rodents, lymphocyte hyperplasia may involve various anatomical compartments of the lymph nodes, including the B-cell–rich follicles (follicular), the T-cell-rich paracortex (paracortical), the medullary cords, or all three. Follicular hyperplasia is identified by an increase in number and size of primary follicles and sometimes includes stimulation that results in secondary follicles (germinal centers). Stimulated germinal centers contain large lymphoblasts (centroblasts) and increased lymphocyte apoptosis with tingible-body macrophages. Paracortical lymphocyte hyperplasia is identified by increased cell density, occasionally accompanied by increased area ( Figure 1 and Figure 2 , arrows). Lymphocyte hyperplasia may be accompanied by increased numbers of lymphocytes within vessels (trafficking) of lymphocytes ( Figure 2 , arrowhead). Lymphocyte hyperplasia can be evident to varying degrees in normal rodents, depending on location (e.g., mesenteric or mandibular lymph nodes), age, animal health status, and the plane of section. This lesion is generally considered to be a reactive or immune response and not a preneoplastic lesion. Lymphocyte hyperplasia should be distinguished from lymphoma. With hyperplasia, lymphocytes are mature, small, and normal in appearance and present within their respective compartments, whereas lymphoma typically features a monomorphic population of neoplastic lymphocytes, effacement of the nodal architecture, increased lymph node size, and invasion of adjacent tissue.
Recommendation
Whenever present, lymphocyte hyperplasia of lymph nodes should be diagnosed, localized (e.g., follicle, paracortex), and graded. Due to lymph node variability, lymphocyte hyperplasia should be diagnosed only after careful evaluation and comparison with concurrent controls. Adequacy of the section (i.e., superficial or tangential) must be taken into consideration in the diagnosis of this lesion. For some lymph nodes (e.g., popliteal), an adequate section may be difficult to obtain.
炎症Inflammation 淋巴结炎症
描述（中文）
炎症细胞可见于淋巴结，其原因可能是给予刺激性受试化合物、对原发性淋巴细胞坏死的反应，或对感染因子或异物的反应。炎症细胞也可见于引流炎症部位的淋巴结，此时应诊断原发病灶，并在相关（引流）淋巴结中诊断“细胞浸润（infiltration, cellular）”。在NTP研究中，炎症的五个标准类别为急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，中性粒细胞是主要的浸润细胞，但也可能存在较少的巨噬细胞和淋巴细胞。水肿或充血可能明显。中性粒细胞也是化脓性炎症中的主要细胞类型，但中性粒细胞聚集，其中许多发生变性（化脓性渗出物）（Figure 1、Figure 2）。渗出物中还可能存在来自驻留细胞群和浸润白细胞的细胞碎片；含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞；以及可能的感染因子。肉眼观察，这些病变的特征是存在渗出物。在渗出物周围的组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也可能存在大量中性粒细胞。慢性和慢性活动性炎症可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的、活化的巨噬细胞（Figure 3、Figure 4）、上皮样巨噬细胞和/或多核巨细胞。巨噬细胞胞质内可能含有含铁血黄素或脂褐素色素或难以降解的物质。淋巴结炎症可伴有淋巴样增生或萎缩以及浆细胞增生。
诊断建议
淋巴结炎症存在时，应诊断并分级。“脓（pus）”和“脓肿（abscess）”一词仅应作为肉眼诊断使用。“慢性活动性（慢性（chronic） active）”可用于描述同时具有急性和慢性炎症成分的病变。在引流炎症和坏死部位的淋巴结中发现的炎症细胞应诊断为“细胞浸润（infiltration, cellular）”，并与淋巴结原发性炎症相区分。相关病变，如坏死或出血，除非因严重程度而有必要，不应单独诊断，但应在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Inflammatory cells can be found in lymph nodes as a result of administration of an irritating test compound, in response to primary lymphocyte necrosis, or as a response to an infectious agent or foreign body. Inflammatory cells can also be found in lymph nodes draining sites of inflammation, in which case the primary lesion should be diagnosed and "infiltration, cellular" should be diagnosed in the associated (draining) lymph node. In NTP studies, the five standard categories of inflammation are acute, suppurative, chronic, chronic active, and granulomatous. In acute inflammation , the neutrophil is the predominant infiltrating cell, though fewer macrophages and lymphocytes may also be present. Edema or hyperemia may be evident. The neutrophil is also the predominant cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate) ( Figure 1 and Figure 2 ). Cell debris from both the resident cell populations and infiltrating leukocytes; proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes, or plasma cells; and, possibly, an infectious agent may also be present within the exudate. Grossly, these lesions would be characterized by the presence of exudate. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation , but there may also be a significant number of neutrophils. Chronic and chronic active inflammation may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages ( Figure 3 and Figure 4 ), epithelioid macrophages, and/ or multinucleated giant cells. Macrophages may contain cytoplasmic hemosiderin or lipofuscin pigment or poorly degradable substances. Lymphoid hyperplasia or atrophy and plasma cell hyperplasia may occur in association with nodal inflammation.
Recommendation
When present, lymph node inflammation should be diagnosed and graded. The terms "pus" and "abscess" should be used as gross diagnoses only. "Chronic active" can be used to describe lesions with components of both acute and chronic inflammation. Inflammatory cells found in lymph nodes draining sites of inflammation and necrosis should be diagnosed as "infiltration, cellular" and distinguished from primary inflammation of the lymph node. Associated lesions, such as necrosis or hemorrhage, should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative.
窦内红细胞增多Sinus Erythrocytosis 淋巴结其他
描述（中文）
窦性红细胞增多症（sinus erythrocytosis）的特征是淋巴窦内存在红细胞（Figure 1，箭头）。该病变通常是由于受累淋巴结引流器官或组织出血所致。急性期可能无反应。慢性病变中，可能出现噬红细胞现象（erythrophagocytosis）（Figure 2，箭头）、退变红细胞的血红蛋白结晶化，以及含铁血黄素色素在淋巴窦、窦组织细胞和髓索巨噬细胞内的蓄积。窦性红细胞增多症必须与血管扩张（angiectasis）、出血、充血、血管瘤和血管肉瘤相鉴别。窦性红细胞增多症与血管扩张的鉴别可能具有挑战性，因为扩张的淋巴管可类似于扩张的血管，且两者均衬以内皮。窦性红细胞增多症可与原发性出血相鉴别，因为血液局限于内皮衬覆的淋巴窦内，而未外渗至组织中。充血同样位于管腔内，但累及血管，血管可能扩张（血管扩张性）也可能不扩张。窦性红细胞增多症可累及整个淋巴结，这将其与血管瘤典型的边界清楚、紧密排列的扩张血管腔隙相区分。血管瘤的血管腔隙衬以内皮，但内皮细胞排列于薄或宽的胶原性间质上。窦性红细胞增多症不具有侵袭性，也不显示内皮细胞异型性，这将其与血管肉瘤相区分。窦性红细胞增多症还必须与安乐死（濒死期）或组织解剖（死后）相关的红细胞外渗相鉴别。调查该淋巴结引流区域内出血的区域可能有助于纳入/排除窦性红细胞增多症。
诊断建议
当存在该病变的生前证据（例如噬红细胞现象或引流区域出血）时，淋巴结窦性红细胞增多症应当被诊断并分级。如果淋巴结内红细胞外渗可归因于濒死期或死后伪影，则不应诊断。
参考切片图（2 张）
查看英文原文
Comment
Sinus erythrocytosis is characterized by the presence of erythrocytes within the lymphatic sinuses ( Figure 1 , arrow). This lesion generally occurs as a result of hemorrhage in organs or tissues drained by the affected node. Acutely, there may be no reaction. In chronic lesions, there may be erythrophagocytosis ( Figure 2 , arrow), crystallization of hemoglobin from degenerate erythrocytes, and accumulation of hemosiderin pigment within lymphatic sinuses, sinus histiocytes, and medullary cord macrophages. Sinus erythrocytosis must be differentiated from angiectasis, hemorrhage, congestion, hemangioma, and hemangiosarcoma. Differentiation of sinus erythrocytosis and angiectasis may be a challenge, since dilated lymphatic vessels can resemble dilated blood vessels and both are lined by endothelium. Sinus erythrocytosis can be differentiated from primary hemorrhage in that blood is confined to endothelial-lined lymphatic sinuses and not extravasated into the tissue. Congestion is also intraluminal but involves blood vessels that may or may not be dilated (angiectatic). Sinus erythrocytosis can occur throughout the lymph node, which differentiates it from the well-circumscribed, tightly packed, dilated vascular spaces typical of hemangioma. The vascular spaces of hemangioma are lined by endothelium, but endothelial cells are aligned on a thin or broad collagenous stroma. Sinus erythrocytosis is not invasive and does not demonstrate endothelial cell atypia, which differentiates it from hemangiosarcoma. Sinus erythrocytosis must be also differentiated from extravasations of erythrocytes associated with euthanasia (perimortem) or tissue dissection (postmortem). A survey for regions of hemorrhage in the drainage field for the node in question may help to rule in/out sinus erythrocytosis.
Recommendation
Sinus erythrocytosis in lymph nodes should be diagnosed and graded when antemortem evidence (e.g., erythrophagocytosis or hemorrhage in drainage field) for the lesion is present. It should not be diagnosed if extravasations of erythrocytes in a lymph node can be attributed to peri- or postmortem artifact.
红细胞吞噬作用Erythrophagocytosis 淋巴结其他
描述（中文）
淋巴结内的噬红细胞现象（erythrophagocytosis）是指窦内巨噬细胞吞噬外渗的、衰老的和/或受损的红细胞（Figure 1、Figure 2，箭头）。噬红细胞现象在正常条件下不发生，最常与淋巴结出血、充血、窦性红细胞增多症以及自身免疫性和其他免疫病理状态相关。
诊断建议
当淋巴结内出现噬红细胞现象时，应当对其进行诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Erythrophagocytosis in lymph nodes consists of macrophages within sinuses that phagocytize extravasated, old, and/or damaged erythrocytes ( Figure 1 and Figure 2 , arrows). Erythrophagocytosis does not occur under normal conditions and is most often associated with lymph node hemorrhage, congestion, sinus erythrocytosis, and autoimmune and other immunopathologic conditions.
Recommendation
When erythrophagocytosis is present within lymph nodes, it should be diagnosed and graded.
组织细胞性细胞浸润Inflitration Cellular Histiocyte 淋巴结其他
描述（中文）
大鼠和小鼠淋巴结中的组织细胞（histiocyte）可能增多。该病变可自发发生（例如，肠系膜淋巴结受到日粮抗原刺激），也可继发于受试物处理。组织细胞增多可能反映驻留窦组织细胞的增殖，或经输入淋巴管进入的组织细胞增多。该病变可位于被膜下窦、副皮质区窦或髓窦内（Figure 1，箭头）。若该病变在特定剂量组的同一淋巴结（例如吸入研究中的支气管淋巴结）中发生，则可能提示与处理相关的效应。受累淋巴结中的组织细胞胞质内可能含有不溶性颗粒物质，如被吞噬的受试物或赋形剂物质（Figure 2，箭头）或色素（含铁血黄素等）。在持续自发抗原或异物刺激下的淋巴结（例如肠系膜淋巴结）中，组织细胞增多必须与处理所致的增多相鉴别。淋巴结组织细胞既往使用的术语为“组织细胞增生（histiocyte hyperplasia）”和“组织细胞浸润（histiocyte infiltrate）”。
诊断建议
大鼠和小鼠淋巴结中组织细胞增多无论何时出现，均应作出诊断并给出严重程度分级。该病变应始终结合受试物、处理组、给药途径和受累淋巴结（与同期对照比较）进行诊断。
参考切片图（2 张）
查看英文原文
Comment
Histiocytes may be increased in the lymph nodes of rats and mice. This lesion can occur spontaneously (e.g., dietary antigenic stimulation of mesenteric lymph nodes) or secondary to treatment. Increases may reflect proliferation of resident sinusoidal histiocytes or an increased influx of histiocytes via the afferent lymphatics. This lesion may be within subcapsular, paracortical, or medullary sinuses ( Figure 1 , arrows). If this lesion occurs in the same lymph node for a particular dose group (e.g., bronchial lymph node in an inhalation study), it may suggest a treatment-related effect. Histiocytes in affected lymph nodes may contain intracytoplasmic insoluble particulate matter, such as phagocytized test article or vehicle material ( Figure 2 , arrow) or pigment (hemosiderin, etc.). Histiocyte increases in lymph nodes under constant spontaneous antigenic or foreign material stimulation (e.g., mesenteric lymph nodes) must be differentiated from increases due to treatment. Previous terms for histiocytes in lymph nodes are "histiocyte hyperplasia" and "histiocyte infiltrate."
Recommendation
Whenever present, histiocyte increases in the lymph nodes of rats and mice should be diagnosed and given a severity grade. This lesion should always be diagnosed in the context of the test article, treatment group, route of administration, and lymph node involved (compare with concurrent controls).
肥大细胞增生Hyperplasia Mast Cell 淋巴结增生
描述（中文）
肥大细胞增生（mast cell hyperplasia）是指淋巴结内肥大细胞数量超过正常水平（即同期对照组）。肥大细胞可在淋巴结窦内和实质内以单个细胞和/或细胞簇的形式聚集（Figure 1、Figure 2，箭头）。肥大细胞通过活化和从抗原接触部位迁移至引流淋巴结，参与初级免疫反应的诱导，在引流淋巴结中表达调节T细胞募集的趋化因子。Giemsa染色或甲苯胺蓝染色可特异性识别呈异染性的肥大细胞颗粒。
诊断建议
肥大细胞增生一旦出现即应作出诊断并进行分级。
参考切片图（2 张）
查看英文原文
Comment
Mast cell hyperplasia is an increase in the number of mast cells above that normally found in lymph nodes (i.e., concurrent controls). Mast cells may accumulate in lymph nodes as individual and/or clusters of cells within the nodal sinuses and parenchyma ( Figure 1 and Figure 2 , arrows). Mast cells contribute to the induction of the primary immune response by activation and migration from the site of antigen encounter to draining lymph nodes, where they express chemokines that regulate T-cell recruitment. Giemsa or toluidine blue can specifically identify the metachromic mast cell granules.
Recommendation
Mast cell hyperplasia should be diagnosed and graded whenever present.
色素Pigment 淋巴结色素沉着
描述（中文）
色素（pigment）是对照组和给药组啮齿动物淋巴结中的常见发现，尤其是在肠系膜淋巴结和下颌淋巴结。通常，色素见于髓窦和髓索的巨噬细胞内，并可能因受试物作用而增多。当明确与受试物相关时，外源性色素一般在受试物给药途径区域引流淋巴结中最为显著。含铁血黄素（hemosiderin）（Figure 1，箭头）和蜡样质/脂褐素（ceroid/lipofuscin）（Figure 2，箭头）是最常见的色素。含铁血黄素是一种含铁的金棕色颗粒状物质，含该色素的巨噬细胞通常与窦内红细胞增多、充血或出血同时可见。脂褐素也是一种黄棕色、细颗粒状色素；但其主要来源于脂质（如细胞膜）的分解产物。蜡样质是脂褐素的一种变体，具有抗酸性（acid-fast）和自发荧光（autofluorescent）特性。仅使用常规苏木精-伊红（hematoxylin and eosin，H&E）染色无法100%确定地区分这些色素。含铁血黄素可用铁染色如Perl’s铁染色和普鲁士蓝（Prussian blue）染色识别，两者均将色素染成蓝色。蜡样质/脂褐素可用Sudan black B、Schmorl反应、Oil Red O、石炭酸脂褐素染色（carbol lipofuscin stain）、过碘酸-雪夫（periodic acid-Schiff，PAS）染色、Ziehl-Neelsen抗酸染色、自发荧光或溶酶体酸性磷酸酶和酯酶染色识别。黑色素（melanin）是另一种可在淋巴结内发现的内源性色素。在黑毛小鼠中这是正常发现。Schmorl法和多巴氧化酶（dopa-oxidase）组织化学染色可用于识别黑色素。
诊断建议
淋巴结中的色素应当进行诊断并给出严重程度分级。然而，并非所有色素都必须诊断，因为有些色素在衰老动物中普遍存在，或与某些其他疾病过程相关，而不具有毒理学意义。病理学家应运用其判断来决定色素沉积是否具有毒理学意义，或是否显著到足以 warrant 单独诊断。即使使用一系列特殊染色，在组织学切片中确定性识别色素通常也很困难。因此，推荐使用“色素”这一诊断（而非诊断色素类型，例如含铁血黄素或脂褐素）最为恰当。病理学描述（pathology narrative）应描述色素沉着的形态学特征。
参考切片图（2 张）
查看英文原文
Comment
Pigment is a common finding in lymph nodes of control and treated rodents, particularly in the mesenteric and mandibular lymph nodes. Typically, pigment is seen within macrophages of the medullary sinuses and cords and may become increased as an effect of treatment. When specifically related to treatment, exogenous pigment is generally most prominent in lymph nodes regional to the route of test article administration. Hemosiderin ( Figure 1 , arrows) and ceroid/lipofuscin ( Figure 2 , arrows) are the most frequently encountered pigments. Hemosiderin is an iron-containing golden-brown granular material, and macrophages containing this pigment are typically observed with sinus erythrocytosis, congestion, or hemorrhage. Lipofuscin is also a yellow-brown, finely granular pigment; however, it is derived mainly from the breakdown products of lipids, such as cell membranes. Ceroid is a variant of lipofuscin that is acid-fast and autofluorescent. Differentiation of these pigments with 100% certainty using only conventional hematoxylin and eosin (H&E) staining is not possible. Hemosiderin can be identified with iron stains such as Perl’s iron and Prussian blue, both of which stain the pigment blue. Ceroid/lipofuscin may be identified with Sudan black B, Schmorl''s reaction, Oil Red O, carbol lipofuscin stain, periodic acid-Schiff, Ziehl-Neelsen acid-fast stain, autofluorescence, or lysosomal acid phosphatase and esterase stains. Melanin is another endogenous pigment that can be found within lymph nodes. This is a normal finding in black mice. Schmorl''s method and dopa-oxidase histochemical stains can be used to identify melanin pigment.
Recommendation
Pigment in lymph nodes should be diagnosed and given a severity grade. However, not all pigments have to be diagnosed, as some are ubiquitous in aging animals or related to some other disease process and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether deposits of pigment are toxicologically significant or prominent enough to warrant a separate diagnosis. Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, it is recommended that a diagnosis of "pigment" (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should describe the morphologic features of the pigmentation.
萎缩Atrophy 淋巴结萎缩
描述（中文）
淋巴结萎缩（lymph node atrophy）可由任何引起淋巴细胞坏死或凋亡的毒性损伤或疾病所致。病变可包括副皮质区淋巴细胞耗竭（Figure 1，箭头）、滤泡数量和体积减少且生发中心极少至无（Figure 1，箭头head），以及髓索细胞密度降低；视严重程度而定，副皮质区基质细胞和高内皮微静脉可能更为显著（Figure 2，箭头）。淋巴细胞的进行性丢失可导致淋巴结缩小（萎缩），在大体或亚大体观察中可见。萎缩的淋巴组织可被脂肪组织及可能的胶原所取代。同一动物不同淋巴结之间的萎缩严重程度也可能存在差异。萎缩可由毒性损伤引起，但也可见于老龄大鼠和小鼠。年龄相关的变化不应诊断。
诊断建议
淋巴结萎缩应予以诊断并分级，除非确定其为年龄相关。评估淋巴结时还应考虑切面和部位。
参考切片图（2 张）
查看英文原文
Comment
Lymph node atrophy may result from any toxic insult or disease that causes lymphocyte necrosis or apoptosis. Changes may include depletion of paracortical lymphocytes ( Figure 1 , arrow), a decrease in the number and size of follicles with few to no germinal centers ( Figure 1 , arrowhead), and a decrease in cellularity of medullary cords; depending on severity, the paracortical stromal cells and high endothelial venules may be more prominent ( Figure 2 , arrows). Progressive loss of lymphocytes may cause shrinking (atrophy) of a lymph node that is apparent grossly or subgrossly. Atrophic lymphoid tissue may be replaced by adipose tissue and possibly collagen. The severity of atrophy may also vary between lymph nodes within the same animal. Atrophy may result from toxic insult but may also be seen in aged rats and mice. Age-related changes should not be diagnosed.
Recommendation
Lymph node atrophy should be diagnosed and graded unless it is determined to be age related. Plane of section and location should also be considered when evaluating the lymph nodes.
血管扩张Angiectasis 淋巴结扩张
描述（中文）
淋巴结血管扩张（angiectasis）的特征是皮质、髓质、被膜、门部或周围结缔组织内薄壁静脉的扩张（Figure 1）。血管腔由无明显异常的内皮细胞衬覆，通常充满血液。血管数量无明显增加。该病变最常见于某些小鼠和大鼠品系的肠系膜淋巴结，可能不伴有出血。血管扩张应与充血（congestion）、窦性红细胞增多（sinus erythrocytosis）、出血（hemorrhage）、血管瘤（hemangioma）和血管肉瘤（hemangiosarcoma）相鉴别。血管扩张与充血之间的区分有时较为困难，但充血时血管扩张的程度被认为是生理性正常的。血管扩张与出血不同；血管扩张时，血液局限于内皮衬覆的血管腔内（Figure 2，箭头），而出血时血液位于血管腔外。血管扩张可能与窦性红细胞增多难以区分，因为扩张的血管可类似于扩张并充满血液的淋巴管。应尝试区分血管扩张与血管瘤，尽管两者之间的差异并不总是显而易见。血管瘤往往为边界清楚、无包膜的肿块，由紧密排列的扩张血管腔构成。每个血管腔均为封闭的，由单层外观正常的内皮细胞衬覆，内皮细胞排列于胶原性间隔上，这些间隔通常较薄，但部分具有宽阔的胶原性间质。血管扩张通常不表现为边界清楚的肿块；扩张的血管通道常不规则地穿行于造血组织中。此外，血管扩张的扩张血管通道不具有侵袭性，也不显示内皮细胞异型性，借此可将该病变与血管肉瘤相区分。血管扩张以往的术语包括“hemangiectasis”“hemangiectasia”“vasodilation”和“vasodilatation”。
诊断建议
只要淋巴结中出现血管扩张，就应作出诊断并赋予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Angiectasis of the lymph node is characterized by the dilatation of thin veins within the cortex, medulla, capsule, hilus, or surrounding connective tissue ( Figure 1 ). The vascular spaces are lined by unremarkable endothelial cells and are typically filled with blood. There is no apparent increase in the number of vessels. It is seen most often in the mesenteric lymph nodes of some mouse and rat strains and may not be associated with hemorrhage. Angiectasis should be distinguished from congestion, sinus erythrocytosis, hemorrhage, hemangioma, and hemangiosarcoma. The distinction between angiectasis and congestion is sometimes difficult, but with congestion, the degree of vascular dilation is considered physiologically normal. Angiectasis differs from hemorrhage; with angiectasis, the blood is contained within endothelium-lined vascular spaces ( Figure 2 , arrows), whereas with hemorrhage, the blood is outside the vascular spaces. Angiectasis may be difficult to differentiate from sinus erythrocytosis because dilated blood vessels can resemble dilated and blood-filled lymphatic vessels. The distinction between angiectasis and hemangioma should be attempted, although the difference is not always obvious. Hemangiomas tend to be well-circumscribed, unencapsulated masses composed of tightly packed, dilated vascular spaces. Each vascular space is enclosed and lined by a single layer of normal-appearing endothelial cells aligned on collagenous septa, which are usually thin, although some have broad collagenous stroma. Angiectasis does not usually present as a well-circumscribed mass; the dilated vascular channels often course irregularly through the hematopoietic tissue. Furthermore, the dilated vascular channels of angiectasis are not invasive and do not demonstrate endothelial cell atypia, which differentiates this lesion from hemangiosarcoma. Previous terms for angiectasis include "hemangiectasis," "hemangiectasia," "vasodilation," and "vasodilatation."
Recommendation
Whenever angiectasis is present in lymph nodes, it should be diagnosed and assigned a severity grade.
髓外造血Extramedullary Hematopoiesis 淋巴结其他
描述（中文）
虽然骨髓是造血的主要部位，但淋巴结可能是髓外造血（extramedullary hematopoiesis，EMH）的部位。淋巴结中的EMH通常是对血液细胞急剧丢失或对额外血液细胞需求增加的生理性反应。诱发因素包括出血、感染、严重炎症、骨髓纤维化和肿瘤。EMH的特征是不同程度地混合存在髓系、红系和巨核系细胞，主要存在于淋巴结髓索内（Figure 1、Figure 2）。某一造血细胞谱系可能占优势，并可见不同程度的未成熟细胞。EMH应与炎性浸润和粒细胞性白血病相鉴别。淋巴结中的炎性浸润通常发育成熟，可为单一或混合细胞类型（见淋巴结-炎症）。粒细胞性白血病的特征是高数量的未成熟肿瘤性髓系细胞累及多个器官。髓外造血的既往术语包括“造血细胞增生”和“髓系增生”。
诊断建议
淋巴结中的髓外造血应当诊断并分级。淋巴结中出现该病变时应促使评估其他器官是否存在EMH（尤其是脾和肝）。相关链接：肝-髓外造血 淋巴结-炎症 脾-髓外造血
参考切片图（2 张）
查看英文原文
Comment
While the bone marrow is the major site of hematopoiesis, lymph nodes may be a site of extramedullary hematopoiesis (EMH). EMH in lymph nodes typically occurs as a physiologic response to a dramatic loss or increased need for additional blood cells. Examples of inciting factors include hemorrhage, infection, severe inflammation, myelofibrosis, and neoplasia. EMH is characterized by a mixture, to varying degrees, of myeloid, erythroid, and megakaryocytic cells and is primarily present within the lymph node medullary cords ( Figure 1 and Figure 2 ). One lineage of hematopoietic cell may predominate, and various degrees of immaturity may be seen. EMH should be distinguished from inflammatory infiltrates and granulocytic leukemia. Inflammatory infiltrates in the lymph node are generally mature in development and may be a single or mixed cell type (see Lymph Node - Inflammation ). Granulocytic leukemia is characterized by high numbers of immature neoplastic myeloid cells that involve multiple organs. Previous terms for extramedullary hematopoiesis include ''hematopoietic cell proliferation" and "myeloid hyperplasia."
Recommendation
Extramedullary hematopoiesis in lymph nodes should be diagnosed and graded. The presence of this lesion in lymph nodes should prompt evaluation of other organs for EMH (especially the spleen and liver). Related Links: Liver - Extramedullary Hematopoiesis Lymph Node - Inflammation Spleen - Extramedullary Hematopoiesis
上皮增生Hyperplasia Epithelial 胸腺增生
描述（中文）
上皮增生常与胸腺的退化（involution）和/或萎缩（atrophy）相关，在某些啮齿动物品系中可能以相对较高的发生率出现。胸腺上皮增生见于髓质，可呈局灶性（focal）至弥漫性（diffuse）分布。上皮细胞呈立方状至柱状，胞质丰富、染色较浅，并可能具有纤毛。它们常形成小管（Figure 1，箭头）、带状或索状结构（Figure 1，箭头head）。小管内可含有数量不等的嗜酸性分泌物（Figure 2，箭头）。上皮性改变在雌性中比雄性更显著，在大鼠中比小鼠更显著。胸腺上皮增生的多形性变异与胸腺瘤的细胞形态谱相似。因此，胸腺上皮增生可能难以与早期良性胸腺瘤相区分。然而，胸腺瘤呈结节状并具有压迫性，而增生则不具有这些特征。
诊断建议
当胸腺上皮增生不与退化相关时，应当予以诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Epithelial hyperplasia is often associated with involution and/or atrophy of the thymus and may occur at relatively high incidences in some rodent strains. Thymic epithelial hyperplasia is found in the medulla and may be focal to diffuse. Epithelial cells are cuboidal to columnar, have paler-staining abundant cytoplasm, and may be ciliated. They often form tubules ( Figure 1 , arrow), ribbons, or cords ( Figure 1 , arrowhead). Tubules can contain variable amounts of eosinophilic secretory material ( Figure 2 , arrow). Epithelial changes are more prominent in females than in males and in rats more so than in mice. Pleomorphic variations of thymic epithelial hyperplasia are similar to the spectrum of cellular forms of thymoma. Consequently, thymic epithelial hyperplasia may be difficult to distinguish from early, benign thymomas. However, thymomas are nodular and compressing, whereas hyperplasias are not.
Recommendation
Epithelial hyperplasia in the thymus should be diagnosed and graded when not associated with involution.
出血Hemorrhage 胸腺出血
描述（中文）
出血（hemorrhage）的特征是胸腺实质内出现外渗的红细胞（Figure 1，箭头）。在啮齿类动物的胸腺皮质和/或髓质中可见出血，可能是濒死性改变。在没有坏死或其他病变（如噬红细胞现象（erythrophagocytosis）（Figure 2，箭头）或载色素巨噬细胞）的情况下，胸腺出血可能归因于剖检技术（医源性），并被视为解剖所致的人工假象，而非血管病变的结果。然而，胸腺出血可发生于某些维生素缺乏症，因此饮食应作为考虑因素。出血应与充血（congestion）相鉴别，后者血液局限于由内皮细胞衬覆的界限清晰的血管腔内。
诊断建议
非归因于剖检技术的胸腺出血应予以诊断并分级。被视为继发于坏死、炎症或肿瘤的出血不应单独诊断，除非其严重程度足以支持单独诊断，但应在病理学描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage is characterized by the presence of extravasated erythrocytes within the thymic parenchyma ( Figure 1 , arrows). Hemorrhage can be seen in the cortex and/or medulla of the thymus of rodents and may be an agonal change. In the absence of necrosis or other lesions such as erythrophagocytosis ( Figure 2 , arrows) or pigment-laden macrophages, hemorrhage in the thymus may be attributed to necropsy technique (iatrogenic) and considered a dissection-induced artifact and not the result of a vascular lesion. However, thymic hemorrhage can occur with some vitamin deficiencies, so diet should be a consideration. Hemorrhage should be distinguished from congestion, where the blood is contained with well-defined vascular spaces lined by endothelial cells.
Recommendation
Hemorrhage in the thymus that is not attributed to necropsy technique should be diagnosed and graded. Hemorrhage that is considered to be secondary to necrosis, inflammation, or neoplasia should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative.
囊肿Cyst 胸腺囊肿
描述（中文）
啮齿类动物的胸腺囊肿（Figure 1，箭头）代表胸腺管状结构的扩张或胸咽管残余。它们是大鼠和小鼠退化性和/或萎缩性胸腺中的常见所见。胸腺囊肿通常由立方至鳞状上皮细胞衬覆（Figure 2，箭头），这些细胞可具有纤毛，并含有数量不等的均质嗜酸性物质（Figure 2，箭头指示）。胸腺囊肿形成随年龄增长而更为显著，并与退化相关。囊肿形成在2岁雌性大鼠中可能比同龄雄性大鼠更常见。
诊断建议
对于常规研究，仅当囊肿提示治疗相关改变时才应作出诊断。首选诊断术语为“胸腺 - 囊肿”。NTP研究中通常不对囊肿进行分级，但如果病理学家认为有必要充分描述对化学物质的反应，则可进行分级。如果存在一个以上囊肿，可在诊断中添加修饰词“multiple”。胸腺囊肿还应在病理学叙述中描述（例如，衬覆内皮的外观、位置、数量）。与另一病变相关的囊肿（例如，继发于胸腺萎缩）不应单独诊断，而应在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Thymic cysts ( Figure 1 , arrows) in the rodent represent either a dilatation of thymic tubular structures or remnants of the thymopharyngeal duct. They are common findings in the involuted and/or atrophied thymus glands of rats and mice. Thymic cysts are typically lined by cuboidal to squamous epithelial cells ( Figure 2 , arrow), which may be ciliated and contain variable amounts of homogeneous eosinophilic material ( Figure 2 , arrowhead). Thymic cyst formation becomes more prominent with age and is associated with involution. Formation of cysts may occur more commonly in 2-year-old female rats than in age-matched males.
Recommendation
For routine studies, cysts should be diagnosed only when indicative of a treatment-related change. The preferred diagnostic term is "Thymus - Cyst." Cysts are not routinely graded in NTP studies, but they may be graded if the pathologist feels it is necessary to fully characterize the response to the chemical. If more than one cyst is present, the modifier "multiple" may be added to the diagnosis. Thymic cysts should also be described in the pathology narrative (e.g., appearance of lining endothelium, location, number). Cysts associated with another lesion (e.g., secondary to thymic atrophy) should not be diagnosed separately, but should be described in the pathology narrative.
异位组织Ectopic Tissue 胸腺其他
描述（中文）
异位组织是指结构正常的组织（如甲状腺、甲状旁腺）出现在异常位置。该病变可为先天性或损伤所致。异位甲状腺组织可发生于啮齿类动物的胸腺内和/或胸腺邻近部位。Figure 1所示的甲状腺组织由被纤细纤维血管间质分隔的、衬覆上皮的含胶质滤泡组成。甲状腺C细胞偶尔可见于滤泡上皮与甲状腺滤泡基底膜之间。异位甲状旁腺组织偶尔发生于大鼠和/或小鼠胸腺被膜邻近部位或嵌入胸腺被膜内。Figure 2所示的甲状旁腺组织由被薄层纤维血管间质分隔的密集排列、高度折叠、分支状的索和簇状多边形细胞组成。异位甲状旁腺组织是一种不常见的偶然发现，但当其存在时，应将其与胸腺瘤或其他可能的早期或小肿瘤相鉴别。
诊断建议
异位组织通常是啮齿类动物胸腺内或胸腺邻近部位的偶然发现。当该病变存在时，应予以诊断但不进行分级。存在的异位组织类型（如甲状腺、甲状旁腺）应作为修饰词纳入诊断（如，胸腺 - 异位组织，甲状腺）。
参考切片图（2 张）
查看英文原文
Comment
Ectopic tissue is a fragment of structurally normal tissue (e.g., thyroid, parathyroid) in an abnormal location. This lesion can be congenital or the result of an injury. Ectopic thyroid tissue may occur in and/or adjacent to the thymus of rodents. The thyroid tissue shown in Figure 1 consists of epithelial-lined, colloid-containing follicles separated by a fine fibrovascular stroma. Thyroid C cells may occasionally be found between the follicular epithelium and the basement membrane of the thyroid follicles. Ectopic parathyroid tissue occasionally occurs either adjacent to or embedded in the thymic capsule of rats and/or mice. The parathyroid tissue shown in Figure 2 consists of densely packed, highly folded, branching cords and clusters of polygonal cells separated by a thin fibrovascular stroma. Ectopic parathyroid tissue is an uncommon, incidental finding, although when present it should be distinguished from thymoma or other possible early or small tumors.
Recommendation
Ectopic tissue is typically an incidental finding in or adjacent to the thymus of rodents. When this lesion is present it should diagnosed but not graded. The type of ectopic tissue present (e.g., thyroid, parathyroid) should be included in the diagnosis as a modifier (e.g., Thymus - Ectopic tissue, Thyroid).
淀粉样物质Amyloid 胸腺其他
描述（中文）
在啮齿类动物中，胸腺的自发性及化学诱导性淀粉样物质沉积罕见。当胸腺出现淀粉样物质时，在苏木精-伊红（H&E）染色下表现为无定形、嗜酸性、玻璃样变的细胞外物质（Figure 1、Figure 2，箭头）。刚果红染色后于偏振光下观察，淀粉样物质可呈现苹果绿双折射现象，据此可予以鉴定。
诊断建议
胸腺中只要出现淀粉样物质，即应作出诊断并进行分级。由于淀粉样变性是一种全身性疾病，还应评估其他组织（如肝脏和肾脏）是否存在淀粉样物质沉积。继发性病变，如实质细胞坏死或变性，除非因严重程度需要或对研究结果的解释具有重要意义，否则不应单独诊断，但应在病理学叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Spontaneous and chemically induced amyloid deposition in the thymus is rare in rodents. When present in the thymus, amyloid appears as amorphous, eosinophilic, and hyalinized extracellular material with hematoxylin and eosin (H&E) staining ( Figure 1 and Figure 2 , arrows). Amyloid can be identified by apple-green birefringence when stained with Congo red and visualized under polarized light.
Recommendation
Whenever present in the thymus, amyloid should be diagnosed and graded. Because amyloidosis is a systemic disease, other tissues, such as liver and kidney, should also be evaluated for amyloid deposition. Secondary lesions, such as necrosis or degeneration of parenchymal cells, should not be diagnosed separately unless warranted by severity or important for interpretation of study results, but should be described in the pathology narrative.
淋巴细胞凋亡Apoptosis Lymphocyte 胸腺凋亡
描述（中文）
胸腺淋巴细胞凋亡可发生于啮齿类动物，作为淋巴细胞阳性和阴性选择的一部分（即生理性凋亡），或继发于应激诱导的肾上腺皮质功能亢进、生长激素水平降低和/或直接毒性（例如皮质类固醇、雌激素或环磷酰胺）。凋亡的特征是单个淋巴细胞皱缩、核染色质（核固缩）和细胞器浓缩，以及凋亡细胞碎裂成膜结合的凋亡小体，随后被巨噬细胞（可染小体巨噬细胞）吞噬（Figure 2，箭头）。大量可染小体巨噬细胞在胸腺皮质形成典型的“星空”外观（Figure 1，箭头）。胸腺淋巴细胞显著凋亡而无细胞再生会导致胸腺萎缩。淋巴细胞凋亡必须与胸腺淋巴细胞坏死相鉴别，尽管在某些化学物（例如地塞米松）作用下二者可同时发生。淋巴细胞坏死通常呈广泛分布或累及相邻细胞，且不与可染小体巨噬细胞相关；一般可见淡嗜酸性碎片、核固缩碎片和炎症。胸腺淋巴细胞大量坏死还可伴有炎症、出血和/或矿化。早期与治疗相关的淋巴细胞凋亡可能难以与年轻大鼠和小鼠生理性正常的低水平背景淋巴细胞丢失相区分。因此，必须与同期对照进行比较。
诊断建议
胸腺淋巴细胞凋亡可以是正常的。如果与同期对照相比增加，则应诊断淋巴细胞凋亡并分级。诊断应基于病理学家的判断。如果淋巴细胞凋亡和坏死同时发生，则应同时诊断这两种病变。
参考切片图（2 张）
查看英文原文
Comment
Apoptosis of thymic lymphocytes may occur in rodents as a part of positive and negative selection of lymphocytes (i.e., physiological apoptosis) or secondary to stress-induced adrenocortical hyperactivity, decreased levels of growth hormone, and/or direct toxicity (e.g., corticosteroids, estrogen, or cyclophosphamide). Apoptosis is characterized by shrinkage of individual lymphocytes, condensation of nuclear chromatin (pyknotic nuclei) and cytoplasmic organelles, and fragmentation of apoptotic cells into membrane-bound bodies (apoptotic bodies), which are subsequently phagocytized by macrophages (tingible-body macrophages) ( Figure 2 , arrows). Numerous tingible-body macrophages create a classic "starry sky" appearance in the thymic cortex ( Figure 1 , arrowheads). Significant apoptosis of thymic lymphocytes without cell regeneration leads to atrophy of the thymus. Apoptosis of lymphocytes must be differentiated from lymphocyte necrosis in the thymus, although they can occur together with some chemicals (e.g., dexamethasone). Necrosis of lymphocytes is typically widespread or affects contiguous cells and is not associated with tingible-body macrophages; there is generally pale eosinophilic debris, pyknotic nuclear debris, and inflammation. Massive necrosis of thymic lymphocytes may also be accompanied by inflammation, hemorrhage, and/or mineralization. Early treatment-related lymphocyte apoptosis may be difficult to differentiate from the low background lymphocyte loss that is physiologically normal in young rats and mice. Therefore, comparison with concurrent controls is necessary.
Recommendation
Lymphocyte apoptosis in the thymus can be normal. If increased compared with concurrent controls, lymphocyte apoptosis should be diagnosed and graded. Diagnosis should be made based on the judgment of the pathologist. If lymphocyte apoptosis and necrosis occur concurrently, both lesions should be diagnosed.
淋巴细胞坏死Necrosis Lymphocyte 胸腺坏死
描述（中文）
胸腺淋巴细胞坏死可作为皮质类固醇、雌激素和环磷酰胺等毒物的直接效应发生于大鼠和/或小鼠，且通常与严重的淋巴细胞凋亡同时存在。皮质和/或髓质淋巴细胞可受累（Figure 1）。坏死也可累及胸腺的所有细胞成分。坏死的特征为细胞肿胀、细胞核浓缩和溶解，以及细胞溶解并伴有大量嗜酸性粒细胞（eosinophil）胞质和嗜碱性粒细胞核碎片的积聚（Figure 2，箭头）。坏死通常伴有炎症，也可伴有出血和/或矿化（Figure 2，箭头head）。显著的淋巴细胞坏死可导致胸腺萎缩，伴或不伴胸腺再生。淋巴细胞坏死必须与淋巴细胞凋亡相鉴别，尽管如果凋亡严重且凋亡因子如caspases和ATP耗竭时二者可同时发生。凋亡通常表现为单个淋巴细胞皱缩、核染色质浓缩以及凋亡细胞碎裂为凋亡小体。凋亡小体被巨噬细胞（可染小体巨噬细胞）吞噬。凋亡通常不伴有炎症、出血或矿化。
诊断建议
每当胸腺淋巴细胞发生坏死而胸腺其他成分未受累时，应诊断为“胸腺 - 坏死，淋巴细胞”并赋予严重程度分级。当胸腺所有细胞成分均坏死时，应诊断为“胸腺 - 坏死”。坏死相关的炎症、出血或矿化不应单独诊断，除非严重程度 warrant，但应纳入病理学描述中。淋巴细胞坏死必须与淋巴细胞凋亡相鉴别。如果淋巴细胞坏死和凋亡同时发生，应对两种病变均进行诊断和分级。
参考切片图（2 张）
查看英文原文
Comment
Necrosis of thymic lymphocytes can occur in rats and/or mice as a direct effect of toxicants such as corticosteroids, estrogen, and cyclophosphamide, and usually in conjunction with severe lymphocyte apoptosis. The cortical and/or medullary lymphocytes may be involved ( Figure 1 ). Necrosis may also involve all cell components of the thymus. Necrosis is characterized by cell swelling, condensation and dissolution of the nucleus, and cell lysis with accumulation of abundant eosinophilic cytoplasmic and basophilic nuclear debris ( Figure 2 , arrows). Necrosis is usually accompanied by inflammation and may also be accompanied by hemorrhage and/or mineralization ( Figure 2 , arrowhead). Significant lymphocyte necrosis may lead to atrophy of the thymus, with or without thymic regeneration. Necrosis of lymphocytes must be differentiated from lymphocyte apoptosis, although they can occur together if apoptosis is severe and apoptotic factors such as caspases and ATP are depleted. Apoptosis typically involves shrinkage of individual lymphocytes, condensation of nuclear chromatin, and fragmentation of apoptotic cells into apoptotic bodies. Apoptotic bodies are phagocytized by macrophages (tingible-body macrophages). Apoptosis is not typically associated with inflammation, hemorrhage, or mineralization.
Recommendation
Whenever there is necrosis of thymic lymphocytes, but other components of the thymus are spared, "Thymus - Necrosis, Lymphocyte" should be diagnosed and assigned a severity grade. A diagnosis of "Thymus - Necrosis" should be made when all cellular components of the thymus are necrotic. Necrosis-associated inflammation, hemorrhage, or mineralization should not be diagnosed separately unless warranted by severity, but should be included in the pathology narrative. Lymphocyte necrosis must be differentiated from lymphocyte apoptosis. If lymphocyte necrosis and apoptosis occur concurrently, diagnose and grade both lesions.
淋巴细胞非典型增生Atypical Hyperplasia Lymphocyte 胸腺增生
描述（中文）
胸腺淋巴细胞非典型性增生（非典型性（atypical） hyperplasia of the thymic lymphocytes）已在经化学处理的B6C3F1小鼠和p53缺陷小鼠中有描述。该病变也发生于其他可发生胸腺淋巴瘤的小鼠品系，并可能发生于化学诱导胸腺淋巴瘤的大鼠。它可以是单侧的或双侧的；当为单侧时，未受累的叶通常大于异常叶（Figure 1，箭头），并且可能发生另一叶的萎缩。该病变的特征是小淋巴细胞耗竭以及正常胸腺皮质髓质交界消失的弥漫性改变。正常胸腺结构被一片大的非典型淋巴细胞所取代，其中包括淋巴母细胞和较少、混杂的小淋巴细胞（Figure 2）；这些细胞不超出胸腺被膜。胸腺淋巴细胞非典型性增生被视为一种增殖性改变，可能进展为淋巴瘤，尽管它也可能不发生进展。这一推测的癌前病变可通过淋巴细胞的异质性细胞群体、核分裂率和缺乏被膜侵袭与淋巴瘤相鉴别。
诊断建议
无论何时出现，胸腺淋巴细胞非典型性增生均应作出诊断并赋予严重程度分级。应在病理学叙述中注明该病变存在于一个还是两个胸腺叶。
参考切片图（2 张）
查看英文原文
Comment
Atypical hyperplasia of the thymic lymphocytes has been described in chemically treated B6C3F1 and p53-deficient mice. This lesion also occurs in other mouse strains that develop thymic lymphomas and possibly in rats with chemically induced thymic lymphomas. It may be unilateral or bilateral; when unilateral, the unaffected lobe is typically larger than the abnormal lobe ( Figure 1 , arrow), and atrophy of the other lobe may occur. This lesion is characterized by depletion of small lymphocytes and a diffuse change with loss of the normal thymic corticomedullary junction. Normal thymic architecture is replaced by a sheet of large, atypical lymphocytes, including lymphoblasts and fewer, admixed small lymphocytes ( Figure 2 ); these cells do not extend beyond the capsule of the thymus. Atypical hyperplasia of the thymic lymphocytes is regarded as a proliferative change that may progress to lymphoma, although it may occur without progression. This putative preneoplastic lesion can be differentiated from lymphoma by the heterogeneous population of lymphocytes, mitotic rate, and lack of capsular invasion.
Recommendation
Whenever present, atypical hyperplasia of the thymic lymphocytes should be diagnosed and assigned a severity grade. It should be noted in the pathology narrative whether the lesion is present in one or both thymic lobes.
炎症Inflammation 胸腺炎症
描述（中文）
原发性炎症在啮齿类动物的胸腺中是一种不常见的病变。如果存在，更可能是其他组织炎症的延伸，尤其是口腔灌胃过程中食管穿孔继发的炎症。在NTP研究中，炎症的五个标准类别是急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，中性粒细胞是主要的浸润细胞，但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要细胞类型，但中性粒细胞聚集，且其中许多发生变性（化脓性渗出物）（Figure 1，箭头）。渗出物中还可能存在细胞碎片（来自 resident 细胞群和浸润的白细胞）、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子（Figure 2，箭头）。大体上，这些病变的特征是脓液的存在。在渗出物周围的组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在显著数量的中性粒细胞。慢性和慢性活动性炎症可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大型、活化巨噬细胞、上皮样巨噬细胞和/或多核巨细胞。炎症与细胞浸润的鉴别在于其他改变的存在，如水肿、出血、变性、坏死或其他组织损伤的证据。
诊断建议
胸腺的炎症性病变无论何时出现，都应进行诊断和分级。应根据存在的主要细胞群，通过在诊断中添加适当的修饰词（急性（acute）、慢性（chronic） active等）对炎症进行分类。“脓肿（abscess）”一词仅应作为大体诊断使用；脓肿应诊断为化脓性炎症。相关病变，如坏死或出血，除非因严重程度而有必要，否则不应单独诊断，但应在病理学叙述中描述。如果炎症继发于其他病变，如坏死或肿瘤形成，除非因严重程度而有必要，否则不应单独诊断，但应在叙述中注明。
参考切片图（2 张）
查看英文原文
Comment
Primary inflammation is an uncommon lesion in the thymus of rodents. If present, it is more likely an extension of inflammation from other tissues, particularly inflammation secondary to perforation of the esophagus during oral gavage. In NTP studies, the five standard categories of inflammation are acute, suppurative, chronic, chronic active, and granulomatous. In acute inflammation , the neutrophil is the predominant infiltrating cell, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate) ( Figure 1 , arrows). Cell debris, both from the resident cell populations and infiltrating leukocytes; proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes, or plasma cells; and, possibly, an infectious agent ( Figure 2 , arrow) may also be present within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation , but there are also a significant number of neutrophils. Chronic and chronic active inflammation may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, and/ or multinucleated giant cells. Inflammation is differentiated from cellular infiltrates by the presence of other changes, such as edema, hemorrhage, degeneration, necrosis, or other evidence of tissue damage.
Recommendation
Whenever present, inflammatory lesions of the thymus should be diagnosed and graded. The inflammation should be categorized based on the predominant cell population present by adding the appropriate modifier to the diagnosis (acute, chronic active, etc.). The word "abscess" should be used as a gross diagnosis only; abscesses should be diagnosed as suppurative inflammation. Associated lesions, such as necrosis or hemorrhage, should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative. If the inflammation is secondary to another lesion, such as necrosis or neoplasia, it should not be diagnosed separately unless warranted by severity, but should be noted in the narrative.
矿化Mineralization 胸腺矿化
描述（中文）
矿化通常不作为胸腺的原发性病变发生。然而，它可继发于肾脏和/或甲状旁腺疾病（转移性矿化），或伴随胸腺坏死（营养不良性矿化）发生。该病变的特征是数量不等的深嗜碱性、无定形和/或颗粒状物质（Figure 1、Figure 2，箭头）。在肾脏或甲状旁腺疾病时，矿物质可作为多灶性（multifocal）病变发生于胸腺内，也可发生于坏死灶内。
诊断建议
与肾脏和/或甲状旁腺疾病相关的胸腺矿化应当诊断并分级。与胸腺坏死相关的矿化不应单独诊断，除非其严重程度足以支持单独诊断，但应在病理描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Mineralization does not typically occur as a primary lesion in the thymus. However, it can occur secondary to renal and/or parathyroid disease (metastatic mineralization) or with thymic necrosis (dystrophic mineralization). This lesion is characterized by variable amounts of densely basophilic, amorphous, and/or granular material ( Figure 1 and Figure 2 , arrows). Mineral may occur as multifocal lesions within the thymus with renal or parathyroid disease or may occur within necrotic foci.
Recommendation
Thymic mineralization should be diagnosed and graded if associated with renal and/or parathyroid disease. Mineralization associated with thymic necrosis should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative.
色素Pigment 胸腺色素沉着
描述（中文）
胸腺中的色素是一种不常见的发现，其主要特征为巨噬细胞内存在金黄色至深棕色色素。色素可能是含铁血黄素（hemosiderin）（Figure 1、Figure 2）或蜡样质/脂褐素（ceroid/lipofuscin）。含铁血黄素是一种含铁的黄金棕色颗粒状物质，含有该色素的巨噬细胞通常与窦状红细胞增多、充血或出血同时观察到。脂褐素也是一种黄棕色、细颗粒状色素；然而，它主要来源于脂质（如细胞膜）的分解产物。蜡样质是脂褐素的一种变体，具有抗酸性且可自发荧光。用常规苏木精和伊红（H&E）染色无法对这些色素进行确定性鉴别。含铁血黄素可通过铁染色如Perl''s铁染色和普鲁士蓝染色来识别，这两种染色均将色素染成蓝色。蜡样质/脂褐素可通过苏丹黑B、Schmorl''s反应、油红O、石炭酸脂褐素染色、过碘酸-雪夫染色、Ziehl-Neelsen抗酸染色、自发荧光或溶酶体酸性磷酸酶和酯酶染色来识别。
诊断建议
胸腺中的色素应当被诊断并给予严重程度分级。然而，并非所有色素都必须诊断，因为有些色素在衰老动物中普遍存在或与其他疾病过程相关，不具有毒理学意义。病理学家应运用其判断力来决定色素沉积是否具有毒理学意义或是否足够显著以值得单独诊断。在组织学切片中，确定性色素鉴别通常很困难，即使使用一系列特殊染色也是如此。因此，推荐使用“色素”这一诊断（而非诊断色素类型，例如含铁血黄素或脂褐素）最为恰当。病理学叙述应描述色素沉着的形态学特征。
参考切片图（2 张）
查看英文原文
Comment
Pigment in the thymus is an uncommon finding and is primarily characterized by the presence of golden to dark brown pigment within macrophages. Pigment may be hemosiderin ( Figure 1 and Figure 2 ) or ceroid/lipofuscin. Hemosiderin is an iron-containing golden-brown granular material, and macrophages containing this pigment are typically observed with sinus erythrocytosis, congestion, or hemorrhage. Lipofuscin is also a yellow-brown, finely granular pigment; however, it is derived mainly from the breakdown products of lipids, such as cell membranes. Ceroid is a variant of lipofuscin that is acid-fast and autofluorescent. Definitive differentiation of these pigments with conventional hematoxylin and eosin (H&E) staining is not possible. Hemosiderin can be identified with iron stains such as Perl''s iron and Prussian blue, both of which stain the pigment blue. Ceroid/lipofuscin can be identified with Sudan black B, Schmorl''s reaction, Oil red O, carbol lipofuscin stain, periodic acid-Schiff, Ziehl-Neelsen acid-fast stain, autofluorescence, or lysosomal acid phosphatase and esterase stains.
Recommendation
Pigment in the thymus should be diagnosed and given a severity grade. However, not all pigments have to be diagnosed, as some are ubiquitous in aging animals or related to some other disease process and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether deposits of pigment are toxicologically significant or prominent enough to warrant a separate diagnosis. Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, it is recommended that a diagnosis of "pigment" (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should describe the morphologic features of the pigmentation.
萎缩Atrophy 胸腺萎缩
描述（中文）
萎缩（atrophy）的特征是胸腺体积和重量减小，继发于胸腺淋巴细胞耗竭。正常胸腺通常具有大小相近的小叶、紧密贴附的被膜、与髓质相比细胞密集的皮质、清晰的皮髓质（corticomedullary，CM）交界，以及约1:1:1的皮质与髓质比值（两个皮质对髓质）（Figure 1、Figure 2）。在极轻微（minimal）萎缩时（Figure 3、Figure 4），皮质可变薄且不规则，随着病变进展为轻微（mild）（Figure 5，Figure 6）和中度（moderate）（Figure 7、Figure 8），CM分界逐渐消失。当病变为显著（marked）时（Figure 9、Figure 10），皮质和髓质的细胞密度降低，CM交界可能不再明显。髓质可能显得比皮质大，胸腺各区的细胞学外观可能呈现反转，即皮质因细胞密度降低而呈淡嗜酸性，髓质因细胞密度增加而呈深嗜碱性。胸腺萎缩可能受营养、肾上腺皮质功能亢进以及激素水平变化（如性激素或生长激素）的影响。胸腺萎缩必须与胸腺退化（involution）相鉴别。年龄相关退化是一种渐进的、不可逆的变化，可能与性类固醇循环有关。除皮质细胞密度降低外，正常退化还可能包括CM交界模糊、被膜和实质的脂肪细胞浸润、髓质上皮细胞突出度增加和/或增生，以及髓质内形成滤泡样B细胞聚集。与年龄无关的萎缩通常由毒性损伤引起，去除致病因素后可能可逆。
诊断建议
胸腺萎缩出现时，应当诊断并分级。如果萎缩仅累及一叶或呈局限性，应在病理学描述中讨论。诱发性萎缩必须与胸腺正常退化相鉴别。具有潜在治疗相关胸腺萎缩的动物应与年龄和性别匹配的同批对照动物进行比较。动物的年龄和明确的剂量-反应关系将有助于区分胸腺萎缩与正常退化。
参考切片图（2 张）
查看英文原文
Comment
Atrophy is characterized by reduced thymus size and weight secondary to thymic lymphocyte depletion. A normal thymus typically has similarly sized lobules, a closely apposed capsule, a densely cellular cortex compared with the medulla, a distinct corticomedullary (CM) junction, and a cortex to medulla ratio of ~1:1:1 (two cortices to the medulla) ( Figure 1 and Figure 2 ). With minimal atrophy ( Figure 3 and Figure 4 ), the cortex may become thinner and irregular, with progressive loss of the CM demarcation as the lesion becomes mild ( Figure 5 , Figure 6 ) and moderate ( Figure 7 and Figure 8 ). As the lesion becomes marked ( Figure 9 and Figure 10 ), cellularity of the cortex and medulla is decreased, and the CM junction may no longer be apparent. The medulla may appear larger than the cortex, and the cellular appearance of thymic compartments may appear reversed, with a pale eosinophilic cortex due to reduced cellularity and a darkly basophilic medulla due to increased cellularity. Thymic atrophy may be influenced by nutrition, adrenocortical hyperactivity, and changes in hormone levels (e.g., sex or growth hormones). Thymic atrophy must be differentiated from thymic involution. Age-related involution is a gradual, nonreversible change, likely associated with sex steroid circulation. In addition to decreased cortical cellularity, normal involution may include blurring of the CM junction, adipocyte infiltration of the capsule and parenchyma, increased prominence and/or hyperplasia of medullary epithelial cells, and formation of follicular-like B-cell aggregates in the medulla. Atrophy that is unrelated to age is generally caused by toxic insult and is potentially reversible with removal of the inciting agent.
Recommendation
When present, atrophy of the thymus should be diagnosed and graded. If atrophy involves only one lobe or is localized, this should be discussed in the pathology narrative. Induced atrophy must be differentiated from normal involution of the thymus. An animal with potential treatment-related thymic atrophy should be compared with age- and sex-matched concurrent controls. Age of the animal and a clear dose-response relationship will help differentiate between thymic atrophy and normal involution.
退化Involution 胸腺其他
描述（中文）
胸腺退化（involution）是一种逐渐发生、不可逆的改变，可能与衰老过程中发生的性类固醇变化有关。它是啮齿类动物与年龄相关的正常生理性改变，在慢性生物试验中常见。胸腺退化的典型改变包括皮质淋巴细胞减少、胸腺小叶皱缩、皮质变薄且不规则、皮髓质交界模糊、被膜和小梁脂肪细胞浸润、髓质上皮细胞突出度增加和/或增生、滤泡样B细胞聚集形成、囊肿形成以及浆细胞增生。如有可能，应将退化与原发性或继发性治疗相关萎缩区分开来。与退化相似，胸腺萎缩的特征是继发于胸腺淋巴细胞耗竭的胸腺体积和重量减小。然而，胸腺萎缩与年龄无关，通常由毒性损伤引起，并且在去除诱因后可能可逆。
诊断建议
胸腺退化不予诊断。如有可能，应将慢性生物试验中常见的正常生理性年龄相关退化与原发性或继发性治疗相关萎缩区分开来（见胸腺-萎缩）。相关链接：胸腺-萎缩
参考切片图（2 张）
查看英文原文
Comment
Involution of the thymus is a gradual, nonreversible change, likely associated with sex steroid changes that occur during aging. It is a normal physiologic age-related change in rodents and is commonly seen in chronic bioassays. Changes typical of thymus involution include decreased cortical lymphocytes, shrinkage of thymic lobules, thinning and irregularity of the cortex, blurring of the corticomedullary junction, adipocyte infiltration of capsule and septae, increased prominence and/or hyperplasia of medullary epithelial cells, formation of follicular-like B-cell aggregates, cyst formation, and plasma cell hyperplasia. If possible, involution should be distinguished from primary or secondary treatment-related atrophy. Similar to involution, atrophy of the thymus is characterized by reduced thymus size and weight secondary to thymic lymphocyte depletion. However, atrophy in the thymus is unrelated to age, generally caused by toxic insult, and potentially reversible with removal of the inciting agent.
Recommendation
Involution of the thymus is not diagnosed. If possible, normal physiologic age-related involution, which is commonly seen in chronic bioassays, should be distinguished from primary or secondary treatment-related atrophy (see Thymus - Atrophy ). Related Links: Thymus - Atrophy
充血Congestion 脾脏其他
描述（中文）
脾充血（splenic congestion）的特征是红髓（red pulp）内血窦（sinuses）被红细胞（erythrocytes）过度扩张（Figure 1、Figure 2，箭头）。脾充血常见，尽管其原因并不总是显而易见。影响大鼠和小鼠脾血窦内血液量的医源性因素（iatrogenic factors）包括死亡方式、安乐死方法以及剖检程序。脾充血的其他原因包括心血管疾病、大鼠的单核细胞白血病（mononuclear cell leukemia）以及继发于治疗的的红细胞损伤。脾充血应与血管扩张（angiectasis）、出血（hemorrhage）、血管瘤（hemangioma）和血管肉瘤（hemangiosarcoma）相鉴别。脾内扩张的血管可发生充血，但“脾充血”通常是一种更弥漫性的病变，累及红髓血窦。充血有时难以与脾出血相区分；然而，充血通常不伴有血肿（hematomas）或肿瘤（neoplasia）（见 Spleen - Hemorrhage）。脾血管瘤和血管肉瘤是起源于脾血管内皮（splenic vascular endothelium）的肿瘤。脾血管瘤和血管肉瘤中可发生肿瘤性血管通道（neoplastic vascular channels）的充血；然而，“Spleen - Congestion”这一诊断应保留用于红髓血窦的充血。
诊断建议
每当认为脾充血与受试物相关或与肉眼可见的病变相关时，应对其作出诊断并赋予严重程度分级。相关链接：Spleen - Hemorrhage
参考切片图（2 张）
查看英文原文
Comment
Congestion of the spleen is characterized by excessive distension of sinuses within the red pulp by erythrocytes ( Figure 1 and Figure 2 , arrows). Splenic congestion is common, although a cause is not always apparent. Iatrogenic factors affecting the amount of blood within the splenic sinuses in rats and mice include the manner of death, the method of euthanasia, and necropsy procedures. Other causes of splenic congestion include cardiovascular disease, mononuclear cell leukemia in rats, and erythrocyte damage secondary to treatment. Congestion of the spleen should be distinguished from angiectasis, hemorrhage, hemangioma, and hemangiosarcoma. Angiectatic blood vessels in the spleen can be congested, but "splenic congestion" is typically a more generalized lesion involving the red pulp sinuses. Congestion can be difficult to differentiate from hemorrhage in the spleen; however, it is not typically associated with hematomas or neoplasia (see Spleen - Hemorrhage ). Splenic hemangiomas and hemangiosarcomas are neoplasms derived from the splenic vascular endothelium. Congestion of neoplastic vascular channels may occur with splenic hemangiomas and hemangiosarcomas; however, the diagnosis "Spleen - Congestion" should be reserved for congestion of the red pulp sinuses.
Recommendation
Whenever congestion in the spleen is believed to be associated with treatment or with a gross lesion, it should be diagnosed and assigned a severity grade. Related Links: Spleen - Hemorrhage
出血Hemorrhage 脾脏出血
描述（中文）
出血（hemorrhage）的特征是脾被膜内（Figure 1，箭头）或脾实质内（Figure 2，箭头）出现外渗的红细胞。出血可为局灶性（focal）至弥漫性（diffuse），并可发生于多种情况下（例如脾梗死）、化学物暴露后、继发于照射或创伤性损伤，以及与恶性肿瘤尤其是血管肉瘤（hemangiosarcoma）相关。脾血肿是血管外血液的局限性聚集，被视为出血的一个亚型（Figure 1，箭头）。脾出血应与血管扩张（angiectasis）、充血（congestion）、血管瘤（hemangioma）和血管肉瘤相鉴别。血管扩张通常是脾内的局灶性病变，并可能与纤维化区域相关。其大小不等的充满血液的腔隙由内皮衬覆。充血可能难以与出血相区分。充血通常局限于红髓窦，可能有也可能没有可识别的原因。血管瘤和血管肉瘤是脾血管内皮肿瘤。
诊断建议
脾内凡出现出血，均应作出诊断并分级。脾血肿不应单独诊断，而应诊断为出血。若出血继发于脾肿瘤，则无需诊断，但应在病理描述中注明。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage is characterized by the presence of extravasated erythrocytes within the splenic capsule ( Figure 1 , arrow) or parenchyma ( Figure 2 , arrow). Hemorrhage can be focal to diffuse and may occur in a variety of conditions (e.g., splenic infarction), following chemical exposure, secondary to irradiation or traumatic injury, and in association with malignant neoplasms, especially hemangiosarcoma. A splenic hematoma is a localized collection of blood outside of blood vessels and is considered a subset of hemorrhage ( Figure 1 , arrow). Hemorrhage in the spleen should be distinguished from angiectasis, congestion, hemangioma, and hemangiosarcoma. Angiectasis is usually a focal lesion in the spleen and may be associated with an area of fibrosis. Its variably sized blood-filled spaces are lined by endothelium. Congestion can be difficult to differentiate from hemorrhage. Congestion is typically confined to the red pulp sinuses and may or may not have an identifiable cause. Hemangiomas and hemangiosarcomas are neoplasms of the splenic vascular endothelium.
Recommendation
Whenever present in the spleen, hemorrhage should be diagnosed and graded. Splenic hematomas should not be diagnosed separately but diagnosed as hemorrhage. Hemorrhage need not be diagnosed if secondary to splenic neoplasia but should be noted in the pathology narrative.
副脾Accessory Spleen 脾脏其他
描述（中文）
副脾（accessory spleen）（Figure 1，箭头）在啮齿类动物中罕见，可能为先天性、脾切除后获得性或创伤性损伤所致。在腹腔内肉眼观察时，副脾可表现为一个或多个暗红色至黑色结节，表面光滑，直径从不足1毫米到数毫米不等。这些脾组织小结节可见于脾的肠系膜附着处（Figure 1，箭头所指）、胰腺及腹腔其他部位。组织学上，副脾可具有全部或部分脾结构成分，如被膜、小梁、红髓和/或白髓（Figure 2）。
诊断建议
副脾应予以诊断，但不进行分级。
参考切片图（2 张）
查看英文原文
Comment
Accessory spleens ( Figure 1 , arrow) are rare findings in rodents and may be congenital, acquired following splenectomy, or a consequence of traumatic injury. When observed grossly in the peritoneal cavity, an accessory spleen may appear as one or more dark red to black nodules that have a smooth surface and range from less than a millimeter to several millimeters in diameter. These small nodules of splenic tissue have been observed in the mesenteric attachment of the spleen ( Figure 1 , arrowhead), pancreas, and elsewhere in the abdominal cavity. Histologically, accessory spleens may have all or some splenic components, such as the capsule, trabeculae, red pulp, and/or white pulp ( Figure 2 ).
Recommendation
Accessory spleen should be diagnosed but not graded.
坏死Necrosis 脾脏坏死
描述（中文）
脾坏死（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6）可在啮齿类动物中通过实验诱导产生；然而，该病变更常与血管阻塞、创伤或肿瘤相关。 expansive坏死可与脾内血栓或肿瘤相关。脾实质成分坏死的特征为细胞肿胀、细胞核浓缩和溶解，以及细胞溶解并伴有大量嗜酸性（eosinophilic）胞质和核碎裂（karyorrhectic）碎屑的积聚。炎症、出血、纤维蛋白、纤维化和/或矿化可伴随脾坏死出现。
诊断建议
无论何时出现，脾坏死均应作出诊断并赋予严重程度分级。如果脾坏死继发于血栓或肿瘤等病变，则不应单独诊断，而应在叙述性描述中加以说明。继发性病变，如炎症或出血，除非严重程度足以支持，否则不应单独诊断，但应在病理学叙述性描述中加以说明。
参考切片图（2 张）
查看英文原文
Comment
Splenic necrosis ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ) may be induced experimentally in rodents; however, this lesion is more often associated with vascular obstruction, trauma, or neoplasia. Expansive necrosis can be associated with a thrombus or neoplasm in the spleen. Necrosis of splenic constituents is characterized by cell swelling, condensation and dissolution of the nucleus, and cell lysis with accumulation of abundant eosinophilic cytoplasmic and karyorrhectic nuclear debris. Inflammation, hemorrhage, fibrin, fibrosis, and/or mineralization may accompany splenic necrosis.
Recommendation
Whenever present, necrosis of the spleen should be diagnosed and assigned a severity grade. If splenic necrosis is secondary to a lesion such as thrombus or neoplasia, it should not be diagnosed but should be described in the narrative. Secondary lesions, such as inflammation or hemorrhage, should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative.
浆细胞增生Hyperplasia Plasma Cell 脾脏增生
描述（中文）
浆细胞增生（plasma cell hyperplasia）是啮齿类动物、尤其是小鼠脾脏中常见的、通常为轻度的病变。它由浆细胞和/或浆母细胞组成，这些细胞在急性或慢性抗原特异性刺激后从白髓（淋巴滤泡、生发中心）迁移至红髓（Figure 1、Figure 2，箭头），并在红髓分泌大量抗体。与正常脾脏细胞成分相混杂的小灶性浆细胞常见于老龄大鼠和小鼠的脾脏。必要时，可通过针对人kappa轻链或免疫球蛋白的免疫组织化学方法识别浆细胞。
诊断建议
当浆细胞数量超过同期对照动物所见时，应诊断为浆细胞增生。诊断时应进行分级。
参考切片图（2 张）
查看英文原文
Comment
Plasma cell hyperplasia is a common, often mild, lesion in the spleen of rodents, particularly mice. It consists of plasma cells and/or plasmablasts that migrate to the red pulp from the white pulp (lymphoid follicles, germinal centers) following acute or chronic antigen-specific stimulation ( Figure 1 and Figure 2 , arrows), where they secrete large volumes of antibodies. Small foci of plasma cells that blend in with normal splenic cellular constituents frequently occur in spleens of aged rats and mice. If needed, plasma cells can be identified with immunohistochemistry for human kappa light chains or immunoglobulins.
Recommendation
Plasma cell hyperplasia should be diagnosed when the number of plasma cells exceeds that seen in concurrent controls. When diagnosed, it should be graded.
淀粉样物质Amyloid 脾脏其他
描述（中文）
淀粉样变性（amyloidosis）是一种系统性疾病，其特征为无定形蛋白质样物质在多种组织（包括脾、肝和肾）的细胞外沉积。在小鼠脾脏中，淀粉样物质沉积于红髓及白髓邻近区域（边缘区）（Figure 1、Figure 2，箭头）。当该病变严重时，可导致白髓萎缩（Figure 1，箭头头）。淀粉样物质经刚果红（Congo red）染色并在偏振光下观察时，可呈现苹果绿色双折射，也可通过免疫组织化学方法检测。淀粉样变性在B6C3F1小鼠和大鼠中罕见。小鼠自发性淀粉样变性的发生率随年龄增长而升高，并可能受多种因素影响，包括繁育来源、饮食、环境和炎症。在小鼠中，自发性年龄相关（老年性）淀粉样变性已被认为与淀粉样载脂蛋白A2（ApoA2）沉积相关，而炎症诱导的淀粉样变性则与血清淀粉样蛋白A（一种急性期蛋白）相关。ApoA2是小鼠血清高密度脂蛋白的主要成分。
诊断建议
脾脏中淀粉样物质无论何时出现，均应作出诊断并赋予严重程度分级。由于淀粉样变性是一种系统性疾病，其他组织（如肝和肾）也应评估是否存在淀粉样物质。继发性病变，如实质细胞坏死或变性，除非因严重程度需要或对研究结果的解释具有重要意义，否则不应单独诊断，但应在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Amyloidosis is a systemic disease characterized by the extracellular deposition of amorphous proteinaceous material in multiple tissues, including spleen, liver, and kidney. In the spleen of mice, amyloid is deposited in the red pulp and adjacent to the white pulp (marginal zone) ( Figure 1 and Figure 2 , arrows). When this lesion is severe, it can result in white pulp atrophy ( Figure 1 , arrowhead). Amyloid can be identified by apple-green birefringence when stained with Congo red and visualized under polarized light, or it can be detected immunohistochemically. Amyloidosis is rare in B6C3F1 mice and rats. The incidence of spontaneous amyloidosis in mice increases with age and may be influenced by various factors, including breeding origin, diet, environment, and inflammation. In mice, spontaneous age-associated (senile) amyloidosis has been associated with amyloid apolipoprotein A2 (ApoA2) deposition, whereas inflammatory-induced amyloidosis has been correlated with serum amyloid A (an acute-phase protein). ApoA2 is a major constituent of serum high-density lipoprotein in mice.
Recommendation
Whenever present, amyloid in the spleen should be diagnosed and assigned a severity grade. Since amyloidosis is a systemic disease, other tissues, such as liver and kidney, should also be evaluated for amyloid. Secondary lesions, such as necrosis or degeneration of parenchymal cells, should not be diagnosed separately unless warranted by severity or important for interpretation of study results, but should be described in the pathology narrative.
淋巴细胞凋亡Apoptosis Lymphocyte 脾脏凋亡
描述（中文）
淋巴细胞凋亡（lymphocyte apoptosis）通常发生于啮齿动物脾脏富含B细胞的滤泡生发中心，但在实验性暴露于辐射、病毒、内毒素或化学物时，B细胞和/或T细胞（动脉周围淋巴鞘）区域内的淋巴细胞凋亡也可能增多。凋亡的特征是单个淋巴细胞皱缩、核染色质浓缩，以及凋亡细胞碎裂成膜包裹的凋亡小体（apoptotic bodies）（Figure 2，箭头），随后被巨噬细胞（可染体巨噬细胞，tingible body macrophages）吞噬（Figure 1、Figure 2，箭头）。显著的淋巴细胞凋亡可导致一个或多个白髓区域萎缩。历史上，淋巴细胞凋亡曾被称为“淋巴细胞坏死（lymphocyte necrosis）”，但该病变的正确术语是“淋巴细胞凋亡”。当主要细胞形态学符合经典坏死形式时，应使用坏死的诊断（见脾脏-坏死，Spleen - Necrosis）。坏死的特征是细胞肿胀、核浓缩、核碎裂和核溶解、细胞溶解，以及大量嗜酸性胞质和核碎裂碎屑的积聚。坏死通常伴有炎症。
诊断建议
当脾脏淋巴细胞凋亡超过同期对照所见时，应当诊断并赋予严重程度分级。淋巴细胞凋亡必须与脾脏坏死相鉴别。相关链接：脾脏-坏死（Spleen - Necrosis）
参考切片图（2 张）
查看英文原文
Comment
Lymphocyte apoptosis normally occurs in the B-cell-rich follicular germinal centers of the spleen of rodents but may also be increased in B-cell and/or T-cell (periarteriolar lymphatic sheaths) compartments with experimental exposures to radiation, viruses, endotoxin, or chemicals. Apoptosis is characterized by shrinkage of individual lymphocytes, condensation of nuclear chromatin, and fragmentation of apoptotic cells into membrane-bound bodies (apoptotic bodies) ( Figure 2 , arrowhead), which are subsequently phagocytized by macrophages (tingible body macrophages) ( Figure 1 and Figure 2 , arrows). Significant lymphocyte apoptosis may lead to atrophy of one or more white pulp compartments. Historically, apoptosis of lymphocytes has been called "lymphocyte necrosis," but the correct terminology for this lesion is "lymphocyte apoptosis." A diagnosis of necrosis should be used when the predominant cytomorphology is consistent with the classic forms of necrosis (see Spleen - Necrosis ). Necrosis is characterized by cell swelling, condensation, fragmentation and dissolution of the nucleus, cell lysis, and accumulation of abundant eosinophilic cytoplasmic and karyorrhectic nuclear debris. Inflammation is generally present with necrosis.
Recommendation
When increased above that seen in concurrent controls, lymphocyte apoptosis in the spleen should be diagnosed and assigned a severity grade. Lymphocyte apoptosis must be differentiated from splenic necrosis. Related Links: Spleen - Necrosis
淋巴细胞增生Hyperplasia Lymphocyte 脾脏增生
描述（中文）
脾脏淋巴细胞增生是指淋巴细胞数量超出同期对照的正常范围。其结果是白髓成分（动脉周围淋巴鞘[PALS]、淋巴滤泡和/或边缘区）的面积和数量出现不同程度的增加（Figure 1、Figure 2，箭头）。该病变可为局灶性（focal）或generalized。脾脏淋巴细胞增生在小鼠中比在大鼠中更常见，且雌性小鼠比雄性小鼠更常受累。显著（marked）淋巴细胞增生可能难以与脾脏早期淋巴瘤区分；然而，淋巴细胞增生时脾脏结构（白髓和红髓分区）应保持完整（Figure 1、Figure 2），而淋巴瘤则预期会出现脾脏结构的丧失。在generalized淋巴细胞增生时，PALS区域可能出现融合（Figure 1），因此应评估细胞形态以与淋巴瘤鉴别。淋巴瘤由单调（或多形性）的肿瘤性淋巴细胞组成，细胞异型性增加，而淋巴细胞增生则由数量增多的正常、成熟淋巴细胞组成。
诊断建议
脾脏淋巴细胞增生无论何时出现，均应作出诊断并赋予严重程度分级。脾脏中淋巴细胞的数量通常存在变异；因此，病理学家必须仔细检查并通过与同期对照比较来确定某一研究的正常范围。评估脾脏时还应考虑切面方向（横切面、纵切面、切线切面或浅切面）。诊断应基于病理学家的最佳判断。
参考切片图（2 张）
查看英文原文
Comment
Lymphocyte hyperplasia of the spleen is an increase in the number of lymphocytes outside the range of normal compared with concurrent controls. The result can be variable increases in the area and number of white pulp elements (periarteriolar lymphoid sheaths [PALS], follicles, and/or marginal zones) ( Figure 1 and Figure 2 , arrows). This lesion can be focal or generalized. Lymphocyte hyperplasia in the spleen occurs more frequently in mice than in rats, and female mice are more commonly affected than male mice. Marked lymphocyte hyperplasia can be difficult to distinguish from early lymphoma of the spleen; however, the splenic architecture (white pulp and red pulp compartments) should be maintained with lymphocyte hyperplasia ( Figure 1 and Figure 2 ), whereas loss of the splenic architecture would be expected with lymphoma. With generalized lymphocyte hyperplasia, there can be confluency of the PALS regions ( Figure 1 ), so cellular morphology should be evaluated to differentiate from lymphoma. Lymphoma consists of monomorphic (or pleomorphic) neoplastic lymphocytes with increased cellular atypia, whereas lymphocyte hyperplasia consists of increased numbers of normal, mature lymphocytes.
Recommendation
Whenever present, lymphocyte hyperplasia of the spleen should be diagnosed and assigned a severity grade. The number of lymphocytes in the spleen is often variable; therefore, the pathologist must carefully examine and determine the range of normal for a study by comparing with concurrent controls. The plane of section should also be taken into consideration (transverse, longitudinal, tangential, or shallow sections) when evaluating the spleen. Diagnosis should be based upon the pathologist’s best judgment.
炎症Inflammation 脾脏炎症
描述（中文）
炎症在啮齿类动物脾脏中是一种不常见的病变，当出现时，感染性病原体是最可能的原因（Figure 1、Figure 2，箭头）。在NTP研究中，炎症的五个标准类别是急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，中性粒细胞是主要的浸润细胞，尽管也可能存在较少的巨噬细胞和淋巴细胞。水肿或充血可能明显可见。中性粒细胞也是化脓性炎症中的主要细胞类型，但中性粒细胞聚集，且其中许多发生变性（化脓性渗出物）（Figure 1、Figure 2，箭头）。渗出物中还可能存在来自 resident 细胞群和浸润白细胞的细胞碎片；含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞；以及可能的感染性病原体（Figure 1、Figure 2，箭头）。肉眼上，这些病变将以脓液的存在为特征。在渗出物周围的组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在显著数量的中性粒细胞。慢性和慢性活动性炎症可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大的活化巨噬细胞、上皮样巨噬细胞和/或多核巨细胞。
诊断建议
当脾脏出现炎症性病变时，应当进行诊断和分级。应根据存在的主要细胞群对炎症进行分类，在诊断中添加适当的修饰词（急性（acute）、慢性（chronic） active等）。"abscess"一词应仅用作肉眼诊断；脓肿应诊断为化脓性炎症。相关病变，如坏死或出血，除非因严重程度而有必要，否则不应单独诊断，但应在病理学叙述中描述。如果炎症继发于另一病变，如坏死或肿瘤形成，除非因严重程度而有必要，否则不应单独诊断，但应在叙述中注明。
参考切片图（2 张）
查看英文原文
Comment
Inflammation is an uncommon lesion in the spleen of rodents, and when present, infectious agents are the most likely cause ( Figure 1 and Figure 2 , arrowheads). In NTP studies, the five standard categories of inflammation are acute, suppurative, chronic, chronic active, and granulomatous. In acute inflammation , the neutrophil is the predominant infiltrating cell, though fewer macrophages and lymphocytes may also be present. Edema or hyperemia may be evident. The neutrophil is also the predominant cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate) ( Figure 1 and Figure 2 , arrows). Cell debris, from both the resident cell populations and infiltrating leukocytes; proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes, or plasma cells; and, possibly, an infectious agent ( Figure 1 and Figure 2 , arrowheads) may also be present within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation , but there are also a significant number of neutrophils. Chronic and chronic active inflammation may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, and/ or multinucleated giant cells.
Recommendation
When present, inflammatory lesions in the spleen should be diagnosed and graded. The inflammation should be categorized based on the predominant cell population present by adding the appropriate modifier to the diagnosis (acute, chronic active, etc.). The word "abscess" should be used as a gross diagnosis only; abscesses should be diagnosed as suppurative inflammation. Associated lesions, such as necrosis or hemorrhage, should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative. If the inflammation is secondary to another lesion, such as necrosis or neoplasia, it should not be diagnosed separately unless warranted by severity, but should be noted in the narrative.
红细胞吞噬作用Erythrophagocytosis 脾脏其他
描述（中文）
脾脏中的噬红细胞现象（erythrophagocytosis）由巨噬细胞（主要位于脾红髓）吞噬外渗的、衰老的和/或受损的红细胞构成（Figure 1、Figure 2，箭头）。在慢性充血或出血、与处理相关的溶血性贫血、或高铁血红蛋白血症等情况下，或继发于恶性肿瘤的存在，脾脏噬红细胞现象可增多。
诊断建议
若认为脾脏噬红细胞现象与处理相关，则应作出诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Erythrophagocytosis in the spleen consists of macrophages (mainly in the splenic red pulp) that phagocytize extravasated, old, and/or damaged erythrocytes ( Figure 1 and Figure 2 , arrows). Splenic erythrophagocytosis can be increased in such conditions as chronic congestion or hemorrhage, treatment-related hemolytic anemia, or methemoglobinemia or secondary to the presence of malignant neoplasms.
Recommendation
Diagnose and grade erythrophagocytosis in the spleen if it is considered to be treatment related.
红髓基质增生Red Pulp Hyperplasia Stromal 脾脏增生
描述（中文）
啮齿类动物脾脏的基质细胞增生（stromal cell hyperplasia）罕见（Figure 1、Figure 2、Figure 3、Figure 4，箭头）。它通常是一种局灶性（focal）病变，主要累及红髓，但可能浸润至动脉周围淋巴鞘和边缘区。在较大的病变中，被包裹的白髓可能发生萎缩。增生的基质细胞呈椭圆形至长形，胞质嗜酸性，细胞核呈椭圆形。窦可能被闭塞或被毛细血管取代，病变内可能存在成熟脂肪细胞。据报道，在充血、全身性肿瘤生长或经血液毒性化合物处理的反应中，基质细胞会增强其收缩特性或细胞外纤维的产生。因此，病变内胶原和平滑肌肌动蛋白（smooth muscle actin）的表达可能增加。该病变所涉及的确切细胞尚未被确定。该病变不应与肿瘤性病变相混淆。基质细胞增生时，可能存在异质性细胞群体（例如组织细胞和成纤维细胞）以及低核分裂指数。
诊断建议
每当脾脏出现基质细胞增生时，均应作出诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Stromal cell hyperplasia in the spleen of rodents is rare ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 , arrows). It is typically a focal lesion primarily affecting the red pulp, but there may be infiltration into the periarteriolar lymphatic sheaths and marginal zones. In larger lesions, entrapped white pulp may be atrophied. The proliferating stromal cells are oval to elongated with eosinophilic cytoplasm and oval nuclei. The sinuses may be obliterated or replaced by capillaries, and there may be mature adipocytes within the lesion. It has been reported that, in response to congestion, systemic tumor growth, or treatment with a hematotoxic compound, the stromal cells increase either their contractile properties or their production of extracellular fibers. Thus, there may be increased collagen and expression of smooth muscle actin within the lesion. The exact cell involved in the lesion has not been identified. This lesion should not be confused with neoplasia. With stromal cell hyperplasia, there may be a heterogeneous cell population (e.g., histiocytes and fibroblasts) and a low mitotic index.
Recommendation
Whenever stromal cell hyperplasia in the spleen is present, it should be diagnosed and graded.
纤维化Fibrosis 脾脏纤维化
描述（中文）
纤维化（fibrosis）的特征是脾脏内胶原性间质沉积增加。纤维化可作为损伤（创伤或毒性）、炎症、梗死或肿瘤形成后的修复过程出现。它可能局限于被膜，也可能作为局灶性（focal）或弥漫性（diffuse）病变发生于实质和/或被膜下区域。实质纤维化可延伸至边缘区并环绕或浸润动脉周围淋巴鞘（Figure 1，箭头）；当病变为显著（marked）时，淋巴组织常萎缩（Figure 2，箭头）。被膜纤维化更为常见，通常表现为localized病变（Figure 3、Figure 4，箭头），尽管它可与实质纤维化同时发生。被膜和/或实质纤维化区域内可能存在出血和/或色素，如含铁血黄素和蜡样脂褐素（Figure 2）。红髓的脾窦可能变窄并含少量红细胞。血管可能扩张（angiectasis）。广泛纤维化可导致脾脏塌陷或皱缩（Figure 1）。被膜纤维化可伴有间皮细胞增生或肥大（Figure 4）。纤维化在B6C3F1 mouse中是不常见的背景病变，但已在未处理的大鼠中检出。化学诱导的纤维化可能导致肉瘤形成。
诊断建议
脾脏纤维化无论何时出现，均应作出诊断并赋予严重程度分级。诊断中应包含部位修饰词（即parenchyma或capsule），以指明纤维化的位置。被认为继发于脾脏肿瘤形成或炎症的脾纤维化不应单独诊断，除非严重程度足以支持单独诊断，但应在病理学叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Fibrosis is characterized by increased deposition of collagenous stroma in the spleen. Fibrosis can occur as a reparative process following injury (trauma or toxicity), inflammation, infarction, or neoplasia. It may be limited to the capsule or occur as a focal or diffuse lesion in the parenchyma and/or subcapsular region. Parenchymal fibrosis can extend into the marginal zone and surround or infiltrate the periarteriolar lymphatic sheaths ( Figure 1 , arrow); when marked, lymphoid tissue is often atrophied ( Figure 2 , arrow). Capsular fibrosis is more common and typically occurs as a localized lesion ( Figure 3 and Figure 4 , arrows), although it can occur concurrently with parenchymal fibrosis. Hemorrhage and/or pigments such as hemosiderin and ceroid/lipofuscin may be present within regions of capsular and/or parenchyma fibrosis ( Figure 2 ). Sinusoids of the red pulp may be narrowed and contain few erythrocytes. Blood vessels may become ectatic (angiectasis). Extensive fibrosis may result in a collapsed or contracted spleen ( Figure 1 ). Mesothelial hyperplasia or hypertrophy may accompany capsular fibrosis ( Figure 4 ). Fibrosis is an uncommon background lesion in the B6C3F1 mouse, but it has been identified in untreated rats. Chemically induced fibrosis may lead to sarcoma formation.
Recommendation
Whenever present, fibrosis of the spleen should be diagnosed and assigned a severity grade. A site modifier (i.e., parenchyma or capsule) should be included in the diagnosis to indicate the location of the fibrosis. Splenic fibrosis that is considered to be secondary to neoplasia or inflammation in the spleen should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative.
肥大细胞增生Hyperplasia Mast Cell 脾脏增生
描述（中文）
在啮齿类动物的脾脏中可见肥大细胞增生（mast cell hyperplasia）。该病变的特征是脾红髓内出现分化良好的肥大细胞疏松聚集，且不与炎症相关。肥大细胞是相对较大的细胞，胞质丰富，通常含有大量密集的嗜碱性胞质内颗粒，这些颗粒可能遮盖细胞核（Figure 1、Figure 2，箭头），但也可能表现为明显的淡嗜碱性胞质和不太明显的颗粒。肥大细胞增生必须与转移性肥大细胞瘤相鉴别。在无原发性肥大细胞瘤的情况下，脾脏内出现肥大细胞支持增生性病变而非肿瘤性病变。
诊断建议
脾脏肥大细胞增生无论何时出现，均应作出诊断并赋予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Mast cell hyperplasia can be seen within the spleen of rodents. This lesion is characterized by loose aggregates of well-differentiated mast cells within the splenic red pulp that are not associated with inflammation. Mast cells are relatively large cells with abundant cytoplasm and typically have numerous densely basophilic intracytoplasmic granules that may obscure the nucleus ( Figure 1 and Figure 2 , arrows), although they may also present with prominent pale basophilic cytoplasm and less apparent granules. Mast cell hyperplasia must be differentiated from metastatic mast cell tumors. Mast cells within the spleen in the absence of a primary mast cell tumor are supportive of a hyperplastic rather than a neoplastic lesion.
Recommendation
Whenever present, mast cell hyperplasia of the spleen should be diagnosed and assigned a severity grade.
脂肪细胞化生Adipocyte Metaplasia 脾脏化生
描述（中文）
在慢性毒性/致癌性研究中，脾脏中偶可见脂肪细胞（adipocyte），但可能与受试物无关。据报道，在暴露于某些芳香胺（如苯胺、盐酸苯胺、对氯苯胺）的大鼠脾脏红髓中以及患有脾脏间叶性肿瘤的大鼠中可见此病变。该病变的特征是红髓内出现分化良好的脂肪细胞（Figure 1、Figure 2，箭头所示），周围环绕纤维性间质（Figure 2，箭头头所示），尽管纤维化不一定总是显著。通常累及红髓，病变可为局灶性（focal）、nodular和/或弥漫性（diffuse）。这些细胞最可能来源于脾脏间质细胞的化生。既往使用的术语包括脾脏的“脂质沉积症（lipidosis）”、“脂肪浸润（fatty infiltration）”、“脂肪变态（fatty metamorphosis）”和“脂质化生（lipid metaplasia）”。
诊断建议
无论何时出现，脾脏脂肪细胞化生均应作出诊断并赋予严重程度分级。如果该病变与肿瘤同时存在或继发于肿瘤，则不应记录，但应在病理学叙述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Adipocytes are occasionally seen in the spleen in chronic toxicity/carcinogenicity studies but may be unrelated to treatment. It has been reported in the red pulp of rats exposed to some aromatic amines (e.g., aniline, aniline hydrochloride, para-chloroaniline) and in rats with splenic mesenchymal neoplasms. This lesion is characterized by well-differentiated adipocytes in the red pulp ( Figure 1 and Figure 2 , arrows), surrounded by a fibrous stroma ( Figure 2 , arrowhead), although fibrosis may not always be prominent. The red pulp is typically involved, and the lesion may be focal, nodular, and/or diffuse. These cells most likely arise by metaplasia of splenic stromal cells. Previous terms include "lipidosis," "fatty infiltration," "fatty metamorphosis," and "lipid metaplasia" of the spleen.
Recommendation
Whenever present, adipocyte metaplasia of the spleen should be diagnosed and assigned a severity grade. If this lesion is present concurrently or secondarily to neoplasia, it should not be recorded but should be described in the pathology narrative.
色素Pigment 脾脏色素沉着
描述（中文）
脾红髓巨噬细胞内存在少量胞质内色素是啮齿类动物的常见背景性所见。色素可为含铁血黄素（hemosiderin）、蜡样质/脂褐素（ceroid/lipofuscin）、黑色素（melanin）或受试物相关色素。色素通常见于红髓（Figure 1，箭头），但也可见于白髓的边缘区和/或动脉周围淋巴鞘（Figure 2，箭头）、被膜或小梁。含铁血黄素色素是巨噬细胞吞噬红细胞（通常为衰老或受损红细胞）或游离血红蛋白的结果，在老龄啮齿类动物和/或治疗诱导的溶血性贫血或高铁血红蛋白血症、慢性充血、造血细胞增殖增加以及红细胞吞噬作用等情况下可能增多。含铁血黄素沉积也可见于继发于恶性肿瘤的局灶性（focal）出血。在老龄啮齿类动物中，大鼠和小鼠含铁血黄素色素的发生率通常均为雌性高于雄性。蜡样质/脂褐素来源于不饱和脂质的氧化和聚合，也可存在于脾巨噬细胞内，但较含铁血黄素少见。含铁血黄素可用Perl’s普鲁士蓝特殊染色识别，而蜡样质/脂褐素呈抗酸染色阳性。黑色素色素可见于小梁黑色素细胞或黑色小鼠红髓的局灶性区域。Fontana-Masson染色或Schmorl’s铁氰化铁还原染色可用于识别黑色素颗粒。只有当特殊染色证实后，色素才可按类型（即含铁血黄素、蜡样质/脂褐素、黑色素）进行亚分类。
诊断建议
当脾红髓和/或白髓中的色素因受试物而增多或减少时，应作出诊断并赋予严重程度分级。诊断中应包含诊断修饰词（即“increased”或“decreased”），以表明色素相对于同期对照是增多还是减少。即使使用一系列特殊染色，在组织学切片中明确鉴定色素类型通常仍很困难。因此，最恰当的诊断是“色素”（而非诊断色素类型，例如含铁血黄素或脂褐素）。色素的形态学特征应在病理学叙述中描述。如果色素的存在继发于年龄或无毒理学意义，则不应作出色素诊断。病理学家应运用其判断来决定继发性色素沉积是否显著到足以需要单独诊断。
参考切片图（2 张）
查看英文原文
Comment
The presence of a small amount of intracytoplasmic pigment within the splenic red pulp macrophages is a common background finding in rodents. Pigment can be hemosiderin, ceroid/lipofuscin, melanin, or test article related. It is typically found in the red pulp ( Figure 1 , arrow) but may also be present in the marginal zone and/or periarteriolar lymphatic sheaths of the white pulp ( Figure 2 , arrow), the capsule, or trabeculae. Hemosiderin pigment is the result of macrophage engulfment of red blood cells (usually effete or damaged) or free hemoglobin and may be increased in aging rodents and/or such conditions as treatment-induced hemolytic anemia or methemoglobinemia, chronic congestion, increased hematopoietic cell proliferation, and erythrophagocytosis. Hemosiderin deposits may also be observed with focal hemorrhage secondary to malignant neoplasms. The incidence of hemosiderin pigment in aging rodents is usually higher in females than in males for both rats and mice. Ceroid/lipofuscin, derived from oxidation and polymerization of unsaturated lipids, may also be present within splenic macrophages but occurs less commonly than hemosiderin. Hemosiderin can be identified with Perl’s Prussian blue special stain, whereas ceroid/lipofuscin is acid-fast positive. Melanin pigment can be seen in trabecular melanocytes or focally in the red pulp of black mice. Fontana-Masson or Schmorl’s ferric-ferricyanide reduction stain can be used to identify melanin granules. Pigment may be subclassified by type (i.e., hemosiderin, ceroid/ lipofuscin, melanin) only when confirmed by special stains.
Recommendation
Pigment in the red and/or white pulp of the spleen should be diagnosed when increased or decreased due to treatment and assigned a severity grade. A diagnostic modifier (i.e., "increased" or "decreased") should be included in the diagnosis to indicate whether the pigment is increased or decreased relative to concurrent controls. Definitive pigment identification is often difficult in histological sections, even with a battery of special stains. Therefore, a diagnosis of "pigment" (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. Morphological features of the pigment should be described in the pathology narrative. If the presence of pigment is secondary to age or not toxicologically meaningful, the pigment should not be diagnosed. The pathologist should use his or her judgment in deciding whether secondary deposits of pigment are prominent enough to warrant a separate diagnosis.
萎缩Atrophy 脾脏萎缩
描述（中文）
萎缩可累及脾脏的白髓和/或红髓部分。白髓的淋巴细胞萎缩以T细胞区（动脉周围淋巴鞘[PALS]）和/或B细胞区（滤泡、生发中心、边缘区）淋巴细胞丢失为特征。根据严重程度，这可导致PALS总体细胞密度/面积或滤泡数量/大小减少（Figure 1、Figure 2，箭头）。红髓萎缩以红髓成分相对量减少为特征，包括造血细胞（Figure 3、Figure 4，箭头）。脾萎缩可见于老年大鼠和小鼠的自发性变化，通常累及红髓和白髓部分。萎缩也可作为直接的治疗相关效应发生，或作为继发于体重减轻或体重增重减少的间接效应发生。
诊断建议
无论何时出现，脾脏萎缩均应诊断并赋予严重程度分级。诊断中应包含部位修饰词，以指示受累的是红髓还是白髓。若两个部分均受累，则诊断为“脾脏 - 萎缩”。若脾萎缩作为继发性病变存在，如肿瘤形成时的情况，则无需记录，但应在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Atrophy can affect the white pulp and/or red pulp compartments of the spleen. Lymphocyte atrophy of the white pulp is characterized by a loss of lymphocytes in the T-cell areas (periarteriolar lymphatic sheaths [PALS]) and/or B-cell areas (follicles, germinal centers, marginal zones). Depending on severity, this can result in a decrease in overall PALS cellularity/area or follicle number/size ( Figure 1 and Figure 2 , arrows). Red pulp atrophy is characterized by a decrease in the relative amount of red pulp components, including hematopoietic cells ( Figure 3 and Figure 4 , arrows). Splenic atrophy can be observed as a spontaneous change in older rats and mice and typically involves red and white pulp compartments. Atrophy can also occur as a direct treatment-related effect or can be an indirect effect secondary to weight loss or reduced body weight gain.
Recommendation
Whenever present, atrophy of the spleen should be diagnosed and assigned a severity grade. A site modifier should be included in the diagnosis to indicate whether the red pulp or the white pulp is affected. If both compartments are involved, diagnose "Spleen - Atrophy." If splenic atrophy is present as a secondary lesion, as in the case of neoplasia, it need not be recorded but should be described in the pathology narrative.
血管扩张Angiectasis 脾脏扩张
描述（中文）
血管扩张（angiectasis）由脾实质内大小不等的充满血液的腔隙构成，衬以纤细至不明显的内皮（Figure 1，箭头）。脾脏血管扩张通常为局灶性（focal）病变，可能与纤维化或瘢痕区域相关（Figure 2，箭头），并且在小鼠中更常见。充血常与血管扩张同时出现。它应与出血、血管瘤和血管肉瘤相鉴别。血管扩张与出血的鉴别在于血管扩张中离散的充满血液的腔隙衬有内皮细胞。血管扩张与血管瘤之间的区别并不总是显而易见。血管瘤倾向于为边界清楚、无包膜的肿块，由紧密排列的扩张血管腔隙构成。每个血管腔隙均被单层外观正常的内皮细胞所包绕并衬覆，这些内皮细胞排列于胶原性间隔上，间隔通常较薄，尽管有些具有宽阔的胶原性间质。血管扩张通常不表现为边界清楚的肿块；扩张的血管通道常不规则地穿行于造血组织中。此外，血管扩张的扩张血管通道不具有侵袭性，也不显示内皮细胞异型性，这可将该病变与血管肉瘤相区分。血管扩张以往的术语包括“hemangiectasis”、“hemangiectasia”、“vasodilation”和“vasodilatation”。
诊断建议
脾脏血管扩张应予以诊断并分级。如果它是肿瘤的组成部分或继发于肿瘤，则不应诊断，而应在病理学叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Angiectasis consists of variable-size blood-filled spaces within the splenic parenchyma, lined by delicate to inapparent endothelium ( Figure 1 , arrow). Angiectasis in the spleen is usually a focal lesion that may be associated with an area of fibrosis or scarring ( Figure 2 , arrow) and is more common in mice. Congestion is often seen with angiectasis. It should be distinguished from hemorrhage, hemangioma, and hemangiosarcoma. Angiectasis can be distinguished from hemorrhage by the presence of endothelial cells lining discrete blood-filled spaces in angiectasis. The distinction between angiectasis and hemangioma is not always obvious. Hemangiomas tend to be well-circumscribed, unencapsulated masses composed of tightly packed, dilated vascular spaces. Each vascular space is enclosed and lined by a single layer of normal-appearing endothelial cells aligned on collagenous septa, which are usually thin, although some have broad collagenous stroma. Angiectasis does not usually present as a well-circumscribed mass; the dilated vascular channels often course irregularly through the hematopoietic tissue. Furthermore, the dilated vascular channels of angiectasis are not invasive and do not demonstrate endothelial cell atypia, which differentiates this lesion from hemangiosarcoma. Previous terms for angiectasis include "hemangiectasis," "hemangiectasia," "vasodilation," and "vasodilatation."
Recommendation
Splenic angiectasis should be diagnosed and graded. If it is a component of or secondary to a neoplasm, then it should not be diagnosed but should be described in the pathology narrative.
髓外造血Extramedullary Hematopoiesis 脾脏其他
描述（中文）
髓外造血（extramedullary hematopoiesis，EMH）在啮齿类动物中常见，是脾红髓的正常组成部分。其在年轻动物中比在老年动物中更常见，在雌性中比在雄性中更常见，在小鼠中比在大鼠中更常见。由于多种情况，如血液毒性损伤、全身性贫血、感染、出血和肿瘤形成，造血细胞数量可能增加至超过正常背景水平（Figure 1、Figure 2、Figure 3、Figure 4）。EMH可包括红系前体细胞（Figure 2、Figure 4，箭头）、髓系前体细胞（Figure 2、Figure 4，箭头head）、巨核细胞（Figure 2、Figure 4）数量增加，或所有三种细胞类型的各种组合。红系前体细胞可继发于出血或红细胞破坏（即溶血性贫血或自身免疫介导的贫血）而占优势，而髓系前体细胞可继发于炎症性、肿瘤性或免疫介导的情况而占优势。浆细胞增生可伴随红髓内的EMH。EMH通常通过其分布和显示不同程度正常分化的造血细胞类型的混合而与肿瘤形成相区分；然而，严重的髓系细胞增殖在组织学上可能类似于粒细胞性白血病。既往术语包括“造血细胞增殖”、“髓系增生”和“红系增生”。
诊断建议
仅当髓外造血相对于同期对照的正常背景水平增加或减少（尽管后者罕见）时，才对其进行诊断和分级。髓外造血的诊断应修饰为增加或减少（即，脾 - 髓外造血，增加 或 脾 - 髓外造血，减少）。需要与同期对照进行仔细比较。如果一种细胞类型占优势（即髓系、红系、巨核系），可在病理学叙述中讨论。如果EMH继发于肿瘤形成而增加，则无需记录，但应在病理学叙述中描述。相关链接：肾上腺 - 髓外造血；肝脏 - 髓外造血；淋巴结 - 髓外造血
参考切片图（2 张）
查看英文原文
Comment
Extramedullary hematopoiesis (EMH) is commonly observed in rodents as a normal component of the splenic red pulp. It occurs more frequently in young than in aged animals, in females than in males, and in mice than in rats. Hematopoietic cell numbers may increase above normal background ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) due to a variety of conditions, such as hematotoxic insult, systemic anemia, infection, hemorrhage, and neoplasia. EMH may include increased numbers of erythroid precursors ( Figure 2 and Figure 4 , arrows), myeloid precursors ( Figure 2 and Figure 4 , arrowheads), megakaryocytes ( Figure 2 and Figure 4 ), or various combinations of all three cell types. Erythroid precursor cells may predominate secondary to hemorrhage or erythrocyte destruction (i.e., hemolytic anemia or autoimmune-mediated anemia), whereas myeloid precursor cells may predominate secondary to inflammatory, neoplastic, or immune-mediated conditions. Plasma cell hyperplasia may accompany EMH within the red pulp. EMH is generally distinguished from neoplasia by its distribution and mixture of hematopoietic cell types showing various degrees of normal differentiation; however, severe myeloid cell proliferation may resemble granulocytic leukemia histologically. Previous terms include "hematopoietic cell proliferation," "myeloid hyperplasia," and "erythroid hyperplasia."
Recommendation
Diagnose and grade extramedullary hematopoiesis only when it is increased or decreased (though this is rare) relative to the normal background level in the concurrent controls. The diagnosis of extramedullary hematopoiesis should be modified as increased or decreased (i.e., Spleen - Extramedullary hematopoiesis, Increased or Spleen - Extramedullary hematopoiesis, Decreased). Careful comparison with concurrent controls is necessary. If one cell type predominates (i.e., myeloid, erythroid, megakaryocytic), this can be discussed in the pathology narrative. If EMH is increased secondary to neoplasia, it need not be recorded but should be described in the pathology narrative. Related Links: Adrenal Gland - Extramedullary Hematopoiesis Liver - Extramedullary Hematopoiesis Lymph Node - Extramedullary Hematopoiesis
Rathke裂扩张Rathke's Cleft Dilation 垂体扩张
描述（中文）
扩张的持续性Rathke裂在大鼠中相对常见，通常含有嗜酸性胶体样蛋白性物质。可能出现胆固醇裂隙（箭头，Figure 1、Figure 2）以及游离红细胞（Figure 3）。也可能存在垂体囊肿（见Pituitary Gland - Cyst）。
诊断建议
由于慢性研究可能包含宫内暴露，可能与受试物相关的发育改变可能影响Rathke裂的最终存在和外观。因此，当该改变存在时应予以记录。如果该改变的发生或严重程度存在潜在的受试物相关影响，则适合进行严重程度分级。扩张的Rathke裂内的出血或胆固醇裂隙不应单独诊断，除非严重程度足以支持单独诊断。相关链接：Pituitary Gland - Cyst
参考切片图（2 张）
查看英文原文
Comment
Dilated persistent Rathke’s clefts are relatively common in rats and typically contain eosinophilic colloid-like proteinaceous material. Cholesterol clefts (arrow, Figure 1 and Figure 2 ), as well as free erythrocytes ( Figure 3 ), may be present. Pituitary cysts may also be present (see Pituitary Gland - Cyst ).
Recommendation
Since chronic studies may incorporate in utero exposure, developmental alterations potentially related to treatment could influence the ultimate presence and appearance of Rathke’s cleft. Thus, this change should be documented when present. A severity grade is appropriate if there is a potential treatment-related effect on the occurrence or severity of this change. Hemorrhage or cholesterol clefts within the dilated Rathke’s cleft should not be diagnosed separately unless warranted by severity. Related Links: Pituitary Gland - Cyst
囊肿Cyst 垂体囊肿
描述（中文）
在超过一年龄的大鼠和小鼠中，垂体远侧部（pars distalis）囊肿是常见的偶然性发现。大多数为颅咽管（Rathke's）囊的残余，与局限于远侧部和中间部（pars intermedia）之间的Rathke's裂隙扩张不同。垂体囊肿可为单个或多个，可含有嗜酸性蛋白性液体或黏蛋白性液体，常衬以纤毛立方至柱状细胞，通常不压迫周围实质。纤毛上皮衬里可能不完整。上皮衬里可将它们与血管扩张（angiectasis）和/或扩大的血管窦以及囊性变性区分开来，后者不规则边缘衬以退变的分泌细胞。偶尔，腺垂体含有小的滤泡样结构，属偶然性发现，不应诊断为囊肿。神经部（pars nervosa）出现多个衬以上皮的囊肿（箭头，Figure 4、Figure 5）提示起源于漏斗腔。也可能存在扩张的Rathke's裂隙（星号，Figure 4、Figure 5）。大多数涉及垂体囊肿的文献提及颅咽管起源，并进一步指出Rathke's囊是颅咽管结构的一部分。因此，Rathke's囊囊肿与颅咽管囊肿是同义词。确定特定囊肿的起源可能较为困难。
诊断建议
虽然试图区分垂体囊肿的起源并不关键，但这些囊肿只要存在就应诊断，并且应在诊断中指明囊肿发生的垂体部位（例如，Pituitary Gland, Pars nervosa - Cyst）。如果有多个囊肿，诊断中应包含修饰词"multiple"。由于慢性研究可能包含宫内暴露，可能与受试物相关的发育改变可能影响垂体囊肿的最终存在和外观。如果该变化的发生或严重程度存在潜在的受试物相关效应，则适合进行严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Pituitary cysts in the pars distalis are frequent incidental findings in rats more than a year old and in mice. Most are remnants of the craniopharyngeal (Rathke's) pouch and are distinct from Rathke's cleft dilation that is localized between the pars distalis and pars intermedia. Pituitary cysts may be single or multiple, may contain eosinophilic proteinaceous or mucoproteinaceous fluid, are often lined by ciliated cuboidal to columnar cells, and typically do not compress surrounding parenchyma. The ciliated epithelial lining may be incomplete. The epithelial lining distinguishes them from angiectasis and/or enlarged vascular sinuses and from cystic degeneration, where irregular edges are lined by degenerating secretory cells. Occasionally, the adenohypophysis contains small follicle-like structures that are incidental and should not be diagnosed as cysts. The presence of multiple epithelium-lined cysts in the pars nervosa (arrows, Figure 4 and Figure 5 ) suggests an origin from the infundibular lumen. A dilated Rathke’s cleft (asterisks, Figure 4 and Figure 5 ) may also be present. The majority of the literature dealing with pituitary cysts makes reference to a craniopharyngeal origin and further indicates that Rathke's pouch is part of the craniopharyngeal structure. Consequently, cysts of Rathke's pouch and craniopharyngeal cysts are synonymous. Determination of the origin of specific cysts may be difficult.
Recommendation
While attempting to distinguish the origin of pituitary cysts is not critical, these cysts should be diagnosed whenever present, and the part of the pituitary in which the cysts occur should be indicated in the diagnosis (e.g., Pituitary Gland, Pars nervosa - Cyst). If there are multiple cysts, the modifier "multiple" should be included in the diagnosis. Since chronic studies may incorporate in utero exposure, developmental alterations potentially related to treatment could influence the ultimate presence and appearance of pituitary cysts. A severity grade would be appropriate if there is a potential treatment-related effect on the occurrence or severity of this change.
增生Hyperplasia 垂体增生
描述（中文）
局灶性（focal） hyperplasia（局灶性增生）是一种常见的自发性及诱发性改变，在大鼠中比小鼠中更常见。其显微镜下表现多样，但主要由单一细胞类型构成，与邻近实质相融合而无压迫（Figure 1、Figure 2、Figure 3、Figure 4）。增生通常是细胞数量增加与细胞体积增大的组合，并随动物年龄增长而增加。有时可出现多个增生灶（Figure 4）。血管扩张（angiectasis）可发生于增生灶内（Figure 5），有时可引起邻近实质的轻度压迫。垂体中间部（pars intermedia）的局灶性 hyperplasia（Figure 6、Figure 7）较远侧部（pars distalis）增生少见。中间部的增生细胞与正常中间部细胞相似，由于可能没有邻近实质的压迫，局灶性增殖性病变的识别可能依赖于生长模式的改变或中间部的不对称增大。弥漫性（diffuse） hyperplasia（弥漫性增生）也可发生，必须与中间部的切向切片相鉴别。弥漫性增生通常为特定细胞类型，可通过免疫组织化学（immunohistochemistry）确认，通常代表一种生理性反应。增生与垂体肿瘤（pituitary neoplasia）之间存在形态学连续谱，邻近实质的压迫是肿瘤的主要诊断特征。针对垂体激素的免疫组织化学可用于确定细胞类型。
诊断建议
局灶性（focal） hyperplasia一旦存在即应作出诊断并给予严重程度分级，且应在诊断中指明所累及的垂体部位（例如：Pituitary Gland, Pars distalis - Hyperplasia）。增生的任何显著特征均可在病理学描述（pathology narrative）中描述。增生性病变内的血管扩张不应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Focal hyperplasia is a frequent spontaneous as well as induced change and is seen more commonly in rats than in mice. The microscopic appearance is variable but consists primarily of a single cell type that blends into the adjacent parenchyma without compression ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Hyperplasia is typically a combination of increased cell number and increased cell size and increases with animal age. On occasion there may be multiple foci of hyperplasia ( Figure 4 ). Angiectasis may occur within a focus of hyperplasia ( Figure 5 ) and may sometimes cause slight compression of adjacent parenchyma. Focal hyperplasia of the pars intermedia ( Figure 6 and Figure 7 ) is less common than hyperplasia of the pars distalis. The hyperplastic cells in the pars intermedia are similar to normal pars intermedia cells, and identification of a focal proliferative lesion may rely on alteration of growth pattern or asymmetrical enlargement of the pars intermedia since there may be no compression of the adjacent parenchyma. Diffuse hyperplasia may also occur and must be distinguished from a tangential section of the pars intermedia. Diffuse hyperplasia is usually of a specific cell type that can be confirmed by immunohistochemistry and typically represents a physiologic response. There is a morphologic continuum between hyperplasia and pituitary neoplasia, with compression of the adjacent parenchyma being a primary diagnostic feature of neoplasia. Immunohistochemistry for pituitary hormones can be used to determine cell type.
Recommendation
Focal hyperplasia should be diagnosed and given a severity grade whenever present, and the part of the pituitary involved should be specified in the diagnosis (e.g., Pituitary Gland, Pars distalis - Hyperplasia). Any remarkable features of hyperplasia may be described in the pathology narrative. Angiectasis within the hyperplastic lesion should not be diagnosed separately.
远侧部坏死Pars Distalis Necrosis 垂体坏死
描述（中文）
远侧部（pars distalis）坏死与来自垂体门脉血管或初级小动脉的血供受到机械性或其他方式中断有关。暂时性反复发作或持续性闭塞性血管痉挛与垂体前叶坏死有关。远侧部的尾侧部分可能免于受累，坏死区域可能界限清晰。血管充血可同时发生于坏死区和非坏死区。在人类远侧部坏死病例中，已有颅内压升高伴循环衰竭及垂体柄破坏的报道。经静脉给予的化学物可引起血管收缩及随后的远侧部坏死。女性严重产后出血（Sheehan综合征）后发生的低血压及垂体动脉血管痉挛与远侧部坏死有关。
诊断建议
垂体的远侧部坏死只要存在即应诊断并分级。病理学描述应说明形态学特征以及与垂体坏死可能相关的任何颅内改变的联系。应检查其他内分泌和生殖组织，以寻找与垂体坏死相关的潜在继发性改变。相关病变如炎症和出血除非其严重程度足以需要，否则不应单独诊断，但可在病理学描述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Necrosis of the pars distalis has been associated with mechanical or other interruption of the blood supply from hypophysial portal vessels or primary arterioles. Temporary recurring or persistent occlusive vasospasm has been linked to necrosis of the anterior pituitary. The caudal part of the pars distalis may be spared, and the necrotic areas may be sharply demarcated. Vascular congestion can occur in both necrotic and nonnecrotic areas. Increased intracranial pressure with circulatory collapse and destruction of the pituitary stalk has been reported in human cases of pars distalis necrosis. Chemicals administered intravenously can cause vasoconstriction and subsequent necrosis of the pars distalis. Hypotension and vasospasms of hypophysial arteries following severe postpartum hemorrhage in women (Sheehan syndrome) is associated with necrosis of the pars distalis.
Recommendation
Necrosis of the pars distalis of the pituitary should be diagnosed and graded whenever present. The pathology narrative should describe morphologic features and any connection with intracranial changes that might be associated with pituitary necrosis. Other endocrine and reproductive tissues should be examined for potential secondary changes related to pituitary necrosis. Associated lesions such as inflammation and hemorrhage should not be diagnosed separately unless warranted by their severity, but otherwise may be described in the pathology narrative.
远侧部萎缩Pars Distalis Atrophy 垂体萎缩
描述（中文）
远侧部（pars distalis）萎缩可作为缺血所致坏死的后遗症发生，和/或由占位性病变对垂体的压迫引起。后者更为常见。萎缩组织内的巨噬细胞内可能存在黄褐色色素（含铁血黄素）（Figure 1、Figure 2、Figure 3、Figure 4）。远侧部的小部分区域可能受累较轻或不受累。相比之下，垂体神经纤维中断很可能导致垂体后叶萎缩。萎缩最常见于远侧部，但也可能累及中间部（pars intermedia）和神经部（pars nervosa）。
诊断建议
垂体萎缩只要存在即应诊断并分级。受累区域应作为部位修饰词纳入诊断（例如，Pituitary, Pars distalis - Atrophy）。若受累区域超过一个，可省略部位修饰词，并在病理描述中注明受累部位。病理描述还可描述形态学特征（包括是否存在载色素巨噬细胞）及病变范围。
参考切片图（2 张）
查看英文原文
Comment
Atrophy of the pars distalis can occur as a sequela of necrosis secondary to ischemia and/or from compression on the pituitary by a space occupying mass. The latter is more common. Yellow-brown pigment (hemosiderin) may be present within macrophages in the atrophic tissue ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Small portions of the pars distalis may be spared. In contrast, interruption of hypophyseal nerve fibers would likely result in atrophy of the posterior lobe of the pituitary. Atrophy is most common in the pars distalis but may also affect the pars intermedia and the pars nervosa.
Recommendation
Atrophy of the pituitary should be diagnosed and graded whenever present. The area affected should be included in the diagnosis as a site modifier (e.g., Pituitary, Pars distalis - Atrophy). If more than one area is affected, the site modifier may be omitted and the affected sites noted in the pathology narrative. The pathology narrative can also describe the morphologic features (including the presence of pigment laden macrophages) and extent of the change.
先天性囊肿Cyst Congenital 甲状旁腺囊肿
描述（中文）
区分甲状旁腺囊肿的甲状舌管起源与鳃后体起源在某种程度上并不明确，因为两者均可能具有纤毛细胞衬里。因此，“先天性囊肿（congenital cyst）”是首选的术语。在 F344/N rat 和 B6C3F1 mouse 中，这些囊肿可见于甲状旁腺内或邻近甲状旁腺处。先天性囊肿通常由立方至柱状上皮衬里，该上皮可能具有纤毛。囊肿腔可能含有异质性蛋白性物质和细胞碎片。
诊断建议
对于包含宫内暴露的研究，可能与受试物相关的发育改变可能影响甲状旁腺囊肿的最终存在和外观。甲状舌管囊肿和鳃后体囊肿均应诊断为“parathyroid gland - cyst, congenital”。不需要进行严重程度分级。如果双侧甲状旁腺均受累，诊断应限定为双侧性（双侧（bilateral））。
参考切片图（2 张）
查看英文原文
Comment
Distinguishing between a thyroglossal and an ultimobranchial origin for parathyroid cysts is somewhat equivocal since either may have a ciliated cell lining. Consequently, "congenital cyst" is the preferred terminology. These can be seen within or adjacent to the parathyroid gland in rats and mice. Congenital cysts are typically lined by cuboidal to columnar epithelium that may be ciliated. Cyst lumens may contain heterogeneous proteinaceous material and cellular debris.
Recommendation
For studies that include in utero exposure, developmental alterations potentially related to treatment could influence the ultimate presence and appearance of parathyroid cysts. Both thyroglossal and ultimobranchial cysts should be diagnosed as "parathyroid gland - cyst, congenital". A severity grade is not necessary. If both parathyroids are involved, the diagnosis should be qualified as bilateral.
合胞体巨细胞Syncytial Giant Cell 甲状旁腺其他
描述（中文）
大鼠甲状旁腺中可出现多核合体细胞（multinucleated syncytial cells）。其数量不一，但这些巨细胞可占据腺体达一半。它们由相邻主细胞（chief cells）的胞质融合形成。胞质可呈致密嗜酸性。合体巨细胞被认为不干扰甲状旁腺功能。对于这是否为生前变化尚无共识。一些科学家认为这是死后人为假象。
诊断建议
推荐对甲状旁腺合体巨细胞形成作出诊断。不需要进行严重程度分级。若两侧甲状旁腺均受累，诊断应限定为双侧性。
参考切片图（2 张）
查看英文原文
Comment
Multinucleated syncytial cells occur in the parathyroid of rats. Their number varies, but these giant cells may occupy up to one-half of the gland. They are formed by cytoplasmic fusion of adjacent chief cells. The cytoplasm may be densely eosinophilic. Syncytial giant cells are not believed to interfere with parathyroid function. There is no consensus that this is an antemortem change. Some scientists consider this a postmortem artifact.
Recommendation
Diagnosis of syncytial giant cell formation in the parathyroid is recommended. A severity grade is not needed. If both parathyroids are involved, the diagnosis should be qualified as bilateral.
局灶性增生Hyperplasia Focal 甲状旁腺增生
描述（中文）
甲状旁腺增生（parathyroid hyperplasia）可为局灶性（focal）或弥漫性（diffuse），在大鼠中发生率低，在小鼠中罕见。局灶性增生是增生与肥大的结合，增生的病灶因正常索状结构的改变和/或构成局灶性增生的肿大肥大细胞染色特性不同而突出于正常甲状旁腺实质。对周围实质的压迫可忽略不计；相比之下，甲状旁腺腺瘤（parathyroid adenoma）会引起邻近组织受压，且往往比增生更大。严重的局灶性增生可导致甲状旁腺肉眼可见的增大。局灶性甲状旁腺增生具有潜在的肿瘤前性质。
诊断建议
局灶性（focal）甲状旁腺增生应当被诊断并赋予严重程度分级。如果两侧甲状旁腺均受累，诊断应限定为双侧（bilateral），严重程度分级应基于受累更严重的一侧腺体。
参考切片图（2 张）
查看英文原文
Comment
Parathyroid hyperplasia can be focal or diffuse and occurs in low incidence in rats and rarely in mice. Focal hyperplasia is a combination of hyperplasia and hypertrophy, with the hyperplastic foci standing out from the normal parathyroid parenchyma by virtue of structural alteration of the normal cords and/or differential tinctorial staining of the enlarged hypertrophic cells comprising the focal hyperplasia. There is negligible compression of surrounding parenchyma; in contrast, parathyroid adenomas cause compression of adjacent tissue and tend to be larger than hyperplasias. Severe focal hyperplasia can result in a grossly enlarged parathyroid. Focal parathyroid hyperplasia is potentially preneoplastic.
Recommendation
Focal parathyroid hyperplasia should be diagnosed and assigned a severity grade. If both parathyroids are involved, the diagnosis should be qualified as bilateral and the severity grade based on the more severely affect gland.
异位组织Ectopic Tissue 甲状旁腺其他
描述（中文）
异位胸腺组织可见于甲状旁腺内或邻近甲状旁腺处，也可见于甲状腺内或邻近甲状腺处。它被认为是一种先天性异常。异位组织中可能同时可见胸腺皮质和髓质的特征。此种改变通常不被认为是处理的结果。在某些病例中，异位胸腺可大部分取代甲状旁腺。
诊断建议
当研究包含宫内暴露时，可能与处理相关的发育改变可影响组织异位的发生。因此，甲状旁腺内或邻近甲状旁腺的异位胸腺应当被诊断。不需要进行严重程度分级。如果双侧甲状旁腺均受累，诊断应限定为双侧性。诊断应使用起源组织进行修饰（例如，甲状旁腺 - 异位组织，胸腺）。
参考切片图（2 张）
查看英文原文
Comment
Ectopic thymic tissue can be found in or adjacent to the parathyroid, as well as in or adjacent to the thyroid. It is considered a congenital anomaly. Both thymic cortical and medullary features may be evident in the ectopic tissue. This change is generally not believed to be a consequence of treatment. In some cases the ectopic thymus can largely replace the parathyroid.
Recommendation
When studies include in utero exposure, developmental alterations potentially related to treatment could influence the occurrence of tissue ectopia. Therefore, ectopic thymus in or adjacent to the parathyroid gland should be diagnosed. A severity grade is not necessary. If both parathyroids are involved, the diagnosis should be qualified as bilateral. The diagnosis should be modified with the tissue of origin (e.g., parathyroid gland - ectopic tissue, thymus).
弥漫性增生Hyperplasia Diffuse 甲状旁腺增生
描述（中文）
甲状旁腺增生（parathyroid hyperplasia）可为局灶性（focal）或弥漫性（diffuse），在大鼠中发生率低，在小鼠中罕见。弥漫性增生可能与肾功能衰竭及长期饮食中钙和/或磷失衡有关，且通常为双侧性。弥漫性增生表现为细胞密度均匀增加，由细胞肥大和增生共同所致。发生弥漫性增生时，正常的细胞巢和细胞索发生改变，其中增生性细胞巢体积增大最为明显。严重增生通常会导致甲状旁腺肉眼可见增大，但如果组织学切片中的组织取样不佳，则可能在组织学上难以判断。与甲状旁腺腺瘤的鉴别在于，腺瘤表现为腺体内一个离散的膨胀性病变，通常为单侧，并伴有邻近实质受压。
诊断建议
只要观察到增生，就应作出诊断并给出严重程度分级。如果双侧甲状旁腺均受累，诊断应限定为双侧性，严重程度分级应基于受累较重的一侧腺体。如果病理学家认为增生与肾脏疾病相关，应在病理学叙述中注明。其他可能与增生相关的病变，如胃或肾脏矿化，也应在病理学叙述中加以评论。
参考切片图（2 张）
查看英文原文
Comment
Parathyroid hyperplasia can be focal or diffuse and occurs in low incidence in rats and rarely in mice. Diffuse hyperplasia may be associated with renal failure and long-term dietary imbalance of calcium and/or phosphorus and is usually bilateral. Diffuse hyperplasia presents as a uniform increase in cellularity due to combined hypertrophy and hyperplasia. With diffuse hyperplasia, the normal cellular nests and cords are altered, with increased size of hyperplastic nests being most obvious. Severe hyperplasia will usually result in a grossly enlarged parathyroid but may be difficult to determine histologically if the tissue in the histologic sections is not well sampled. Distinction from parathyroid adenoma is based on the adenoma appearing as a discrete expansile lesion, usually unilateral, within the gland and with compression of adjacent parenchyma.
Recommendation
Hyperplasia should be diagnosed and given a severity grade whenever observed. If both parathyroids are involved, the diagnosis should be qualified as bilateral and the severity grade should be based on the more severely affected gland. If the pathologist feels the hyperplasia is associated with renal disease, it should be noted in the pathology narrative. Other lesions that may be associated with the hyperplasia, such as gastric or renal mineralization, should also be commented on in the pathology narrative.
纤维化Fibrosis 甲状旁腺纤维化
描述（中文）
甲状旁腺纤维化（parathyroid fibrosis）的特征是纤维状、嗜酸性物质使甲状旁腺间质扩张，严重时取代实质。这是一种罕见的变化。病变可延伸至邻近的甲状腺实质。该病变的意义尚不确定。
诊断建议
此类罕见病变应当作出诊断并给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Parathyroid fibrosis is characterized by fibrillar, eosinophilic material that expands the interstitium of the parathryorid gland and, when severe, replaces the parenchyma. It is a rarely seen change. There may be extension into the adjacent thyroid parenchyma. The significance of this lesion is uncertain.
Recommendation
Rare lesions such as this should be diagnosed and given a severity grade.
血管扩张Angiectasis 甲状旁腺扩张
描述（中文）
小鼠和大鼠的甲状旁腺中可见血管腔扩张（dilation of vascular spaces），尽管较为罕见。扩张的血管腔散布于整个腺体内，代表由扁平内皮细胞衬覆的原有血管通道。Figure 1 中，扩张的血管通道内充满红细胞。与血管瘤（hemangioma）不同，血管扩张性病变不代表性血管结构的新生增殖。血管瘤通常边界更为清楚，伴有在纤细纤维性间质上新生血管通道的增殖。
诊断建议
甲状旁腺血管扩张（parathyroid angiectasis）应当作出诊断并给出严重程度分级。若严重程度为显著（marked），病理学描述中应当讨论其与血管瘤的鉴别。若双侧甲状旁腺均受累，诊断中应当包含“双侧（bilateral）”一词，严重程度分级应基于受累较重的一侧腺体。由于血管瘤性病变可能为多部位及全身性，病理学描述中应当说明该甲状旁腺病变与其他组织中类似改变之间可能存在的任何关系。
参考切片图（2 张）
查看英文原文
Comment
Dilation of vascular spaces may be seen in the parathyroid of mice and rats, although it is rare. The dilated vascular spaces are disseminated throughout the gland and represent preexisting vascular channels lined by flattened endothelial cells. In Figure 1 , the dilated vascular channels are filled with erythrocytes. In contrast to hemangiomas, angiectatic lesions do not represent proliferation of new vascular structures. Hemangiomas are usually more circumscribed, with proliferation of new vascular channels on a delicate fibrous stroma.
Recommendation
Parathyroid angiectasis should be diagnosed and given a severity grade. If the severity is marked, the pathology narrative should discuss its distinction from hemangioma. If both parathyroids are involved, the term “bilateral” should be included in the diagnosis and the severity grade based on the more severely affected gland. Since angiomatous lesions may be multisite and systemic, the pathology narrative should address any relationship that this parathyroid lesion might have to similar changes in other tissues.
C 细胞增生C Cell Hyperplasia 甲状腺增生
描述（中文）
C细胞增生（C-cell hyperplasia）是大鼠慢性研究中的常见所见，可呈弥漫性（弥漫性（diffuse））（Figure 1、Figure 2）、局灶性（局灶性（focal））（Figure 3、Figure 4）或多灶性（多灶性（multifocal））。C细胞增生与C细胞腺瘤（C-cell adenoma）的区分依据是任一给定局灶性增生的体积大小。C细胞增生普遍公认的判断标准为：局灶性C细胞簇小于五个平均滤泡直径，或散在于滤泡间间隙的类似小体积C细胞簇。与C细胞腺瘤不同，C细胞增生不伴有对邻近实质的明显压迫。C细胞增生内可含有单个陷入的滤泡（Figure 1、Figure 2）。C细胞增生一般由圆形至多面体形细胞构成，胞质嗜酸性（eosinophilic）且丰富（Figure 2）；部分病例中核质比高于典型水平（Figure 4）。
诊断建议
C细胞增生存在时应当作出诊断，并给出严重程度分级。若为双侧性，则应在诊断中注明，并依据受累较重的甲状腺给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
C-cell hyperplasia is a common finding in chronic rat studies and can be diffuse ( Figure 1 and Figure 2 ), focal ( Figure 3 and Figure 4 ), or multifocal. C-cell hyperplasia is distinguished from C-cell adenoma based on the size of any given focal proliferation. The generally accepted criteria for C-cell hyperplasia is a focal C-cell cluster less than five average follicular diameters or similarly small-sized clusters of C cells scattered in interfollicular spaces. In contrast to C-cell adenomas, C-cell hyperplasia is not associated with significant compression of adjacent parenchyma. C-cell hyperplasias may contain individual trapped follicles ( Figure 1 and Figure 2 ). C-cell hyperplasia generally consists of round to polyhedral cells with abundant eosinophilic cytoplasm ( Figure 2 ); in some cases there is a higher than typical nuclear-to-cytoplasmic ratio ( Figure 4 ).
Recommendation
C-cell hyperplasia should be diagnosed when present, given a severity grade. If bilateral it should be indicated in the diagnosis with a severity grade based on the more severely affected thyroid gland.
先天性囊肿Cyst Congenital 甲状腺囊肿
描述（中文）
甲状腺及邻近甲状旁腺中发现的囊肿代表胚胎残余，可衬以扁平或纤毛上皮（Figure 1、Figure 2）。当囊内充满角化物质时（Figure 3、Figure 4），通常被认为是鳃后囊肿（ultimobranchial cyst）；然而，鳃后囊肿有时也可衬以纤毛上皮。另一方面，甲状舌管囊肿（thyroglossal duct cyst）通常位于中央，衬以多层甲状腺源性上皮。然而，鉴于精确分类囊肿存在困难，更倾向于使用“先天性囊肿（congenital cyst）”这一更为通用的命名。由于慢性研究可能包含宫内暴露，与受试物相关的发育改变可能影响先天性甲状腺囊肿的存在及其最终外观。
诊断建议
先天性囊肿只要存在即应诊断。除非病理学家认为分级有助于突出受试物效应，否则囊肿无需分级。
参考切片图（2 张）
查看英文原文
Comment
Cysts found in the thyroid and adjacent parathyroid represent embryonal rests and may be lined by flattened or ciliated epithelium ( Figure 1 and Figure 2 ). When filled with keratinized material ( Figure 3 and Figure 4 ), they are typically considered to be ultimobranchial cysts; however, ultimobranchial cysts can sometimes be lined by ciliated epithelium. Thyroglossal duct cysts, on the other hand, are usually centrally located and lined by multilayered thyroidogenic epithelium. However, given the difficulty in precisely classifying cysts, the more generic nomenclature of “congenital cyst” is preferred. Since chronic studies may incorporate in utero exposures, developmental alterations related to treatment could influence the presence and ultimate appearance of congenital thyroid cysts.
Recommendation
Congenital cysts should be diagnosed whenever present. Grading of cysts is not necessary unless the pathologist feels grading would highlight a treatment effect.
异位组织Ectopic Tissue 甲状腺其他
描述（中文）
异位胸腺组织是一种先天性改变，胸腺外组织位于甲状腺邻近（Figure 1）或甲状腺内（Figure 2）。异位胸腺可同时具有皮质和髓质组织，以及哈索尔小体（Hassall's corpuscles）。异位胸腺是一种发育异常，偶尔可见于大鼠和小鼠，通常与处理无关，但胚胎期开始的暴露可能潜在影响胸腺异位的发生。
诊断建议
甲状腺内的异位组织只要存在即应诊断，但该改变不需要严重程度分级。诊断应注明组织来源进行修饰（例如，甲状腺 - 异位组织，胸腺）。
参考切片图（2 张）
查看英文原文
Comment
Ectopic thymic tissue is a congenital change with the extrathymic tissue located either adjacent to ( Figure 1 ) or within ( Figure 2 ) the thyroid gland. The ectopic thymus may have both cortical and medullary tissue, as well as Hassall’s corpuscles. Ectopic thymus is a developmental abnormality that can occasionally be found in rats and mice and is generally unrelated to treatment, but exposures beginning during embryogenesis may potentially affect the occurrence of thymic ectopia.
Recommendation
Ectopic tissue in the thyroid gland should be diagnosed whenever present, but a severity grade is not needed for this change. The diagnosis should be modified with the tissue of origin (e.g., Thyroid gland - Ectopic tissue, thymus).
滤泡上皮增生Follicle Epithelium Hyperplasia 甲状腺增生
描述（中文）
滤泡上皮增生（hyperplasia of follicular epithelium）可为局灶性（focal）、弥漫性（diffuse），有时呈囊性。局灶性或多灶性（multifocal）滤泡增生可存在于单个或少数几个滤泡中。局灶性增生无包膜，不压迫周围实质，借此与良性肿瘤相鉴别。受累滤泡可较小、含极少量胶质，或较大而不规则，增生的上皮呈乳头状突起伸入滤泡腔（Figure 1、Figure 2）。甲状腺滤泡肥大（hypertrophy）与增生常同时发生（Figure 3）。亦可出现以滤泡上皮细胞核拥挤、向滤泡腔内突起极轻微为特征的增生（Figure 4）。
诊断建议
尽管滤泡增生可自发发生，但一旦存在即应作出诊断并给予严重程度分级。严重程度可依据受累腺体的百分比及增生的形态学复杂程度判定。增生的性质与范围以及为单侧抑或双侧，均应在病理描述中予以说明。建议区分局灶性（focal）、弥漫性（diffuse）与囊性甲状腺滤泡增生，并应将其作为诊断的限定词纳入诊断。伴增生的滤泡中任何相关肥大的性质不应单独诊断，除非其严重程度足以支持单独诊断。若未作诊断，则应在病理描述中说明肥大情况。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of follicular epithelium may be focal, diffuse, or sometimes cystic. Focal or multifocal follicular hyperplasia can be present in a single or in a few follicles. Focal hyperplasia is not encapsulated and does not compress surrounding parenchyma, which differentiates it from benign tumors. Affected follicles may be small with minimal colloid or large and irregular with papillary projections of hyperplastic epithelium extending into the follicular lumen ( Figure 1 and Figure 2 ). Thyroid follicular hypertrophy and hyperplasia often occur together ( Figure 3 ). Hyperplasia characterized by crowding of follicular epithelium nuclei and minimal protrusion into the follicular lumen may occur ( Figure 4 ).
Recommendation
Although follicular hyperplasia can occur spontaneously, it should be diagnosed and given a severity grade whenever present. Severity may be based on the percentage of the gland involved and the morphologic complexity of the hyperplasia. The nature and extent of the hyperplasia and whether it is unilateral or bilateral should be described in the pathology narrative. Distinction between focal, diffuse, and cystic thyroid follicular hyperplasia is recommended and should be included as a qualifier of the diagnosis. The nature of any associated hypertrophy in follicles with hyperplasia should not be diagnosed separately, unless warranted by severity. If not diagnosed, hypertrophy should be described in the pathology narrative.
滤泡变性Follicle Degeneration 甲状腺变性
描述（中文）
滤泡变性包括滤泡扩张和正常滤泡形态丧失、相邻滤泡融合以及胶质染色强度减弱（Figure 1、Figure 2）。该病变在小鼠中常见，在大鼠中不常见。在与处理相关的滤泡变性已在至少一项 NTP 小鼠亚慢性研究中出现；在该研究中，它与甲状腺色素沉着相关。在慢性研究中，对照组和处理组小鼠中已出现大量病例，其中一些病例中，衬覆退化扩张滤泡的上皮细胞具有纤毛（Figure 2，箭头）。
诊断建议
无论何时出现，这种退行性改变都应记录并分级。如果变性为双侧性，应在诊断中指明，且严重程度分级应基于受累最严重的腺体。
参考切片图（2 张）
查看英文原文
Comment
Follicular degeneration consists of dilatation and loss of normal follicular shape, coalescence of adjacent follicles, and decreased intensity of colloid staining ( Figure 1 and Figure 2 ). It occurs commonly in mice but uncommonly in rats. Treatment-associated follicular degeneration has occurred in at least one NTP subchronic study in mice; in that study it was associated with thyroid pigmentation. A large number of cases have occurred in control and treated mice in chronic studies, and in some the epithelial cells lining the degenerating dilated follicles are ciliated ( Figure 2 , arrows).
Recommendation
Whenever present, this degenerative change should be documented and graded. If the degeneration is bilateral, it should be indicated in the diagnosis, and the severity grade should be based on the most severely affected gland.
滤泡扩张Follicle Dilation 甲状腺扩张
描述（中文）
一个或多个扩张的滤泡是小鼠和大鼠甲状腺中常见的、与年龄相关的改变。受累滤泡的胶质可呈淡染（Figure 1、Figure 2）或缺失，管腔内可见脱落细胞。扩张的滤泡常见于甲状腺外周（Figure 3、Figure 4）。扩张的滤泡衬以低立方至扁平上皮。
诊断建议
推荐对扩张滤泡进行记录和分级。诊断应指明扩张是否为双侧性，严重程度分级应基于受累更严重的甲状腺。扩张滤泡管腔内出现细胞无需单独诊断，除非其严重程度足以需要单独诊断。
参考切片图（2 张）
查看英文原文
Comment
One or more dilated follicles occur as a common and age-associated change in mouse and rat thyroids. Affected follicles may have pale ( Figure 1 and Figure 2 ) or absent colloid, and exfoliated cells may be present in the lumen. The dilated follicles are frequently seen at the periphery of the thyroid gland ( Figure 3 and Figure 4 ). Dilated follicles are lined by low cuboidal to flattened epithelium.
Recommendation
Documentation and grading of dilated follicles are recommended. The diagnosis should indicate whether the dilation is bilateral, with a severity grade based on the more severely affected thyroid gland. The presence of cells within the lumens of the dilated follicles need not be diagnosed separately unless warranted by severity.
滤泡矿化Follicle Mineralization 甲状腺矿化
描述（中文）
成年动物中偶见孤立甲状腺滤泡内矿化（mineralization），可表现为颗粒状嗜碱性沉积物，不伴炎症。
诊断建议
甲状腺滤泡内矿化属偶然发现，仅在严重或怀疑与受试物相关时才应记录并给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Mineralization within solitary thyroid follicles is occasionally seen in adults and may appear as granular basophilic deposits not associated with inflammation.
Recommendation
Mineralization in the thyroid follicles is an incidental finding and should be documented and given a severity grade only when severe or suspected of being treatment related.
滤泡细胞肥大Follicular Cell Hypertrophy 甲状腺肥大
描述（中文）
在滤泡细胞肥大（follicular cell hypertrophy）中，甲状腺滤泡可能由立方状至柱状上皮衬覆，中央滤泡紧密排列且小于正常（Figure 1、Figure 2）。滤泡上皮的局灶性（focal）增生有时可伴随滤泡肥大（Figure 1，箭头）。双侧肥大是对垂体促甲状腺激素分泌增加的系统性反应，属预期所见。肥大的滤泡上皮可含有淡嗜酸性胞质和小而清亮的空泡（Figure 3）。在更为慢性的滤泡上皮肥大中，所有滤泡均可能小于正常，伴有分泌耗竭或分泌异常及上皮脱落（Figure 4）。甲状腺滤泡细胞肥大的出现可能继发于肝细胞微粒体酶诱导，并且在甲状腺滤泡细胞肥大的大鼠中常同时可见肝细胞肥大。
诊断建议
甲状腺滤泡细胞肥大存在时应当诊断并分级。病理学描述可说明肥大滤泡上皮的性质，以及是否为双侧、是否伴有滤泡增生，或是否与胶质改变相关。
参考切片图（2 张）
查看英文原文
Comment
In follicular cell hypertrophy, thyroid follicles may be lined by cuboidal to columnar epithelium with central follicles tightly packed and smaller than normal ( Figure 1 and Figure 2 ). Focal hyperplasia of follicular epithelium may sometimes accompany follicular hypertrophy ( Figure 1 , arrows). Bilateral hypertrophy is expected as a systemic response to increased pituitary secretion of thyroid-stimulating hormone. Hypertrophic follicular epithelium may contain pale eosinophilic cytoplasm and small clear vacuoles ( Figure 3 ). In more chronic follicular epithelial hypertrophy, all follicles may be smaller than normal, with secretory depletion or abnormal secretion and exfoliated epithelium ( Figure 4 ). The presence of thyroid follicular cell hypertrophy may be secondary to hepatocellular microsomal enzyme induction, and hepatocellular hypertrophy is often seen concomitantly in rats with thyroid gland follicular cell hypertrophy.
Recommendation
Thyroid follicular cell hypertrophy should be diagnosed and graded when present. The pathology narrative can describe the nature of the hypertrophic follicular epithelium and whether bilateral, accompanied by follicular hyperplasia, or associated with alterations in colloid.
滤泡色素沉着Follicle Pigment 甲状腺色素沉着
描述（中文）
甲状腺色素沉着可由铁和/或脂褐素在滤泡上皮或胶质中沉积所致。在啮齿类及其他物种中，暴露于米诺环素（minocycline，一种四环素的半合成衍生物）后可见类似黑色素的深黑色色素（Figure 1、Figure 2）。NTP测试的至少4种化学物可引起甲状腺色素沉着。在对照和治疗大鼠中均可见轻微色素沉着作为背景性改变（Figure 3、Figure 4）。
诊断建议
即使使用一系列特殊染色，在组织学切片中明确鉴定色素通常也很困难。因此，推荐诊断为色素沉着（而非诊断色素类型，例如含铁血黄素或脂褐素）最为恰当。病理学描述应描述色素的形态学特征。并非所有色素都必须诊断，因为有些色素在衰老动物中普遍存在，或与其他疾病过程相关，而无毒理学意义。病理学家应运用其判断力决定继发性色素沉积是否显著到足以需要单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Thyroid pigmentation can occur as a result of iron and/or lipofuscin deposition in follicular epithelium or colloid. Dark black pigment with resemblance to melanin is seen in rodents and other species following exposure to minocycline, a semisynthetic derivative of tetracycline ( Figure 1 and Figure 2 ). At least 4 chemicals tested by the NTP have caused thyroid pigmentation. Subtle pigmentation can be seen as a background change in both control and treated rats ( Figure 3 and Figure 4 ).
Recommendation
Definitive pigment identification is often difficult in histological sections, even with a battery of special stains. Therefore, it is recommended that a diagnosis of pigment (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should describe the morphological features of the pigment. Not all pigments have to be diagnosed, as some are ubiquitous in aging animals or related to some other disease process and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether or not secondary deposits of pigment are prominent enough to warrant a separate diagnosis.
炎症Inflammation 甲状腺炎症
描述（中文）
NTP研究将炎症分为五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞是中性粒细胞（neutrophil），但也可能存在较少的巨噬细胞（macrophage）和淋巴细胞（lymphocyte）。还可能有水肿或充血（hyperemia）的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但它们聚集在一起，其中许多已变性（化脓性渗出物，化脓性 exudate）。渗出物中还可能存在来自 resident 细胞群和浸润白细胞的细胞碎片、含纤维蛋白（fibrin）的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞（plasma cell），以及可能的感染因子。肉眼观察，这些病变以脓液存在为特征。渗出物周围组织可能有成纤维细胞（fibroblast）、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在大量中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的、活化的巨噬细胞、上皮样巨噬细胞（epithelioid macrophage）或多核巨细胞（multinucleated giant cell）。在小鼠和大鼠的甲状腺中，自发性细胞浸润是罕见的。这些受处理小鼠的甲状腺中存在多种变化（Figure 1、Figure 2、Figure 3）。淋巴样细胞浸润存在于滤泡之间（Figure 1、Figure 2）以及血管周围间隙（Figure 3）。此外，还存在滤泡上皮的肥大（hypertrophy）、变性（degeneration）和坏死（necrosis）。
诊断建议
甲状腺炎症只要存在就应诊断并给予严重程度分级。炎症类型应在诊断中通过修饰词标明（例如，甲状腺 - 炎症，慢性）。在缺乏其他炎症特征性变化（例如，水肿、坏死、变性）的情况下，可能更倾向于诊断为细胞浸润并注明细胞类型（例如，甲状腺 - 浸润，淋巴样）。其他变化（例如，胶质耗竭、滤泡细胞变性、坏死）除非其严重程度足以支持，否则不应单独诊断。这些其他变化可在病理学叙述中描述。诊断应指明炎症是否为双侧性，严重程度分级应基于受影响更严重的甲状腺。
参考切片图（2 张）
查看英文原文
Comment
NTP studies have five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation, the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris from both the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in within the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may have fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Spontaneously occurring cellular infiltrates are rare in thyroid glands of mice and rats. Multiple changes are present in the thyroids of these treated mice ( Figure 1 , Figure 2 , and Figure 3 ). Lymphoid cell infiltrates are present between follicles ( Figure 1 and Figure 2 ) and in perivascular spaces ( Figure 3 ). Additionally there is hypertrophy, degeneration, and necrosis of follicular epithelium.
Recommendation
Inflammation of the thyroid gland should be diagnosed and given a severity grade whenever present. The type of inflammation should be indicated in the diagnosis with a modifier (e.g., thyroid gland - Inflammation, chronic). In the absence of other changes characteristic of inflammation (e.g., edema, necrosis, degeneration), a diagnosis of cellular infiltrate with the cell type identified (e.g., thyroid gland - infiltrate, lymphoid) may be preferred. Other changes (e.g., colloid depletion, follicular cell degeneration, necrosis) not be diagnosed separately unless warranted by their severity. These other changes can be described in the pathology narrative. The diagnosis should indicate whether the inflammation is bilateral, with the severity grade based on the more severely affected thyroid.
出血Hemorrhage 肾上腺出血
描述（中文）
肾上腺出血（Adrenal gland hemorrhage，Figure 1、Figure 2、Figure 3、Figure 4）的特征是皮质和/或髓质内出现数量不等的外渗血细胞。出血可为局灶性（focal）或弥漫性（diffuse），严重程度从小的局灶性区域到广泛受累不等，广泛受累可扭曲甚至破坏正常结构（Figure 1、Figure 2、Figure 3、Figure 4）。肾上腺出血可继发于许多自发性或治疗相关的病理过程，如原发性血管疾病、全身性凝血病、梗死和败血症。已知许多化学物质以及极高剂量的外源性促肾上腺皮质激素（adrenocorticotropic hormone，ACTH）可引起肾上腺出血（主要发生在皮质），且常与坏死相关。
诊断建议
肾上腺出血应予以诊断，并赋予严重程度分级、部位修饰词（即皮质、髓质）和分布修饰词（即局灶性（focal）、弥漫性（diffuse））。如果皮质和髓质均存在出血，可省略部位修饰词，并在病理学描述中说明位置。继发于其他病变（如囊性变性、炎症或坏死）的出血不应单独诊断，除非严重程度足以支持单独诊断，但可在病理学描述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Adrenal gland hemorrhage ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is characterized by the presence of variable amounts of extravasated blood cells in the cortex and/or medulla. Hemorrhage can be focal or diffuse and range in severity from a small focal area to extensive involvement that can distort or even obliterate normal architecture ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Adrenal hemorrhage can be secondary to many spontaneous or treatment-related pathologic processes such as primary vascular disease, systemic coagulopathy, infarction, and septicemia. Many chemicals, as well as very high doses of exogenous adrenocorticotropic hormone (ACTH), are known to cause adrenal hemorrhage (primarily in the cortex), often in association with necrosis.
Recommendation
Adrenal hemorrhage should be diagnosed and assigned a severity grade, site modifier (i.e., cortex, medulla), and distribution modifier (i.e., focal, diffuse). If it is present in both the cortex and medulla, the site modifier may be omitted and the location described in the pathology narrative. Hemorrhage secondary to other lesions (e.g., cystic degeneration, inflammation, or necrosis) should not be diagnosed separately, unless warranted by severity, but may be described in the pathology narrative.
囊肿Cyst 肾上腺囊肿
描述（中文）
肾上腺囊肿（Adrenal cysts）（Figure 1、Figure 2、Figure 3）由立方上皮至纤毛柱状上皮衬覆，可含有无定形至絮状、嗜酸性物质。它们可位于皮质或髓质，并可导致邻近组织不同程度的扭曲或压迫。这些轻微病变在小鼠中比在大鼠中更常见，通常为偶然发生的、自发性的改变，无临床或毒理学意义。皮质囊肿必须与血管扩张（angiectasis，即含血液、由扁平内皮细胞衬覆的扩张血管通道）相鉴别。大鼠的皮质囊肿还必须与囊性变性（cystic degeneration）相鉴别，后者是某些大鼠品系中的常见病变，其特征为不规则的、常为较大的空腔化空间，充满蛋白性液体，但缺乏真性囊肿的上皮衬覆（Figure 2、Figure 3）。
诊断建议
肾上腺囊肿仅在以与处理相关的发生率增加出现时才应诊断。在这些情况下，应予以诊断，但不赋予严重程度分级。诊断时，应在诊断中纳入适当的部位修饰词（即皮质或髓质），以指示囊肿的位置。
参考切片图（2 张）
查看英文原文
Comment
Adrenal cysts ( Figure 1 , Figure 2 , and Figure 3 ) are lined by cuboidal to ciliated columnar epithelium and may contain amorphous to flocculent, eosinophilic material. They may be located in the cortex or medulla and may cause variable distortion or compression of the adjacent tissue. These minor findings are more common in mice than in rats and are usually incidental, spontaneous changes of no clinical or toxicologic relevance. Cortical cysts must be distinguished from angiectasis (dilated vascular channels containing blood and lined by flat endothelial cells). Cortical cysts in rats must also be distinguished from cystic degeneration, a common lesion in certain rat strains, which features irregular, often large cavitated spaces filled with proteinaceous fluid but lack the epithelial lining of true cysts ( Figure 2 and Figure 3 ).
Recommendation
Adrenal gland cysts should be diagnosed only if they occur with treatment-related increased incidences. In these cases, they should be diagnosed but not assigned of a severity grade. When diagnosed, an appropriate site modifier (i.e., cortex or medulla) should be included in the diagnosis to indicate the location of the cyst.
坏死Necrosis 肾上腺坏死
描述（中文）
肾上腺坏死（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5）可发生于肾上腺的任何区域，但皮质（尤其是束状带和网状带）比髓质更常受累。坏死可为局灶性（focal）或弥漫性（diffuse）。坏死的特征为正常结构破坏或消失，伴组成细胞的碎裂、嗜酸性增强、核固缩、核碎裂和/或核溶解（Figure 2、Figure 5）。也可存在相关的出血和/或炎性细胞浸润。肾上腺坏死（尤其是皮质坏死）通常继发于其他病理过程，如应激、缺血、出血、炎症和全身性肿瘤（例如大鼠的单核细胞白血病）。然而，肾上腺皮质坏死也可由实验性给予各种物质诱导，如细菌毒素或某些外源性化学物。肾上腺髓质坏死虽较少见，但也可由某些外源性化学物诱导。
诊断建议
肾上腺坏死应当诊断，并赋予严重程度分级和部位修饰词（即皮质或髓质）。如果皮质和髓质均存在，可省略部位修饰词，并在病理学描述中描述其位置。当坏死继发于另一过程（例如炎症、变性或肿瘤）时，不应单独诊断，除非严重程度足以支持单独诊断。继发于坏死的病变（例如炎症、矿化）不应单独诊断，除非严重程度足以支持单独诊断，但应在病理学描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Adrenal gland necrosis ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , and Figure 5 ) can occur in any region of the adrenal gland, though the cortex (especially the zonae fasciculata and reticularis) is more frequently affected than the medulla. Necrosis can be focal or diffuse. Necrosis is characterized by disruption or obliteration of normal architecture, with fragmentation, hypereosinophilia, pyknosis, karyorrhexis, and/or karolysis of the constituent cells ( Figure 2 and Figure 5 ). Associated hemorrhage and/or inflammatory cell infiltrates may also be present. Adrenal gland necrosis (especially cortical) is usually secondary to other pathologic processes, such as stress, ischemia, hemorrhage, inflammation, and systemic neoplasia (e.g., mononuclear cell leukemia in rats). However, adrenal cortical necrosis can also be induced by experimental administration of various agents, such as bacterial toxins or certain exogenous chemicals. Adrenal medullary necrosis, though less common, can also be induced by certain exogenous chemicals.
Recommendation
Adrenal gland necrosis should be diagnosed and assigned a severity grade and site modifier (i.e., cortex or medulla). If it is present in both the cortex and medulla, the site modifier may be omitted and the location described in the pathology narrative. When necrosis is secondary to another process (e.g., inflammation, degeneration, or neoplasia), it should not be diagnosed separately unless warranted by severity. Lesions that are secondary to necrosis (e.g., inflammation, mineralization) should not be diagnosed separately, unless warranted by severity, but should be described in the pathology narrative.
增生Hyperplasia 肾上腺增生
描述（中文）
增生（hyperplasia）定义为细胞数量的局灶性（focal）至弥漫性（diffuse）增加。增生通常为局灶性，但也可能发生弥漫性增生。可累及一侧或双侧肾上腺。在大鼠和小鼠中，皮质增生最常发生于束状带（zona fasciculata）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6），但网状带（zona reticularis）也可受累。皮质和髓质中的增生灶通常为圆形、边界清楚的区域，直径不一，以皮质细胞数量增多为特征。在皮质中，正常的放射状索状结构通常得以保持。增生灶可边界清晰，也可与邻近正常组织几乎难以察觉地融合；压迫一般不存在或极轻微。与正常皮质细胞相比，增生细胞通常（但并非总是）较小，胞质可呈空泡化和/或染色特性不同（常更嗜碱性）。在髓质中，增生灶常位于肾上腺髓质周边部、皮髓质交界处或其附近（Figure 7、Figure 8），但也可发生于更靠近中央的髓质（Figure 9、Figure 10）。与正常髓质细胞相比，增生细胞通常较小，胞质更嗜碱性（Figure 7、Figure 8、Figure 9、Figure 10）。在皮质和髓质中，均可能罕见核分裂象，但增生细胞通常缺乏细胞异型性特征。皮质增生和髓质增生可为自发性衰老性改变，在大鼠中比小鼠更常见。皮质增生的其他原因包括应激，以及因任何干扰下丘脑-垂体-肾上腺激素轴和/或肾上腺类固醇生成的因子所致的促肾上腺皮质激素（ACTH）水平异常升高。髓质增生也可由实验性遗传修饰、饮食调控和给予各种化学物所致。增生也可能是对变性、萎缩或坏死所致细胞丢失的再生性反应。局灶性皮质增生和髓质增生被视为形态学连续谱中的增殖性病变，可进展为肿瘤（皮质中的腺瘤和癌，髓质中的良性和恶性嗜铬细胞瘤）。将大的局灶性增生与较小的腺瘤或嗜铬细胞瘤相鉴别可能具有挑战性，但与增生灶相比，肿瘤更具压迫性、结构紊乱更明显，并具有一定程度的细胞多形性。皮质增生（细胞数量增多）和皮质肥大（细胞体积增大）常可同时存在于同一腺体甚至同一病灶中。因此，在实际操作中，确定某一给定病变和/或肾上腺中以增生还是肥大为主可能非常困难。
诊断建议
肾上腺-增生应予以诊断，并赋予严重程度分级以及部位修饰词（即cortex、medulla）和分布修饰词（即局灶性（focal）、弥漫性（diffuse））。当两侧腺体均存在增生时，应添加修饰词“双侧（bilateral）”。当同一肾上腺同一部位（cortex或medulla）同时存在局灶性增生和肿瘤时，仅当病理学家认为二者为独立病变时方可将两者均予以诊断；否则仅诊断肿瘤。当同一病灶中同时存在皮质增生和肥大时，仅应诊断增生，肥大应在病理学描述中予以描述。相关链接：肾上腺-皮质-细胞异型性
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia is defined as a focal to diffuse increase in cell number. Hyperplasia is generally focal, though diffuse hyperplasia may occur. One or both adrenal glands can be affected. In both rats and mice, cortical hyperplasia most commonly occurs in the zona fasciculata ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ), though the zona reticularis can also be affected. Hyperplastic foci in the cortex and medulla are generally rounded, circumscribed areas of variable diameter, characterized by increased numbers of cortical cells. In the cortex, the normal radial cord-like architecture is usually maintained. The hyperplastic foci can be well-demarcated or can blend almost imperceptibly with the adjacent normal tissue; compression is generally absent to minimal. Compared with normal cortical cells, hyperplastic cells are usually but not always smaller, with cytoplasm that can be vacuolated and/or tinctorially different (often more basophilic). In the medulla, foci of hyperplasia are often located at the periphery of the adrenal medulla, at or near the corticomedullary junction ( Figure 7 and Figure 8 ), though they can also occur in the more central medulla ( Figure 9 and Figure 10 ). Compared with normal medullary cells, hyperplastic cells are usually smaller with more basophilic cytoplasm ( Figure 7 , Figure 8 , Figure 9 , and Figure 10 ). In both the cortex and medulla, rare mitotic figures may be present, but the hyperplastic cells typically lack features of cellular atypia. Cortical and medullary hyperplasia can be a spontaneous aging change, which occurs more commonly in rats than mice. Other causes of cortical hyperplasia include stress, and abnormally elevated adrenocorticotropic hormone (ACTH) levels due to any factor that perturbs the hypothalamic-pituitary-adrenal hormonal axis and/or adrenal steroidogenesis. Medullary hyperplasia can also result from experimental genetic modifications, dietary manipulations, and administration of various chemicals. Hyperplasia may also be a regenerative response to cell loss from degeneration, atrophy, or necrosis. Focal cortical and medullary hyperplasias are considered proliferative lesions in a morphologic continuum that can progress to neoplasia (adenoma and carcinoma in the cortex and benign and malignant pheochromocytoma in the medulla). Differentiating large focal hyperplasias from smaller adenomas or pheochromocytomas can be challenging, but the neoplasms, compared with hyperplastic foci, are more compressive, exhibit more disorganization, and have some degree of cellular pleomorphism. Cortical hyperplasia (increased cell numbers) and cortical hypertrophy (increased cell size) can often be concurrent lesions in the same gland or even in the same focus. Thus, as a practical matter, determining whether hyperplasia or hypertrophy is predominant in a given lesion and/or adrenal gland can be very difficult.
Recommendation
Adrenal gland - Hyperplasia should be diagnosed and assigned a severity grade and site modifier (i.e., cortex, medulla) and distribution modifier (i.e., focal, diffuse). The modifier "bilateral" should be added when hyperplasia is present in both glands. When there is focal hyperplasia and a neoplasm in the same site (cortex or medulla) in the same adrenal gland, both should be diagnosed only if the pathologist feels they are separate lesions; otherwise, only the neoplasm is diagnosed. In cases where cortical hyperplasia and hypertrophy are present in the same lesion, only hyperplasia should be diagnosed, with the hypertrophy described in the pathology narrative. Related Links: Adrenal Gland - Cortex - Cellular Atypia
梗死Infarct 肾上腺其他
描述（中文）
肾上腺梗死可能与局部组织或血管损伤、高凝状态或任何其他导致血栓形成的原因有关。因此，散发性肾上腺梗死可作为背景病变出现。肾上腺梗死可为局灶性（focal）或多灶性（multifocal），并可为急性或慢性。急性肾上腺梗死导致特征性楔形病变内的凝固性坏死（Figure 1、Figure 2），并可能伴有程度不等的出血。该病变在慢性阶段进展为组织塌陷、萎缩及纤维化替代；也可能出现矿化或色素沉着。肾上腺的多灶性或弥漫性（diffuse）梗死可能提示全身性血管病、全身性炎症或脓毒症。
诊断建议
梗死应诊断为梗死，而不是分别诊断其各个组成部分（例如坏死、炎症、纤维化）。应根据肾上腺受累范围进行分级。在病理学描述中，梗死应标明为急性或慢性，如有可能，应确定梗死的原因。
参考切片图（2 张）
查看英文原文
Comment
Infarction of the adrenal gland may be associated with local tissue or vascular damage, hypercoagulation, or any other cause of thrombosis. Thus, sporadic infarction of the adrenal gland may occur as a background lesion. Adrenal infarction may be focal or multifocal, and acute or chronic. Acute adrenal infarction results in coagulative necrosis in a characteristic wedge-shaped lesion ( Figure 1 and Figure 2 ) and may be associated with variable amounts of hemorrhage. This lesion progresses to tissue collapse, atrophy, and replacement by fibrosis in chronic stages; mineralization or pigmentation may also be present. Multifocal or diffuse infarction of the adrenal gland may indicate a systemic vasculopathy, generalized inflammation, or sepsis.
Recommendation
Infarcts should be diagnosed as infarcts rather than diagnosing the individual components (e.g., necrosis, inflammation, fibrosis). They should be graded according to the extent of adrenal gland involvement. In the pathology narrative, infarcts should be designated as either acute or chronic, and if possible, the cause of the infarct should be identified.
淀粉样物质Amyloid 肾上腺其他
描述（中文）
“淀粉样物质（amyloid）”一词经典上指多种不溶性、纤维状蛋白质，它们具有相似的构型（β-折叠片层）。这些异常折叠的蛋白质在许多组织中形成并在细胞内和细胞外蓄积，原因众多，如遗传易感性以及各种病因引起的局部和全身性炎症。在大鼠中，局灶性（focal）或全身性淀粉样物质沉积很少发生于任何组织，包括肾上腺。在小鼠中，肾上腺及其他组织的淀粉样物质沉积总体上远为常见。发病率存在遗传相关性差异，某些品系如B6C3F1/N小鼠发病率很低，而其他品系如（Swiss）CD-1和Swiss Webster小鼠发病率则高得多。在小鼠中，淀粉样变性通常是一种自发性、与年龄相关的全身性疾病，肾上腺是较常受累的组织之一。严重程度（淀粉样物质/组织的量）在所有组织中，包括肾上腺，也倾向于随年龄增长而增加。在小鼠中，肾上腺淀粉样物质沉积通常首先表现为内皮质细胞之间的小团块，并呈进行性向心性扩展至外皮质（束状带）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6）。淀粉样蛋白质可形成大的、膨胀性聚集体（Figure 1、Figure 2），使正常结构变形，并最终可融合成环绕髓质的厚环状带（Figure 3、Figure 4）。淀粉样物质可延伸至髓质或球状带，但这些区域一般不受累。经苏木精和伊红（H&E）染色，淀粉样物质沉积物表现为均质、无定形、淡嗜酸性物质（Figure 1、Figure 2、Figure 3、Figure 4）。特殊组织化学染色常用于将淀粉样物质与纤维结缔组织、纤维蛋白及其他物质相区分。最广泛使用的染色之一为刚果红（Congo red）。经刚果红染色的淀粉样物质在非偏振光下呈淡至暗红色（Figure 5），但在偏振光下表现出明亮的双折射（通常为“苹果绿”）（Figure 6）。其他淀粉样物质检测方法包括荧光或异染性染色以及免疫组织化学。
诊断建议
肾上腺中的淀粉样物质应诊断为存在，但不赋予严重程度分级。任何相关的细胞丢失或变性不应单独诊断，而应在病理学描述中加以描述。肾上腺淀粉样物质沉积是局限性的还是全身性分布的一部分，也应在描述中说明。如果双侧肾上腺均可见淀粉样物质，应在诊断中添加修饰词“双侧（bilateral）”（除非另有说明，病变假定为单侧）。
参考切片图（2 张）
查看英文原文
Comment
The term "amyloid" classically denotes various insoluble, fibrillar proteins that share a similar configuration (β-pleated sheets). These abnormally folded proteins form and accumulate intra- and extracellularly in many tissues due to many causes, such as genetic predisposition and local and systemic inflammation of various etiologies. In rats, focal or generalized amyloid deposition rarely occurs in any tissue, including the adrenal gland. In mice, amyloid deposition in the adrenal gland and other tissues is overall far more common. There are genetically related differences in incidence, with very low incidences in some strains, such as the B6C3F1/N mouse, and much higher incidences in other strains, such as (Swiss) CD-1 and Swiss Webster mice. In mice, amyloidosis is usually a spontaneous, age-related systemic disease, with the adrenal gland one of the more commonly affected tissues. Severity (amount of amyloid/tissue) also tends to increase with age in all tissues, including the adrenal gland. In mice, adrenal amyloid deposition usually first appears as small clumps between cells of the inner cortex, with progressive centripetal extension into the outer cortex (zona fasciculata) ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ). The amyloid proteins can form large, expansile aggregates ( Figure 1 and Figure 2 ), which distort the normal architecture and can eventually coalesce into thick circumferential bands that surround the medulla ( Figure 3 and Figure 4 ). The amyloid may extend into the medulla or zona glomerulosa, but these regions are generally unaffected. With hematoxylin and eosin (H&E) stain, amyloid deposits appear as homogeneous, amorphous, pale eosinophilic material ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Special histochemical stains are often used to distinguish amyloid from fibrous connective tissue, fibrin, and other substances. One of the most widely used stains is Congo red. Amyloid stained with Congo red appears pale to dull red under nonpolarized light ( Figure 5 ) but exhibits brilliant birefringence (usually "apple green") under polarized light ( Figure 6 ). Other methods for amyloid detection include fluorescent or metachromatic stains and immunohistochemistry.
Recommendation
Amyloid in the adrenal should be diagnosed as present without assignment of a severity grade. Any associated loss or degeneration of cells should not be diagnosed separately but should be described in the pathology narrative. Whether the adrenal amyloid deposits are localized or part of a systemic distribution should also be addressed in the narrative. If amyloid is seen in both adrenal glands, the modifier "bilateral" should be added to the diagnosis (lesions are assumed to be unilateral unless otherwise indicated).
炎症Inflammation 肾上腺炎症
描述（中文）
在F344/N大鼠和B6C3F1/N小鼠中，肾上腺炎症不常见。它通常继发于全身性疾病，或作为邻近组织（如肾脏或腹膜后脂肪）炎症的延伸。肾上腺炎症必须与髓外造血（未成熟造血细胞灶）以及全身性淋巴或造血肿瘤性浸润（低分化、常为间变性细胞，通常呈广泛聚集，扭曲或破坏正常腺体结构）相鉴别。在NTP研究中，炎症有五个标准类别：急性、化脓性、慢性、慢性活动性和肉芽肿性。急性炎症的特征是中性粒细胞浸润（Figure 1、Figure 2），可能伴有嗜酸性粒细胞和巨噬细胞，偶见肥大细胞、淋巴细胞和浆细胞。化脓性炎症的特征是离散的退化中性粒细胞和细胞碎片聚集区。这些聚集区周围可能有慢性化的证据，如纤维化和淋巴浆细胞浸润。慢性炎症的特征是存在单核细胞（淋巴细胞、巨噬细胞和浆细胞），可能伴有纤维化。慢性活动性炎症的特征是慢性炎症成分（淋巴细胞、巨噬细胞、纤维化）与叠加的急性炎症（中性粒细胞和/或嗜酸性粒细胞浸润）共存。肉芽肿性炎症的特征是巨噬细胞、多核巨细胞以及数量不等的淋巴细胞和浆细胞或中性粒细胞的聚集。炎症与细胞浸润的鉴别在于是否存在其他变化，如水肿、出血、变性、坏死或其他组织损伤的证据。
诊断建议
肾上腺炎症应当被诊断，并赋予严重程度分级和适当的类型修饰词（如急性、慢性）。诊断中应当包含部位修饰词（即皮质或髓质）以指示病变位置。如果皮质和髓质均存在，可省略部位修饰词，并在病理学叙述中描述位置。如果肾上腺炎症是全身性过程的一部分或为邻近组织炎症的延伸，应当在叙述中注明。相关病变（如坏死、出血）仅在严重程度需要时应当单独诊断。如果两侧肾上腺均存在炎症，诊断中应当包含修饰词“双侧（bilateral）”（除非另有说明，病变假定为单侧）。
参考切片图（2 张）
查看英文原文
Comment
Inflammation of the adrenal gland is uncommon in F344/N rats and B6C3F1/N mice. It is usually secondary to systemic disease or as an extension of inflammation in adjacent tissues, such as the kidney or retroperitoneal fat. Adrenal gland inflammation must be distinguished from extramedullary hematopoiesis (foci of immature hematopoietic cells) and from systemic lymphoid or hematopoietic neoplastic infiltrates (poorly differentiated, often anaplastic cells usually in extensive accumulations that distort or obliterate normal glandular architecture). In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. Acute inflammation is characterized by infiltration of neutrophils ( Figure 1 and Figure 2 ), which may be accompanied by eosinophils and macrophages, and occasional mast cells, lymphocytes, and plasma cells. Suppurative inflammation is characterized by discrete pockets of degenerate neutrophils and cellular debris. There may be evidence of chronicity, such as fibrosis and lymphoplasmacytic infiltrates, surrounding these pockets. Chronic inflammation is characterized by the presence of mononuclear cells (lymphocytes, macrophages, and plasma cells) and may be accompanied by fibrosis. Chronic-active inflammation is characterized by coexistence of elements of chronic inflammation (lymphocytes, macrophages, fibrosis) and superimposed acute inflammation (neutrophilic and/or eosinophilic infiltrates). Granulomatous inflammation is characterized by accumulations of macrophages, multinucleated giant cells, and variable numbers of lymphocytes and plasma cells, or neutrophils. Inflammation is differentiated from cellular infiltrates by the presence of other changes, such as edema, hemorrhage, degeneration, necrosis, or other evidence of tissue damage.
Recommendation
Adrenal gland inflammation should be diagnosed and assigned a severity grade and appropriate type modifier (e.g., acute, chronic). A site modifier (i.e., cortex or medulla) should be included in the diagnosis to indicate the location of the lesion. If it is present in both the cortex and medulla, the site modifier may be omitted and the location described in the pathology narrative. If the adrenal inflammation is part of a systemic process or an extension of inflammation in adjacent tissues, this should be noted in the narrative. Associated lesions (e.g., necrosis, hemorrhage) should be diagnosed separately only if warranted by severity. If inflammation is present in both adrenal glands, the modifier "bilateral" should be included in the diagnosis (lesions are assumed to be unilateral unless otherwise indicated).
皮质X带萎缩Cortex X Zone Atrophy 肾上腺萎缩
描述（中文）
X带在小鼠出生后数天出现于雌雄两性，至断奶时充分发育。X带位于皮质与髓质交界处，其内细胞质较束状带细胞更具嗜酸性（Figure 1、Figure 2）。在雄性小鼠中，X带于青春期（约5周龄）退化。在雌性中，X带在青春期后持续数周，随后在未产雌性中较为逐渐地退化，或在首次妊娠时较为迅速地退化。X带的发育程度及退化速率也可随小鼠品系而异。在许多小鼠品系（包括B6C3F1品系）的雌性中，X带的正常退化（复旧）以形态学上不同的阶段进展。退化的起始以散在组成细胞的空泡化为开端（Figure 1、Figure 2）。随着退化继续，空泡化细胞的数量逐渐增加，直至几乎所有X带细胞均受累。在后期阶段，空泡化的X带细胞发生变性和坏死，随后整体X带结构崩解、凝缩并最终消失。常见的终末期后遗症为含色素细胞残留积聚于原先由X带占据的髓质周围区域。在雄性中，X带退化相似，只是通常不发生空泡化。X带的功能未知。其正常发育和退化由性腺激素和甲状腺激素介导，因此改变这些激素水平的因素可影响X带。例如，去势可延长雌性小鼠及青春期前雄性小鼠中X带的存留时间，并可导致青春期后雄性中X带重新出现。给予雄激素（如睾酮）后，雌性小鼠的X带迅速消失。给予某些其他化学物也可影响X带，导致非同步性偏差，例如与年龄匹配的同批对照（Figure 1、Figure 2）相比，处理组中出现加速退化（Figure 3、Figure 4）。
诊断建议
肾上腺皮质X带退化是正常生理过程，其各阶段常为雌雄两性及不同年龄小鼠的偶然发现。正常X带退化阶段的特征（如空泡化、变性）及其终末期后遗症（如X带崩解、纤维化和色素细胞积聚）不应被误认为病理学病变。因此，在给定研究中，当生理性X带退化以相似的、与年龄和性别相适应的方式发生于对照和处理小鼠两者时，不应诊断该退化。异常加速（快速）退化，或相反地，X带过度长久存留，可为各种化学物和外源性激素处理所致效应。然而，在这些情况下，处理动物的X带形态将不具独特性，也不表现出特征性病理学特征。相反，毒性效应的存在仅表现为处理动物X带外观（时间阶段）与正常、与年龄和性别相适应的同批研究对照相比存在差异。由于这些原因，处理动物的X带毒性不能孤立地诊断，而必须在研究对照中所发生的生理性时间阶段的背景下进行评估。
参考切片图（2 张）
查看英文原文
Comment
The X-zone appears a few days after birth in mice of both sexes and is fully developed by weaning. The X-zone is located at the junction of the cortex and the medulla and is populated by cells with more eosinophilic cytoplasm than those of the zona fasciculata ( Figure 1 and Figure 2 ). In male mice, the X-zone regresses at puberty (by about 5 weeks of age). In females, the X-zone persists for several weeks past puberty and then regresses more gradually in nulliparous females or more rapidly at first pregnancy. The extent of X-zone development and the rate of involution can also vary with mouse strain. Normal regression (involution) of the X-zone in females of many mouse strains, including the B6C3F1 strain, progresses in morphologically distinct stages. The onset of regression begins with vacuolization of scattered constituent cells ( Figure 1 and Figure 2 ). As regression continues, the number of vacuolated cells progressively increases until virtually all X-zone cells are affected. In later stages, the vacuolated X-zone cells undergo degeneration and necrosis, with subsequent overall X-zone architectural collapse, condensation, and eventual disappearance. A common end-stage sequela is the residual accumulation of pigment-laden cells in the perimedullary area formerly occupied by the X-zone. In males, X-zone regression is similar except that it usually occurs without vacuolization. The function of the X-zone is unknown. Its normal development and regression are mediated by gonadal and thyroid hormones, so factors that alter levels of these hormones can affect the X-zone. For example, gonadectomy prolongs the persistence of the X-zone in female mice and prepubertal male mice and can cause the reappearance of the X-zone in postpubertal males. Administration of androgens like testosterone is followed by rapid disappearance of the X-zone in female mice. Administration of certain other chemicals can also affect the X-zone, resulting in asynchronous deviations, such as accelerated regression ( Figure 3 and Figure 4 ) in treated groups compared with age-matched concurrent controls ( Figure 1 and Figure 2 ).
Recommendation
Adrenal cortical X-zone regression is a normal physiologic process, and its various stages are often incidental findings in mice of both sexes and at various ages. Features of normal X-zone regression stages (e.g., vacuolization, degeneration) and its end-stage sequelae (e.g., X-zone collapse, fibrosis, and pigment-cell accumulation) should not be mistaken for pathologic lesions. Thus, physiologic X-zone regression should not be diagnosed when it occurs in a similar, age- and sex-appropriate manner in both the control and treated mice in a given study. Abnormally accelerated (rapid) regression or, conversely, excessively lengthy persistence of the X-zone can be effects of treatment with various chemicals and exogenous hormones. However, in these cases, the X-zone morphology of treated animals will not be distinctive or exhibit pathognomonic pathologic features. Instead, the existence of a toxic effect manifests only as a disparity in the appearance (temporal stage) of the X-zone in treated animals compared with normal, age- and sex-appropriate concurrent study controls. For these reasons, X-zone toxicity in treated animals cannot be diagnosed in isolation but must be evaluated in the context of the physiologic temporal stage occurring in the study controls.
皮质囊性变性Cortex Degeneration Cystic 肾上腺变性
描述（中文）
肾上腺皮质的囊性变性（cystic degeneration）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5）发生于许多品系的大鼠，但显然尚未在小鼠中报道。发生率随大鼠品系而异，某些品系（如 Sprague-Dawley、Wistar）的发生率远高于其他品系（如 F344）。在所有大鼠品系中，囊性变性在雌性中远比雄性常见。它通常是自发性的、与年龄相关的变化，但已有报道称给予某些化学物后发生率呈处理相关性的升高。囊性变性的早期阶段以束状带内小的、无压迫性的皮质窦隙增宽灶和血管扩张灶为特征；其间索内的皮质细胞可呈空泡化或轻度扁平。随着病变进展，受累区域扩大并可压迫邻近实质（Figure 3、Figure 4）。窦隙和血管扩张逐渐变得更加广泛，形成大的、常为融合性的囊样腔隙（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5），其内充满蛋白性液体、红细胞和/或纤维素性血栓，但缺乏真性囊肿所特有的上皮衬里。空泡化或肿胀的皮质细胞团簇可散布于扩张的腔隙之间。囊性变性区域也可为大的皮质增生性或肥大性灶或皮质肿瘤的特征之一；然而，在囊性变性中，细胞数量较正常皮质减少。
诊断建议
肾上腺皮质的囊性变性应当诊断并赋予严重程度分级。发生于增生或肥大灶内或皮质肿瘤内的囊性变性区域不应单独诊断，而应在病理学描述中加以描述。如果双侧肾上腺均可见囊性变性，则应在诊断中添加修饰词“双侧（bilateral）”（除非另有说明，病变假定为单侧）。
参考切片图（2 张）
查看英文原文
Comment
Cystic degeneration of the adrenal cortex ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , and Figure 5 ) occurs in many strains of rats but has apparently not been reported in mice. Incidences vary with rat strain, with some strains (e.g., Sprague-Dawley, Wistar) exhibiting much higher incidences than others (e.g., F344). In all rat strains, cystic degeneration is much more common in females than in males. It is usually a spontaneous, age-related change, though treatment-related increased incidences have been reported after administration of certain chemicals. Early stages of cystic degeneration are characterized by small, noncompressive foci of widened cortical sinusoids and dilated blood vessels in the zona fasciculata; cortical cells in the intervening cords can be vacuolated or slightly flattened. As the lesion progresses, affected areas enlarge and can compress adjacent parenchyma ( Figure 3 and Figure 4 ). The sinusoidal and vascular ectasia progressively becomes more extensive, resulting in large, often confluent, cyst-like cavitations ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , and Figure 5 ) that are filled with proteinaceous fluid, red blood cells, and/or fibrinous thrombi but lack the epithelial lining characteristic of true cysts. Clusters of vacuolated or swollen cortical cells can be scattered among the dilated spaces. Areas of cystic degeneration can also be features of large cortical hyperplastic or hypertrophic foci or of cortical neoplasms; however, in cystic degeneration the number of cells is decreased compared with normal cortex.
Recommendation
Cystic degeneration of the adrenal cortex should be diagnosed and assigned a severity grade. Areas of cystic degeneration occurring in foci of hyperplasia or hypertrophy or in cortical neoplasms should not be diagnosed separately but should be described in the pathology narrative. If cystic degeneration is seen in both adrenal glands, the modifier "bilateral" should be added to the diagnosis (lesions are assumed to be unilateral unless otherwise indicated).
皮质细胞异型性Cortex Cellular Atypia 肾上腺异型性
描述（中文）
肾上腺皮质细胞异型性（Atypia）（Figure 1、Figure 2、Figure 3）在大鼠和小鼠中是一种不常见的发现。其特征为肥大的皮质细胞，除细胞质体积增大外，细胞核还表现出多形性、深染、形状不规则及其他非典型特征。在皮质肥大的区域内，可能有少数细胞具有不规则细胞核，但肾上腺皮质细胞异型性的诊断仅保留给那些大部分细胞均呈非典型的病变。病理学家必须运用其判断力来决定非典型细胞的数量是否足够多，以支持细胞异型性的诊断。非典型细胞也可见于皮质增生的病灶中。肾上腺皮质非典型细胞的病灶必须与肾上腺皮质腺瘤相鉴别。腺瘤通常引起邻近组织受压，并且细胞索正常的放射状排列消失；这些特征在细胞异型性的病灶中不存在。
诊断建议
肾上腺，皮质 - 细胞异型性（Cellular atypia）应予以诊断并赋予严重程度分级。该诊断应用于肥大病灶中大部分细胞同时具有上述非典型特征细胞核的病例。在此类病例中，仅应记录“细胞异型性”的诊断（而非“肥大”）。当肥大病灶中非典型细胞的数量不足以支持异型性的诊断时（病理学家必须运用其判断力来确定是否属于这种情况），则应诊断肥大，并在叙述中描述少数散在的非典型细胞。若非典型细胞出现在皮质增生区域中相当数量的细胞内，则诊断应为“增生，非典型性”（Hyperplasia, 非典型性（atypical））（见肾上腺 - 增生）。若两侧肾上腺均可见细胞异型性，则应在诊断中添加修饰词“双侧（bilateral）”（双侧）（除非另有说明，病变假定为单侧）。相关链接：肾上腺 - 增生
参考切片图（2 张）
查看英文原文
Comment
Atypia of adrenocortical cells ( Figure 1 , Figure 2 , and Figure 3 ) is an uncommon finding in rats and mice. It is characterized by hypertrophic cortical cells that, in addition to expanded cytoplasmic volume, also have nuclei with pleomorphism, hyperchromasia, irregular shape, and other atypical features. There may be a few cells within a region of cortical hypertrophy that have irregular nuclei, but the diagnosis of cellular atypia in the adrenal cortex is reserved for those lesions in which a large proportion of the cells are atypical. The pathologist must use his or her judgment in deciding whether the number of atypical cells is large enough to warrant a diagnosis of cellular atypia. Atypical cells can also be found in foci of cortical hyperplasia. Foci of atypical adrenocortical cells must be differentiated from adrenocortical adenomas. Adenomas typically cause compression of adjacent tissue, and there is loss of the normal radial arrangement of the cords; these features are not present in foci of cellular atypia.
Recommendation
Adrenal gland, Cortex - Cellular atypia should be diagnosed and assigned a severity grade. The diagnosis should be used in cases where a large proportion of the cells in a hypertrophic focus also have nuclei that exhibit features of atypia as described above. In such cases, only the diagnosis of "Cellular atypia" (and not "Hypertrophy") should be recorded. When the number of atypical cells in a focus of hypertrophy does not warrant a diagnosis of atypia (the pathologist must use his or her judgment to determine if this is the case), then hypertrophy should be diagnosed and the few scattered atypical cells described in the narrative. In cases where atypical cells occur in a significant number of cells in an area of cortical hyperplasia, the diagnosis should be "Hyperplasia, Atypical" (see Adrenal Gland - Hyperplasia ). If cellular atypia is seen in both adrenal glands, the modifier "bilateral" should be added to the diagnosis (lesions are assumed to be unilateral unless otherwise indicated). Related Links: Adrenal Gland - Hyperplasia
皮质细胞质空泡化Cortex Vacuolization Cytoplasmic 肾上腺其他
描述（中文）
大鼠和小鼠的肾上腺皮质空泡化（adrenal cortical vacuolization）的特征是皮质细胞内积聚通常为清亮的空泡，主要位于束状带（zona fasciculata），尽管网状带（zona reticularis）和球状带（zona glomerulosa）也常受累。空泡化可为局灶性（focal）（Figure 1、Figure 2）或弥漫性（diffuse）（Figure 3、Figure 4）。即使较大的局灶性病变通常也几乎不引起压迫，或无压迫。空泡可为单个至几个大空泡，也可为多个较小的空泡。在许多情况下，已证明这些空泡代表各种脂质或胆固醇的积聚。皮质空泡化可作为自发性、年龄相关的变化（尤其在大鼠中）发生；继发于各种原因引起的应激；以及由给予许多外源性药物和毒物引起，尤其是那些干扰肾上腺皮质正常类固醇生成和/或扰乱下丘脑-垂体-肾上腺激素轴（包括促肾上腺皮质激素[ACTH]的正常分泌和代谢）的药物和毒物。皮质空泡化也可由实验性给予过量ACTH或皮质酮引起。
诊断建议
肾上腺皮质细胞质空泡化应予以诊断并赋予严重程度分级。诊断中还应包括适当的分布修饰词（即局灶性（focal）或弥漫性（diffuse））。如果局限于皮质的某一特定带，应在病理学叙述中注明。在伴有部分组成性空泡化细胞的肾上腺皮质增生或肥大的病例中，空泡化不应单独诊断，但应在叙述中描述为增生或肥大的一个特征。如果两侧肾上腺均见空泡化，诊断中应加上修饰词“双侧（bilateral）”（除非另有说明，病变假定为单侧）。
参考切片图（2 张）
查看英文原文
Comment
Adrenal cortical vacuolization in rats and mice is characterized by the accumulation of usually clear vacuoles within cortical cells, mainly in the zona fasciculata, although the zonae reticularis and glomerulosa are also often affected. The vacuolization can be focal ( Figure 1 and Figure 2 ) or diffuse ( Figure 3 and Figure 4 ). Even large focal lesions generally cause little to no compression. The vacuoles can range from a single to a few large vacuoles to multiple smaller ones. In many cases, the vacuoles have been shown to represent accumulations of various lipids or cholesterol. Cortical vacuolization can occur as a spontaneous, age-related change (especially in rats); secondary to stress from various causes; and from administration of many exogenous drugs and toxins, especially those that interfere with normal steroidogenesis in the adrenal cortex and/or perturb the hypothalamic-pituitary-adrenal hormonal axis (including normal secretion and metabolism of adrenocorticotropic hormone [ACTH]). Cortical vacuolization can also result from experimental administration of excess ACTH or corticosterone.
Recommendation
Adrenal cortical cytoplasmic vacuolization should be diagnosed and assigned a severity grade. An appropriate distribution modifier (i.e., focal or diffuse) should also be included in the diagnosis. If localized to a particular zone of the cortex, this should be noted in the pathology narrative. In cases of adrenal cortical hyperplasia or hypertrophy with some constituent vacuolated cells, the vacuolization should not be diagnosed separately, though it should be described in the narrative as a feature of the hyperplasia or hypertrophy. If vacuolization is seen in both adrenal glands, the modifier "bilateral" should be added to the diagnosis (lesions are assumed to be unilateral unless otherwise indicated).
皮质肥大Cortex Hypertrophy 肾上腺肥大
描述（中文）
肾上腺皮质肥大（Adrenal cortical hypertrophy）是指细胞体积增大而细胞数量无明显增多。肥大的皮质细胞胞质增多，可呈淡染至亮嗜酸性（Figure 1、Figure 2、Figure 3、Figure 4），但也可呈透明、空泡化和/或嗜碱性。细胞核常增大。肥大灶内少数细胞核可具有非典型性特征。若肥大细胞中非典型细胞占较大比例，则应诊断为非典型性而非肥大（见Adrenal Gland - Cortex - Cellular Atypia）。皮质肥大可为局灶性（focal）或弥漫性（diffuse）。局灶性肥大（Figure 1、Figure 2、Figure 3、Figure 4）最常累及束状带。小的肥大灶通常无压迫性，但较大的局灶性病变可对邻近皮质实质造成不同程度的压迫（Figure 3）。与未受累的正常肾上腺（Figure 7、Figure 8）相比，弥漫性皮质肥大（Figure 5、Figure 6）常导致皮质明显增宽及腺体整体增大。大鼠和小鼠的（束状带）皮质肥大通常由促肾上腺皮质激素（adrenocorticotropic hormone，ACTH）水平升高所致，而ACTH升高又可源于多种原因，如原发性下丘脑或垂体疾病，或肾上腺皮质毒性或退行性病变所致的糖皮质激素反馈调节减弱。束状带的弥漫性、双侧（bilateral）且常为显著的肥大也可为各种原因所致应激的后遗症，该表现在大鼠中尤为常见。球状带细胞的肥大（及增生）可由肾素-血管紧张素系统紊乱导致血管紧张素II升高而引起。无论局灶性还是弥漫性，皮质肥大通常不被认为是肿瘤前性改变。然而，皮质肥大（细胞体积增大）和增生（细胞数量增多）常可同时存在于同一腺体甚至同一病灶中。因此，在实际操作中，确定某一病变和/或腺体中以哪种改变为主可能非常困难。皮质肥大还可与许多胞质空泡化病例中所见的皮质细胞增大相混淆。
诊断建议
肾上腺皮质肥大应予以诊断，并赋予严重程度分级和适当的分布修饰词（即局灶性（focal）、弥漫性（diffuse））。当两侧腺体均存在肥大时，应使用修饰词“双侧（bilateral）”。应努力区分皮质肥大与增生，尽管这两种改变在同一病变中频繁叠加可使该判断非常具有挑战性。若同一病灶中两种所见同时存在，则仅记录增生，并在病理学描述中描述肥大特征。若肥大灶中存在少量非典型细胞，应在描述中予以描述。然而，若病理学家认为非典型细胞所占比例足够大，则应诊断细胞非典型性（见Adrenal Gland - Cortex - Cellular Atypia）。相关链接：Adrenal Gland - Cortex - Cellular Atypia
参考切片图（2 张）
查看英文原文
Comment
Adrenal cortical hypertrophy refers to an increased cell size without an appreciable increase in cell numbers. Hypertrophic cortical cells have increased amounts of cytoplasm, which may be pale to brightly eosinophilic ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) but may also be clear, vacuolated, and/or basophilic. The nucleus is frequently enlarged. Small numbers of nuclei in a focus of hypertrophy may have features of atypia. If a large proportion of the hypertrophic cells are atypical, then atypia should be diagnosed rather than hypertrophy (see Adrenal Gland - Cortex - Cellular Atypia ). Cortical hypertrophy may be focal or diffuse. Focal hypertrophy ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) most often involves the zona fasciculata. Small hypertrophic foci are generally noncompressive, but larger focal lesions may cause variable compression of the adjacent cortical parenchyma ( Figure 3 ). Diffuse cortical hypertrophy ( Figure 5 and Figure 6 ) often results in pronounced widening of the cortex and overall gland enlargement compared with unaffected normal adrenal glands ( Figure 7 and Figure 8 ). Cortical hypertrophy (of the zona fasciculata) in rats and mice usually results from elevated levels of adrenocorticotropic hormone (ACTH), which in turn can be elevated due to various causes, such as primary hypothalamic or pituitary disease or decreased glucocorticoid feedback regulation caused by adrenal cortical toxic or degenerative lesions. Diffuse, bilateral, and often prominent hypertrophy in the zona fasciculata can also be a sequela to stress from various causes, a finding that is especially common in rats. Hypertrophy (and hyperplasia) of zona glomerulosa cells can result from derangements of the renin-angiotensin system that result in elevated angiotensin II. Whether focal or diffuse, cortical hypertrophy is generally not considered to be a preneoplastic change. However, cortical hypertrophy (increased cell size) and hyperplasia (increased cell numbers) can often be concurrent lesions in the same gland or even in the same focus. Thus, as a practical matter, determining which change is predominant in a given lesion and/or gland can be very difficult. Cortical hypertrophy can also be confused with the cortical cell enlargement that occurs in many cases of cytoplasmic vacuolization.
Recommendation
Adrenal cortical hypertrophy should be diagnosed and assigned a severity grade and appropriate distribution modifier (i.e., focal, diffuse). The modifier "bilateral" should be used when hypertrophy is present in both glands. An attempt should be made to distinguish cortical hypertrophy from hyperplasia, though the frequent superimposition of both changes in the same lesion can make this determination very challenging. In cases where both findings are concurrent in the same focus, only hyperplasia should be recorded, with the hypertrophy feature described in the pathology narrative. If there are a small number of atypical cells in the focus of hypertrophy, they should be described in the narrative. However, if the pathologist feels there is a large enough proportion of atypical cells, cellular atypia should be diagnosed (see Adrenal Gland - Cortex - Cellular Atypia ). Related Links: Adrenal Gland - Cortex - Cellular Atypia
皮质萎缩Cortex Atrophy 肾上腺萎缩
描述（中文）
肾上腺皮质萎缩（Figure 1、Figure 2）可为局灶性（focal）或弥漫性（diffuse）。与正常肾上腺皮质（Figure 3、Figure 4）相比，萎缩的皮质以一层或多层皮质层厚度减少为特征，其原因是细胞体积减小或细胞丢失。束状带和网状带比球状带更常受累。腺体整体大小有不同程度的减小，常伴有腺体轮廓的扭曲。腺体被膜可因纤维化而增厚（Figure 1、Figure 2）。大鼠和小鼠肾上腺皮质萎缩的原因包括任何使糖皮质激素水平升高的因素，例如外源性给药或同侧或对侧腺体功能性肾上腺皮质肿瘤的内源性过度分泌，其继发性导致促肾上腺皮质激素（ACTH）水平降低。萎缩也可由更为直接的ACTH缺乏引起，例如可能随垂体功能异常而发生。皮质萎缩还可由外源性毒物直接作用引起，这些毒物干扰正常的肾上腺皮质类固醇生成和/或肾素-血管紧张素系统对肾上腺的生理作用。由于下丘脑、垂体、甲状腺和性腺与肾上腺之间复杂的生理相互作用，其他直接损伤这些组织或调节其分泌功能的外源性毒物和实验操作可在肾上腺皮质引起继发性效应，包括萎缩。皮质萎缩还可能是其他病理过程（如变性或坏死）的后遗症，也可与细胞质空泡化或色素蓄积同时存在。
诊断建议
肾上腺皮质萎缩应当被诊断，并赋予严重程度分级和分布修饰词（即局灶性（focal）、弥漫性（diffuse））。相关病变（例如皮质变性或被膜纤维化）不应单独诊断，除非其严重程度足以支持单独诊断。如果双侧肾上腺均可见萎缩，应在诊断中加上修饰词“双侧（bilateral）”（除非另有说明，病变假定为单侧）。
参考切片图（2 张）
查看英文原文
Comment
Adrenal cortical atrophy ( Figure 1 and Figure 2 ) may be focal or diffuse. Compared with the normal adrenal cortex ( Figure 3 and Figure 4 ), the atrophic cortex is characterized by reduced thickness of the one or more of the cortical layers due to a decrease in cell size or a loss of cells. The zonae fasciculata and reticularis are more often affected than the zona glomerulosa. There is variably decreased overall size of the gland, often with distortion of the gland outline. The glandular capsule may be thickened due to fibrosis ( Figure 1 and Figure 2 ). Causes of adrenal cortical atrophy in rats and mice include any factor that increases levels of glucocorticoids, such as exogenous administration or endogenous hypersecretion by a functional adrenocortical neoplasm in the same or contralateral gland, which secondarily results in decreased adrenocorticotropic hormone (ACTH) levels. Atrophy can also result from more direct ACTH deficiency, such as may occur with abnormal pituitary function. Cortical atrophy can also be a direct effect of exogenous toxicants that interfere with normal adrenocortical steroidogenesis and/or the physiologic effects of the renin-angiotensin system on the adrenal. Because of the complex physiologic interactions of hypothalamus, pituitary, thyroid, and gonads with the adrenal gland, other exogenous toxicants and experimental manipulations that directly damage these tissues or modulate their secretory functions can result in secondary effects in the adrenal cortex, including atrophy. Cortical atrophy may also be a sequela to other pathologic processes, such as degeneration or necrosis, and may also be concurrent with cytoplasmic vacuolization or pigment accumulation.
Recommendation
Adrenal cortical atrophy should be diagnosed and assigned a severity grade and distribution modifier (i.e., focal, diffuse). Associated lesions (e.g., cortical degeneration or capsular fibrosis) should not be diagnosed separately unless warranted by severity. If atrophy is seen in both adrenal glands, the modifier "bilateral" should be added to the diagnosis (lesions are assumed to be unilateral unless otherwise indicated).
皮质被膜下增生Cortex Hyperplasia Subcapsular 肾上腺增生
描述（中文）
肾上腺皮质被膜下增生（Adrenal cortical subcapsular hyperplasia）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6、Figure 7、Figure 8）仅见于小鼠，未见於大鼠。这是大多数品系老年小鼠中非常常见的自发性病变，因此发生率和严重程度通常随年龄增长而增加。该病变在雌性小鼠中也远比雄性小鼠常见，且通常更为广泛。在某些小鼠品系中，去势可诱导被膜下细胞增殖（增生和肿瘤形成）。该变化的特征为肾上腺皮质被膜下细胞数量增多，这些细胞通常被认为是多能干细胞/祖细胞，负责补充内层皮质区衰老的细胞。在适当激素刺激下，被膜下细胞可转分化为类似性腺间质细胞的性类固醇生成细胞。被膜下增生病灶中可能存在两种形态不同的被膜下细胞：细长的梭形或纺锤形A型细胞（Figure 5），核呈椭圆形，胞质少而嗜碱性；以及较大的圆形或多边形B型细胞（Figure 6），胞质更丰富、淡染至透明，核圆形。早期增生病灶（Figure 1、Figure 2）由小的、常呈线状排列的病灶组成，主要由梭形样A型细胞构成。细胞簇最初位于紧邻被膜的球状带（Figure 1、Figure 2），但随着细胞聚集因增殖而增大，它们向心性延伸，呈窄至宽的楔形插入下方束状带细胞索之间，并呈与肾上腺被膜平行的线状片层（Figure 1、Figure 2、Figure 3）。随着增生病灶增大，B型细胞出现，并随病变进一步进展，多边形B型细胞与梭形A型细胞的比例通常增加（Figure 3、Figure 4）。同一肾上腺中的多个病灶可融合，形成被膜下几乎连续的增生细胞带（Figure 7）。非常大的病灶（Figure 8）通常几乎完全由多边形B型细胞组成，细长的A型细胞很少，并可表现出一定程度的压迫和膨胀。局灶性（focal）被膜下增生被认为是一种形态学连续谱中的增殖性病变，可进展为腺瘤，罕见进展为癌。被膜下腺瘤也由分化良好的“梭形”和“多边形”细胞以不同比例混合组成，因此区分大的局灶性增生与较小的腺瘤可能具有挑战性。与增生病灶相比，腺瘤更大、结节性更明确、明显压迫肾上腺实质，并且由于显著的膨胀性增殖，甚至可能明显突出于被膜表面。
诊断建议
肾上腺皮质被膜下增生应予以诊断并赋予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Adrenal cortical subcapsular hyperplasia ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 , Figure 7 , and Figure 8 ) has been seen only in mice, and not in rats. It is a very common spontaneous finding in older mice of most strains, so incidences and severity generally increase with age. The lesion is also much more common and typically more extensive in female than in male mice. Subcapsular cell proliferation (hyperplasia and neoplasia) can be induced in certain mouse strains by gonadectomy. This change is characterized by increased numbers of adrenal cortical subcapsular cells, generally considered to be the multipotential stem/progenitor cells that replenish senescent cells in the inner cortical zones. Under appropriate hormonal stimulation, the subcapsular cells can transdifferentiate into sex-steroid–producing cells resembling stromal gonadal cells. Two morphologically different types of subcapsular cells may be present in subcapsular hyperplastic lesions: elongated, spindle or fusiform type A cells ( Figure 5 ) with elliptical nuclei and scanty basophilic cytoplasm, and larger, round or polygonal type B cells ( Figure 6 ) with more abundant, pale to clear cytoplasm and round nuclei. Early hyperplastic lesions ( Figure 1 and Figure 2 ) consist of small, often linear foci composed primarily of the spindle-like type A cells. The cell clusters are located initially in the zona glomerulosa adjacent to the capsule ( Figure 1 and Figure 2 ), but as the cell aggregates enlarge due to proliferation, they extend centripetally as narrow to broad wedges intercalated between the underlying zona fasciculata cell cords and in linear sheets parallel to the adrenal capsule ( Figure 1 , Figure 2 , and Figure 3 ). As the hyperplastic lesions enlarge, type B cells appear, and with further progression the ratio of polygonal type B cells to spindle type A cells usually increases ( Figure 3 and Figure 4 ). Multiple foci in a given adrenal gland may coalesce to form an almost continuous band of hyperplastic cells subjacent to the capsule ( Figure 7 ). Very large foci ( Figure 8 ) are often composed almost entirely of polygonal type B cells, with few elongated type A cells, and can exhibit some degree of compression and expansion. Focal subcapsular hyperplasia is considered a proliferative lesion in a morphologic continuum that can progress to adenoma and, rarely, to carcinoma. Subcapsular adenomas are also composed of variable mixtures of well-differentiated "spindle" and "polygonal" cells, so differentiating large focal hyperplasias from smaller adenomas can be challenging. Compared with hyperplastic foci, adenomas are larger, are more discretely nodular, clearly compress the adrenal parenchyma, and may even bulge prominently above the capsular surface due to pronounced expansile proliferation.
Recommendation
Adrenal cortical subcapsular hyperplasia should be diagnosed and assigned a severity grade.
矿化Mineralization 肾上腺矿化
描述（中文）
大鼠和小鼠肾上腺内的矿化（Figure 1、Figure 2）通常为营养不良性形式，是坏死、出血或血栓形成等其他病变的继发结果。因此，其发生率往往总体较低且呈散发性，与受试物无关。皮质受累比髓质更为常见。矿化的特征为大小不一、离散的细至粗颗粒状深嗜碱性物质聚集（Figure 1、Figure 2），散布于肾上腺实质中，常邻近或位于纤维化、变性、坏死、出血和/或血栓形成区域之内。
诊断建议
如果肾上腺矿化作为原发性、与受试物相关的改变出现，则应予以诊断，并赋予严重程度分级和部位修饰词（即皮质、髓质或被膜）。作为另一病理过程（如纤维化或血栓形成）特征的矿化不应单独诊断，除非严重程度足以支持单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Mineralization in the adrenal gland ( Figure 1 and Figure 2 ) in rats and mice is usually the dystrophic form and is a sequela to other lesions, such as necrosis, hemorrhage, or thrombosis. It therefore tends to occur with generally low, sporadic incidences unrelated to treatment. The cortex is more often affected than the medulla. Mineralization is characterized as variably sized, discrete aggregates of finely to coarsely granular dark basophilic material ( Figure 1 and Figure 2 ) that are scattered through the adrenal parenchyma, often adjacent to or within areas of fibrosis, degeneration, necrosis, hemorrhage, and/or thrombosis.
Recommendation
If mineralization of the adrenal gland occurs as a primary, treatment-related change, it should be diagnosed and assigned a severity grade and site modifier (i.e., cortex, medulla, or capsule). Mineralization that is a feature of another pathologic process (e.g., fibrosis or thrombosis) should not be diagnosed separately, unless warranted by severity.
纤维化Fibrosis 肾上腺纤维化
描述（中文）
肾上腺纤维化（Adrenal gland fibrosis）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6、Figure 7、Figure 8）是小鼠和大鼠中不常见的偶然性发现。它通常是其他病理过程的继发结果，如坏死（Figure 8）、萎缩、血栓形成（Figure 5、Figure 6）或炎症。肾上腺纤维化可为皮质和/或髓质（Figure 1、Figure 2、Figure 5、Figure 6）和/或被膜（Figure 3、Figure 4、Figure 7、Figure 8）内 局灶性（focal） 至广泛的改变。在所有区域，纤维化的特征为 局灶性 至 弥漫性（diffuse） 的纤维结缔组织积聚，取代和/或扭曲正常组织结构。纤维结缔组织可为不成熟（含大量成纤维细胞和血管，胶原少）至成熟（主要为致密胶原板层，纤维细胞和血管少）。
诊断建议
肾上腺纤维化应予以诊断并赋予严重程度分级。诊断中应包含部位修饰词（即皮质、髓质或被膜）。若皮质和髓质均存在，可省略部位修饰词，并在病理学描述中说明位置。必要时诊断中可包含分布修饰词（如 局灶性（focal））。继发于其他病变（如炎症或坏死）的纤维化不应单独诊断，除非严重程度足以支持。纤维化的特征（如矿化或色素）不应单独诊断，但应在病理学描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Adrenal gland fibrosis ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 , Figure 7 , and Figure 8 ) is an uncommon incidental finding in mice and rats. It is usually a sequela to other pathologic processes, such as necrosis ( Figure 8 ), atrophy, thrombosis ( Figure 5 and Figure 6 ), or inflammation. Adrenal gland fibrosis can be a focal to extensive change in the cortex and/or medulla ( Figure 1 , Figure 2 , Figure 5 , and Figure 6 ) and/or the capsule ( Figure 3 , Figure 4 , Figure 7 , and Figure 8 ). In all areas, fibrosis is characterized by focal to diffuse accumulations of fibrous connective tissue, which replace and/or distort normal tissue architecture. The fibrous connective tissue may be immature (with abundant fibroblasts and blood vessels and little collagen) to mature (primarily dense collagenous sheets with few fibrocytes and blood vessels).
Recommendation
Adrenal gland fibrosis should be diagnosed and assigned a severity grade. A site modifier (i.e., cortex, medulla, or capsule) should be included in the diagnosis. If it is present in both the cortex and medulla, the site modifier may be omitted and the location described in the pathology narrative. A distribution modifier (e.g., focal) may be included in the diagnosis if necessary. Fibrosis secondary to other lesions (e.g., inflammation or necrosis) should not be diagnosed separately unless warranted by severity. Features of fibrosis (e.g., mineralization or pigment) should not be diagnosed separately, though they should be described in the pathology narrative.
肾上腺皮质副结节Accessory Adrenocortical Nodule 肾上腺其他
描述（中文）
副肾上腺皮质结节（Accessory adrenocortical nodule）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6）在大鼠和小鼠中相当常见。该病变还有许多其他名称（如异位肾上腺组织、副皮质组织、错构瘤、副肾上腺、多余肾上腺和肾上腺皮质残留），副肾上腺皮质结节是起源于体腔上皮原基（肾上腺皮质即由此发生）部分或完全分离的残留物的轻微发育异常。它们最常位于与肾上腺一极被膜接触处（Figure 1、Figure 2、Figure 3、Figure 4），但也可完全与肾上腺分离，发生于腹膜后脂肪（Figure 5、Figure 6）、附着于肾被膜或腹膜腔任何部位。就其本身而言，副肾上腺皮质结节几乎总是无害的偶然发现，无临床或毒理学意义。然而，它们可发生与肾上腺皮质本身相同的退行性、增生性甚至肿瘤性改变。大多数结节为球形至卵圆形结构，周围通常有纤细的纤维性被膜，由分化良好的球状带型和束状带型细胞组成（Figure 1、Figure 2），有时混合存在，有时呈典型的分层排列。部分肾上腺皮质副组织由较疏松、外观更原始的皮质细胞巢组成（Figure 3、Figure 4）。典型的周围纤维性被膜可将副肾上腺皮质结节与局灶性（focal）皮质增生及皮质组织被膜外突出相区分。副结节还必须与皮质腺瘤和癌相鉴别，后者表现为细胞多形性和异型性及皮质分层丧失，但通常无被膜。
诊断建议
肾上腺 - 副肾上腺皮质结节：无论何时出现均应诊断，但无需进行严重程度分级。若结节位于肾上腺周围脂肪（与肾上腺分离），则该组织应列为肾上腺周围脂肪。若结节与另一器官（如肾）相关，则该器官的异位组织是更合适的诊断（如肾 - 异位组织，肾上腺）。
参考切片图（2 张）
查看英文原文
Comment
Accessory adrenocortical nodules ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ) are fairly common in rats and mice. Also known by many other terms (e.g., ectopic adrenal tissue, accessory cortical tissue, hamartoma, accessory adrenal gland, supernumary adrenal, and adrenocortical rest), accessory adrenocortical nodules are minor developmental anomalies arising from partly or completely detached rests of the coelomic epithelial primordia from which the adrenal cortex is derived. They are most frequently located in contact with the capsule at one pole of the adrenal gland ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) but can occur completely separated from the adrenal gland in the retroperitoneal fat ( Figure 5 and Figure 6 ), attached to the kidney capsule, or anywhere in the peritoneal cavity. In and of themselves, accessory adrenocortical nodules are almost always innocuous incidental findings without clinical or toxicologic relevance. However, they can develop the same degenerative, hyperplastic, and even neoplastic changes as the adrenal cortex proper. Most nodules are spherical to ovoid structures surrounded by a usually delicate fibrous capsule and composed of well-differentiated zonae glomerulosa-type and fasciculata-type cells ( Figure 1 and Figure 2 ), sometimes admixed and sometimes arranged in typical layers. Some adrenocortical accessory tissue consists of less densely packed nests of more primitive-appearing cortical cells ( Figure 3 and Figure 4 ). The typical surrounding fibrous capsule distinguishes accessory adrenocortical nodules from focal cortical hyperplasia and from extracapsular protrusions of cortical tissue. Accessory nodules must also be distinguished from cortical adenomas and carcinomas, which exhibit cellular pleomorphism and atypia and loss of cortical layering but are not commonly encapsulated.
Recommendation
Adrenal gland - Accessory adrenocortical nodule should be diagnosed whenever present, but a severity grade is not necessary. If a nodule is located in the periadrenal fat (separated from the adrenal gland), the tissue should be listed as periadrenal fat. If a nodule is associated with another organ (e.g., kidney), ectopic tissue of that organ is a more appropriate diagnosis (e.g., Kidney - Ectopic tissue, Adrenal gland).
色素Pigment 肾上腺色素沉着
描述（中文）
肾上腺中的色素最常见于皮质，但也可见于髓质和肾上腺被膜。小鼠和大鼠的肾上腺皮质色素通常为脂褐素沉积，其特征为胞质内黄色至深棕色、颗粒状至无定形物质，充盈并使肾上腺皮质细胞扩张。肿胀细胞的胞质可呈现不同程度的空泡化或“泡沫状”（Figure 1、Figure 2）。脂褐素沉积可具有自发荧光，通常为苏丹染色阳性，且过碘酸-雪夫（PAS）染色和抗酸染色阳性；铁染色阳性程度不一。含铁血黄素色素也可作为出血的后遗症而存在。含铁血黄素色素通常见于巨噬细胞，呈金黄色至深棕色。脂褐素是指胞质内、通常为溶酶体内、不可降解的脂质和蛋白质氧化/聚合残留物（以及其他部分，如晚期糖基化终产物）的异质性混合物，其因衰老或其他因素而在各种体细胞中蓄积。过度和/或时间上不适当的肾上腺脂褐素色素聚集（与年龄匹配的对照相比）也可为皮质细胞变性和/或萎缩（由各种原因所致）的特征，或可由饮食失衡（如维生素E缺乏）或给予某些外源性化学物质所致。在小鼠中，充满脂褐素色素的肾上腺皮质细胞最常作为X带生理性退化的晚期特征或后遗症出现。因此，它们是老年小鼠中常见的偶然发现。充满色素的细胞聚集体主要位于毗邻皮髓质交界处、原为X带占据的区域。较轻、时间上进展较少的病例由散在的充满色素细胞的小灶组成，但随着动物年龄增长，细胞簇常增大并可融合成环绕髓质的环状带。含有类似脂褐素和/或含铁血黄素的巨噬细胞可散布于受累皮质细胞之间。在大鼠中，肾上腺皮质内含脂褐素色素的细胞也是一种常见的年龄相关偶然性改变。尽管大鼠没有X带，但充满色素的细胞往往最常见于内皮质，通常为单个细胞或非常小的细胞簇（Figure 1、Figure 2），不同于小鼠中常见的大型、显著的聚集体。
诊断建议
看似与处理相关原发改变的色素沉积应予以诊断，并赋予严重程度分级和部位修饰词（即皮质、髓质或被膜）。如果同时存在于皮质和髓质，可省略部位修饰词，并在病理学叙述中描述其位置。在各种组织的组织学切片中，即使使用一系列特殊染色，明确鉴定色素也往往很困难。因此，推荐的诊断为“色素”，不加类型修饰词（而非诊断色素类型，例如“色素，含铁血黄素”或“色素，脂褐素”）。色素的形态学特征应在病理学叙述中描述。然而，并非所有色素沉积都必须诊断，因为有些几乎是老年动物中普遍存在的自发性改变和/或继发于无关的疾病过程。与小鼠X带退化相关的色素不应单独诊断。在大鼠和小鼠中作为自发性衰老改变而蓄积的皮质细胞色素不应诊断，除非在发生率或严重程度上存在处理相关差异。病理学家应自行判断此类继发性色素沉积是否显著到足以需要单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Pigments in the adrenal gland are most commonly found in the cortex but can also be seen in the medulla and adrenal capsule. Adrenal cortical pigment in mice and rats is usually lipofuscin deposition, which is characterized by the intracytoplasmic, yellow to dark brown, granular to amorphous material that fills and distends adrenal cortical cells. The cytoplasm of the swollen cells may appear variably vacuolated or "foamy" ( Figure 1 and Figure 2 ). Lipofuscin deposits may be autofluorescent and are usually sudanophilic and positive with periodic acid-Schiff (PAS) and acid-fast stains; positivity with iron stains is variable. Hemosiderin pigment may also be present as a sequela to hemorrhage. Hemosiderin pigment is typically found in macrophages and is golden brown to dark brown. Lipofuscin refers to heterogeneous mixtures of intracytoplasmic, usually intralysosomal, nondegradable residues of lipid and protein oxidation/polymerization (as well as other moieties, such as advanced glycosylated end products) that accumulate in various somatic cells due to aging or other factors. Excessive and/or temporally inappropriate adrenal lipofuscin pigment aggregations (compared with age-matched controls) can also be a feature of cortical cell degeneration and/or atrophy (due to various causes) or can result from dietary imbalances (e.g., vitamin E deficiency) or administration of certain exogenous chemicals. In mice, lipofuscin pigment-laden adrenal cortical cells occur most often as late-stage features or sequelae to physiologic regression of the X-zone. Thus, they are common incidental findings in aging mice. The pigment-laden cell aggregates are located primarily in the region adjacent to the corticomedullary junction formerly occupied by the X-zone. Milder, less temporally advanced cases consist of scattered small foci of pigment-laden cells, but as the animal ages the cell clusters often enlarge and can coalesce into circumferential bands surrounding the medulla. Macrophages containing similar lipofuscin and/or hemosiderin can be interspersed among the affected cortical cells. In rats, cells in the adrenal cortex containing lipofuscin pigment are also a common age-related incidental change. Even though rats do not have an X-zone, the pigment-laden cells tend to be most common in the inner cortex, usually as single cells or very small clusters ( Figure 1 and Figure 2 ), unlike the large, prominent aggregates often seen in mice.
Recommendation
Pigment deposits that appear to be primary treatment-related changes should be diagnosed and assigned a severity grade and site modifier (i.e., cortex, medulla, or capsule). If it is present in both the cortex and medulla, the site modifier may be omitted and the location described in the pathology narrative. Definitive identification of pigments in various tissues is often difficult in histologic sections, even with a battery of special stains. Therefore, the recommended diagnosis is "pigment" without a type modifier (as opposed to diagnosing the type of pigment, e.g., "pigment, hemosiderin" or "pigment, lipofuscin"). The morphologic features of the pigment should be described in the pathology narrative. Not all pigment deposits have to be diagnosed, however, as some are almost ubiquitous spontaneous changes in aging animals and/or secondary to extraneous disease processes. Pigment associated with X-zone regression in mice should not be diagnosed separately. The cortical cell pigment that accumulates as a spontaneous aging change in rats and mice should not be diagnosed unless there are treatment-related differences in incidence or severity. The pathologist should use his or her judgment as to whether such secondary pigment deposits are prominent enough to warrant a separate diagnosis.
血管扩张Angiectasis 肾上腺扩张
描述（中文）
大鼠和小鼠肾上腺皮质和髓质的血管扩张（angiectasis）（Figure 1、Figure 2）以血管（毛细血管和/或静脉）的局灶性（focal）至弥漫性（diffuse）扩张为特征。扩张的血管排列疏松至不规则，不形成离散的团块。血管内衬单层分化良好的内皮细胞，由纤细的纤维性间质支撑，内含数量不等的血液。血管扩张可与其他肾上腺病变（如炎症、萎缩、变性和肿瘤）相关或继发于这些病变。它也可作为老年大鼠和小鼠的spontaneous年龄相关变化出现。血管扩张与血管瘤可能难以区分，但应尝试进行鉴别。血管瘤往往为边界清楚、无包膜的团块，由密集排列的扩张血管腔隙构成。血管腔隙内衬单层外观正常的内皮细胞，这些细胞排列在通常纤细的胶原性间隔上，尽管部分病例表现出更丰富的胶原性间质。相比之下，尽管血管扩张同样以扩张的血管通道为特征且内衬无明显异常的内皮，但血管通道排列更为疏松或不规则，而非表现为边界清楚的团块。
诊断建议
肾上腺血管扩张应予以诊断并赋予严重程度分级。诊断中应包含部位修饰词（即cortex或medulla）以指示病变位置。如果皮质和髓质均存在，可省略部位修饰词并在病理学描述中描述位置。如果血管扩张被认为是其他病变（如囊性变性、炎症或肿瘤）的组成部分或继发于这些病变，则不应单独诊断，而应在病理学描述中予以描述。如果双侧肾上腺均可见血管扩张，诊断中应添加修饰词“双侧（bilateral）”（除非另有说明，病变假定为单侧）。
参考切片图（2 张）
查看英文原文
Comment
Angiectasis ( Figure 1 and Figure 2 ) in the adrenal cortex and medulla of rats and mice is characterized by focal to diffuse dilation of blood vessels (capillaries and/or veins). The dilated vessels are loosely to irregularly arranged and do not form discrete masses. They are lined by single layers of well-differentiated endothelial cells supported by a delicate fibrous stroma and contain variable amounts of blood. Angiectasis can be associated with or secondary to other adrenal lesions such as inflammation, atrophy, degeneration, and neoplasia. It can also occur as a spontaneous age-related change in old rats and mice. Angiectasis and hemangioma can be difficult to differentiate, but a distinction should be attempted. Hemangiomas tend to be well-circumscribed, unencapsulated masses composed of densely packed, dilated vascular spaces. The vascular spaces are lined by a single layer of normal-appearing endothelial cells aligned on usually delicate collagenous septa, though some cases exhibit more abundant collagenous stroma. In contrast, although angiectasis is also characterized by dilated vascular channels lined by unremarkable endothelium, the vascular channels are more loosely or irregularly arranged rather than presenting as a well-demarcated mass.
Recommendation
Adrenal angiectasis should be diagnosed and assigned a severity grade. A site modifier (i.e., cortex or medulla) should be included in the diagnosis to indicate the location of the lesion. If it is present in both the cortex and medulla, the site modifier may be omitted and the location described in the pathology narrative. If angiectasis is considered a component of or secondary to other lesions (e.g., cystic degeneration, inflammation, or neoplasia), it should not be diagnosed separately but should be described in the pathology narrative. If angiectasis is seen in both adrenal glands, the modifier "bilateral" should be added to the diagnosis (lesions are assumed to be unilateral unless otherwise indicated).
髓外造血Extramedullary Hematopoiesis 肾上腺其他
描述（中文）
髓外造血（extramedullary hematopoiesis，EMH）可发生于多种组织，包括肾上腺皮质和髓质。EMH在肾上腺中不常见，因此若存在，很可能也存在于其他器官，最可能是脾和肝（见脾-髓外造血和肝-髓外造血）。EMH通常由混合的髓系造血细胞和红系造血细胞组成，但也可主要（罕见情况下完全）由其中某一谱系组成。髓外髓系造血通常继发于各种炎症或免疫反应，是对需要额外白细胞的一种反应。髓外红系造血常常是对某些类型贫血（例如溶血性贫血或失血）以及某些导致缺氧的情况（例如呼吸系统疾病）的一种反应。大鼠、尤其是小鼠肾上腺中的低级别EMH也可在没有任何明确诱因的情况下发生。肾上腺EMH由大小不一、无压迫性的未成熟造血细胞和/或巨核细胞簇组成，散布于皮质和/或髓质（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6）。髓系造血细胞通常大于红系造血细胞，且胞质更多，而红系造血细胞通常颜色深得多。肾上腺EMH必须与炎症（成熟白细胞，常伴有组织坏死或变性）以及全身性淋巴或造血肿瘤性浸润（低分化、常为间变性细胞，通常呈广泛聚集，使正常结构扭曲或破坏）相鉴别。
诊断建议
只有当肾上腺髓外造血（EMH）的发生率和/或严重程度出现与处理相关的增加时，才应作出诊断并赋予严重程度分级。作出诊断时，诊断中应包含部位修饰词（即皮质或髓质），以指明病变的位置。如果EMH同时存在于皮质和髓质，可省略部位修饰词，并在病理学描述中说明位置。如果双侧肾上腺均可见EMH，应在诊断中加入修饰词“双侧（bilateral）”（除非另有说明，病变假定为单侧）。如果病变主要由某一特定细胞谱系（例如髓系造血或红系造血）组成或完全由该谱系组成，应在病理学描述中说明。相关链接：肝-髓外造血 脾-髓外造血
参考切片图（2 张）
查看英文原文
Comment
Extramedullary hematopoiesis (EMH) can occur in various tissues, including the adrenal cortex and medulla. EMH is not commonly seen in the adrenal gland, so if it is present, it will likely also be present in other organs, most likely the spleen and liver (see Spleen - Extramedullary Hematopoiesis and Liver - Extramedullary Hematopoiesis ). EMH is typically composed of mixed myelopoietic and erythropoietic cells but may be primarily (rarely exclusively) composed of one or the other lineage. Extramedullary myelopoiesis is usually secondary to various inflammatory or immune responses and is a reaction to the need for additional white blood cells. Extramedullary erythropoiesis is frequently a response to certain types of anemia (e.g., hemolytic anemia or blood loss) and some situations leading to hypoxia (e.g., respiratory disease). Low-grade EMH in the adrenal gland of rats and especially mice can also occur without any clear inciting cause. Adrenal EMH consists of variably sized, noncompressive clusters of immature hematopoietic cells and/or megakaryocytes scattered throughout the cortex and/or medulla ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ). Myelopoietic cells are typically larger than erythropoietic cells and have more cytoplasm, whereas erythropoietic cells typically are much darker. Adrenal EMH must be distinguished from inflammation (mature leukocytes, often associated with tissue necrosis or degeneration) and from systemic lymphoid or hematopoietic neoplastic infiltrates (poorly differentiated, often anaplastic cells usually in extensive accumulations that distort or obliterate normal architecture).
Recommendation
Adrenal extramedullary hematopoiesis (EMH) should be diagnosed and assigned a severity grade only if there are treatment-related increases in incidence and/or severity. When it is diagnosed, a site modifier (i.e., cortex or medulla) should be included in the diagnosis to indicate the location of the lesion. If EMH is present in both the cortex and medulla, the site modifier may be omitted and the location described in the pathology narrative. If EMH is seen in both adrenal glands, the modifier "bilateral" should be added to the diagnosis (lesions are assumed to be unilateral unless otherwise indicated). If the lesion is composed primarily or exclusively of a particular cell lineage (e.g., myelopoietic or erythropoietic), this should be indicated in the pathology narrative. Related Links: Liver - Extramedullary Hematopoiesis Spleen - Extramedullary Hematopoiesis
发育不全Hypoplasia 胰岛其他
描述（中文）
胰岛细胞发育不全是先天性改变。在胰岛细胞发育不全的病例中，通常切片中仅存在一或两个发育不全的胰岛（例如，Figure 1、Figure 2、Figure 3 中仅有两个发育不全的胰岛，Figure 4 中有一个发育不全的胰岛）。由于胰岛的大小和密度在胰腺内不同区域存在差异，因此需要足够的切片才能确认此诊断。
诊断建议
只要存在胰腺胰岛发育不全，就应作出诊断并给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Islet cell hypoplasia is considered a congenital change. In cases of islet cell hypoplasia, typically one or two hypoplastic islets are the only islets present in the section (e.g., only two hypoplastic islets in Figure 1 , Figure 2 , and Figure 3 and one hypoplastic islet in Figure 4 ). An adequate section is necessary to confirm this diagnosis since islet size and density vary by region within the pancreas.
Recommendation
Hypoplasia of the pancreatic islets should be diagnosed and given a severity grade whenever present.
囊肿Cyst 胰岛囊肿
描述（中文）
胰腺切片中仅见于一个胰岛的囊肿，需与血管扩张（angiectasis）相鉴别，鉴别依据为其体积大、缺乏内皮衬覆，以及其他血管腔隙无扩张（Figure 1、Figure 2）。
诊断建议
胰岛囊肿不常见，但存在时应予以记录。无需进行严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
A cyst present in only one islet in a section of pancreas is distinguished from angiectasis based on its large size, lack of an endothelial lining, and the absence of dilation of other vascular spaces ( Figure 1 and Figure 2 ).
Recommendation
Islet cysts are uncommon but should be documented when present. A severity grade is not required.
坏死Necrosis 胰岛坏死
描述（中文）
胰岛（pancreatic islets）中β细胞（beta cell）的坏死与锌缺乏以及与结合锌的外源化学物（xenobiotics）有关。受影响的β细胞通常皱缩、呈强嗜酸性（hypereosinophilic），并伴有核固缩（pyknotic nuclei）。β细胞的丢失可遗留空泡（Figure 1）。
诊断建议
出现该病变时，应当作出诊断并进行分级。严重程度分级依据受累胰岛的数量和坏死的程度确定。相关病变，如炎症，若其严重程度足以需要诊断，则应单独诊断。
参考切片图（1 张）
查看英文原文
Comment
Necrosis of beta cells in pancreatic islets has been associated with zinc deficiency and with xenobiotics that bind zinc. Affected beta cells are typically shrunken and hypereosinophilic with pyknotic nuclei. The loss of beta cells can leave empty vacuoles ( Figure 1 ).
Recommendation
When present, this change should be diagnosed and graded. Severity grading is determined by the number of islets affected and the magnitude of the necrosis. Associated lesions, such as inflammation, should be diagnosed separately if warranted by severity.
增生Hyperplasia 胰岛增生
描述（中文）
在小鼠中，胰岛大小差异很大，直径从50至300微米不等。由于小鼠的胰岛被认为是一个增殖群体，倍增时间为500天，因此其大小预期会随年龄增长而增加。由于这种大小差异，可能难以明确诊断增生。当胰岛更为显著时，可能看起来数量有所增加。然而，据报道小鼠每个胰腺中胰岛数量相对恒定，约为1,000个。胰岛细胞增生可自发发生于小鼠和大鼠，并且在小鼠中可能表现显著。它通常与年龄相关，并且通常累及多个胰岛。在大鼠中，胰岛细胞增生在雄性中比雌性更常见。如果有数个胰岛直径大于300微米，应作出胰岛细胞增生的诊断。此外，如果胰腺某切片中胰岛占据的总面积大于对照组，则作出胰岛细胞增生的诊断可能是恰当的。受累胰岛可能相互连续，呈小叶状外观（Figure 3），或明显分离（Figure 4）。增生与腺瘤之间的区别在很大程度上受腺瘤中存在压迫证据而增生中缺乏压迫的影响（Figure 5、Figure 6）。在胰岛细胞腺瘤中，可能存在一些细胞异型性或多形性，这在增生性病变中通常不见。偶见的腺泡细胞可能陷入融合的增生性胰岛中（Figure 7、Figure 8、Figure 9），不应与胰岛细胞癌的浸润相混淆。
诊断建议
胰岛细胞增生存在时应记录并给予严重程度分级。严重程度分级由受累胰岛的大小和数量共同确定。如果在某一研究中存在治疗相关效应和/或胰岛腺瘤的证据，病理学描述应提供用于区分增生与腺瘤的诊断特征（例如，增生中缺乏压迫、异型性或坏死），并说明任何治疗相关反应的程度。
参考切片图（2 张）
查看英文原文
Comment
In mice, islets vary greatly in size, ranging from 50 to 300 micrometers in diameter. Since islets in mice are considered to be an expanding population with a doubling time of 500 days, their size would be expected to increase with age. Because of this size variation, it may be difficult to definitively diagnose hyperplasia. When islets are more prominent, they may appear to have increased in number. However, mice are reported to have a relatively constant 1,000 islets per pancreas. Islet cell hyperplasia occurs spontaneously in mice and rats and may be dramatic in mice. It is often age associated and typically involves multiple islets. In rats, islet cell hyperplasia occurs more frequently in males than females. If there several islets greater than 300 micrometers in diameter, a diagnosis of islet cell hyperplasia should be made. Also, if the overall area occupied by the islets in a section of pancreas is greater than that of the controls, a diagnosis of islet cell hyperplasia may be appropriate. Affected islets may be contiguous, giving a lobular appearance ( Figure 3 ) or distinctly separated ( Figure 4 ). The distinction between hyperplasia and adenoma is largely influenced by evidence of compression in adenomas and lack of compression in hyperplasia ( Figure 5 and Figure 6 ). In islet cell adenomas, there may be some cellular atypia or pleomorphism, which is not typically seen in hyperplastic lesions. Occasional acinar cells may become trapped within coalescing hyperplastic islets ( Figure 7 , Figure 8 , and Figure 9 ) and should not be confused with invasion of an islet cell carcinoma.
Recommendation
Islet cell hyperplasia should be documented when present and given a severity grade. Severity grading is determined by both size and number of affected islets. If there is evidence of treatment-related effect and/or the presence of islet adenomas in a given study, the pathology narrative should provide the diagnostic features used to distinguish between hyperplasia and adenoma (e.g., lack of compression, atypia, or necrosis in hyperplasia) and address the magnitude of any treatment-related response.
肝细胞化生Metaplasia Hepatocyte 胰岛化生
描述（中文）
胰岛细胞肝细胞化生（hepatocyte metaplasia）的特征是偶见胰岛内出现肝细胞，通常位于胰岛周边。虽然在大鼠中这可能是偶然发现，但肝细胞化生可由过氧化物酶体增殖物（peroxisome proliferators）、甲基缺乏饮食诱导，也可通过实验性铜给予/撤除诱导。在外源性物质（xenobiotics）诱导后15周内可出现化生的肝细胞。
诊断建议
由于此病变与外源性物质暴露相关，故只要存在即应诊断并分级。分级应基于受累胰岛的数量及存在的肝细胞数量。
参考切片图（2 张）
查看英文原文
Comment
Hepatocyte metaplasia of pancreatic islet cells is characterized by the presence of hepatocytes in an occasional islet, usually at the islet periphery. While it may be an incidental finding in rats, hepatocyte metaplasia can be induced by peroxisome proliferators, by methyl-deficient diets, and experimentally by copper administration/withdrawal. Metaplastic hepatocytes can occur within 15 weeks following induction by xenobiotics.
Recommendation
Because this change has been associated with exposure to xenobiotics, it should be diagnosed whenever present and graded. Grading should be based on number of islets affected and number of hepatocytes present.
血管扩张Angiectasis 胰岛扩张
描述（中文）
血管扩张（angiectasis）通常表现为形态不规则的扩张腔隙，腔内含有红细胞和/或血浆，内皮细胞衬覆极少。这是一种自发性改变，已知与给药无关，也不因给药而加重。通常一张切片中仅见一个受累的胰岛。红细胞周围也可能伴有含铁血黄素（hemosiderin）色素沉着（Figure 4）。
诊断建议
出现该改变时应予以诊断并分级。若血管扩张不广泛，严重程度分级通常为极轻微（minimal）。若在其他组织中观察到血管扩张或相关改变，应在病理学描述中补充相应评论。若存在含铁血黄素，则无需同时诊断色素沉着。
参考切片图（2 张）
查看英文原文
Comment
Angiectasis typically involves irregular dilated spaces that contain erythrocytes and/or plasma with a negligible endothelial cell lining. This is a spontaneous change with no known association with, or exacerbation by, treatment. Typically only one affected islet is seen in a section. There may also be hemosiderin pigment along with erythrocytes ( Figure 4 ).
Recommendation
When present, this change should be diagnosed and graded. A severity grade will most often be minimal if the angiectasis is not widespread. If angiectasis or related changes are observed in other tissues, a comment to this effect should be added to the pathology narrative. If hemosiderin is present, a concurrent diagnosis of pigment is not necessary.
上皮变性Epithelium Degeneration 肺变性
描述（中文）
变性（Figure 1、Figure 2、Figure 3、Figure 4）和坏死被认为是细胞损伤连续过程的一部分，其中变性代表可逆性细胞损伤，坏死代表不可逆性细胞损伤。可逆性细胞损伤（变性）的光镜特征包括细胞肿胀、胞质空泡化、核周透明间隙、胞质泡形成、Clara 细胞正常顶端泡丢失以及纤毛丢失。在某些情况下，存活细胞从上皮表面脱落以及上皮内散在细胞的核浓缩（pyknosis）和细胞皱缩，提示单个细胞即将死亡，可被解释为上皮变性，因为这可能与上皮表面的可逆性损伤相一致，且可能缺乏明确的坏死证据。坏死的光镜特征包括核浓缩、核碎裂或核溶解、细胞肿胀、细胞细节丢失、细胞碎裂以及胞质嗜酸性增强（其中胞质常呈均质外观）。毒性损伤所致气道被覆上皮细胞坏死，常以坏死细胞或细胞碎片脱落入管腔为特征。其他病变常伴随坏死和变性出现，如炎症和出血。变性病变的解剖位置可能因受试物的理化性质或特定细胞类型对受试物的易感性而有所不同。终末细支气管和肺泡管上皮（即中心腺泡区）及肺泡特别易受损伤，这是由于表面积大且 I 型肺泡细胞脆弱、Clara 细胞中 P450 酶的代谢活性以及黏液层通常较薄。
诊断建议
肺，上皮——变性只要存在就应诊断并分级。诊断中应包含部位修饰词以指示病变在肺内的位置（例如肺泡、细支气管），因为毒性损伤可优先靶向特定部位。变性与坏死在形态学上存在显著重叠，因此病理学家在诊断这些病变时需要运用其最佳判断。如果变性继发于另一过程，如严重炎症，则最好诊断主要过程并在叙述中描述变性。如果变性和并发的相关病变（例如炎症）均显著，病理学家可选择记录两者并分别分级。同样，病理学家在决定是否单独诊断变性时需要运用其判断。
参考切片图（2 张）
查看英文原文
Comment
Degeneration ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) and necrosis are considered to be parts of the continuum of cell damage, with degeneration representing reversible cell damage and necrosis representing irreversible cell damage. The light microscopic hallmarks of reversible cell damage (degeneration) include cellular swelling, cytoplasmic vacuolation, perinuclear clear spaces, formation of cytoplasmic blebs, loss of normal apical blebs from Clara cells, and loss of cilia. In some cases, detachment of viable cells from the epithelial surface and nuclear condensation (pyknosis) and cellular shrinkage of scattered cells within the epithelium, suggestive of imminent death of individual cells, may be interpreted as epithelial degeneration because it may be consistent with reversible damage to an epithelial surface and evidence of outright necrosis may be lacking. The light microscopic features of necrosis include nuclear pyknosis, karyorrhexis, or karyolysis, cell swelling, loss of cellular detail, cell fragmentation, and cytoplasmic hypereosinophilia (in which the cytoplasm often has a homogeneous appearance). Necrosis of the epithelial cells lining the airways as a result of toxic injury is often characterized by sloughing of necrotic cells or cellular debris into the lumen. Other lesions often accompany necrosis and degeneration, such as inflammation and hemorrhage. The anatomic location of degenerative lesions may vary due to the physicochemical properties of the test agent or the susceptibility of a particular cell type to the test agent. The epithelium of the terminal bronchioles and alveolar ducts (i.e., the centriacinar region) and alveoli are particularly susceptible to injury due to the large surface area and fragility of the alveolar type I cells, the metabolic activity of P450 enzymes in Clara cells, and the generally thinner mucous layer.
Recommendation
Lung, Epithelium - Degeneration should be diagnosed and graded whenever present. A site modifier should be included in the diagnosis to indicate the location of the lesion within the lung (e.g., alveolus, bronchiole) since toxic insults can preferentially target specific sites. There is significant overlap, morphologically, between degeneration and necrosis, so the pathologist will need to use his or her best judgment when diagnosing these lesions. If the degeneration is secondary to another process, such as severe inflammation, it is preferable to diagnose the major process and to describe the degeneration in the narrative. If degeneration and a concurrent, related lesion (e.g., inflammation) are both prominent, the pathologist may choose to record both lesions and grade them separately. Again, the pathologist will need to use his or her judgment in deciding whether or not to diagnose the degeneration separately.
上皮坏死Epithelium - Necrosis 肺坏死
描述（中文）
坏死（Figure 1、Figure 2、Figure 3、Figure 4）与变性被认为是细胞损伤连续统一体的组成部分，其中坏死代表不可逆的细胞损伤，变性代表可逆的细胞损伤。坏死的 light microscopic 特征包括核固缩、核碎裂或核溶解、细胞肿胀、细胞细节丧失、细胞碎裂以及胞质嗜酸性增强（其中胞质常呈均质外观）。大面积坏死（Figure 2、Figure 3、Figure 4）还可能伴有组织结构破坏、大面积坏死碎屑、染色强度丧失以及炎性细胞。毒性损伤所致气道被覆上皮细胞坏死，常以坏死细胞或细胞碎屑脱落入管腔为特征。可逆性细胞损伤的 light microscopic 标志包括细胞肿胀、胞质空泡化、核周透明间隙、胞质泡形成、Clara 细胞正常顶端泡丧失以及纤毛丧失。在某些情况下，存活细胞从上皮表面脱落，以及上皮内散在细胞的核浓缩（固缩）和细胞皱缩，提示单个细胞即将死亡，可判读为上皮变性，因为其可能与上皮表面的可逆性损伤相一致，且可能缺乏明确的坏死证据。其他病变常伴随坏死和变性出现，如炎症和出血。坏死性病变的解剖位置可能因受试物的理化性质或特定细胞类型对受试物的易感性而有所不同。终末细支气管和肺泡管的上皮（即 centriacinar 区域）以及肺泡尤其易受损伤，原因在于表面积大、I 型肺泡细胞脆弱、Clara 细胞中 P450 酶的代谢活性以及黏液层通常较薄。
诊断建议
肺，上皮 - 坏死：只要存在即应诊断并分级。诊断中应包含部位修饰词，以指示病变在肺内的位置（例如 alveolus、bronchiole），因为毒性损伤可优先靶向特定部位。如果受累部位超过一个，可省略部位修饰词，并在病理学描述中描述各部位。变性与坏死在形态学上存在显著重叠，因此病理学家在诊断这些病变时需要运用其最佳判断。如果坏死继发于另一过程，例如严重炎症，则宜诊断主要过程并在描述中描述坏死。如果坏死与并发的相关病变（例如炎症）均显著，病理学家可选择记录两者并分别分级。同样，病理学家在决定是否单独诊断坏死或变性时需要运用其判断。如果坏死细胞已脱落，暴露出下方组织，则应使用术语“ulcer”或“erosion”（见 Lung - Ulceration）。然而，如果坏死细胞仍存在并覆盖基底膜，则坏死是首选诊断。相关链接：Lung - Ulceration
参考切片图（2 张）
查看英文原文
Comment
Necrosis ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) and degeneration are considered to be parts of the continuum of cell damage, with necrosis representing irreversible cell damage and degeneration representing reversible cell damage. The light microscopic features of necrosis include nuclear pyknosis, karyorrhexis, or karyolysis, cell swelling, loss of cellular detail, cell fragmentation, and cytoplasmic hypereosinophilia (in which the cytoplasm often has a homogeneous appearance). Large areas of necrosis ( Figure 2 , Figure 3 , and Figure 4 ) may also have disrupted tissue architecture, large areas of necrotic debris, loss of staining intensity, and inflammatory cells. Necrosis of the epithelial cells lining the airways as a result of toxic injury is often characterized by sloughing of necrotic cells or cellular debris into the lumen. The light microscopic hallmarks of reversible cell damage include cellular swelling, cytoplasmic vacuolation, perinuclear clear spaces, formation of cytoplasmic blebs, loss of normal apical blebs from Clara cells, and loss of cilia. In some cases, detachment of viable cells from the epithelial surface and nuclear condensation (pyknosis) and cellular shrinkage of scattered cells within the epithelium, suggestive of imminent death of individual cells, may be interpreted as epithelial degeneration because it may be consistent with reversible damage to an epithelial surface, and evidence of outright necrosis may be lacking. Other lesions often accompany necrosis and degeneration, such as inflammation and hemorrhage. The anatomic location of necrotic lesions may vary due to the physicochemical properties of the test agent or the susceptibility of a particular cell type to the test agent. The epithelium of the terminal bronchioles and alveolar ducts (i.e., the centriacinar region) and alveoli are particularly susceptible to injury due to the large surface area and fragility of the alveolar type I cells, the metabolic activity of P450 enzymes in Clara cells, and the generally thinner mucous layer.
Recommendation
Lung, Epithelium - Necrosis should be diagnosed and graded whenever present. A site modifier should be included in the diagnosis to indicate the location of the lesion within the lung (e.g., alveolus, bronchiole) since toxic insults can preferentially target specific sites. If more than one site is affected, the site modifier may be omitted and the locations described in the pathology narrative. There is significant overlap, morphologically, between degeneration and necrosis, so the pathologist will need to use his or her best judgment when diagnosing these lesions. If the necrosis is secondary to another process, such as severe inflammation, it is preferable to diagnose the major process and to describe the necrosis in the narrative. If the necrosis and a concurrent, related lesion (e.g., inflammation) are both prominent, the pathologist may choose to record both lesions and grade them separately. Again, the pathologist will need to use his or her judgment in deciding whether or not to diagnose the necrosis or degeneration separately. If the necrotic cells have detached, exposing the underlying tissue, the term "ulcer" or "erosion" should be used (see Lung - Ulceration ). However, if the necrotic cells are still present and covering the basement membrane, necrosis is the preferred diagnosis. Related Links: Lung - Ulceration
再生Regeneration 肺其他
描述（中文）
再生（regeneration）是指被覆上皮表面（即气道和肺泡）裸露部分得以修复的过程。一旦上皮发生坏死或溃疡，邻近的存活上皮细胞即取代丢失的细胞。在气道中，该过程始于邻近上皮细胞的伸长，这些细胞变扁平，并迁移越过创面覆盖基底膜（Figure 1、Figure 2）。在后期阶段，上皮开始增殖以取代丢失的细胞，使上皮衬里恢复正常状态。在肺泡中，II型肺泡上皮细胞（type II pneumocytes）是祖细胞，经历上述过程以取代丢失的I型肺泡上皮细胞。在某些情况下，再生的上皮可能超过正常上皮细胞数量而变为增生（hyperplastic）（Figure 3）。在此类情况下，在缺乏可识别的坏死或溃疡时，可能难以确定增生是源于再生还是对受试物暴露的原发性反应。因此，“再生”一词保留用于存在上皮损伤证据的病例。再生的其他特征可能包括与细胞增殖相符的特征，如核增大（karyomegaly）和细胞增大（cytomegaly）。此外，增殖细胞可能具有轻度非典型外观，因此病理学家可能需要区分再生与细胞非典型性（cellular atypia）。
诊断建议
肺 - 再生（Lung - Regeneration）：只要存在，且同时存在坏死或变性证据，即应诊断。如果上皮细胞数量超出正常范围，则应诊断增生（hyperplasia），无论其是受试物暴露的直接效应还是过度再生，但增生的发病机制应在病理学描述中讨论。诊断中应包含部位修饰词（如支气管、细支气管、肺泡），以指示病变位置。再生不应进行分级。为传达病变的严重程度，必须同时诊断并分级坏死或变性（见 Lung - Epithelium - Degeneration 和 Lung - Epithelium - Necrosis）。其他相关病变，如炎症，应单独诊断。如果病理学家判断再生上皮表现出显著的非典型特征，则应诊断并分级 Lung - Atypia, Cellular。相关链接：Lung - Atypia, Cellular；Lung - Epithelium - Degeneration；Lung - Epithelium - Necrosis
参考切片图（2 张）
查看英文原文
Comment
Regeneration is the process whereby denuded portions of epithelium-lined surfaces (i.e., airways and alveoli) are repaired. Once the epithelium becomes necrotic or ulcerated, the adjacent, viable epithelial cells replace the lost cells. In the airways, the process begins with elongation of the adjacent epithelial cells, which become flattened, and migration of these cells across the wound to cover the basement membrane ( Figure 1 and Figure 2 ). In later stages, the epithelium begins to proliferate to replace the lost cells to return the epithelial lining to its normal state. In the alveoli, the type II pneumocytes are the progenitor cells and undergo these processes to replace lost alveolar type I cells. In some cases, the regenerating epithelium may overshoot the normal number of epithelial cells and become hyperplastic ( Figure 3 ). In such cases, in the absence of recognizable necrosis or ulceration, it may be difficult to determine whether the hyperplasia is due to regeneration or is a primary response to test article exposure. For this reason, the term "regeneration" is reserved for those cases where there is evidence of epithelial damage. Other features of regeneration may include characteristics consistent with cellular proliferation, such as karyomegaly and cytomegaly. Additionally, the proliferating cells may have a slightly atypical appearance, so the pathologist may need to distinguish between regeneration and cellular atypia.
Recommendation
Lung - Regeneration should be diagnosed whenever present and evidence of necrosis or degeneration is also present. If the number of epithelial cells exceeds that which would be considered within normal limits, hyperplasia should be diagnosed, regardless of whether it is a direct effect of test article exposure or excessive regeneration, but the pathogenesis of the hyperplasia should be discussed in the pathology narrative. A site modifier (e.g., bronchus, bronchiole, alveolus) should be included in the diagnosis to indicate the location of the lesion. Regeneration should not be graded. To convey the severity of the lesion, either necrosis or degeneration must be diagnosed concurrently and graded (see Lung - Epithelium - Degeneration and Lung - Epithelium - Necrosis ). Other associated lesions, such as inflammation, should be diagnosed separately. If the pathologist judges that the regenerating epithelium exhibits significant features of atypia, then Lung - Atypia, Cellular should be diagnosed and graded. Related Links: Lung - Atypia, Cellular Lung - Epithelium - Degeneration Lung - Epithelium - Necrosis
出血Hemorrhage 肺出血
描述（中文）
出血（Hemorrhage）（Figure 1、Figure 2、Figure 3、Figure 4）的特征是气道内、肺血管周围和/或肺泡腔内有外渗的血细胞积聚。当肺毒素引起广泛实质或内皮细胞损伤时，肺内可发生出血。在此类情况下，常同时存在坏死、炎症或纤维化（作为慢性后遗症）。小量出血可继发于心力衰竭，最常表现为含红细胞或含铁血黄素色素的肺泡巨噬细胞聚集（“心力衰竭细胞”）。无论出血原因如何，在外渗的红细胞之间常可见含红细胞（红细胞吞噬现象）和含铁血黄素色素的肺泡巨噬细胞。与二氧化碳安乐死相关的出血常可见于胸膜下。此外，使用70%二氧化碳进行麻醉可诱发大鼠肺泡内小面积出血，这通常见于对照动物以及受试动物，且与出血相关的不会有含铁血黄素的巨噬细胞。
诊断建议
当出血由肺毒物直接引起时，应诊断为肺－出血并给出严重程度分级。当出血是其他病变（如肿瘤、坏死或炎症）的特征时，不应诊断出血，但应在病理学叙述中描述。然而，如果出血是炎症性或慢性病变的显著组成部分，则可由病理学家酌情诊断。继发于二氧化碳暴露的出血无需诊断（病理学家应运用其判断来确定是否属于这种情况）。如果未诊断出血，但出血与研究相关（例如，如果它掩盖或混淆了其他诊断），则应在病理学叙述中提及。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is characterized by accumulations of extravasated blood cells in airways, around pulmonary vessels, and/or in alveolar lumina. Hemorrhage may occur in the lung when there is extensive parenchymal or endothelial cell damage caused by pulmonary toxins. In such cases, necrosis, inflammation, or fibrosis (as a chronic sequela) often is present concurrently. Small hemorrhages can occur secondary to heart failure, which most commonly manifests as collections of alveolar macrophages containing erythrocytes or hemosiderin pigment ("heart failure cells"). Regardless of the cause of the hemorrhage, alveolar macrophages containing erythrocytes (erythrophagocytosis), and hemosiderin pigment are frequently seen amid extravasated erythrocytes. Hemorrhage is frequently observed subpleurally when related to euthanasia with carbon dioxide. In addition, the use of 70% carbon dioxide for anesthesia may induce small areas of hemorrhage in alveoli of rats, which will typically be seen in control as well as treated animals, and no hemosiderin-laden macrophages will be associated with the hemorrhage.
Recommendation
Lung - Hemorrhage should be diagnosed and given a severity grade when directly caused by a pulmonary toxicant. Hemorrhage should not be diagnosed when it is a feature of another lesion, such as neoplasia, necrosis, or inflammation, but should be described in the pathology narrative. If, however, the hemorrhage is a prominent component of an inflammatory or chronic lesion, it may be diagnosed at the discretion of the pathologist. Hemorrhage that is secondary to carbon dioxide exposure need not be diagnosed (the pathologist should use his/her judgment in determining if this is the case). If the hemorrhage is not diagnosed, it should be mentioned in the pathology narrative if it has relevance to the study (e.g., if it obscures or confounds other diagnoses).
平滑肌肥大Hypertrophy Smooth Muscle 肺肥大
描述（中文）
支气管平滑肌肥大（bronchial smooth muscle hypertrophy）（Figure 1）的特征是平滑肌细胞体积增大以及气道周围平滑肌层增厚。这是类似慢性哮喘的疾病状态下气道壁重塑的一个特征。气道平滑肌质量增加通常由平滑肌细胞增生（hyperplasia）和肥大（hypertrophy）两者共同构成，并可能促进支气管狭窄和气道高反应性。在毒性研究的对照动物中偶尔可见该病变（Figure 1），但其意义尚不清楚。
诊断建议
肺，平滑肌 - 肥大（Lung, Smooth muscle - Hypertrophy）应当作出诊断并赋予严重程度分级。应当包含部位修饰词（即支气管或细支气管），以指明受累的是哪种类型的气道。如果两种类型的气道均受累，则可省略部位修饰词，并在病理学描述中描述受累气道。相关病变，如炎症或纤维化，应当单独诊断。在某些情况下，当平滑肌肥大是更为显著的炎症性或反应性过程的次要成分时，可在病理学描述中将平滑肌肥大作为该过程的一个组成部分加以描述，而不作出诊断。如果同时存在平滑肌细胞增生，可在病理学描述中加以描述。
参考切片图（1 张）
查看英文原文
Comment
Bronchial smooth muscle hypertrophy ( Figure 1 ) is characterized by increased size of smooth muscle cells and thickening of the smooth muscle layer around airways. It is a feature of airway wall remodeling in disease states resembling chronic asthma. Increased airway smooth muscle mass usually consists of both smooth muscle cell hyperplasia and hypertrophy, and may contribute to bronchial narrowing and airway hyperresponsiveness. It is occasionally seen in control animals ( Figure 1 ) in toxicity studies, but the significance of the lesion is unclear.
Recommendation
Lung, Smooth muscle - Hypertrophy should be diagnosed and assigned a severity grade. A site modifier (i.e., bronchus or bronchiole) should be included to indicate which type of airway is affected. If both types of airways are affected, the site modifier may be omitted and the affected airways described in the pathology narrative. Associated lesions, such as inflammation or fibrosis, should be diagnosed separately. In some cases, where the smooth muscle hypertrophy is a minor component of a more prominent inflammatory or reactive process, the smooth muscle hypertrophy may be described in the pathology narrative as a component of that process, in lieu of a diagnosis. If hyperplasia of the smooth muscle cells is present concurrently, it may be described in the pathology narrative.
异物Foreign Body 肺其他
描述（中文）
“异物（foreign body）”一词可涵盖肺内存在多种环境性或异常物质，例如意外吸入的、代表垫料或饲料的植物碎片（Figure 1、Figure 2、Figure 3、Figure 4）、毛发（Figure 5、Figure 6、Figure 7），或与灌胃失误相关的玉米油（corn oil）赋形剂（Figure 8）。如果该异物的形态与受试物一致、该物质仅见于暴露动物，且该物质的量与暴露浓度相关，则应使用“异物（foreign material）”一词，而不是foreign body。毛干呈半透明且多层。玉米油由半透明、淡黄色、双折射的液滴组成。饲料或植物性垫料可通过植物细胞壁的存在加以识别。吸入的物质通常引起局灶性（focal）化脓性、肉芽肿性或脓性肉芽肿性反应，并且通常被聚集的巨噬细胞和/或中性粒细胞所包围。对玉米油的反应可因油中是否存在受试物以及受试物的类型而异。在赋形剂对照动物中，对玉米油的反应可能有限，且主要由油周围的肺泡巨噬细胞组成。异物通常为散发性所见，与暴露浓度无关。肺内大量颗粒物质的蓄积曾被诊断为尘肺（pneumoconiosis），但该术语被认为已过时，一般不再使用。
诊断建议
肺－异物（Lung - Foreign body）存在时应作出诊断，但不应进行分级。具体部位（例如肺泡、支气管或细支气管）应作为部位修饰词在诊断中注明。伴随异物的炎症（或组织细胞浸润）不应单独诊断，除非其严重程度足以支持单独诊断。当根据形态、与暴露浓度的相关性以及仅见于暴露动物而认为该物质为受试物时，应使用“异物（foreign material）”一词。
参考切片图（2 张）
查看英文原文
Comment
The term "foreign body" can encompass the presence of a variety of environmental or aberrant material within the lung, such as accidentally inhaled bits of plant material representing bedding or feed ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ), hair ( Figure 5 , Figure 6 , and Figure 7 ), or corn oil vehicle related to gavage error ( Figure 8 ). If the morphology of the foreign material is consistent with the test agent, the material is seen only in exposed animals, and the amount of material correlates with the exposure concentration, the term "foreign material" should be used rather than foreign body. Hair shafts are translucent and multilayered. Corn oil ( Figure 8 ) consists of translucent, pale yellow, birefringent droplets. Feed or plant-based bedding can be identified by the presence of plant cell walls. The inhaled material typically incites a focal suppurative, granulomatous, or pyogranulomatous reaction and is usually surrounded by accumulations of macrophages and/or neutrophils. The reaction to corn oil can vary depending upon whether test material is present in the oil and type of test material. In a vehicle control animal, the reaction to corn oil may be limited and consist primarily of alveolar macrophages around the oil. Foreign bodies are typically sporadic findings with no correlation to exposure concentration. The accumulation of substantial amounts of particulate matter in the lung has been diagnosed as pneumoconiosis, but this term is considered outdated and generally not used.
Recommendation
Lung - Foreign body should be diagnosed when present but should not be graded. The specific location (e.g., alveolus, bronchus, or bronchiole) should be indicated in the diagnosis as a site modifier. The inflammation (or histiocytic infiltration) that accompanies a foreign body should not be diagnosed separately unless warranted by severity. The term "foreign material" should be used when the material is thought to be the test agent based on morphology, correlation with exposure concentration, and presence only in exposed animals.
异物Foreign Material 肺其他
描述（中文）
异物（foreign material）（Figure 1、Figure 2、Figure 3、Figure 4）是指吸入的受试物或推定的受试物。“色素沉着（pigmentation）”一词专用于肺内发现的内源性色素（含铁血黄素、脂褐素），不应用于外源性物质。如果该物质具有预期的形态学外观、仅见于受试动物，且其数量随暴露水平升高而增加，则可推定其为受试物。“异物（foreign body）”一词专用于吸入的植物性物质碎片（饲料或垫料）、毛发碎片、灌胃事故所致的玉米油，或其他并非仅见于受试动物、或严重程度不随暴露水平升高而增加的物质。对吸入受试物的反应从相对惰性物质所致的组织细胞浸润，到更为严重的炎症反应不等，后者可为急性（在短期研究中）、慢性活动性、慢性或肉芽肿性，取决于该外源物质的理化性质。其他病变可与炎症反应相关，如肺泡蛋白沉积症、坏死、纤维化，或气道和/或肺泡的上皮增生。
诊断建议
肺——异物（吸入的受试物或推定的受试物）只要存在即应作出诊断并分级。具体部位（如肺泡、支气管或细支气管）应作为部位修饰词在诊断中标明。如果异物存在于一个以上部位，可省略部位修饰词，并在病理学描述中描述这些部位。相关病变（如组织细胞浸润、炎症、坏死、纤维化、上皮增生）应单独作出诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Foreign material ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) refers to inhaled test material or presumed test material. The term "pigmentation" is reserved for endogenous pigments (hemosiderin, lipofuscin) found in the lung and should not be used for exogenous material. If the material has the expected morphologic appearance, is found only in treated animals, and increases in amount with increasing exposure level, it may be assumed to be the test agent. The term "foreign body" is reserved for inhaled bits of plant material (feed or bedding), hair fragments, corn oil from gavage accidents, or other substances that are not found only in the treated animals or do not increase in severity with increasing exposure level. The response to inhaled test material varies from histiocyte infiltration with relatively inert material to a more severe inflammatory reaction that may be acute (in short-term studies), chronic active, chronic, or granulomatous, depending on the physicochemical properties of the foreign material. Other lesions may be associated with an inflammatory response, such as alveolar proteinosis, necrosis, fibrosis, or epithelial hyperplasia of the airways and/or alveoli.
Recommendation
Lung - Foreign material (inhaled test material or presumed test material) should be diagnosed and graded whenever present. The specific location (e.g., alveolus, bronchus, or bronchiole) should be indicated in the diagnosis as a site modifier. If the foreign material is present in more than one location, the site modifier may be omitted and the locations described in the pathology narrative. Associated lesions (e.g., histiocytic infiltration, inflammation, necrosis, fibrosis, epithelial hyperplasia) should be diagnosed and graded separately.
支气管扩张Bronchiectasis 肺其他
描述（中文）
支气管扩张（bronchiectasis）（Figure 1），即气道的永久性扩张，在NTP研究中非常罕见。受累气道扩张，且常伴有炎症。可能存在黏膜损伤，包括黏膜下腺体，并可能存在上皮的再生、增生或化生。随着病程慢性化，受累气道可能发生纤维化。支气管扩张可能需要与肺气肿相鉴别。支气管扩张是气道的病变，而肺气肿是由肺泡间隔壁破坏所致的肺泡实质内气腔扩大（见 Lung - Emphysema）。支气管扩张通常继发于支气管炎，例如由肺部感染、吸入所致者，或较少见地由受试物相关效应所致。在大鼠中，它常由感染所致。
诊断建议
支气管扩张只要存在即应诊断，并给出严重程度分级。诊断中应包含部位修饰词，以指明受累的气道。如果支气管和细支气管均受累，则可省略部位修饰词，并在病理学描述中描述病变位置。应在病理学描述中注明气道扩张是否与处理相关，或是否继发于感染性疾病。相关链接：Lung - Emphysema
参考切片图（1 张）
查看英文原文
Comment
Bronchiectasis ( Figure 1 ), permanent dilation of the airways, is very uncommon in NTP studies. The affected airways are dilated and often are inflamed. There may be damage to the mucosa, including the submucosal glands, and there may be regeneration, hyperplasia, or metaplasia of the epithelium. With chronicity, there may be fibrosis of the affected airways. Bronchiectasis may need to be differentiated from emphysema. While bronchiectasis is a lesion of the airways, emphysema is an enlarged airspace in the alveolar parenchyma caused by breakdown of the septal walls (see Lung - Emphysema ). Bronchiectasis is usually secondary to bronchitis, such as that caused by pulmonary infection, aspiration, or, less commonly, test-article-associated effects. In rats, it has often been caused by infection with).
Recommendation
Bronchiectasis should be diagnosed whenever present and given a severity grade. A site modifier should be included in the diagnosis to indicate which airways are affected. If bronchi and bronchioles are both affected, the site modifier may be omitted and the location of the lesion described in the pathology narrative. It should be noted in the pathology narrative whether or not the airway dilation is treatment related, or secondary to an infectious disease. Related Links: Lung - Emphysema
杯状细胞化生Metaplasia Goblet Cell 肺化生
描述（中文）
关于该病变的恰当术语（化生与增生）一直存在诸多争议，但由于杯状细胞（goblet cell）通常不存在于较小气道的上皮中，且在上气道中通常不可见，因此在NTP研究中应将其诊断为杯状细胞化生（goblet cell metaplasia）。大鼠和小鼠肺内杯状（黏液）细胞数量极少。在正常条件下，主支气管（mainstem bronchi）、一级支气管（primary bronchi）和叶支气管（lobar bronchi）（约至第六级气道）上皮细胞中不足1-2%为杯状细胞。在段支气管（segmental bronchi）（第7-11级）或终末细支气管（terminal bronchioles）中尚未发现杯状细胞。杯状细胞化生的特征为支气管或细支气管衬覆上皮中出现杯状细胞（数量超过正常范围；见上文）（Figure 1、Figure 2、Figure 3）。在大鼠和小鼠中，杯状细胞化生可与感染性病原体或吸入性刺激物暴露相关。该病变常与炎症同时出现，较少与纤维化同时出现，但也可见于无上述病变的情况下。黏液可用Alcian blue法染色，有助于识别该病变。黏液在Mason三色染色法（Mason's trichrome staining method）中也呈蓝色（Figure 2），但该染色通常不用于识别杯状细胞，首选Alcian blue。
诊断建议
该病变的首选术语为肺-化生，杯状细胞（Lung - Metaplasia, Goblet cell）。该病变存在时应记录并分级。化生的部位（即支气管或细支气管）应在诊断中作为部位修饰词标明。若病变存在于多个部位，可省略部位修饰词，并在病理学描述中描述各部位。相关病变，如炎症和细支气管上皮增生，应分别诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
There has been much debate regarding the proper term for this lesion (metaplasia vs. hyperplasia), but since goblet cells are not normally present in the epithelium of the smaller airways and are not normally visible in the upper airways, it should be diagnosed as goblet cell metaplasia in NTP studies. Rats and mice have very low numbers of goblet (mucous) cells in their lungs. Under normal conditions, <1-2% of the epithelial cells of the mainstem bronchi, primary bronchi, and lobar bronchi (up to approximately the sixth-generation airway) are goblet cells. No goblet cells have been identified in the segmental bronchi (generations 7-11) or in the terminal bronchioles. Goblet cell metaplasia is characterized by the presence of goblet cells (above the normal number; see above) in the epithelium lining the bronchi or bronchioles ( Figure 1 , Figure 2 , and Figure 3 ). Goblet cell metaplasia may occur in association with infectious agents or exposure to inhaled irritants in both rats and mice. It is frequently seen concurrently with inflammation and, less frequently, fibrosis, though it may be seen in the absence of these lesions. Mucus can be stained with the Alcian blue method, which can facilitate the identification of this lesion. Mucus also stains blue with the Mason''s trichrome staining method ( Figure 2 ), but this stain is not typically used to identify goblet cells, and Alcian blue is preferred.
Recommendation
The preferred terminology for this lesion is Lung - Metaplasia, Goblet cell. This lesion should be recorded and graded when present. The location of the metaplasia (i.e., bronchus or bronchiole) should be indicated in the diagnosis as a site modifier. If the lesion is present in more than one location, the site modifier may be omitted and the locations described in the pathology narrative. Associated lesions, such as inflammation and bronchiolar epithelial hyperplasia, should be diagnosed and graded separately.
淀粉样物质Amyloid 肺其他
描述（中文）
淀粉样物质（Amyloid）（Figure 1、Figure 2、Figure 3、Figure 4）是指不溶性、细胞外和/或细胞内的蛋白质，在组织学上表现为无定形、嗜酸性、无细胞成分的物质。刚果红（Congo red）染色呈阳性，在偏振光下具有特征性的苹果绿双折射。淀粉样物质的沉积可为局灶性（focal）、多灶性（multifocal）或弥漫性（diffuse）。累及血管壁并不少见，但也可见于支气管周围区域。严重病例中，肺实质可被破坏。约90%的沉积物由错误折叠蛋白聚集形成的淀粉样纤维构成，10%的沉积物由糖胺聚糖、载脂蛋白E和血清淀粉样P组成。淀粉样变性在某些品系中作为背景性改变被发现，如CD-1小鼠。肺淀粉样变性是老龄啮齿动物的自发性病变，可局限于肺，也可为累及脾、肾、肝及其他器官的全身性淀粉样变性的组成部分。它也可能与慢性炎症相关。由于肺内淀粉样物质沉积与外源性物质给药之间的关联尚未见报道，淀粉样物质沉积通常被认为是背景性所见。然而，它可能是一些动物发病或死亡的原因，并可影响研究的结果。
诊断建议
由于该病变具有生物学重要性，肺-淀粉样物质（Lung - Amyloid）一旦出现即应作出诊断并赋予严重程度分级。淀粉样物质沉积的部位应在诊断中通过部位修饰词加以标明。任何继发性病变，如坏死或变性，除非严重程度确有必要，否则不应单独诊断，但应在病理学叙述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Amyloid ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) refers to insoluble, extracellular and/or intracellular proteins that appear as amorphous, eosinophilic, acellular material histologically. It stains positively with Congo red stain and has a characteristic apple green birefringence under polarized light. Deposition of amyloid can be focal, multifocal, or diffuse. Involvement of vascular walls is not uncommon, but it may also be seen in peribronchial areas. In severe cases, the pulmonary parenchyma may be effaced. Approximately 90% of the deposits consist of amyloid fibrils formed by the aggregation of misfolded proteins, and 10% of the deposits consist of glycosaminoglycans, apolipoprotein E, and serum amyloid P. Amyloidosis is found as a background change in some strains, such as CD-1 mice. Pulmonary amyloidosis is a spontaneous lesion in aging rodents and may be localized to the lung, or it may be a component of systemic amyloidosis involving spleen, kidney, liver, and other organs. It may also be associated with chronic inflammation. Since an association between amyloid deposition in the lung and xenobiotic administration has not been reported, amyloid deposition is generally considered a background finding. It may, however, be the cause of morbidity or mortality in some animals and can affect the outcome of a study.
Recommendation
Because this lesion is biologically important, Lung - Amyloid should be diagnosed and assigned a severity grade whenever present. The location of the amyloid deposits should be indicated in the diagnosis by using a site modifier. Any secondary lesions, such as necrosis or degeneration, should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative.
溃疡形成Ulceration 肺溃疡
描述（中文）
支气管或细支气管上皮的溃疡（ulceration）表现为被覆上皮的缺失（Figure 1、Figure 2），暴露出下方的基底膜。必须区分溃疡与坏死，以及溃疡与再生。如果坏死细胞仍附着于基底膜，则应视为坏死而非溃疡。如果坏死细胞已被存活的上皮细胞所取代，这些细胞伸展并覆盖受累区域，则应视为再生。溃疡通常由上皮细胞损伤引起，损伤原因可以是直接毒性，也可以与炎症相关，在炎症中上皮细胞损伤可能由活性氧或其他介质所致。尽管急性溃疡可能不伴炎症，但溃疡通常伴有混合性炎症反应。在呼吸道上皮坏死和溃疡的部位，常可见纤维素性渗出物。在某些病例中，成纤维细胞可浸润渗出物，导致纤维化，严重病例中纤维化可跨越管腔（管腔内纤维化，intraluminal fibrosis）并阻塞气流。仙台病毒感染（Sendai virus infection）可引起支气管和细支气管上皮的溃疡。
诊断建议
肺 – 溃疡：只要存在即应诊断并赋予严重程度分级。诊断中应包含部位修饰词（例如支气管、细支气管、肺泡），以指示病变的位置。如果坏死细胞仍附着于气道表面，则应诊断坏死；如果相邻细胞已变平并迁移覆盖溃疡面，则应诊断再生（参见 Lung - Epithelium - Necrosis 和 Lung - Regeneration）。相关病变，如炎症，除非严重程度确有必要，否则不应单独诊断，但应在病理学叙述中描述。相关链接：Lung - Epithelium - Necrosis Lung - Regeneration
参考切片图（2 张）
查看英文原文
Comment
Ulceration of the bronchial or bronchiolar epithelium represents loss of the lining epithelium ( Figure 1 and Figure 2 ) exposing the underlying basement membrane. A distinction must be made between ulceration and necrosis and between ulceration and regeneration. If necrotic cells remain attached to the basement membrane, this would be considered necrosis rather than an ulcer. If the necrotic cells have been replaced by viable epithelial cells that have stretched across and cover the affected region, this would be considered regeneration. Ulceration is typically caused by damage to the epithelial cells either by direct toxicity or in association with inflammation in which epithelial cell damage may be caused by reactive oxygen species or other mediators. Though there may be no inflammation with acute ulcers, ulcers are typically associated with a mixed inflammatory response. A fibrinous exudate can often be seen at the site of respiratory epithelial necrosis and ulceration. In some cases, fibroblasts can infiltrate the exudate, resulting in fibrosis, which in severe cases can cross the lumen (intraluminal fibrosis) and obstruct air flow. Sendai virus infection can cause ulceration of bronchial and bronchiolar epithelium.
Recommendation
Lung – Ulceration should be diagnosed and assigned a severity grade whenever present. A site modifier (e.g., bronchus, bronchiole, alveolus) should be included in the diagnosis to indicate the location of the lesion. If the necrotic cells are still attached to the airway surface, then necrosis should be diagnosed; if the adjacent cells have flattened and migrated across the ulcer, then regeneration should be diagnosed (see Lung - Epithelium - Necrosis and Lung - Regeneration ). Associated lesions, such as inflammation, should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative. Related Links: Lung - Epithelium - Necrosis Lung - Regeneration
炎症Inflammation 肺炎症
描述（中文）
肺部炎症是吸入研究中最为常见的病变之一。在NTP研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在肺－细胞浸润，组织细胞（Lung - Infiltration Cellular, Histiocyte）及Figure 2）中，主要浸润细胞为中性粒细胞（neutrophil），但也可能存在较少的巨噬细胞（macrophage）和淋巴细胞（lymphocyte）。还可能有水肿（edema）或充血（hyperemia）的证据。中性粒细胞也是Figure 4、Figure 5、Figure 6）中的主要浸润细胞类型，但它们聚集在一起，其中许多已发生退变（化脓性渗出物，化脓性 exudate）。渗出物中还可能存在来自 resident 细胞群和浸润白细胞的细胞碎片、含纤维蛋白（fibrin）的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞（plasma cell），以及可能的感染因子。肉眼观察时，这些病变以脓液存在为特征。渗出物周围组织可能含有成纤维细胞（fibroblast）、纤维结缔组织（fibrous connective tissue）和混合性炎症细胞，具体取决于病变的慢性程度。淋巴细胞在Figure 8、Figure 9、Figure 10、Figure 11、Figure 12）中占优势。淋巴细胞也在Figure 14、Figure 15、Figure 16、Figure 17）中占优势，但也存在大量中性粒细胞。两种病变均可能含有巨噬细胞。Figure 19、Figure 20）是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的、活化的巨噬细胞、上皮样巨噬细胞（epithelioid macrophage）或多核巨细胞（multinucleated giant cell）。在所有形式的炎症中，还可能存在水肿、出血（hemorrhage）、纤维蛋白、蛋白沉积症（proteinosis）、变性（degeneration）或坏死（necrosis）。炎症与细胞浸润的鉴别在于是否存在其他改变，如水肿、出血、变性、坏死或其他组织损伤证据。受试物可能刺激上皮细胞和 resident 巨噬细胞分泌细胞因子（cytokine），从而诱导炎症反应。或者，受试物可能导致组织损伤，继而引起炎症。肺内多个区域可能发生炎症，包括气道（支气管和细支气管）、肺泡或肺泡间隔（间质）、终末细支气管/肺泡管区域（腺泡区域）、血管周围区域和胸膜（pleura）。偶尔，肺内局灶性（focal）、极轻微（minimal）的炎症在小鼠和大鼠中作为背景病变可见（Figure 9、Figure 10），尤其是在胸膜下区域。肺泡组织细胞的小聚集也可作为背景病变见到（见），必须与炎症相鉴别。炎症也可由多种感染因子引起，但在当前饲养管理条件下这些情况罕见。经血流影响肺间质的全身性细菌感染通常产生化脓性肺泡炎（化脓性 alveolitis），而病毒感染倾向于诱导化脓性或单核细胞性血管周围炎症。炎症也可与肺肿瘤相关。
诊断建议
只要存在，肺－炎症（Lung - Inflammation）就应诊断并赋予严重程度分级。诊断中应包含部位修饰词（如perivascular、interstitial、bronchial、bronchiolar、pleural或subpleural），以指示病变的位置。此外，诊断中应包含炎症类型（如急性（acute）、慢性（chronic））作为修饰词。如果炎症累及一个以上部位，可省略部位修饰词，并在病理学叙述中明确受累部位。当炎症细胞伴有其他提示炎症的改变时，应使用“炎症”一词，这些改变如血管改变（可能导致出血或水肿）、细胞坏死或变性，或正常结构破坏。被视为炎症过程一部分的病变，如水肿和出血，除非严重程度需要，不必单独诊断，但应在叙述中描述。细胞坏死或变性可能是原发性的，引发炎症反应，也可能是继发于炎症。因此，确定哪个病变（坏死或炎症）是原发性的、哪个是继发性的可能非常困难。病理学家应运用其判断来决定是单独诊断这些病变，还是将这些相关病变合并为单一诊断。如果合并为单一诊断，则应在叙述中全面描述病变的所有组成部分。炎症细胞的小局灶性（focal）聚集，无其他炎症证据（如水肿、出血、细胞肿胀、变性或坏死、肺泡间隔增厚、纤维蛋白沉积），应诊断为“细胞浸润”（infiltration cellular）而非炎症。当作为肿瘤的继发发现存在时，炎症不必单独诊断，但应在病理学叙述中描述。相关链接：肺－细胞浸润，组织细胞（Lung - Infiltration Cellular, Histiocyte）
参考切片图（2 张）
查看英文原文
Comment
Inflammation of the lungs is one of the most common lesions seen in inhalation studies. In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic active, and granulomatous. In Lung - Infiltration Cellular, Histiocyte and Figure 2 ), the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in, Figure 4 , Figure 5 , and Figure 6 ), but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris, from both the resident cell populations and infiltrating leukocytes, and proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present within the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may contain fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in, Figure 8 , Figure 9 , Figure 10 , Figure 11 , and Figure 12 ). Lymphocytes also predominate in, Figure 14 , Figure 15 , Figure 16 , and Figure 17 ), but there are also a significant number of neutrophils. Both lesions may contain macrophages., Figure 19 , and Figure 20 ) is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. In all forms of inflammation, there may also be edema, hemorrhage, fibrin, proteinosis, degeneration, or necrosis. Inflammation is differentiated from cellular infiltrates by the presence of other changes, such as edema, hemorrhage, degeneration, necrosis, or other evidence of tissue damage. A test agent may stimulate epithelial cells and resident macrophages to secrete cytokines, thus inducing an inflammatory response. Alternatively, a test agent may cause tissue damage, which secondarily results in inflammation. Several compartments within the lung may be inflamed, including the airways (bronchi and bronchioles), the alveoli or alveolar septa (interstitium), the terminal bronchiole/alveolar duct region (acinar region), perivascular areas, and the pleura. Occasionally, focal, minimal inflammation in the lung is seen as a background lesion in mice and rats ( Figure 9 and Figure 10 ), particularly in the subpleural region. Small aggregates of alveolar histiocytes can also be seen (see) as a background lesion and must be differentiated from inflammation. Inflammation can also be caused by a number of infectious agents, but these are rare under current husbandry practices. Systemic bacterial infections affecting the pulmonary interstitium via the bloodstream often produce a suppurative alveolitis, whereas viral infections tend to induce suppurative or mononuclear perivascular inflammation. Inflammation can also be associated with pulmonary neoplasms.
Recommendation
Whenever present, Lung - Inflammation should be diagnosed and assigned a severity grade. A site modifier (e.g., perivascular, interstitial, bronchial, bronchiolar, pleural, or subpleural) should be included in the diagnosis to indicate the location of the lesion. Also, the type of inflammation (e.g., acute, chronic) should be included in the diagnosis as a modifier. If the inflammation affects more than one site, the site modifier may be omitted and the affected locations identified in the pathology narrative. The term "inflammation" should be used when the inflammatory cells are accompanied by other changes indicative of inflammation, such as vascular changes (which may result in hemorrhage or edema), necrosis or degeneration of cells, or disruption of the normal architecture. Lesions that are considered part of the inflammatory process, such as edema and hemorrhage, need not be diagnosed separately unless warranted by severity but should be described in the narrative. Necrosis or degeneration of cells may be primary, inciting an inflammatory response, or it may be secondary to the inflammation. Therefore, it can be very difficult to determine which lesion (necrosis or inflammation) is primary and which is secondary. The pathologist should use his or her judgment in determining whether to diagnose these lesions separately or to combine these related lesions into a single diagnosis. If they are combined into a single diagnosis, all components of the lesions should be thoroughly described in the narrative. A small, focal accumulation of inflammatory cells with no other evidence of inflammation (e.g., edema, hemorrhage, cell swelling, degeneration, or necrosis, alveolar septal thickening, fibrin deposition), should be diagnosed as "infiltration cellular" rather than inflammation. When present as a secondary finding to a neoplasm, the inflammation need not be diagnosed separately but should be described in the pathology narrative. Related Links: Lung - Infiltration Cellular, Histiocyte
矿物质Mineral 肺其他
描述（中文）
矿物质（钙化）表现为颗粒状、团块状、层状、角状或线状嗜碱性物质的沉积，可位于细胞内或细胞外（Figure 1、Figure 2、Figure 3、Figure 4）。转移性钙化由与甲状旁腺激素升高、维生素 D 相关疾病或肾衰竭导致继发性甲状旁腺功能亢进相关的高钙血症引起。营养不良性矿物质沉积发生于坏死区域（无论钙代谢是否紊乱）；它见于坏死组织内，通常不认为是间质性的。老年大鼠肺泡间质（肺泡间隔）中的转移性矿物质沉积常继发于慢性进行性肾病所致的肾衰竭。
诊断建议
肺 - 当矿物质沉积被认为是原发性的而非继发于坏死时（即转移性矿物质沉积），应当作出诊断。诊断中应包含部位修饰词（例如 interstitium、blood vessel）以指明矿物质沉积的位置。首选术语为“mineral”而非“mineralization”。作出诊断时，应赋予严重程度分级。相关病变，如炎症，应单独诊断。继发于坏死的矿物质沉积（营养不良性矿物质沉积）仅在病理学家认为其严重程度足以需要单独诊断时才应诊断。所诊断的任何与处理相关的矿物质沉积，其发病机制应在病理学叙述中讨论。
参考切片图（2 张）
查看英文原文
Comment
Mineral (calcification) is seen as deposits of granular, clumped, laminated, angular, or linear basophilic material that can be intracellular or extracellular ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Metastatic calcification results from hypercalcemia related to increased parathyroid hormone, vitamin D-related disorders, or renal failure resulting in secondary hyperparathyroidism. Dystrophic mineral occurs in areas of necrosis (regardless of derangements of calcium metabolism); it is found within the necrotic tissue and is not generally considered to be interstitial. Metastatic mineral in the alveolar interstitium (alveolar septa) in aged rats is often secondary to renal failure caused by chronic progressive nephropathy.
Recommendation
Lung - Mineral should be diagnosed when it is considered to be primary and not secondary to necrosis (i.e., metastatic mineralization). A site modifier (e.g., interstitium, blood vessel) should be included in the diagnosis to indicate the location of the mineral. The term "mineral" is preferred over "mineralization." When diagnosed, it should be assigned a severity grade. Associated lesions, such as inflammation, should be diagnosed separately. Mineral secondary to necrosis (dystrophic mineralization) should be diagnosed only when, in the pathologist’s opinion, it is severe enough to warrant a separate diagnosis. The pathogenesis of any treatment-related mineral that is diagnosed should be discussed in the pathology narrative.
纤维化Fibrosis 肺纤维化
描述（中文）
纤维化在显微镜下表现为纤维组织数量增加，取代或扩张正常结构。纤维化可发生于肺内任何部位，包括肺泡间隔或间质（Figure 1、Figure 2、Figure 3）、气道（Figure 4、Figure 5、Figure 6）以及胸膜（Figure 7、Figure 8），具体取决于特定受试物产生损伤的部位。纤维化通常由成熟、致密的胶原组成，但也可能存在疏松未成熟胶原的区域。在气道中，纤维化常表现为纤维组织呈局灶性（focal）突起突入气道腔，可部分阻塞管腔（Figure 4），但也可能表现为气道壁的circumferential增厚（Figure 5、Figure 6）。由于纤维化通常是组织损伤的一种反应（当无法修复时，用以取代受损组织），因此常伴有炎症。纤维化可通过胶原特殊染色予以确认。采用Mason三色染色技术时，成熟胶原染成蓝色（Figure 2）。
诊断建议
肺 - 纤维化只要存在即应诊断并分级。纤维化的部位（肺泡、支气管/细支气管、胸膜）应作为部位修饰词纳入诊断。累及肺泡间隔（肺泡壁）的纤维化首选术语为肺，间质 - 纤维化。若纤维化与炎症同时发生，应分别诊断，但若纤维化程度极轻微或为sporadic（仅发生于少数动物），则可在病理学叙述中描述，而不单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Fibrosis appears microscopically as an increase in the amount of fibrous tissue that either replaces or expands normal structures. Fibrosis can occur anywhere in the lung, including alveolar septa or interstitium ( Figure 1 , Figure 2 , and Figure 3 ), airways ( Figure 4 , Figure 5 , and Figure 6 ), and pleura ( Figure 7 and Figure 8 ), depending on the site at which a particular agent produces damage. Fibrosis generally consists of mature, dense collagen, although areas of loose immature collagen may also be present. In airways, the fibrosis commonly occurs as focal projections of fibrous tissue into the airway lumen that may partially occlude the lumen (Figure 4) but may also occur as circumferential thickening of the airway wall ( Figure 5 and Figure 6 ). Because fibrosis is often a response to tissue damage (it is meant to replace damaged tissue when repair is not possible), it is often associated with inflammation. Fibrosis can be confirmed with special stains for collagen. With the Mason''s trichrome staining technique, mature collagen stains blue ( Figure 2 ).
Recommendation
Lung - Fibrosis should be diagnosed and graded whenever present. The location of the fibrosis (alveolus, bronchus/bronchiole, pleura) should be included in the diagnosis as a site modifier. The preferred terminology for fibrosis involving the interalveolar septa (alveolar walls) is Lung, Interstitium - Fibrosis. If fibrosis occurs in conjunction with inflammation, it should be diagnosed separately, though if the degree of fibrosis is very minimal or sporadic (occurring in only a few animals), it may be described in the pathology narrative in lieu of a separate diagnosis.
组织细胞性细胞浸润Infiltration Cellular Histiocyte 肺浸润
描述（中文）
吸入毒物后的反应常包括肺泡内肺泡巨噬细胞的积聚。肺泡巨噬细胞的积聚也是坏死反应的一部分，并可能与肺肿瘤或肺泡/细支气管增生相关。可自发观察到局灶性（focal）组织细胞浸润，最常见于老年动物的胸膜下区域。肺泡组织细胞浸润由肺泡内巨噬细胞的积聚构成。巨噬细胞可表现为活化状态（增大，胞质呈泡沫状）或静息状态。尽管该病变通常仅限于肺泡巨噬细胞的积聚（Figure 1、Figure 3、Figure 4、Figure 5、Figure 6），但可能存在相关所见，如少量其他炎性细胞（淋巴细胞或中性粒细胞）、极轻微（minimal）水肿、出血或肺泡间隔增厚（Figure 2）。此外，巨噬细胞可含有色素，可能为含铁血黄素，或与受试物一致的外来物质（Figure 5、Figure 6）。必须将组织细胞浸润与炎症相鉴别，后者有时可能较为困难。一般而言，组织细胞浸润的特征是肺泡组织细胞数量增多，而无（或仅有极轻微）其他炎症证据（例如，存在其他类型的炎性细胞、水肿、出血、肺泡间隔增厚）。
诊断建议
肺 - 细胞浸润，组织细胞在大多数情况下应被诊断并给予严重程度分级。如果组织细胞含有受试物，则应单独诊断为外来物质并分级（见肺 - 外来物质）。如果肺泡巨噬细胞被认为是炎症反应的组成部分，则应诊断炎症而非组织细胞浸润。与肿瘤明确相关的肺泡组织细胞积聚不应记录，而应在叙述中描述为继发于肿瘤。肺泡巨噬细胞的小型胸膜下积聚在大鼠中常作为背景病变见到。如果组织细胞浸润是与受试物给药相关的弥漫性（diffuse）改变，而局灶性（focal）、胸膜下（背景）聚集可能使发病率统计数据产生偏倚，则慢性研究中非受试物相关的胸膜下病灶要么不应记录（即视为在正常范围内），要么可使用修饰词单独记录（例如，细胞浸润，组织细胞，局灶性或细胞浸润，组织细胞，弥漫性）。在某些情况下，最好对两种病变均作出诊断。例如，如果从低剂量组的肺泡组织细胞浸润（无炎症改变）到高剂量组的伴有炎症区域的肺泡组织细胞浸润存在连续过程，则可能需要对两种病变均作出诊断，以充分捕捉受试物的效应。病理学家在记录这些病变时需要运用其判断力，并且必须注意在整个研究过程中保持一致性。相关链接：肺 - 外来物质
参考切片图（2 张）
查看英文原文
Comment
Responses to inhaled toxicants often include the accumulation of alveolar macrophages within alveoli. Accumulation of alveolar macrophages is also part of the response to necrosis and may be associated with pulmonary neoplasms or alveolar/bronchiolar hyperplasia. Focal histiocytic infiltrates may be observed spontaneously, most often in subpleural regions of older animals. Alveolar histiocytic infiltrates consist of intra-alveolar accumulations of macrophages. The macrophages can appear activated (enlarged with foamy cytoplasm) or quiescent. Though the lesion is often limited to the accumulation of alveolar macrophages ( Figure 1 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ), associated findings may be present, such as a few other inflammatory cells (lymphocytes or neutrophils), minimal edema, hemorrhage, or thickening of alveolar septa ( Figure 2 ). Also, the macrophages may contain pigment, which may represent hemosiderin, or foreign material consistent with the test article ( Figure 5 and Figure 6 ). Histiocytic infiltration must be differentiated from inflammation, which can sometimes be difficult. In general, histiocytic infiltration is characterized by increased numbers of alveolar histiocytes with no (or minimal) other evidence of inflammation (e.g., the presence of other types of inflammatory cells, edema, hemorrhage, alveolar septal thickening).
Recommendation
Lung - Infiltration cellular, Histiocyte should be diagnosed and given a severity grade in most cases. If the histiocytes contain the test agent, it should be diagnosed and graded separately foreign material (see Lung - Foreign Material ). If the alveolar macrophages are considered to be a component of an inflammatory response, then inflammation should be diagnosed in lieu of histiocytic infiltration. Accumulations of alveolar histiocytes that are clearly associated with a neoplasm should not be recorded but should be described in the narrative as being secondary to the neoplasm. Small, subpleural accumulations of alveolar macrophages are frequently seen as background lesions in rats. If histiocytic infiltration is a diffuse change related to test article administration, and focal, subpleural (background) aggregates might skew incidence statistics, then either the non-test-article-related subpleural foci in chronic studies should not be recorded (i.e., considered to be within normal limits), or they may be recorded separately using modifier (e.g., Infiltration cellular, Histiocyte, Focal or Infiltration cellular, Histiocyte, Diffuse). In some cases, it may be best to diagnose both lesions. For example, if there is a continuum from alveolar histiocyte infiltration (with no inflammatory changes) in the low-dose groups to alveolar histiocyte infiltration with areas of inflammation in the high-dose groups, then it may be necessary to diagnose both lesions to fully capture the effects of the test article. The pathologist will need to use his or her judgment in recording these lesions and must take care to maintain consistency throughout the study. Related Links: Lung - Foreign Material
细胞异型性Atypia Cellular 肺异型性
描述（中文）
异型性可见于气道（Figure 1、Figure 2）或肺泡（Figure 3、Figure 4）。啮齿类动物肺脏的细胞异型性以以下一项或多项特征为特点：胞质嗜碱性、核深染、核极性丧失、核质比增高、核增大、核大小不一以及多形性。异型细胞常分化差，并可能为双核。它们可能具有多个和/或增大的核仁。在病理学文献中，细胞异型性、异型性增生和异型性腺瘤样增生与发育不良（dysplasia）同义使用，用以表示细胞和细胞核在大小、形状、组织结构和/或染色特性方面异常。虽然肺泡内的单个细胞可能具有异型性特征，但细胞异型性也可见于支气管、细支气管或肺泡上皮增生或鳞状化生的区域。上述某些特征也可见于再生细胞（例如细胞增大、核增大、胞质嗜碱性、核质比增高）。该病变的生物学意义尚不清楚；在没有明显再生的情况下，它可能代表一种癌前改变，尤其是当伴有增生或鳞状化生时。
诊断建议
肺 - 细胞异型性应作出诊断并赋予严重程度分级。应使用部位修饰词（例如细支气管或肺泡上皮）来指明受影响的细胞。如果受影响的细胞类型不止一种，则应在所有受累部位作出诊断。如果它发生于上皮增生区域，则应使用术语“增生，异型性”（见肺 - 上皮，肺泡 - 增生）。如果它发生于鳞状化生区域，则应使用术语“化生，鳞状，异型性”（见肺 - 化生，鳞状）。由于异型性的某些特征可见于再生细胞，必须注意不要过度诊断该病变。相关病变，如炎症，应单独诊断。相关链接：肺 - 上皮，肺泡 - 增生 肺 - 化生，鳞状
参考切片图（2 张）
查看英文原文
Comment
Atypia can be seen in the airways ( Figure 1 and Figure 2 ) or in the alveoli ( Figure 3 and Figure 4 ). Cellular atypia in rodent lungs is characterized by one or more of the following features: cytoplasmic basophilia, hyperchromatic nuclei, loss of nuclear polarity, high nuclear to cytoplasmic ratio, karyomegaly, anisokaryosis, and pleomorphism. The atypical cells are often poorly differentiated and may be binucleated. They may have multiple and/or enlarged nucleoli. In the pathology literature, cellular atypia, atypical hyperplasia, and atypical adenomatous hyperplasia have been used synonymously with dysplasia to signify cells and nuclei with abnormal size, shape, organization, and/or tinctoral properties. While individual cells in the alveoli may have features of atypia, cellular atypia can also be seen in areas of bronchial, bronchiolar, or alveolar epithelial hyperplasia or squamous metaplasia. Some of the features listed above may also be seen in regenerating cells (e.g., cytomegaly, karyomegaly, cytoplasmic basophilia, increased nuclear to cytoplasmic ratio). The biological significance of this lesion is not known; in the absence of obvious regeneration, it may represent a preneoplastic change, particularly when associated with hyperplasia or squamous metaplasia.
Recommendation
Lung - Atypia, Cellular should be diagnosed and assigned a severity grade. A site modifier (e.g., bronchiolar or alveolar epithelium) should be used to indicate which cells are affected. If more than one cell type is affected, the lesion should be diagnosed in all affected sites. If it occurs in areas of epithelial hyperplasia, the term "hyperplasia, atypical" should be used (see Lung - Epithelium, Alveolus - Hyperplasia ). If it occurs in an area of squamous metaplasia, the term "metaplasia, squamous, atypical" should be used (see Lung - Metaplasia, Squamous ). Since some features of atypia can be seen in regenerating cells, care must be taken not to overdiagnose this lesion. Associated lesions, such as inflammation, should be diagnosed separately. Related Links: Lung - Epithelium, Alveolus - Hyperplasia Lung - Metaplasia, Squamous
细胞质空泡化Vacuolization Cytoplasmic 肺其他
描述（中文）
肺内的细胞质空泡化（cytoplasmic vacuolization）最常见于小鼠的气道上皮（Figure 1、Figure 2、Figure 3、Figure 4），但也可见于其他物种及其他类型的上皮细胞。细胞质空泡化通常被认为是一种可逆的退行性改变。空泡化可能代表扩张并断裂的内质网。线粒体损伤可能导致β-氧化不足以及甘油三酯在线粒体或细胞质内蓄积。参与蛋白质合成的细胞成分受损可能导致载脂蛋白水平降低，进而导致脂质转运减少和脂质在细胞质内蓄积。空泡可能较大并使细胞质扩张，但空泡常常非常小（即仅在电子显微镜下可见）且数量众多，使细胞质呈苍白或蓝灰色外观。由于细胞质空泡化被认为是一种退行性改变，因此常伴有与组织损伤相关的其他改变，如炎症和坏死。
诊断建议
肺 - 空泡化，细胞质（Lung - Vacuolization, Cytoplasmic）应予以诊断并分级。应在诊断中指明部位（如支气管、细支气管、肺泡）。如果细胞质空泡化是更严重的退行性或坏死性改变的特征，则应将退行性变或坏死作为记录的病变（见肺 - 上皮 - 坏死和肺 - 再生），并应在描述中叙述空泡化。相关病变，如炎症，应单独诊断并分级。相关链接：肺 - 上皮 - 坏死 肺 - 再生
参考切片图（2 张）
查看英文原文
Comment
Cytoplasmic vacuolization in the lungs is most commonly seen in the airway epithelium of mice ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) but may also be seen in other species and in other types of epithelial cells. Cytoplasmic vacuolization is generally thought to represent a reversible degenerative change. The vacuolization may represent distended and pinched off endoplasmic reticulum. Mitochondrial damage may lead to insufficient beta-oxidation and accumulation of triglycerides within the mitochondria or cytoplasm. Damage to cellular components involved in protein synthesis may lead to decreased levels of apolipoproteins, which lead to decreased lipid transport and the accumulation of lipid in the cytoplasm. The vacuoles may be large and distend the cytoplasm, but frequently the vacuoles are very small (i.e., visible only with electron microscopy) and numerous and give the cytoplasm a pale or bluish gray appearance. Since cytoplasmic vacuolization is thought to be a degenerative change, it is often accompanied by other changes associated with tissue damage, such as inflammation and necrosis.
Recommendation
Lung - Vacuolization, Cytoplasmic should be diagnosed and graded. The site (e.g., bronchus, bronchiole, alveolus) should be specified as part of the diagnosis. If the cytoplasmic vacuolization is a feature of a more severe degenerative or necrotic change, then degeneration or necrosis should be the recorded lesion (see Lung - Epithelium - Necrosis and Lung - Regeneration ) and the vacuolization should be described in the narrative. Associated lesions, such as inflammation, should be diagnosed and graded separately. Related Links: Lung - Epithelium - Necrosis Lung - Regeneration
结晶Crystals 肺其他
描述（中文）
在NTP研究中，肺内晶体最常见于采用颗粒物吸入研究的小鼠（Figure 1、Figure 2、Figure 3），或与肿瘤相关。这些晶体常与引起显著肺泡蛋白沉积症的药物同时出现。晶体呈嗜酸性（eosinophilic）且为针状或纺锤形。部分较大的晶体可能呈 elongated rectangles 或“砖块状”。它们通常存在于肺泡腔内，并伴有组织细胞浸润，或在更严重的病例中伴有肉芽肿性炎症。晶体常被大的巨噬细胞包围，这些巨噬细胞可能为多核，部分较小的晶体可能位于巨噬细胞和多核巨细胞的细胞质内。部分巨噬细胞可能含有大量小晶体（Figure 3）。通常，间质或肺泡腔内存在数量不等的其他炎症细胞（淋巴细胞、浆细胞、中性粒细胞）。血红蛋白晶体偶尔见于出血区域（Figure 4），常伴有炎症。此类晶体最常见于大鼠，因为大鼠血红蛋白比其他物种的血红蛋白更易结晶。在其他物种中，只有结构异常的血红蛋白才会在体内结晶。血红蛋白晶体通常呈矩形，与嗜酸性结晶性肺炎的嗜酸性晶体不同，其形成于细胞外空间，尽管较小的血红蛋白晶体可能被肺泡巨噬细胞吞噬。其颜色通常类似红细胞，且通常与外渗的红细胞在空间上相关。嗜酸性结晶性肺炎是一种发生于小鼠的特发性疾病。它可以是散发性背景病变，严重程度从 轻微（mild） 和亚临床到 severe 不等，严重时可导致死亡。它可见于某些基因工程小鼠（例如 p47 phox-/- 小鼠）或由自然发生的突变培育而成的小鼠品系（例如 Ptpn6 me 裸鼠）。易感品系包括 C57BL/6 和 129Sv 小鼠。嗜酸性结晶性肺炎的发病机制尚不清楚。在易感品系中，它曾与嗜酸性炎症相关，例如由寄生虫和真菌感染引起的嗜酸性炎症，尽管与晶体相关的主要细胞类型是肺泡巨噬细胞。这些晶体对 anti-Ym1 protein 抗体（又称 T 淋巴细胞来源的嗜酸性粒细胞趋化因子）呈免疫反应性。嗜酸性结晶性肺炎在组织学上与颗粒物吸入相关的晶体（及炎症）相似，但与任何处理均无关联，并且也可见于对照小鼠。在啮齿类动物肺中已鉴定出其他类型的晶体。大鼠亚慢性暴露于氯法齐明（一种抗麻风药物）会导致红橙色晶体沉积于许多组织，包括肺。在 F344 大鼠中长期经饮食给予曲酸可产生含有晶体的肺部微肉芽肿。C57BL/6 小鼠感染新型隐球菌（Cryptococcus neoformans）后产生杆状晶体结构，这些结构可见于与酵母细胞相关或游离于宿主细胞质中。尽管这些晶体在形态上类似于小鼠嗜酸性结晶性肺炎中所见的晶体，但推测这些晶体是宿主蛋白与隐球菌荚膜多糖相互作用的产物。
诊断建议
细胞内和气道内游离的晶体只要存在，均应诊断为 Lung - Crystals 并进行分级。病理学描述中应包含对晶体的详尽描述，包括大小、形状、颜色、位置以及是细胞内还是细胞外（以及所见于何种细胞类型）。伴随的炎症应单独诊断并分级。如果晶体是与肿瘤相关的炎症性病变的一部分，则无需诊断，但应在病理学描述中予以描述。如果病理学家认为晶体是小鼠嗜酸性结晶性肺炎的一部分，也应在病理学描述中注明。
参考切片图（2 张）
查看英文原文
Comment
In NTP studies, intrapulmonary crystals are most often seen in mice in inhalation studies with particulates ( Figure 1 , Figure 2 , and Figure 3 ) or associated with neoplasms. The crystals are frequently seen with agents that cause significant alveolar proteinosis. The crystals are eosinophilic and acicular, or spindle shaped. Some larger crystals may be elongated rectangles, or "brick shaped." They are usually present in the alveolar spaces and are associated with histiocytic infiltrates or, in more severe cases, granulomatous inflammation. The crystals are often surrounded by large macrophages, which may be multinucleated, and some smaller crystals may be within the cytoplasm of the macrophages and multinucleated giant cells. Some macrophages may contain numerous small crystals ( Figure 3 ). Typically, variable numbers of other inflammatory cells (lymphocytes, plasma cells, neutrophils) are present in the interstitium or in the alveolar spaces. Hemoglobin crystals are occasionally seen in areas of hemorrhage ( Figure 4 ), often associated with inflammation. This type of crystal is most commonly seen in rats because rat hemoglobin crystallizes more readily than does hemoglobin in other species. Only structurally abnormal hemoglobin crystallizes in vivo in other species. Hemoglobin crystals are typically rectangular and, as opposed to the eosinophilic crystals of eosinophilic crystalline pneumonia, form in the extracellular space, though smaller hemoglobin crystals may be phagocytosed by alveolar macrophages. They typically resemble red blood cells in color and are usually spatially associated with extravasated erythrocytes. Eosinophilic crystalline pneumonia is an idiopathic disease that occurs in mice. It can be a sporadic background lesion, with the severity varying from mild and subclinical to severe, in which case it may cause death. It may be seen in some genetically engineered mice (e.g., p47 phox-/- mice) or mouse strains developed from naturally occurring mutations (e.g., Ptpn6 me motheaten mice). Susceptible strains include C57BL/6 and 129Sv mice. The pathogenesis of eosinophilic crystalline pneumonia is unclear. It has been associated with eosinophilic inflammation in susceptible strains, such as that caused by parasitic and fungal infections, though the main cell type associated with the crystals is the alveolar macrophage. The crystals are immunoreactive to anti-Ym1 protein antibodies (a.k.a. T-lymphocyte-derived eosinophil chemotactic factor). Eosinophilic crystalline pneumonia is histologically similar to the crystals (and inflammation) associated with inhalation of particulates but does not occur with any relation to treatment and would also be seen in control mice. Other types of crystals have been identified in rodent lungs. Subchronic exposure of rats to clofazimine, an antileprotic drug, leads to deposition of reddish orange crystals in many tissues, including lung. Chronic dietary administration of kojic acid in F344 rats produced pulmonary microgranulomas containing crystals. Cryptococcus neoformans infection in C57BL/6 mice generated rod-like crystalline structures found associated with yeast cells or free in host cell cytoplasm. Though these crystals appear morphologically similar to those seen in murine eosinophilic crystalline pneumonia, these crystals are presumed to be the product of interaction of a host protein and a capsular cryptococcal polysaccharide.
Recommendation
Crystals both intracellular and free within airspaces should be diagnosed as Lung - Crystals and graded whenever present. A thorough description of the crystals, including size, shape, color, location, and whether they are intra- or extracellular (and the cell types in which they are found), should be included in the pathology narrative. Accompanying inflammation should be diagnosed and graded separately. If they are part of an inflammatory lesion associated with a neoplasm, they need not be diagnosed but should be described in the pathology narrative. If, in the opinion of the pathologist, the crystals are part of murine eosinophilic crystalline pneumonia, this should also be noted in the pathology narrative.
肺气肿Emphysema 肺气肿
描述（中文）
肺气肿（pulmonary emphysema，Figure 1、Figure 2）是指终末细支气管远端肺泡气腔扩大，伴肺泡间隔破坏。根据时间范围不同，可能存在也可能不存在肺泡间隔活动性破坏的证据。肺泡间隔的损伤不可逆。病变可为局灶性（focal）或多灶性（multifocal），并可累及多个肺叶。肺气肿应与剖检时肺内灌注固定液过度充盈所致的变化相鉴别，后者可能难以区分；然而，肺过度充盈可导致血管周围间隙人为增大。肺气肿可由多种原因引起。多种蛋白酶（如猪胰弹性蛋白酶、木瓜蛋白酶和人中性粒细胞弹性蛋白酶）、内毒素、香烟烟雾及其他因素已被用于在啮齿类动物中构建人类肺气肿模型。炎性病变可通过阻塞气道、允许吸入但阻碍呼出（“球阀效应”）而导致肺过度充气；这必须与真性肺气肿相鉴别。据报道，仙台病毒（Sendai virus）可在新生大鼠中引起肺气肿，推测是上皮坏死和炎症的结果，不过由于现代动物饲养管理措施，该病原体感染现已罕见。
诊断建议
肺－肺气肿应作出诊断并赋予严重程度分级。相关病变，如炎症，应单独诊断。若该病变被认为是人为假象，则不应诊断肺气肿，但可录入组织备注以说明此情况。相关链接：肺－支气管扩张（Lung - Bronchiectasis）
参考切片图（2 张）
查看英文原文
Comment
Pulmonary emphysema ( Figure 1 and Figure 2 ) refers to enlargement of the alveolar airspaces distal to the terminal bronchioles with destruction of alveolar septa. Depending on the time frame, there may or may not be evidence of active destruction of the septa. The damage to the septa is irreversible. It can be focal or multifocal and may involve multiple lobes. Emphysema should be differentiated from the effects of overfilling the lungs with fixative at necropsy, which can be difficult; however, overfilling of the lungs can result in artifactually increased perivascular space. Emphysema can result from a number of causes. Various proteases (e.g., porcine pancreatic elastase, papain, and human neutrophils elastase), endotoxin, cigarette smoke, and other agents have been used in rodents to model emphysema in humans. Inflammatory lesions may produce overinflation of the lungs by obstructing airways and allowing inhalation but hindering exhalation (the "ball and valve effect"); this must be differentiated from true emphysema. Sendai virus has been reported to cause emphysema in neonatal rats, presumably as a result of epithelial necrosis and inflammation, though infection by this agent is now rare due to modern animal husbandry practices.
Recommendation
Lung - Emphysema should be diagnosed and assigned a severity grade. Associated lesions, such as inflammation, should be diagnosed separately. If the lesion is considered to be an artifact, emphysema should not be diagnosed, but a tissue note may be entered to that effect. Related Links: Lung - Bronchiectasis
肺泡上皮增生Epithelium Alveolus Hyperplasia 肺增生
描述（中文）
肺泡上皮增生（alveolar epithelial hyperplasia）是II型肺泡上皮细胞（type II pneumocyte）的增生，可为原发性（Figure 1、Figure 2、Figure 3、Figure 4）或继发于I型肺泡上皮细胞损伤或炎症（Figure 5）。II型肺泡上皮细胞被认为是I型细胞的祖细胞。I型肺泡上皮细胞对氧化剂损伤尤为易感，I型细胞损伤和丢失后常可见II型肺泡上皮细胞增生。当肺泡上皮增生继发于I型肺泡上皮细胞损伤时，通常伴有炎症，而原发性肺泡上皮增生通常不伴有炎症。增生灶的特征为肺泡隔内衬的II型细胞增多、排列紧密、呈立方状。细胞缺乏细胞异型性，罕见核分裂象，胞质空泡可有可无、可明显可不明显。肺泡结构保持完整，增生灶不压迫周围肺实质。这些形态学特征可将增生与腺瘤相鉴别，后者可出现细胞异型性、核分裂象及对邻近组织的压迫，且正常结构扭曲。肺泡巨噬细胞聚集可与原发性增生相关（尽管这种聚集在伴发于肺泡细支气管癌时最为严重）。在某些病例中，肺泡上皮增生灶（原发性或继发性）内部分细胞可具有异型性特征（Figure 6），如核增大、核形状怪异或双核。原发性肺泡上皮增生被认为是肺泡/细支气管腺瘤和癌的前驱病变，尤其当存在细胞异型性特征时。
诊断建议
肺、上皮、肺泡——增生：只要存在即应作出诊断并给出严重程度分级。当肺泡上皮增生继发于I型肺泡上皮细胞损伤或炎症时，无需单独记录，除非病理学家认为其严重程度值得单独诊断。若未单独诊断，则应在病理描述中将其作为炎症病变的组成部分加以描述。若一项研究中同时存在原发性和继发性肺泡上皮增生，且病理学家认为两者均应诊断，则必须为其指定不同的术语。这可通过添加适当的修饰词来实现，例如“局灶性（focal）”。也就是说，原发性肺泡上皮增生可记录为肺、上皮、肺泡——增生，局灶性，继发性肺泡上皮增生可记录为肺、上皮、肺泡——增生。但必须在病理描述中加以区分。若增生细胞具有明显的异型性特征，诊断中应包含修饰词“非典型性（atypical）”（即肺、上皮、肺泡——增生，非典型性）。相关链接：肺——细胞异型性
参考切片图（2 张）
查看英文原文
Comment
Alveolar epithelial hyperplasia is a proliferation of type II pneumocytes and may be primary ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) or secondary to type I pneumocyte injury or inflammation ( Figure 5 ). Type II pneumocytes are thought to be the progenitors of type I cells. Type I pneumocytes are especially vulnerable to oxidant injury, and proliferation of type II pneumocytes is often seen following injury and loss of type I cells. When alveolar epithelial hyperplasia is secondary to type I pneumocyte damage, it is usually associated with inflammation, as opposed to primary alveolar epithelial hyperplasia, which is typically not associated with inflammation. Foci of hyperplasia are characterized by an increase in closely spaced, cuboidal type II cells lining alveolar septa. The cells lack cellular atypia, seldom contain mitotic figures, and may or may not have prominent cytoplasmic vacuoles. The alveolar architecture is maintained, and the focus does not compress the surrounding parenchyma. These morphologic characteristics differentiate hyperplasia from adenoma, in which cellular atypia, mitotic figures, and compression of adjacent tissue may be present and the normal architecture is distorted. Accumulations of alveolar macrophages may be associated with primary hyperplasia (although the accumulations are most severe when associated with alveolar bronchiolar carcinomas). In some cases, some of the cells in a focus of alveolar epithelial hyperplasia (primary or secondary) may have features of atypia ( Figure 6 ), such as enlarged or oddly shaped nuclei or binucleation. Primary alveolar epithelial hyperplasia is thought to be the precursor lesion to alveolar/bronchiolar adenomas and carcinomas, especially when there are features of cellular atypia.
Recommendation
Lung, Epithelium, Alveolus - Hyperplasia should be diagnosed and given a severity grade whenever present. When the alveolar epithelial hyperplasia is secondary to type I pneumocyte injury or inflammation, it need not be recorded separately unless the pathologist feels that its severity warrants a separate diagnosis. If it is not diagnosed separately, it should be described in the pathology narrative as a component of the inflammatory lesion. If both primary and secondary alveolar epithelial hyperplasia is present in a study, and the pathologist feels that both should be diagnosed, then they must be assigned different terms. This can be accomplished by adding an appropriate modifier, such as "focal." That is, primary alveolar epithelial hyperplasia can be recorded as Lung, Epithelium, Alveolus - Hyperplasia, Focal and secondary alveolar epithelial hyperplasia can be recorded as Lung, Epithelium, Alveolus - Hyperplasia. However, the distinction must be made in the pathology narrative. If the hyperplastic cells have significant features of atypia, the modifier "atypical" should be included in the diagnosis (i.e., Lung, Epithelium, Alveolus - Hyperplasia, Atypical). Related Links: Lung - Atypia, Cellular
腺体囊肿Glands Cyst 肺囊肿
描述（中文）
衬覆支气管的黏膜下腺囊性扩张（Figure 1、Figure 2、Figure 3、Figure 4）在啮齿类动物毒性研究中偶见。可累及单个（Figure 1、Figure 2）或多个（Figure 3、Figure 4）腺体。受累腺体通常含有细胞碎片、腺体分泌物和炎性细胞。衬覆上皮细胞通常变薄，可呈低立方状或扁平状。黏膜下腺囊肿可能由分泌管阻塞所致，其原因可能是覆盖其上的黏膜上皮发生鳞状化生，导致分泌物潴留和腺体扩张。通常，腺体囊肿为偶然发现，不伴有其他气道病变，且与衰老有关。尚未见有化学物质诱导支气管和细支气管腺体发生囊肿的报道。
诊断建议
肺，腺体 - 囊肿：当与处理相关时应作出诊断，但不进行分级。
参考切片图（2 张）
查看英文原文
Comment
Cystically dilated submucosal glands lining the bronchi ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) are occasionally seen in rodent toxicity studies. Single ( Figure 1 and Figure 2 ) or multiple ( Figure 3 and Figure 4 ) glands may be affected. The affected glands typically contain cellular debris, glandular secretions, and inflammatory cells. The lining epithelial cells are typically attenuated and may be low cuboidal or flattened. Submucosal gland cysts may be caused by obstruction of the secretory ducts, possibly due to squamous metaplasia of the overlying mucosal epithelium that results in trapped secretions and glandular dilatation. Typically, the glandular cyst is an incidental finding with no other airway lesions and is related to aging. Chemical agents inducing cysts in the bronchial and bronchiolar glands have not been reported.
Recommendation
Lung, Glands - Cyst should be diagnosed when treatment related but not graded.
色素Pigment 肺色素沉着
描述（中文）
“色素（pigment）”一词专用于内源性物质。肺内可见多种类型的色素，包括含铁血黄素（hemosiderin）（Figure 1、Figure 2）和脂褐素（lipofuscin）。在肺内表现为棕色至黑色物质的受试物应诊断为异物（foreign material）而非色素（见肺——异物）。含铁血黄素是肺内最常见且最重要的色素类型。含铁血黄素在巨噬细胞内表现为细颗粒状、金棕色物质。当肺泡巨噬细胞吞噬红细胞时（如出血时发生），血红蛋白转化为含铁血黄素，即铁最稳定的储存形式。含铁血黄素见于出血之后，出血可由肺血管充血（如充血性心力衰竭时发生）或血管损伤引起。酸性血褐素（acid hematin）是低pH福尔马林固定产生的人工假象，表现为黑色至棕色无定形至微晶颗粒，易与含铁血黄素混淆。酸性血褐素由酸作用于血红蛋白产生，故可出现在出血区域。含铁血黄素的存在可通过Perls’普鲁士蓝染色技术确认。
诊断建议
当认为肺——色素与研究相关（或不确定是否与研究相关）或异常显著时，应予以诊断。并非所有色素都必须诊断，因为有些色素在老龄动物中普遍存在，或继发于其他疾病过程（如出血）而无毒理学意义。病理学家应运用其判断决定是否应诊断该色素。当诊断色素时，应给出严重程度分级，并在适当时使用部位修饰词（如支气管、细支气管）以确定病变位置。即使使用一系列特殊染色，在组织学切片中确定色素鉴定通常也很困难。因此，诊断色素（而非诊断色素类型，如含铁血黄素或脂褐素）最为恰当。病理学描述应包括色素的形态学特征、其在组织内的分布以及受累细胞类型。相关病变，如出血、肺泡巨噬细胞浸润或炎症，应单独诊断。相关链接：肺——异物
参考切片图（2 张）
查看英文原文
Comment
The term "pigment" is reserved for endogenous substances. Various types of pigment can be seen in the lungs, including hemosiderin ( Figure 1 and Figure 2 ) and lipofuscin. Test agents that appear as brown to black material in the lungs should be diagnosed as foreign material rather than pigment (see Lung - Foreign Material ). Hemosiderin is the most common and most important type of pigment seen in the lungs. Hemosiderin appears as finely granular, golden brown material in macrophages. When alveolar macrophages ingest erythrocytes, as occurs with hemorrhage, the hemoglobin is converted into hemosiderin, the most stable storage form of iron. Hemosiderin is seen following hemorrhage, which can result from vascular congestion in the lung (as occurs, e.g., with congestive heart failure) or vascular injury. Acid hematin, an artifact of fixation in formalin with a low pH, appears as black to brown amorphous to microcrystalline granules and can easily be confused with hemosiderin. Acid hematin is produced by acid acting on hemoglobin, so it may appear in areas of hemorrhage. The presence of hemosiderin can be confirmed with the Perls’ Prussian blue staining technique.
Recommendation
Lung - Pigment should be diagnosed when it is considered to be relevant to the study (or if it is unclear whether it is relevant to the study) or if it is unusually prominent. Not all pigments have to be diagnosed, as some are ubiquitous in aging animals or are secondary to another disease process (e.g., hemorrhage) and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether or not the pigment should be diagnosed. When pigment is diagnosed, it should be given a severity grade, and if appropriate, a site modifier (e.g., bronchus, bronchiole) should be used to identify the location of the lesion. Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, a diagnosis of pigment (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should include a description of the morphologic features of the pigment, its distribution within the tissue, and the cell type affected. Associated lesions, such as hemorrhage, alveolar macrophage infiltration, or inflammation, should be diagnosed separately. Related Links: Lung - Foreign Material
蛋白沉积症Proteinosis 肺其他
描述（中文）
肺泡蛋白沉积症（alveolar proteinosis，Figure 1、Figure 2、Figure 3、Figure 4）的特征是肺泡内游离存在亮嗜酸性、无定形、periodic acid-Schiff 阳性的物质。通常，该物质伴随的炎症很少，但巨噬细胞数量可能增多。分布可为 局灶性（focal），仅少数肺泡受累；可为 patchy，累及肺叶的部分区域；或为 弥漫性（diffuse），累及整个肺叶。该物质被认为由脂质和肺蛋白组成。该病变的发病机制尚不清楚，但可能由表面活性物质产生增加和/或因巨噬细胞功能受损导致清除减少所致。肺泡蛋白沉积症必须与水肿液鉴别，水肿液更均质，在 hematoxylin and eosin 染色下嗜酸性染色不如前者明亮或深染，且 periodic acid-Schiff 阴性。肺泡蛋白沉积症可见于暴露于各种粉尘颗粒（如石英）的情况下。该病变在 rats 中似乎比在 mice 中更常见。
诊断建议
Lung - Proteinosis 只要存在就应诊断，并根据病变范围进行分级。由于肺泡巨噬细胞常与该病变相关而增多，无需单独诊断，除非它们构成病变的显著成分。炎症应单独诊断，因为它通常与该病变无关。继发于肿瘤的蛋白沉积症不应诊断，但可在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Alveolar proteinosis ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is characterized by brightly eosinophilic, amorphous, periodic acid-Schiff–positive material that is free within the alveoli. Typically, little inflammation is associated with the material, but there may be increased numbers of macrophages. The distribution may be focal, with few alveoli affected; patchy, affecting portions of lung lobes; or diffuse, affecting entire lobes. The material is thought to comprise lipids and pulmonary proteins. The pathogenesis of the lesion is not known but may be caused by increased surfactant production and/or decreased clearance due to macrophage impairment. Alveolar proteinosis must be distinguished from edema fluid, which is more homogeneous, does not stain as brightly or deeply eosinophilic with hematoxylin and eosin, and is periodic acid-Schiff negative. Alveolar proteinosis may be seen with exposure to various dust particles (e.g., quartz). The lesion appears to be more common in rats than in mice.
Recommendation
Lung - Proteinosis should be diagnosed whenever present and graded based on the extent of the lesion. Since alveolar macrophages are often increased in association with this lesion, they need not be diagnosed separately unless they comprise a significant component of the lesion. Inflammation should be diagnosed separately since it is not typically associated with this lesion. Proteinosis that is secondary to a neoplasm should not be diagnosed but may be described in the pathology narrative.
角化性囊肿Keratinizing Cyst 肺囊肿
描述（中文）
角化囊肿（keratinizing cyst）典型见于大鼠吸入颗粒性物质（如滑石粉、二氧化钛）后，也可见于经口灌胃暴露于二噁英类化合物的大鼠。尚未在小鼠或仓鼠中报道。角化囊肿由囊壁和囊腔构成，囊壁为分化良好的鳞状上皮细胞，呈有序成熟，围绕囊腔，腔内含亮嗜酸性、同心圆层状角蛋白（Figure 1、Figure 2、Figure 3、Figure 4）。囊肿可见于任何肺叶，常位于胸膜下。囊肿可变得相当大，直径可达数厘米，并取代或压迫正常肺实质。构成囊肿的鳞状上皮细胞被认为起源于衬覆肺泡和/或细支气管上皮的化生。角化囊肿也曾被称为“鳞状囊肿（squamous cyst）”和“表皮囊肿（epidermal cyst）”。角化囊肿被认为是大鼠角化性病变连续谱的一部分，该谱还包括肺泡上皮鳞状化生、囊性角化上皮瘤和鳞状细胞癌。囊性角化上皮瘤与角化囊肿的鉴别在于上皮瘤的壁更厚、更复杂，外缘更粗糙（囊肿外缘更光滑），且鳞状上皮细胞可能缺乏有序成熟，核分裂象可能增多。鳞状细胞癌可能与囊性角化上皮瘤相似，但表现出恶性证据（侵袭、细胞异型性、细胞极性丧失等）。大鼠中也曾报道仅由纤维组织衬覆的先天性囊性腔隙，其与角化囊肿的鉴别在于缺乏鳞状上皮。
诊断建议
肺 - 角化囊肿只要存在就应诊断，但不应进行分级。然而，如果囊肿数量和/或大小呈剂量相关性增加，且病理学家认为必须对囊肿进行分级才能充分描述该病变与染毒的关系，则可以对囊肿进行分级。如果对囊肿进行分级，则必须在病理学叙述中完整描述分级方案。病理学叙述中还应包括不同剂量组中囊肿的肺叶分布及大致数量和大小的描述。相关病变，如炎症，应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Keratinizing cysts are typically seen in rats after inhalation exposure to particulate material (e.g., talc, titanium dioxide), though they are also seen in rats exposed by gavage to dioxin-like compounds. They have not been reported in mice or hamsters. Keratinizing cysts consist of a cyst wall composed of well-differentiated squamous epithelial cells undergoing orderly maturation surrounding a lumen containing brightly eosinophilic, concentrically laminated keratin ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Cysts can be observed in any lung lobe and are often subpleural. Cysts can become quite large, up to several centimeters in diameter, and replace or compress the normal lung parenchyma. The squamous epithelial cells comprising the cyst are considered to originate from metaplasia of epithelium lining the alveoli and/or bronchioles. Keratinizing cysts have also been called "squamous cysts" and "epidermal cysts." Keratinizing cysts are thought to be part of a continuum of keratinizing lesions seen in rats that also includes squamous metaplasia of the alveolar epithelium, cystic keratinizing epithelioma, and squamous cell carcinoma. Cystic keratinizing epitheliomas can be differentiated from keratinizing cysts by virtue of the thicker, more complex wall of epitheliomas, which has a rougher outer margin (cysts have a smoother outer margin) and may lack orderly maturation of the squamous epithelial cells and may have increased mitotic figures. Squamous cell carcinomas may appear similar to cystic keratinizing epitheliomas but show evidence of malignancy (invasion, cellular atypia, loss of cellular polarity, etc.). Congenital cystic spaces lined only by fibrous tissue have also been reported in the rat, and these are distinguishable from keratinizing cysts by the lack of squamous epithelium.
Recommendation
Lung - keratinizing cyst should be diagnosed whenever present but should not be graded. However, if a dose-related increase in the number and/or size is present, and the pathologist feels that grading the cysts is necessary to fully characterize the relationship of the lesion to treatment, the cysts may be graded. If the cysts are graded, the grading scheme must be fully described in the pathology narrative. A description of the lobar distribution and approximate number and size of the cysts in the different dose groups should also be included in the pathology narrative. Associated lesions, such as inflammation, should be diagnosed separately.
骨性化生Metaplasia Osseous 肺化生
描述（中文）
骨性化生（osseous metaplasia）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6）在 NTP 研究中常作为背景性肺部病变出现。尚未显示其与受试物给药相关。它可发生于肺内任何部位，包括胸膜（Figure 4）。骨性化生表现为嗜酸性骨样组织或编织骨或嗜碱性矿化骨的灶状区域，其中散布有陷窝。罕见情况下，形成的骨含有造血成分（骨髓）。肺内也可见软骨性化生（cartilaginous metaplasia），由嗜两性至嗜碱性的软骨样基质灶组成，其中散布有陷窝。在实验室啮齿类动物中，骨性化生最常见于 B6C3F1 mouse 的肺。软骨性和骨性化生可作为对损伤或炎症的反应而发生。当成纤维细胞组织受到刺激或被诱导形成非肿瘤性骨和/或软骨时，即发生这些病变。新骨形成伴有或不伴有软骨模板，并且可由成纤维细胞组织包绕。骨性或软骨性化生灶必须分别与转移性骨肉瘤或软骨肉瘤相鉴别。
诊断建议
肺 - 化生，骨性通常被视为背景性病变，但为完整性起见应予以诊断。同样，存在软骨性化生时也应予以诊断。这些病变无需分级。
参考切片图（2 张）
查看英文原文
Comment
Osseous metaplasia ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ) is frequently seen as a background lung lesion in NTP studies. No association with test article administration has been shown. It may occur anywhere in the lung, including the pleura ( Figure 4 ). Osseous metaplasia is seen as foci of eosinophilic osteoid or woven bone or basophilic mineralized bone that contain interspersed lacunae. Rarely, bone is formed that contains hematopoietic elements (bone marrow). Cartilaginous metaplasia is also seen in the lung, comprising amphophilic to basophilic foci of chondroid matrix that contain interspersed lacunae. In laboratory rodents, osseous metaplasia is most common in the lungs of B6C3F1 mice. Cartilaginous and osseous metaplasia may occur as a response to injury or inflammation. These lesions occur when fibroblastic tissue is stimulated or induced to form nonneoplastic bone and/or cartilage. New bone forms with or without a cartilage template and can be bordered by fibroblastic tissue. Foci of osseous or cartilaginous metaplasia must be distinguished from metastatic osteosarcoma or chondrosarcoma, respectively.
Recommendation
Lung - Metaplasia, Osseous is generally considered a background lesion but should be diagnosed for completeness. Similarly, cartilaginous metaplasia should also be diagnosed when present. These lesions need not be graded.
鳞状化生Metaplasia Squamous 肺化生
描述（中文）
肺泡上皮的鳞状化生（squamous metaplasia）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6、Figure 7、Figure 8）以I型和II型肺泡上皮细胞（type I and type II pneumocytes）被鳞状上皮取代为特征。气道黏膜上皮的鳞状化生以细支气管或支气管上皮被鳞状上皮取代为特征。鳞状上皮是一种复层上皮，细胞从基底膜处的立方状基底细胞到表面的扁平鳞状细胞呈有序的成熟过程。上皮可发生角化，细胞可含有透明角质颗粒（keratohyalin granules）。早期鳞状化生仅表面细胞变扁平，可能难以识别。鳞状化生不应与再生混淆，因为再生的上皮细胞可呈扁平形态（伸展以覆盖裸露的基底膜）。通常，鳞状化生中存在一层以上的细胞。鳞状化生可见于对慢性刺激或损伤的反应，并被认为是一种适应性改变，因为鳞状上皮比呼吸道上皮或肺泡上皮对损伤更具抵抗力。因此，鳞状化生常伴有炎症、纤维化、坏死、溃疡以及上皮增生区域。虽然通常不被认为是肿瘤前病变，但在某些条件下鳞状化生可导致肿瘤形成（囊性角化上皮瘤或鳞状细胞癌）。存在非典型细胞的化生上皮（Figure 8）可能是肿瘤前病变。
诊断建议
肺——化生，鳞状：只要存在即应诊断并赋予严重程度分级。诊断中应包含部位修饰词（即肺泡、细支气管或支气管）以指示病变的位置。相关病变，如炎症、纤维化、坏死或增生，应单独诊断。如果存在非典型性，则应在诊断中加入修饰词“非典型”（非典型性（atypical））。
参考切片图（2 张）
查看英文原文
Comment
Squamous metaplasia of the alveolar epithelium ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 , Figure 7 , and Figure 8 ) is characterized by replacement of type I and type II pneumocytes with squamous epithelium. Squamous metaplasia of the airway epithelium is characterized by replacement of bronchiolar or bronchial epithelium with squamous epithelium. Squamous epithelium is a stratified epithelium with orderly progression of cell maturation from cuboidal basal cells at the basement membrane to flattened squamous cells at the surface. The epithelium may be keratinized, and the cells may contain keratohyalin granules. Early squamous metaplasia, where only the surface cells are flattened, can be difficult to identify. Squamous metaplasia should not be confused with regeneration, since regenerating epithelial cells can assume a flattened morphology (stretching out to cover a denuded basement membrane). Generally, more than one layer of cells is present in squamous metaplasia. Squamous metaplasia can be seen as a response to chronic irritation or injury and is thought to be an adaptive change, as the squamous epithelium is more resistant to injury than is respiratory or alveolar epithelium. Consequently, squamous metaplasia is often accompanied by inflammation, fibrosis, necrosis, ulceration, and areas of epithelial hyperplasia. Though not typically considered preneoplastic, under some conditions squamous metaplasia may give rise to neoplasia (cystic keratinizing epithelioma or squamous cell carcinoma). Metaplastic epithelium in which there are atypical cells ( Figure 8 ) may be preneoplastic.
Recommendation
Lung - Metaplasia, Squamous should be diagnosed whenever present and assigned a severity grade. A site modifier (i.e., alveolus, bronchiole, or bronchus) should be included in the diagnosis to indicate the location of the lesion. Associated lesions, such as inflammation, fibrosis, necrosis, or hyperplasia, should be diagnosed separately. If atypia is present, then the modifier "atypical" should be added to the diagnosis.
上皮再生Epithelium Regeneration 鼻其他
描述（中文）
再生（Regeneration，Figure 1）是鼻结构上皮缺失后的再上皮化。新生的上皮层通常是一层扁平的、细长的细胞，取代缺失的上皮。这些细胞的细胞核常大小不一（anisokaryotic），且相对于缺损长度而言，细胞数量可能显得偏少。细胞大小不一（anisocytotic）并缺乏正常极性。受累细胞的细胞质一般呈嗜碱性。由于再生是对细胞缺失的一种反应，故通常见于变性和/或坏死区域，并可能与增生和化生同时存在。
诊断建议
只要存在再生，且同时有坏死或变性的证据，就应诊断再生。再生不应进行分级。为传达病变的严重程度，必须同时诊断坏死或变性并对其进行分级（见 Nose - Epithelium - Degeneration 和 Nose - Epithelium - Necrosis）。诊断中应通过将本应存在的上皮类型（如呼吸上皮、嗅上皮）作为部位修饰词纳入，以指明病变在鼻腔内的位置。如果上皮细胞数量超出正常范围，则应诊断增生，无论其是受试物暴露的直接效应还是过度再生所致，但增生的发病机制应在病理学叙述中讨论。其他相关病变，如炎症、萎缩或化生，应单独诊断。如果再生上皮表现出显著的异型性特征，根据病理学家的判断，则应诊断“细胞异型性（atypia, cellular）”并进行分级。相关链接：Nose - Epithelium - Degeneration Nose - Epithelium - Necrosis
参考切片图（1 张）
查看英文原文
Comment
Regeneration ( Figure 1 ) is the re-epithelialization of nasal structures following loss of the epithelium. The new epithelial layer is usually a thin layer of flattened, elongated cells that replaces the lost epithelium. The nuclei of these cells are often anisokaryotic, and there may seem to be fewer cells than there should be for the length of the defect. The cells are anisocytotic and lack normal polarity. The cytoplasm of involved cells is generally basophilic. Because it is a response to the loss of cells, regeneration is typically seen in areas of degeneration and/or necrosis, and it may coincide with hyperplasia and metaplasia.
Recommendation
Regeneration should be diagnosed whenever present and evidence of necrosis or degeneration is also present. Regeneration should not be graded. To convey the severity of the lesion, either necrosis or degeneration must be diagnosed concurrently and graded (see Nose - Epithelium - Degeneration and Nose - Epithelium - Necrosis ). The location of the lesion in the nasal cavity should be indicated in the diagnosis by including as a site modifier the type of epithelium that should be present (e.g., respiratory, olfactory). If the number of epithelial cells exceeds that which would be considered within normal limits, hyperplasia should be diagnosed, regardless of whether it is a direct effect of test article exposure or excessive regeneration, but the pathogenesis of the hyperplasia should be discussed in the pathology narrative. Other associated lesions, such as inflammation, atrophy, or metaplasia, should be diagnosed separately. If the regenerating epithelium exhibits significant features of atypia, based on the pathologist’s judgment, then "atypia, cellular" should be diagnosed and graded. Related Links: Nose - Epithelium - Degeneration Nose - Epithelium - Necrosis
上皮变性Epithelium Degeneration 鼻变性
描述（中文）
鼻上皮的变性（Figure 1、Figure 2、Figure 3、Figure 4）以以下一项或多项为特征：纤毛丢失、上皮细胞起泡形成、细胞排列紊乱、细胞嗜酸性增强、肿胀、细胞间接触丧失或上皮内空泡样改变。变性可能意味着当前正在进行的过程，因此当该过程似乎处于活动状态时，“变性”一词可能是合适的。退行性改变也可发生于副鼻结构的上皮，且可能在其他部位被覆上皮未见退行性改变的情况下出现。“囊性变性”专用于黏膜或固有层内衬覆上皮的结构。此类囊肿通常含有均质或颗粒状物质。上皮变性是毒性研究中常见的与受试物相关的病变，但也可见于对照动物。
诊断建议
上皮变性只要存在即应作出诊断并赋予严重程度分级。诊断中应将该上皮类型作为部位修饰词纳入（例如：鼻、嗅上皮 - 变性）。报告中应包含对病变的详尽描述，包括尽可能明确靶细胞（例如嗅上皮中的感觉细胞或支持细胞）。副鼻器官上皮的退行性改变，若其他上皮部位未见变性，应单独诊断；若其作为更广泛的上皮退行性过程的一部分出现，则不应单独诊断，而应视为该过程的一个组成部分，仅在病理学描述中加以说明。当鼻黏膜内存在内衬上皮的结构时，囊性变性的诊断是合适的；该改变应赋予严重程度分级并明确部位。相关病变，如炎症，若严重程度足以支持，应单独诊断。相关链接：鼻 - 上皮 - 坏死；鼻 - 上皮 - 再生
参考切片图（2 张）
查看英文原文
Comment
Degeneration of the nasal epithelium ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is characterized by one or more of the following: loss of cilia, epithelial cell bleb formation, cellular disorientation, cellular eosinophilia, swelling, loss of cell-to-cell contact, or vacuolar changes within the epithelium. Degeneration may imply a current, ongoing process, so when the process seems to be active, the term "degeneration" may be appropriate. Degenerative changes may also occur in the epithelia of accessory nasal structures, possibly in the absence of degenerative changes in the lining epithelia. "Cystic degeneration" is reserved for epithelial-lined structures within the mucosa or lamina propria. Such cysts usually contain homogeneous or granular material. Epithelial degeneration is a common treatment-related lesion in toxicity studies but may also be seen in control animals.
Recommendation
Epithelial degeneration should be diagnosed and assigned a severity grade whenever present. The type of epithelium should be included in the diagnosis as a site modifier (e.g., Nose, Olfactory epithelium - Degeneration). A thorough description of the lesion should be included in the report narrative, including identification of the target cell (e.g., sensory or sustentacular cells in the olfactory epithelium) if possible. Degenerative changes in the epithelium of an accessory nasal organ, in the absence of degeneration in other epithelial sites, should be diagnosed separately; if they occur as part of a more widespread degenerative epithelial process, then they should not be diagnosed separately but considered a component of that process and simply described in the pathology narrative. A diagnosis of cystic degeneration is appropriate when there are epithelial-lined structures in the nasal mucosa; this change should be given a severity grade and site identification. Associated lesions, such as inflammation, should be diagnosed separately if warranted by severity. Related Links: Nose - Epithelium - Necrosis Nose - Epithelium - Regeneration
上皮坏死Epithelium Necrosis 鼻坏死
描述（中文）
上皮坏死（epithelial necrosis，Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6）是吸入研究中常见的病变，尤其是在强刺激物作用下，但也可见于其他类型的研究。上皮坏死时可出现多种变化，包括细胞核固缩（pyknosis）或核碎裂（karyorrhexis）、核溶解（karyolysis）、细胞碎裂、胞质嗜酸性增强、细胞碎片的存在、细胞轮廓不清以及细胞脱落。任何上皮细胞或其他细胞类型均可受累，坏死可延伸至相关结构，如鼻腺、鼻泪管和鼻甲骨（Figure 6）。嗅上皮中感觉细胞的丢失常伴有固有层神经束的萎缩。
诊断建议
上皮坏死只要存在就应诊断并分级。要诊断坏死，必须存在坏死细胞或其残余物。如果不存在坏死细胞，则应诊断溃疡或糜烂。诊断中应包含部位修饰词（例如呼吸上皮、移行上皮、鳞状上皮或嗅上皮、犁鼻器、泪管），以指示病变的位置。如果病变存在于一个以上的部位，则应针对其作为显著变化的每个部位分别诊断。坏死可与其他嗅部变化同时存在，当其作为独立、清晰明确的病变存在时应予以诊断。继发于其他病变（如炎症）的坏死性病变，除非严重程度足以支持，否则不应单独诊断，但应在病理学叙述中描述。相关病变，如炎性细胞浸润、炎症、鼻甲骨坏死或出血，除非严重程度足以支持，否则不应单独诊断。相关链接：鼻－上皮－变性；鼻－上皮－再生
参考切片图（2 张）
查看英文原文
Comment
Epithelial necrosis ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ) a common lesion in inhalation studies, particularly with strong irritants, but may also be seen in other types of studies. A number of changes may manifest with epithelial necrosis, including pyknosis or karyorrhexis of nuclei, karyolysis, cell fragmentation, increased cytoplasmic eosinophilia, the presence of cell debris, indistinct cell outlines, and exfoliation of cells. Any of the epithelial or other cell types may be affected, and the necrosis may extend into associated structures such as the nasal glands, nasolacrimal ducts, and nasal turbinate bone ( Figure 6 ). Loss of sensory cells in the olfactory epithelium is frequently accompanied by atrophy of the nerve bundles in the lamina propria.
Recommendation
Epithelial necrosis should be diagnosed and graded whenever present. The necrotic cells, or remnants thereof, must be present if necrosis is to be diagnosed. If necrotic cells are not present, then ulcer or erosion should be diagnosed. A site modifier (e.g., respiratory, transitional, squamous, or olfactory epithelium, vomeronasal organ, lacrimal duct) should be included in the diagnosis to indicate the location of the lesion. If the lesion is present in more than one location, it should be diagnosed separately for each location in which it is a prominent change. Necrosis may occur in the presence of other olfactory changes and should be diagnosed when present as a distinct, clearly defined entity. Necrotic lesions that are secondary to other lesions, such as inflammation, should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative. Associated lesions, such as inflammatory cell infiltrate, inflammation, turbinate bone necrosis, or hemorrhage, should not be diagnosed separately unless warranted by severity. Related Links: Nose - Epithelium - Degeneration Nose - Epithelium - Regeneration
上皮增生Epithelium Hyperplasia 鼻增生
描述（中文）
移行上皮或呼吸道上皮增生是一种相对常见的与处理相关的变化，也可见于异物和感染性病原体引起的炎性病变中。增生是细胞数量的增加，不应与再生相混淆，再生是丢失或受损细胞的替代。增生导致上皮增厚（Figure 2、Figure 3、Figure 6），并可能因细胞拥挤而使上皮形成皱褶（Figure 2、Figure 3）。然而，鼻甲尾腹侧的黏膜表面正常情况下即呈皱褶状；这不应被解释为呼吸道上皮增生。增生上皮的黏膜内陷（Figure 4、Figure 5）可延伸至固有层，并可能含有一些炎性细胞或凝结物。增生上皮的内陷被认为随增生时间延长而发生。杯状细胞增殖（Figure 6）是上皮的常见反应，常与增生同时出现。嗅上皮增生通常导致上皮层增厚（Figure 7）。
诊断建议
移行上皮或呼吸道上皮增生一经出现即应诊断，并赋予严重程度分级。诊断中所列部位应反映受累的上皮细胞类型。如果能够确定增殖细胞为某一特定细胞类型（例如基底细胞或杯状细胞），则该细胞类型应作为修饰词纳入。由于这些细胞正在增殖，它们通常比非增殖的呼吸道上皮细胞略大（肥大）。只有当病理学家确信其增大程度超出增殖细胞的预期时，才应单独诊断肥大。如果上皮细胞看起来异常（例如细胞或核多形性、间变或增大）或存在异常或畸变的生长模式（例如细胞排列紊乱、角化不良或核分裂象增多或异常），则应添加“非典型（非典型性（atypical））”作为诊断修饰词（见Nose - Epithelium - Hyperplasia, 非典型性）。再生上皮细胞的细胞学特征和排列可能有一些不规则；必须注意不要将其误认为非典型增生。相关链接：Nose - Epithelium - Hyperplasia, 非典型性
参考切片图（2 张）
查看英文原文
Comment
Transitional or respiratory epithelial hyperplasia is a relatively common treatment-related change and can also be seen in inflammatory lesions caused by foreign bodies and infectious agents. Hyperplasia is an increase in the number of cells and should not be confused with regeneration, which is replacement of lost or damaged cells. Hyperplasia results in thickening of the epithelium ( Figure 2 , Figure 3 , and Figure 6 ) and may result in cellular crowding that forces the epithelium into folds ( Figure 2 and Figure 3 ). However, the mucosal surface of the caudoventral nasoturbinate is normally folded; this should not be interpreted as respiratory epithelial hyperplasia. Mucosal invaginations of hyperplastic epithelium ( Figure 4 and Figure 5 ) may extend into the lamina propria and may contain some inflammatory cells or concretions. Invagination of hyperplastic epithelium is thought to occur with prolonged hyperplasia. Goblet cell proliferation ( Figure 6 ) is a common response of the epithelium and is often seen concurrently with hyperplasia. Hyperplasia of the olfactory epithelium typically results in thickening of the epithelial layer ( Figure 7 ).
Recommendation
Hyperplasia of the transitional or respiratory epithelium should be diagnosed whenever present and assigned a severity grade. The site listed in the diagnosis should reflect the epithelial cell type affected. If a particular cell type can be identified as the proliferating cell (e.g., basal cell or goblet cell), that cell type should be included as a modifier. Since these cells are proliferating, they are often slightly larger (hypertrophy) than nonproliferating respiratory epithelial cells. Hypertrophy should be diagnosed separately only if the pathologist is confident that the enlargement is beyond that expected for proliferating cells. If the epithelial cells appear to be abnormal (e.g., cellular or nuclear pleomorphism, anaplasia, or enlargement) or there is an abnormal or aberrant growth pattern (e.g., disorganization of the cells, dyskeratosis, or increased or abnormal mitotic figures), the term “atypical” should be added as a diagnostic modifier (see Nose - Epithelium - Hyperplasia, Atypical ). Regenerating epithelial cells may have some irregularity in their cytologic features and arrangement; care must be taken not to mistake this for atypical hyperplasia. Related Links: Nose - Epithelium - Hyperplasia, Atypical
上皮纤维化Epithelium Fibrosis 鼻纤维化
描述（中文）
纤维化在显微镜下表现为纤维结缔组织数量增加，取代或扩张正常结构。由于纤维化通常是对严重组织损伤的反应，因此常与炎症和/或坏死相关。鼻部固有层中的纤维化（Figure 1；与Figure 2所示的对照相比）不常见。
诊断建议
纤维化在鼻腔中是一种不常见的病变，观察到时应予以诊断并赋予严重程度分级。与炎症一样，与纤维化相关的上皮细胞类型应作为部位修饰词记录。其他病变，如上述炎症和增生，应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Fibrosis appears microscopically as an increase in the amount of fibrous connective tissue that either replaces or expands normal structures. Because it is often a response to severe tissue damage, fibrosis is often associated with inflammation and/or necrosis. Fibrosis in the lamina propria of the nose ( Figure 1 ; compare with control shown in Figure 2 ) is uncommon.
Recommendation
Fibrosis is an uncommon lesion in the nasal cavity and should be diagnosed and assigned a severity grade whenever it is observed. As with inflammation, the epithelial cell type associated with the fibrosis should be recorded as a site modifier. Other lesions, such as the inflammation and hyperplasia noted above, should be diagnosed separately.
上皮细胞透明滴蓄积Epithelium Accumulation Hyaline Droplet 鼻其他
描述（中文）
透明滴（hyaline droplet）（Figure 1、Figure 2、Figure 3、Figure 4）在小鼠和大鼠中均可见到，其特征为嗜酸性、均质、球状、玻璃样物质在呼吸道上皮细胞、嗅上皮支持细胞（sustentacular cell）或浆液黏液腺上皮细胞的细胞质内蓄积。这些滴状物可位于核下或核上，并可使细胞变形。它们偶尔伴有细胞内或细胞外嗜酸性结晶。嗅上皮与呼吸道上皮的交界处是观察到此变化的非常常见部位，尤其是在 II 级切片的鼻中隔和背侧鼻道。该物质尚未被明确鉴定，但据报道可与羧酸酯酶（carboxylesterase）抗体及 Ym2 蛋白的 Ym1 序列抗体发生反应。在对照大鼠和小鼠中可见少量此类滴状物，并随年龄增长而增多。滴状物的数量和大小可因处理而加重，但其不被视为退行性改变。
诊断建议
由于透明滴可见于对照动物，将其诊断为病变（“蓄积，透明滴”）一般应代表滴状物的大小和/或数量相对于对照有所增加。如果对照动物与处理动物之间没有差异，则无需诊断此变化。当作出诊断时，应赋予该病变严重程度分级，并应将上皮类型作为部位修饰词纳入诊断。由于此不被视为退行性改变，任何并发的细胞退行性变均应单独诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
The presence of hyaline droplets ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ), which is seen in both mice and rats, is characterized by the accumulation of eosinophilic, homogeneous, globular, hyaline material in the cytoplasm of cells of the respiratory epithelium, sustentacular cells of the olfactory epithelium, or epithelial cells of seromucous glands. The droplets may be subnuclear or supranuclear and can distort the cells. They are occasionally accompanied by intra- or extracellular eosinophilic crystals. The junction of the olfactory and respiratory epithelia is a very common site to see this change, particularly on the nasal septum of the level II section and in the dorsal meatus. The material has not been definitively identified, but it has been reported to react to antibodies for carboxylesterase and the Ym1 sequence of the Ym2 protein. The droplets are found in low numbers in control rats and mice and increase with age. The number and size of droplets can be exacerbated by treatment, but it is not considered a degenerative change.
Recommendation
Because the hyaline droplets can be found in control animals, diagnosis of this as a lesion ("Accumulation, Hyaline droplet") should generally represent an increase in the size and/or number of droplets relative to controls. If there is no difference between the control and treated animals, this change need not be diagnosed. When diagnosed this lesion should be assigned a severity grade, and the epithelial type should be included in the diagnosis as the site modifier. Since this is not considered a degenerative change, any concurrent cellular degeneration should be diagnosed and graded separately.
上皮非典型增生Epithelium Hyperplasia Atypical 鼻增生
描述（中文）
非典型性增生（非典型性（atypical） hyperplasia）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5）是一种局灶性（focal）或多灶性（multifocal）的增生性改变（即细胞数量增多），具有细胞非典型性（cellular atypia）的特征，提示其行为更具侵袭性。“细胞非典型性”是指存在与分化改变（细胞多形性、间变）或生长改变（细胞排列紊乱、角化不良、异常核分裂象）相符的形态学特征。非典型性增生可发生于鼻腔内任何类型的上皮细胞或腺体（鼻中隔腺、Bowman腺或Steno腺），但最常见于移行上皮或呼吸上皮。嗅上皮的非典型性增生常表现为基底上皮细胞增生并延伸至基底膜以下。非典型性增生被认为代表一种癌前病变（preneoplastic change）。
诊断建议
非典型性增生是一项重要发现，只要存在即应作出诊断并赋予严重程度分级。当非典型性出现在化生性病变内时，应诊断化生，但应在诊断中加上修饰词“非典型性”（例如：Nose, Olfactory epithelium - Metaplasia, Respiratory, 非典型性（atypical））。受累上皮的类型应作为部位修饰词纳入诊断（即squamous、transitional、respiratory或olfactory epithelium）。相关链接：Nose - Epithelium - Hyperplasia
参考切片图（2 张）
查看英文原文
Comment
Atypical hyperplasia ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , and Figure 5 ) is a focal or multifocal hyperplastic change (i.e., increased numbers of cells) with features of cellular atypia, which suggests a more aggressive behavior. "Cellular atypia" refers to the presence of morphologic features that are consistent with altered differentiation (cellular pleomorphism, anaplasia) or growth (disorganization of cells, dyskeratosis, abnormal mitotic figures). Atypical hyperplasia can occur in any of the epithelial cell types found in the nasal cavity or in the glands (septal, Bowman''s, or Steno''s glands) but is most commonly seen in the transitional or respiratory epithelium. Atypical hyperplasia of the olfactory epithelium often manifests as proliferation of basal epithelial cells that extends below the basement membrane. Atypical hyperplasia is thought to represent a preneoplastic change.
Recommendation
Atypical hyperplasia is an important finding that should be diagnosed whenever present and assigned a severity grade. When atypia occurs within a metaplastic lesion, the metaplasia should be diagnosed, but the modifier "atypical" should be added to the diagnosis (e.g., Nose, Olfactory epithelium - Metaplasia, Respiratory, Atypical). The type of epithelium affected should be included in the diagnosis as a site modifier (i.e., squamous, transitional, respiratory, or olfactory epithelium). Related Links: Nose - Epithelium - Hyperplasia
上皮鳞状化生Epithelium Metaplasia Squamous 鼻化生
描述（中文）
鳞状化生（squamous metaplasia）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5）定义为移行上皮、呼吸上皮或嗅上皮被鳞状上皮取代。该病变在对照动物中罕见，但在刺激性物质的吸入研究中相对常见。早期变化包括上皮细胞排列紊乱，表层细胞相对于基底膜呈水平方向排列。该病变必须与再生相鉴别，再生通常为1或2层细胞厚度。然而，在通常仅有2或3层细胞的移行上皮中，这种区分可能较为困难。移行上皮中表层细胞极性的改变可能是鳞状化生的唯一指征。在严重病变中，化生上皮可能明显增厚，并可能出现网嵴形成或角化。化生性改变可累及上皮下腺体的导管或鼻泪管。鳞状化生被认为是一种适应性改变，因为鳞状上皮比其他上皮类型更能抵抗损伤。化生上皮可能含有异型性区域，这些区域可能是癌前病变。随着暴露停止，鳞状化生可能是可逆的，但在慢性研究中，取决于受试物的性质，鳞状化生可能发展为鳞状细胞乳头状瘤或鳞状细胞癌。
诊断建议
鼻上皮的鳞状化生无论何时出现均应作出诊断并赋予严重程度分级。受累及的上皮应作为部位修饰词纳入诊断。其他病变，如炎症，在严重程度需要时应当单独诊断。如存在，鲍曼腺扩张和嗅神经萎缩应在叙述中描述，除非该病变足够显著而需要单独诊断（见 Nose - Olfactory Epithelium, Glands - Metaplasia）。角化可能是鳞状化生的一个组成部分，无需单独诊断；但应在叙述中描述。化生性鳞状上皮可能含有相对于未受影响鳞状上皮的增生特征（例如增厚、网嵴形成），这些特征也应在叙述中描述。如存在异型性特征，应通过添加修饰词“非典型性（atypical）”作出诊断。相关链接：Nose - Olfactory Epithelium, Glands - Metaplasia
参考切片图（2 张）
查看英文原文
Comment
Squamous metaplasia ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , and Figure 5 ) is defined as the replacement of transitional, respiratory, or olfactory epithelium by squamous epithelium. It is rarely seen in control animals but is relatively common in inhalation studies of irritants. Early changes include disorganization of the epithelial cells, with the superficial cells becoming oriented horizontally with respect to the basal lamina. This lesion must be differentiated from regeneration, which is typically 1 or 2 cell layers thick. However, in the transitional epithelium, which normally has only 2 or 3 cellular layers, this distinction can be difficult. The change in polarity of the superficial cells in the transitional epithelium may be the only indication of squamous metaplasia. In severe lesions, the metaplastic epithelium may be quite thickened, and there may be rete peg formation or keratinization. The metaplastic change can affect the ducts of subepithelial glands or the nasolacrimal ducts. Squamous metaplasia is considered an adaptive change, since squamous epithelium is more resistant to injury than are the other epithelial types. The metaplastic epithelium may contain areas of atypia, which may be preneoplastic. With cessation of exposure, squamous metaplasia may be reversible, but in chronic studies, depending on the nature of the test article, squamous metaplasia may give rise to squamous cell papilloma or squamous cell carcinoma.
Recommendation
Squamous metaplasia of the nasal epithelium should be diagnosed whenever present and assigned a severity grade. The affected epithelium should be included in the diagnosis as site modifier. Other lesions, such as inflammation, should be diagnosed separately when warranted by severity. If present, Bowman’s gland dilation and olfactory nerve atrophy should be described in the narrative, unless the lesion is prominent enough to warrant a separate diagnosis (see Nose - Olfactory Epithelium, Glands - Metaplasia ). Keratinization may be a component of squamous metaplasia and need not be diagnosed separately; however, it should be described in the narrative. Metaplastic squamous epithelium may contain features of hyperplasia relative to unaffected squamous epithelium (e.g., thickening, rete peg formation), and these features should also be described in the narrative. If features of atypia are present, it should be diagnosed by adding the modifier, "atypical." Related Links: Nose - Olfactory Epithelium, Glands - Metaplasia
凝结物Concretion 鼻其他
描述（中文）
在鼻腔内，结石几乎总是与炎症相关（Figure 1、Figure 2）。结石见于鼻道内，由浓缩的鼻腔分泌物和/或渗出物构成。组织学上，结石由嗜酸性物质组成，偶见嵌入的核物质，通常具有明显的层状结构。结石应与淀粉样小体（corpora amylacea，见 Renne et al. 2009）相鉴别，后者为小的、层状的嗜碱性小体，在大鼠和小鼠的呼吸道上皮及鼻腺腔内偶见。
诊断建议
由于结石通常是炎症的结果，可将其视为炎症反应的一个组成部分，在病理学描述中加以叙述，而不单独诊断。然而，如果结石的发生率出现与处理相关的增加，或者结石在无炎症的情况下出现，则必须在整项研究中单独诊断并赋予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
In the nasal cavity, concretions are almost always associated with inflammation ( Figure 1 and Figure 2 ). Concretions are found within the meatuses and are composed of inspissated nasal secretions and/or exudate. Histologically, concretions consist of eosinophilic material, occasionally with embedded nuclear material, and are typically distinctly laminated. Concretions should be distinguished from corpora amylacea (shown in Renne et al. 2009), which are small, laminated, basophilic bodies that are infrequently seen in the respiratory mucosa and nasal gland lumina of rats and mice.
Recommendation
Since they are usually a consequence of inflammation, concretions may be considered a component of the inflammatory response and described in the pathology narrative rather than diagnosed separately. If, however, there is a treatment-related increase in the incidence of concretions, or if they occur in the absence of inflammation, then they must be diagnosed separately throughout that study and assigned a severity grade.
呼吸上皮腺体扩张Respiratory Epithelium Glands Dilation 鼻扩张
描述（中文）
呼吸道上皮固有层内腺体扩张超过正常范围时，可能改变鼻中隔或鼻甲的 normal contour（正常轮廓）（Figure 1、Figure 2、Figure 3）。腺体扩张通常与炎症、上皮增生或化生等其他病变同时发生，但也可能作为原发性改变单独出现。
诊断建议
当这些腺体出现明显扩张且无明显的腺体增生时，应诊断为“鼻、呼吸道上皮、腺体 - 扩张”。诊断时，应对该病变进行严重程度分级。如果同时存在腺体增生，则应诊断增生，并在叙述中描述扩张。其他病变，如炎症或上皮变性，如果其显著程度或严重程度足以支持，则应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Dilation of glands in the lamina propria of the respiratory epithelium in excess of normal may alter the normal contour of the nasal septum or turbinates ( Figure 1 , Figure 2 , and Figure 3 ). Glandular dilation typically occurs concurrently with other lesions, such as inflammation and epithelial hyperplasia or metaplasia, but it may be seen separately as a primary change.
Recommendation
"Nose, Respiratory epithelium, Glands - Dilation" should be diagnosed when there is a clear dilation of these glands in the absence of obvious glandular hyperplasia. When diagnosed, this lesion should be assigned a severity grade. If glandular hyperplasia is present concurrently, the hyperplasia should be diagnosed and the dilation described in the narrative. Other lesions, such as inflammation or epithelial degeneration, should be diagnosed separately, if warranted by their prominence or degree of severity.
嗅上皮呼吸上皮化生Olfactory Epithelium Metaplasia Respiratory 鼻化生
描述（中文）
呼吸道上皮化生（respiratory metaplasia）定义为嗅上皮被纤毛呼吸上皮所取代（Figure 1、Figure 2、Figure 3、Figure 4）。呼吸道上皮化生的存在意味着嗅上皮已通过坏死或萎缩发生了丧失。在受影响的嗅上皮下方，可发生与处理相关的嗅神经萎缩。在对照动物中，有时可见小的 局灶性（focal）、单侧呼吸道上皮化生区域（Figure 4）。
诊断建议
呼吸道上皮化生应当被诊断并分级。当鼻为明显或潜在靶器官时，对照动物中所见的小的、局灶性（focal） 病变应当被诊断。与嗅上皮呼吸道上皮化生相关的坏死或萎缩不应被诊断，除非它明确是一个独立过程，且嗅上皮其他部位存在萎缩或坏死区域。呼吸道上皮化生常见于受影响的嗅上皮下方 Bowman 腺（Bowman’s glands）的上皮中。这可在叙述中描述，而不单独诊断，除非其显著程度或严重程度 warrant（需要）单独诊断（见 Nose - Olfactory Epithelium, Glands - Metaplasia）。嗅神经萎缩也应在叙述中描述，除非其严重程度 warrant 单独诊断。相关链接：Nose - Olfactory Epithelium, Glands - Metaplasia
参考切片图（2 张）
查看英文原文
Comment
Respiratory metaplasia is defined as the replacement of olfactory epithelium with a ciliated, respiratory epithelium ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). The presence of respiratory metaplasia implies that loss of olfactory epithelium has occurred through necrosis or atrophy. Treatment-related atrophy of olfactory nerves beneath the affected olfactory epithelium can occur. Small focal, unilateral areas of respiratory metaplasia can sometimes be seen in control animals ( Figure 4 ).
Recommendation
Respiratory metaplasia should be diagnosed and graded. Small, focal lesions seen in control animals should be diagnosed when the nose is an obvious or potential target organ. Necrosis or atrophy associated with respiratory metaplasia of the olfactory epithelium should not be diagnosed unless it is clearly a separate process and atrophic or necrotic areas are present elsewhere in the olfactory epithelium. It is common for respiratory metaplasia to be present in the epithelium of the Bowman’s glands beneath the affected olfactory epithelium. This can be described in the narrative and not diagnosed separately unless warranted by its prominence or severity (see Nose - Olfactory Epithelium, Glands - Metaplasia ). Atrophy of the olfactory nerves should also be described in the narrative, unless its severity warrants a separate diagnosis. Related Links: Nose - Olfactory Epithelium, Glands - Metaplasia
嗅上皮基底细胞增生Olfactory Epithelium Hyperplasia Basal Cell 鼻增生
描述（中文）
嗅上皮基底细胞增生（basal cell hyperplasia of the olfactory epithelium）的特征是基底细胞沿嗅上皮基底膜（basement membrane）增生。增生的细胞在基底膜上方形成一层清晰可辨的细胞层。这些细胞以基底膜为界，不延伸至下方的固有层（lamina propria）（后者是非典型嗅上皮增生的特征——见鼻——上皮——增生，非典型）。通常伴有并发的嗅上皮改变，如变性或呼吸上皮化生。
诊断建议
当增生的基底细胞未越过基底膜延伸至固有层时，应诊断鼻嗅上皮基底细胞增生并给出严重程度分级。若基底细胞越过基底膜延伸，则应诊断非典型增生（见鼻——上皮——增生，非典型）。相关病变，如炎症或变性，应单独诊断。相关链接：鼻——上皮——增生，非典型
参考切片图（2 张）
查看英文原文
Comment
Basal cell hyperplasia of the olfactory epithelium is characterized by a proliferation of basal cells along the basement membrane of the olfactory epithelium. The proliferating cells form a distinctly identifiable layer above the basement membrane. The cells are bounded by the basement membrane and do not extend into the subjacent lamina propria (which is a feature of atypical olfactory epithelial hyperplasia - see Nose - Epithelium - Hyperplasia, Atypical ). Usually, there are concurrent olfactory epithelial changes, such as degeneration or respiratory metaplasia.
Recommendation
Basal cell hyperplasia of the nasal olfactory epithelium should be diagnosed and given a severity grade when the proliferating basal cells do not extend beyond the basement membrane into the lamina propria. If the basal cells extend beyond the basement membrane, atypical hyperplasia should be diagnosed (see Nose - Epithelium - Hyperplasia, Atypical ). Associated lesions, such as inflammation or degeneration, should be diagnosed separately. Related Links: Nose - Epithelium - Hyperplasia, Atypical
嗅上皮腺体化生Olfactory Epithelium Glands Metaplasia 鼻化生
描述（中文）
鲍曼腺化生（Bowman's gland metaplasia）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6、Figure 7）与嗅上皮化生（参见 Nose - Epithelium - Metaplasia, Squamous 和 Nose - Olfactory Epithelium - Metaplasia, Respiratory）相似，但发生于衬覆鲍曼腺的上皮。在呼吸上皮化生中，正常的鲍曼腺上皮被纤毛呼吸上皮取代（杯状细胞数量可能不等）。在鳞状化生中，上皮被鳞状上皮取代。部分病例中可能存在鳞状与呼吸上皮混合性化生，并可伴有增生、扩张、萎缩和/或炎症。诊断应基于所存在的最显著病变。
诊断建议
当“Nose, Olfactory epithelium, Glands - Metaplasia”存在于被覆上皮无病变的情况下、当化生类型与被覆上皮的化生类型不同时（例如被覆上皮为鳞状化生而腺体为呼吸上皮化生）、或当其显得过于严重或过度时，应作出该诊断。否则，该化生应作为被覆上皮化生的组成部分在病理学描述中加以描述。所存在的化生上皮类型（呼吸上皮或鳞状上皮）应作为修饰词纳入诊断。与嗅上皮相关的腺体被假定为鲍曼腺，因此诊断中不必注明“Bowman's”。应根据病变范围赋予其严重程度分级。相关链接：Nose - Epithelium - Metaplasia, Squamous Nose - Olfactory Epithelium, Glands - Hyperplasia Nose - Olfactory Epithelium - Metaplasia, Respiratory
参考切片图（2 张）
查看英文原文
Comment
Bowman's gland metaplasia ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 , and Figure 7 ) is similar to metaplasia of olfactory epithelium (see Nose - Epithelium - Metaplasia, Squamous and Nose - Olfactory Epithelium - Metaplasia, Respiratory ) but occurs in the epithelium lining the Bowman’s glands. In respiratory metaplasia, the normal Bowman’s gland epithelium is replaced by ciliated respiratory epithelium (there may be variable numbers of goblet cells). In squamous metaplasia, the epithelium is replaced by squamous epithelium. There may be mixed squamous and respiratory metaplasia in some cases, as well as the presence of hyperplasia, dilation, atrophy, and/or inflammation. Diagnoses should be based on the most prominent lesion(s) present.
Recommendation
"Nose, Olfactory epithelium, Glands - Metaplasia" should be diagnosed whenever it is present in the absence of lesions to the overlying epithelium, when the type of metaplasia differs from that of the overlying epithelium (e.g., squamous in the overlying epithelium and respiratory in the glands), or if it appears to be overly severe or excessive. Otherwise, the metaplasia should be described in the pathology narrative as a component of the metaplasia of the overlying epithelium. The type of metaplastic epithelium present (respiratory or squamous) should be included in the diagnosis as a modifier. Glands associated with the olfactory epithelium are assumed to be Bowman's glands, so it is not necessary to specify "Bowman's" in the diagnosis. It should be assigned a severity grade based on the extent of the lesion. Related Links: Nose - Epithelium - Metaplasia, Squamous Nose - Olfactory Epithelium, Glands - Hyperplasia Nose - Olfactory Epithelium - Metaplasia, Respiratory
嗅上皮腺体增生Olfactory Epithelium Glands Hyperplasia 鼻增生
描述（中文）
鲍曼腺（Bowman's glands）的增生和扩张（Figure 1、Figure 2）是相对常见的病变，并且与嗅上皮改变伴随出现，程度不一。增生可能伴有鳞状化生或呼吸上皮化生（见鼻-嗅上皮，腺体-化生）。
诊断建议
鲍曼腺的增生应当进行诊断并分级，分级依据为存在的鲍曼腺数量。部位应记录为“嗅上皮，腺体”。部位中不必特别注明“鲍曼腺”，因为与嗅上皮相关的腺体将被默认为鲍曼腺。当鲍曼腺的增生和扩张同时存在时，只诊断鲍曼腺增生并给出严重程度分级，扩张则在病理描述中叙述。如果仅存在扩张，则诊断扩张并给出严重程度分级。当存在呼吸上皮化生时，一般不需要单独诊断，除非其严重程度足以支持单独诊断。然而，化生的存在应在病理描述中叙述。相关链接：鼻-嗅上皮，腺体-化生
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia and dilation of the Bowman’s glands ( Figure 1 and Figure 2 ) are relatively common lesions and are seen to variable degrees in conjunction with olfactory epithelial changes. The hyperplasia may be accompanied by squamous metaplasia or respiratory metaplasia (see Nose - Olfactory Epithelium, Glands - Metaplasia ).
Recommendation
Hyperplasia of the Bowman's glands should be diagnosed and graded with grading based on the number of Bowman's glands present. The site should be "olfactory epithelium, glands." It is not necessary to specify "Bowman's glands" in the site because glands associated with the olfactory epithelium will be assumed to be Bowman's glands. When both hyperplasia and dilation of the Bowman's glands are present, only Bowman's gland hyperplasia should be diagnosed and given a severity grade, with the dilation described in the pathology narrative. If only dilation is present, then dilation is diagnosed and given a severity grade. A separate diagnosis of respiratory metaplasia, when present, is generally not needed unless warranted by severity. The presence of metaplasia, however, should be described in the pathology narrative. Related Links: Nose - Olfactory Epithelium, Glands - Metaplasia
嗅上皮萎缩Olfactory Epithelium Atrophy 鼻萎缩
描述（中文）
嗅上皮萎缩（olfactory epithelial atrophy）是指上皮细胞丢失，导致上皮变薄、细胞数量减少（Figure 1、Figure 2、Figure 3、Figure 4）。上皮表面可能覆盖立方至柱状无纤毛上皮。它通常是鼻部一系列变化的一部分，这些变化包括炎症、变性或坏死，以及呼吸上皮或鳞状上皮化生。事实上，嗅上皮萎缩往往是嗅上皮变性或坏死的最终结果。下方的鼻甲骨也可能发生萎缩。
诊断建议
当病变与其他嗅上皮变化（如变性、坏死或呼吸上皮化生）明显分开时，应诊断嗅上皮萎缩。炎症、嗅神经萎缩和鼻甲萎缩可能伴随上皮变化出现，应分别诊断（见 Nose - Inflammation；Nose - Nerve - Atrophy；和 Nose - Turbinate - Atrophy）。相关链接：Nose - Inflammation Nose - Nerve - Atrophy Nose - Turbinate - Atrophy
参考切片图（2 张）
查看英文原文
Comment
Olfactory epithelial atrophy is a loss of cells from the epithelium, resulting in a thinner and less cellular epithelium ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). The epithelial surface may be covered with cuboidal to columnar nonciliated epithelium. It is often part of a spectrum of changes in the nose that includes inflammation, degeneration or necrosis, and respiratory or squamous metaplasia. In fact, olfactory epithelial atrophy is often the end result of degeneration or necrosis of the olfactory epithelium. The underlying turbinate bone may also be atrophic.
Recommendation
Olfactory epithelial atrophy should be diagnosed when a lesion is clearly separate from other olfactory epithelial changes such as degeneration, necrosis, or respiratory epithelial metaplasia. Inflammation, olfactory nerve atrophy, and turbinate atrophy may accompany the epithelial changes and should be diagnosed separately (see Nose - Inflammation ; Nose - Nerve - Atrophy ; and Nose - Turbinate - Atrophy ). Related Links: Nose - Inflammation Nose - Nerve - Atrophy Nose - Turbinate - Atrophy
嗜酸性物质Eosinophilic Material 鼻其他
描述（中文）
鼻——嗜酸性物质（eosinophilic material）是鼻腔黏膜下可能蓄积的任何无定形、嗜酸性物质的总称，包括淀粉样物质（amyloid）。嗜酸性物质蓄积的常见部位是犁鼻器（vomeronasal organ）背侧的腹侧鼻中隔（Figure 1）。该物质此前因其形态学外观而被认为是淀粉样物质，但Doi等人（2007、2009、2010）近期的数篇论文表明，该物质在许多情况下并非淀粉样物质，而是由胶原和复杂碳水化合物组成，可能由鼻腔腺上皮细胞产生，且刚果红（Congo red）染色阴性。然而，在某些情况下，淀粉样物质沉积相对常见，并可在鼻腔内发现。
诊断建议
在缺乏特殊染色或免疫组化染色证明该物质为淀粉样物质的情况下，此变化应诊断为“鼻——嗜酸性物质”。由于这是一种随年龄增长而增加的自发性变化，且迄今未知其会随受试物处理而增加，因此除非有明确证据表明存在处理相关效应，否则不应诊断该病变。此变化无需分级，除非分级有助于阐明处理效应。
参考切片图（2 张）
查看英文原文
Comment
Nose - Eosinophilic material is a general term for any amorphous, eosinophilic material that may accumulate in the submucosa in the nasal cavity, including amyloid. A common site for accumulation of eosinophilic material is the ventral nasal septum just dorsal to the vomeronasal organ ( Figure 1 ). This material was previously thought to be amyloid due to its morphologic appearance, but several recent publications by Doi et al. (2007, 2009, 2010) have shown that this material is not, in many cases, amyloid but consists of collagen and complex carbohydrates that may be produced by nasal gland epithelial cells that is Congo red negative. In some cases, however, amyloid deposition is relatively common and can be found in the nasal cavity.
Recommendation
In the absence of special or immunohistochemical stains showing that the material is amyloid, this change should be diagnosed as "Nose - Eosinophilic material." Since this is a spontaneous change that increases with age and, to date, is not known to be increased with treatment, this lesion should not be diagnosed unless there is clear evidence of a treatment-related effect. This change need not be graded unless grading would clarify a treatment effect.
异物Foreign Body 鼻其他
描述（中文）
异物（foreign body）是大鼠和小鼠常见的背景性病变，通常不与暴露浓度相关。“异物”一词指鼻腔内任何异常物质。如果异物形态与受试物一致、仅见于暴露动物，且其数量与暴露浓度相关，则应使用“外来物质（foreign material）”一词而非异物（见 Nose - Foreign Material）。最常见的异物为毛干（Figure 1）和植物性物质（饲料或垫料）。毛干呈半透明、多层结构，饲料或植物性垫料可通过植物细胞壁的存在加以识别。通常该物质无法被识别（Figure 2、Figure 3，箭头）。异物可见于鼻腔任何部位、泪管、切牙管或嵌埋于组织中。吸入的物质通常引起局灶性（focal）化脓性、化脓性肉芽肿性或肉芽肿性反应，且通常被聚集的巨噬细胞和/或中性粒细胞所包围。异物邻近的上皮也可能出现改变（例如坏死或变性、鳞状化生或增生）。
诊断建议
异物存在时应作出诊断，但不应进行分级。如果异物位于鼻腔腔道以外的部位（例如泪管或鼻咽管），应在诊断中以部位修饰词标明该部位。异物可能伴随的炎症及任何上皮改变不应单独诊断，除非其严重程度足以支持单独诊断。当根据形态、与暴露浓度的相关性以及仅见于暴露动物而认为该物质为受试物时，应使用“外来物质”一词。相关链接：Nose - Foreign Material
参考切片图（2 张）
查看英文原文
Comment
Foreign bodies are a common background finding in rats and mice and are not typically correlated with exposure concentration. The term "foreign body" refers to any aberrant material in the nasal cavity. If the morphology of the foreign material is consistent with the test agent, if the material is seen only in exposed animals, and if the amount of material correlates with the exposure concentration, the term “foreign material” should be used rather than foreign body (see Nose - Foreign Material ). The most common foreign bodies are hair shafts ( Figure 1 ) and plant material (feed or bedding). Hair shafts are translucent and multilayered, and feed or plant-based bedding can be identified by the presence of plant cell walls. Often the material cannot be identified ( Figure 2 and Figure 3 , arrows). Foreign bodies can be found anywhere in the nasal cavity, in the lacrimal ducts, in the incisive ducts, or embedded in the tissues. The inhaled material typically incites a focal suppurative, pyogranulomatous, or granulomatous reaction and is usually surrounded by accumulations of macrophages and/or neutrophils. The epithelium adjacent to the foreign body may also show changes (e.g., necrosis or degeneration, squamous metaplasia, or hyperplasia).
Recommendation
Foreign bodies should be diagnosed when present but should not be graded. If the foreign body is in a location other than the nasal lumen (e.g., lacrimal duct or nasopharyngeal duct), the location should be identified in the diagnosis with a site modifier. The inflammation and any epithelial changes that may accompany a foreign body should not be diagnosed separately unless warranted by severity. The term "foreign material" should be used when the material is thought to be the test agent based on morphology, correlation with exposure concentration, and presence only in exposed animals. Related Links: Nose - Foreign Material
异物Foreign Material 鼻其他
描述（中文）
异物（foreign material）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5）是指吸入的颗粒状受试物或推定的受试物。因此，该术语仅适用于吸入研究或受试物被吸入或呼出至鼻腔的灌胃研究。“色素沉着（pigmentation）”一词专用于鼻腔内发现的内源性色素（含铁血黄素、脂褐素），不应用于外源性物质（见 Nose - Pigment）。如果该物质具有预期的形态学外观、仅在染毒动物中发现、且数量随暴露水平升高而增加，则可假定其为受试物。可将异物的形态学外观与肺内发现的物质进行比较（Figure 5），在吸入研究中，肺内的该物质通常更为丰富。“异物（foreign body）”一词专用于在对照动物和染毒动物中均发现的、或严重程度不随暴露水平升高而增加的吸入性植物碎片（饲料或垫料）、毛发碎片或其他物质（见 Nose - Foreign Body）。在鼻腔中见到受试物并不常见。少量惰性颗粒可能仅引起轻微反应，但反应性较强的物质可能引起炎症反应和鼻上皮的改变（例如变性或坏死、化生、萎缩）。
诊断建议
异物（受试物或推定的受试物）只要存在即应作出诊断并分级。具体部位（例如呼吸上皮或嗅上皮、鼻咽管）应作为部位修饰词在诊断中标明。如果异物存在于鼻腔腔内或存在于一个以上部位，则可省略部位修饰词，并在病理学描述中描述这些部位。相关病变（例如炎症、坏死、纤维化、上皮增生）应单独诊断并分级。相关链接：Nose - Foreign Body Nose - Pigment
参考切片图（2 张）
查看英文原文
Comment
Foreign material ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , and Figure 5 ) refers to inhaled particulate test material or presumed test material. Therefore, this term applies only to inhalation studies or gavage studies in which the test material has been inhaled or exhaled into the nasal cavity. The term "pigmentation" is reserved for endogenous pigments (hemosiderin, lipofuscin) found in the nose and should not be used for exogenous material (see Nose - Pigment ). If the material has the expected morphologic appearance, is found only in treated animals, and increases in amount with increasing exposure level, it may be assumed to be the test agent. The morphologic appearance of the foreign material can be compared to the material found in the lung ( Figure 5 ), where, in inhalation studies, it will usually be more abundant. The term “foreign body” is reserved for inhaled bits of plant material (feed or bedding), hair fragments, or other substances that are found in control and treated animals or do not increase in severity with increasing exposure level (see Nose - Foreign Body ). It is uncommon to see the test agent in the nose. There may be little response to small amounts of inert particles, but more reactive materials may elicit an inflammatory response and changes in the nasal epithelium (e.g., degeneration or necrosis, metaplasia, atrophy).
Recommendation
Foreign material (test material or presumed test material) should be diagnosed and graded whenever present. The specific location (e.g., respiratory or olfactory epithelium, nasopharyngeal duct) should be indicated in the diagnosis as a site modifier. If the foreign material is present in the nasal lumen or in more than one location, the site modifier may be omitted and the locations described in the pathology narrative. Associated lesions (e.g., inflammation, necrosis, fibrosis, epithelial hyperplasia) should be diagnosed and graded separately. Related Links: Nose - Foreign Body Nose - Pigment
斯滕森腺变性Steno's Glands Degeneration 鼻变性
描述（中文）
Steno's glands（斯坦诺腺），也称为侧鼻腺（lateral nasal glands），环绕上颌窦（maxillary sinuses）并延伸至外侧壁（Figure 1）。这些腺体的导管开口于鼻前庭（nasal vestibule）。在 mice 中，局灶性（focal） 萎缩可作为衰老性改变出现，但较为罕见。已知 Steno's glands 具有高代谢能力，可成为某些化学物的靶标。萎缩是细胞因坏死、凋亡或变性而丢失的最终结果，表现为腺体缺失或数量减少，或腺体皱缩（Figure 2、Figure 3、Figure 4）。通常，腺体导管仍然保留。腺体丢失或皱缩所留下的空间可能仅含有正常的细胞外基质（extracellular matrix），或者腺体可能被纤维化（fibrosis）所取代。Steno's glands 的坏死以出现核固缩（pyknotic nuclei）、胞质嗜酸性（cytoplasmic eosinophilia）、细胞轮廓不清（indistinct cell outlines），或细胞及细胞碎片脱落（exfoliation）为特征。变性被认为是细胞损伤的可逆形式，以细胞起泡（cell blebbing）、细胞排列紊乱（cellular disorientation）、细胞嗜酸性（cellular eosinophilia）、肿胀、细胞间接触丧失，或上皮内空泡化改变（vacuolar changes）为特征，并且也可能伴有炎症（inflammation）。变性和坏死可能伴有炎症。
诊断建议
无论何时出现，Steno's glands 的变性、坏死和萎缩均应作出诊断并赋予严重程度分级。当 Steno's gland 组织量减少但几乎没有变性、坏死或炎症的证据时，应诊断为 Steno's glands 萎缩。如果存在上述变性或坏死的特征，则诊断应按此记录。如果同时存在炎症，不应单独诊断，除非其显著程度或严重程度足以支持单独诊断，但应在病理学描述（pathology narrative）中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Steno's glands, also called the lateral nasal glands, surround the maxillary sinuses and extend into the lateral wall ( Figure 1 ). The ducts of these glands empty into the nasal vestibule. Focal atrophy can be seen as an aging change in mice, but this is rare. Steno's glands are known to have high metabolic capacity and can be targeted by certain chemicals. Atrophy, the end product of cell loss due to necrosis, apoptosis, or degeneration, manifests as the absence or a decrease in number of glands, or shrunken glands ( Figure 2 , Figure 3 , and Figure 4 ). Often, the glandular ducts remain. The space left by the loss or shrinkage of the glands may simply contain the normal extracellular matrix, or the glands may be replaced by fibrosis. Necrosis of Steno's glands is characterized by the presence of pyknotic nuclei, cytoplasmic eosinophilia, indistinct cell outlines, or exfoliation of cells and cellular debris. Degeneration, which is considered to be reversible form of cell damage, is characterized by cell blebbing, cellular disorientation, cellular eosinophilia, swelling, loss of cell-to-cell contact, or vacuolar changes within the epithelium and also may be accompanied by inflammation. Degeneration and necrosis may be accompanied by inflammation.
Recommendation
Whenever present, degeneration, necrosis, and atrophy of Steno's glands should be diagnosed and assigned a severity grade. Atrophy of Steno's glands should be diagnosed when the amount of Steno's gland tissue is decreased but there is little evidence of degeneration, necrosis, or inflammation. If the features of degeneration or necrosis described above are present, then the diagnosis should be recorded as such. If inflammation is present concurrently, it should not be diagnosed separately unless warranted by its prominence or severity, but should be described in the pathology narrative.
杯状细胞增生Hyperplasia Goblet Cell 鼻增生
描述（中文）
杯状（黏液）细胞增生（Goblet (mucous) cell hyperplasia）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5）见于暴露于某些刺激物之后，可能是对轻度刺激物短期暴露的唯一反应性改变。最常发生于鼻腔内衬覆移行上皮和呼吸上皮的区域（level I 和 II）。呼吸上皮正常情况下含有少量杯状细胞；当病变位于移行上皮（正常情况下缺乏杯状细胞）时，“化生（metaplasia）”一词可能更为准确。然而，为保持一致性，NTP 倾向于对该病变使用“增生（hyperplasia）”一词，无论上皮类型如何。该病变的特征是上皮衬覆中出现杯状细胞（在移行上皮中）或杯状细胞数量增多（在呼吸上皮中）。杯状细胞可形成上皮内腺体，或相互融合形成黏液囊肿（mucous cysts）（Figure 5，箭头）。杯状细胞增生在短期和长期研究中均可见到。它被认为是暴露于刺激物的一种适应性反应，不被视为癌前性改变。
诊断建议
杯状细胞增生一旦出现即应诊断，并赋予严重程度分级。受影响的皮类型应通过部位修饰词在诊断中注明（例如，呼吸上皮或移行上皮）。杯状细胞可能增大或肥大，但不应同时诊断杯状细胞肥大；肥大的情况应在病理描述中叙述。相关病变，如炎症或上皮增生，应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Goblet (mucous) cell hyperplasia ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , and Figure 5 ) is seen after exposure to some irritants and may be the only change noted in response to short-term exposure to a mild irritant. It is most often seen in areas of the nasal cavity that are lined by transitional and respiratory epithelium (levels I and II). The respiratory epithelium normally contains a few goblet cells; the term "metaplasia" may be more correct when the lesion is present in the transitional epithelium (which normally lacks goblet cells). However, to maintain consistency, the NTP prefers the term "hyperplasia" for this lesion, regardless of the epithelial type. The lesion is characterized by the presence of (in transitional epithelium) or increase in the number of (in respiratory epithelium) goblet cells in the epithelial lining. The goblet cells may form intraepithelial glands, or they may coalesce to form mucous cysts ( Figure 5 , arrow). Goblet cell hyperplasia has been seen in both short- and long-term studies. It is thought to be an adaptive response to irritant exposure and is not considered a preneoplastic change.
Recommendation
Goblet cell hyperplasia should be diagnosed whenever it is present and assigned a severity grade. The type of epithelium affected should be indicated in the diagnosis by a site modifier (e.g., respiratory epithelium or transitional epithelium). The goblet cells may be enlarged or hypertrophied, but goblet cell hypertrophy should not be concurrently diagnosed; rather, the hypertrophy should be described in the pathology narrative. Associated lesions, such as inflammation or epithelial hyperplasia, should be diagnosed separately.
炎性息肉Polyp Inflammatory 鼻炎症
描述（中文）
炎性息肉（inflammatory polyp）是增殖性、成熟、非肿瘤性的纤维结缔组织向鼻腔腔内突出的结构（Figure 1、Figure 2）。其内通常有数量不等的混合性炎性细胞浸润，表面覆盖分化良好的立方或柱状上皮。炎性息肉与慢性刺激有关，例如与牙发育不良相关的刺激或由受试物暴露引起的刺激。
诊断建议
炎性息肉只要存在即应诊断。邻近组织中的炎症及其他变化应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
An inflammatory polyp is a projection of proliferative, mature, nonneoplastic, fibrous connective tissue into the nasal lumen ( Figure 1 and Figure 2 ). It is typically infiltrated by variable numbers of mixed inflammatory cells and covered with a well-differentiated cuboidal or columnar epithelium. Inflammatory polyps have been associated with chronic irritation, such as that associated with dental dysplasia or caused by test article exposure.
Recommendation
Inflammatory polyps should be diagnosed whenever present. Inflammation and other changes in adjacent tissues should be diagnosed separately.
炎症Inflammation 鼻炎症
描述（中文）
在NTP研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞是中性粒细胞（neutrophil），尽管也可能存在较少的巨噬细胞（macrophage）和淋巴细胞（lymphocyte）。还可能有水肿或充血（hyperemia）的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但中性粒细胞聚集，其中许多发生退变（化脓性渗出物，化脓性 exudate）。渗出物中还可能存在来自 resident 细胞群和浸润白细胞的细胞碎片；含纤维蛋白（fibrin）的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞（plasma cell）；以及可能的感染因子。肉眼上，这些病变以脓液存在为特征。渗出物周围组织可能含有成纤维细胞（fibroblast）、纤维结缔组织（fibrous connective tissue）和混合性炎症细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导。淋巴细胞在慢性活动性炎症中也占主导，但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大的、活化的巨噬细胞、上皮样巨噬细胞（epithelioid macrophage）或多核巨细胞（multinucleated giant cell）。炎症与细胞浸润的鉴别在于存在其他改变，如水肿、出血、变性、坏死或其他组织损伤证据。鼻部炎症常与其他病变同时出现，如邻近上皮的坏死、增生、化生或萎缩。也可能见到其他可能为病因的相关病变，如异物（foreign body）（Figure 1）或鼻甲（turbinate）骨坏死（Figure 3）。当观察到的鼻部病变符合提示性模式时（例如Figure 4、Figure 5、Figure 6、Figure 7所示），需要考虑反流诱导的鼻部病变。反流相关病变倾向于在鼻腔腹侧和外侧更为严重，在鼻背内侧切面较不明显，在后部鼻切面更为严重，严重程度在前部鼻切面逐渐减弱。反流诱导的鼻部病变可能以单侧为主。
诊断建议
当鼻部炎症是原发性病变时，应当诊断并分级。如果在整个研究过程中炎症被认为是另一过程（例如坏死）的继发性改变，则不应单独诊断炎症，而应在叙述中将其描述为原发性病变的组成部分，除非炎症严重到足以需要单独诊断，或与原发性病变相比严重程度不成比例。炎症的诊断应包括炎症类型（急性、慢性等）作为修饰词，以及鼻腔内病变位置作为部位修饰词（例如呼吸上皮、嗅上皮、鼻咽管、犁鼻器）。如果多个部位受累，诊断应按受累上皮类型（即鳞状、移行、呼吸或嗅上皮）分开，但同时受累部位（如鼻泪管或犁鼻器）的炎症可在病理学叙述中描述。病理学叙述应描述炎症的特征、鼻腔内浆液性、纤维蛋白性或黏液性液体的存在，并注明相关病变。骨和软骨改变以及粘连（synechia）（如果存在）应单独诊断。如果有感染因子（如真菌）或与病变相关的异物，也应单独诊断（细菌除外，细菌不应单独诊断，而应在叙述中描述）。相关链接：鼻 - 嗅上皮 - 萎缩
参考切片图（2 张）
查看英文原文
Comment
In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate). Cell debris, from both the resident cell populations and infiltrating leukocytes; proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells; and, possibly, an infectious agent may also be present in within the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may contain fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammation is differentiated from cellular infiltrates by the presence of other changes, such as edema, hemorrhage, degeneration, necrosis, or other evidence of tissue damage. Nasal inflammation is frequently seen in conjunction with other lesions, such as necrosis, hyperplasia, metaplasia, or atrophy of the adjacent epithelium. Other associated lesions that may be causative, such as a foreign body ( Figure 1 ) or bone necrosis in the turbinates ( Figure 3 ) may also be seen. Reflux-induced nasal lesions need to be considered when the observed nasal lesions fit a suggestive pattern (e.g., as shown in Figure 4 , Figure 5 , Figure 6 , and Figure 7 ). Reflux-related lesions tend to be more severe ventrally and laterally in the nasal cavity, less pronounced in the dorsal medial sections of the nose, and more severe in the posterior nasal sections, with severity tapered off in the anterior nasal sections. Reflux-induced nasal lesions may have a unilateral predominance.
Recommendation
Inflammation of the nose should be diagnosed and graded when it is a primary lesion. If the inflammation is considered to be secondary to another process (e.g., necrosis) throughout the study, then the inflammation should not be diagnosed separately but should be described in the narrative as a component of the primary lesion, unless the inflammation is severe enough to warrant a separate diagnosis or is disproportionately severe compared to the primary lesion. The diagnosis of inflammation should include the type of inflammation (acute, chronic, etc.) as a modifier, and the location of the lesion within the nasal cavity as a site modifier (e.g., respiratory epithelium, olfactory epithelium, nasopharyngeal duct, vomeronasal organ). If multiple sites are affected, the diagnoses should be separated by type of epithelium affected (i.e., squamous, transitional, respiratory, or olfactory), but inflammation of concurrently affected sites, such as the nasolacrimal ducts or the vomeronasal organ, may be described in the pathology narrative. The pathology narrative should describe the features of the inflammation, presence of serous, fibrinous, or mucous fluid within the nasal cavity, and note associated lesions. Osseous and cartilaginous changes, as well as synechia, if present, should be diagnosed separately. If there is an infectious agent, such as fungus, or a foreign body associated with the lesion, it should also be diagnosed separately (except for bacteria, which should not be diagnosed separately but should be described in the narrative). Related Links: Nose - Olfactory Epithelium - Atrophy
真菌Fungus 鼻其他
描述（中文）
在NTP毒性/致癌性研究的小鼠和大鼠鼻腔中偶尔可见真菌生物体，在大鼠中更为常见。真菌菌丝垫可能出现在鼻腔内（Figure 1、Figure 2、Figure 3、Figure 4），但组织侵袭极为罕见。根据真菌形态（特征性的分生孢子头和菌丝分支模式）及文献报道，这些真菌生物体通常为曲霉属（Aspergillus sp.），其中烟曲霉（Aspergillus fumigatus）最为常见。曲霉属（Aspergillus spp.）具有特征性的分生孢子头和菌丝分支模式（Figure 3）。真菌通常伴有化脓性炎症。邻近上皮通常存在增生和化生等改变，相关固有层下方常可见急性至慢性活动性炎症。
诊断建议
真菌存在时应予以诊断，但不应进行分级。真菌生物体的形态学特征应在描述中予以记录。仅凭组织病理学无法确切鉴定真菌的属/种；但可以表述其形态学特征与某一特定类型的真菌生物体相符。当严重程度需要时，所有相关病变应分别诊断并赋予严重程度分级。在可能的情况下，应在描述中注明相关病变是继发于真菌的存在，还是可能与受试物相关。
参考切片图（2 张）
查看英文原文
Comment
Fungal organisms are occasionally seen in the nasal cavities of mice and rats from NTP toxicity/carcinogenicity studies, more commonly in rats. Mats of fungal mycelia may occur within the nasal passages ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ), but tissue invasion is extremely rare. Based on fungal morphology (characteristic fruiting heads and hyphal branching patterns) and reports in the literature, the fungal organisms are usually an Aspergillus sp., with Aspergillus fumigatus being the most common. Aspergillus spp. have characteristic fruiting heads and hyphal branching patterns ( Figure 3 ). The fungi are typically accompanied by suppurative inflammation. Changes such as hyperplasia and metaplasia are usually present in the adjacent epithelium, and there is often acute to chronic-active inflammation in the associated underlying lamina propria.
Recommendation
Fungus should be diagnosed whenever present but should not be graded. The morphologic features of the fungal organisms should be described in the narrative. The fungal genera/species cannot be definitively identified by histopathology alone; however, it may be stated that the morphologic features are consistent with a particular type of fungal organism. When warranted by severity, all associated lesions should be diagnosed separately and assigned severity grades. Whenever possible, it should be noted in the narrative whether or not the associated lesions are secondary to the presence of the fungus or if they may be related to treatment.
神经萎缩Nerve Atrophy 鼻萎缩
描述（中文）
固有层（lamina propria）中的嗅神经（olfactory nerves）是来自嗅神经元（olfactory neurons）的轴突束，这些神经元的胞体位于嗅上皮（olfactory epithelium）中。这些神经无髓鞘，穿过筛骨（ethmoid bone）的孔洞，终止于嗅球（olfactory bulbs）。该病变的特征是嗅神经体积缩小、数量减少，严重病例中则完全消失（Figure 3）。嗅神经萎缩（Figure 1、Figure 2、Figure 3；与 Figure 4 中的正常对照比较）继发于嗅上皮中嗅神经细胞的丢失或脑嗅球的损伤。它最常见是嗅上皮中嗅神经元丢失的结果，因此该病变几乎总是伴随嗅上皮的改变，如萎缩或呼吸上皮化生（respiratory metaplasia）。由于这些病变通常是鼻腔内更大范围病变谱的一部分，因此也常同时存在炎症和呼吸上皮的改变。
诊断建议
嗅神经萎缩只要存在，就应诊断为“鼻，神经 - 萎缩”。应根据受累嗅神经的大小和数量进行分级。其他病变，包括嗅上皮萎缩或呼吸上皮化生，应单独诊断。观察到该病变应促使对脑嗅叶进行仔细检查。相关链接：鼻 - 嗅上皮 - 萎缩
参考切片图（2 张）
查看英文原文
Comment
The olfactory nerves in the lamina propria are bundles of axons from the olfactory neurons whose cell bodies lie in the olfactory epithelium. These nerves are unmyelinated and traverse openings in the ethmoid bone and terminate at the olfactory bulbs. The lesion is characterized by decreased size and number, or complete loss in severe cases ( Figure 3 ), of the olfactory nerves. Atrophy of the olfactory nerves ( Figure 1 , Figure 2 , and Figure 3 ; compare with normal control in Figure 4 ) is secondary to loss of olfactory nerve cells from the olfactory epithelium or to damage to the olfactory bulb of the brain. It is most commonly the result of loss of olfactory neurons in the olfactory epithelium, so the lesion almost always accompanies changes in the olfactory epithelium, such as atrophy or respiratory metaplasia. Since these lesions are usually part of a larger spectrum of lesions in the nasal cavity, inflammation and changes to the respiratory epithelium are often present as well.
Recommendation
Olfactory nerve atrophy should be diagnosed as "Nose, Nerve - Atrophy" whenever present. It should be graded based on the size and number of affected olfactory nerves. Other lesions, including olfactory epithelial atrophy or respiratory metaplasia, should be diagnosed separately. Observation of this lesion should prompt close examination of the olfactory lobe of the brain. Related Links: Nose - Olfactory Epithelium - Atrophy
色素Pigment 鼻色素沉着
描述（中文）
色素最常见于鼻腔被覆上皮及紧邻的固有层（Figure 1、Figure 2），但可发生于鼻腔任何部位，包括犁鼻器（Figure 3、Figure 4）。色素蓄积可继发于多种病理过程，包括炎症、变性或出血，其化学成分可有所不同。色素常含铁，可通过普鲁士蓝染色法显示（Figure 2、Figure 4）。由于受试物在组织中蓄积，鼻腔内可能见到色素性物质，此种情况下，该物质可引起坏死、炎症、呼吸上皮化生、上皮再生及其他病变。如果该物质仅见于染毒动物而对照组缺如，且该物质的量随染毒浓度增加而增加，则提示该物质为受试物。
诊断建议
色素一旦出现即应作出诊断并赋予严重程度分级。应通过在诊断中纳入部位修饰词来标明色素的位置（例如，呼吸上皮或嗅上皮、犁鼻器）。由于在组织学切片中，即使使用一系列特殊染色，往往也难以对色素作出明确鉴定，因此诊断为“色素”（而非诊断色素的类型，例如，含铁血黄素或脂褐素）最为恰当。色素的形态学特征应在病理学描述中予以描述。并非所有色素都应作出诊断，因为有些色素在老龄动物中普遍存在，或与其他某种疾病过程相关，而不具有毒理学意义。病理学家应运用其判断力来决定继发性色素沉积是否显著到足以 warrant 单独诊断。当病理学家确信该色素代表受试物的蓄积时，应将其诊断为异物（见 Nose - Foreign Material）。相关链接：Nose - Foreign Material
参考切片图（2 张）
查看英文原文
Comment
Pigment is most commonly seen in the epithelium lining the nasal cavity and the subjacent lamina propria ( Figure 1 and Figure 2 ) but can occur anywhere in the nasal cavity, including the vomeronasal organ ( Figure 3 and Figure 4 ). Pigment accumulation can be secondary to a number of pathologic processes, including inflammation, degeneration, or hemorrhage, and its chemical composition can vary. Pigment often contains iron, which can be demonstrated by the Prussian blue staining method ( Figure 2 and Figure 4 ). Pigmented material may be seen in the nasal cavity due to accumulation of the test agent in the tissues, in which case it may cause necrosis, inflammation, respiratory metaplasia, epithelial regeneration, and other lesions. If the material is seen only in treated animals and is absent from controls, and the amount of material increases with exposure concentration, this suggests that the material is the test agent.
Recommendation
Pigment should be diagnosed whenever present and assigned a severity grade. The location of the pigment should be indicated by including a site modifier in the diagnosis (e.g., respiratory or olfactory epithelium, vomeronasal organ). Since definitive pigment identification is often difficult in histologic sections, even with a battery of special stains, a diagnosis of "pigment" (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The morphologic features of the pigment should be described in the pathology narrative. Not all pigments should be diagnosed, as some are ubiquitous in aging animals or related to some other disease process and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether secondary deposits of pigment are prominent enough to warrant a separate diagnosis. When the pathologist is confident that the pigment represents accumulation of the test article, it should be diagnosed as foreign material (see Nose - Foreign Material ). Related Links: Nose - Foreign Material
骨骨膜增生Bone Periosteal Proliferation 鼻其他
描述（中文）
骨膜增生（periosteal proliferation）（Figure 1、Figure 2）可见于暴露于强刺激物（如催泪瓦斯）时，通常与上皮坏死、炎症、鳞状化生及其他刺激性病变相关。骨膜增生表现为骨小梁增厚，伴成骨细胞数量增多。
诊断建议
在无黏膜病变的情况下出现的骨膜增生必须作出诊断并赋予严重程度分级。然而，若该病变继发于黏膜病变或是黏膜病变的组成部分，则不应单独诊断，除非严重程度足以支持单独诊断，但应在病理学叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Periosteal proliferation ( Figure 1 and Figure 2 ) may be seen with exposure to severe irritants (e.g., tear gas) and is typically associated with epithelial necrosis, inflammation, squamous metaplasia, and other irritant lesions. Periosteal proliferation appears as thickening of the trabecular bone with increased numbers of osteoblasts.
Recommendation
Periosteal proliferation that is present in the absence of a mucosal lesion must be diagnosed and assigned a severity grade. If, however, this lesion is secondary to or a component of a mucosal lesion, it should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative.
鼻中隔穿孔Septum Perforation 鼻其他
描述（中文）
鼻中隔穿孔（septal perforation）（Figure 1、Figure 2）尚未被视为背景性病变。它通常发生于暴露于高度刺激性物质之后，这些物质引起黏膜坏死和溃疡以及鼻甲萎缩。因此，它通常先有或伴有上皮性病变，如鳞状化生、溃疡或坏死、炎症和鼻甲萎缩。它最常见于慢性吸入研究中。
诊断建议
鼻中隔穿孔只要存在就应诊断，但不必分级。其他病变，包括上皮性病变（变性、坏死、溃疡、鳞状化生等）、鼻甲萎缩和炎症，应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Septal perforation ( Figure 1 and Figure 2 ) has not been seen as a background lesion. It typically occurs after exposure to highly irritating agents that cause necrosis and ulceration of the mucosa and atrophy of the nasal turbinates. Therefore, it is typically preceded or accompanied by epithelial lesions, such as squamous metaplasia, ulceration or necrosis, inflammation, and turbinate atrophy. It is most commonly seen in chronic inhalation studies.
Recommendation
Septal perforation should be diagnosed whenever present but need not be graded. Other lesions, including epithelial lesions (degeneration, necrosis, ulceration, squamous metaplasia, etc.), turbinate atrophy, and inflammation, should be diagnosed separately.
鼻甲粘连Turbinate Synechia 鼻其他
描述（中文）
当一侧鼻甲与另一侧鼻甲（Figure 1、Figure 2、Figure 3）、同一鼻甲的另一部位、侧壁（Figure 4）或较少见地与鼻中隔发生粘连时，即可诊断为鼻甲粘连（turbinate synechia）。粘连通常是伴有上皮溃疡或其他黏膜炎症性、退行性/坏死性、再生性/增生性或化生性病变的慢性鼻腔病变的后遗症。大多数粘连倾向于累及上颌鼻甲（maxilloturbinate）和鼻鼻甲（nasoturbinate），但筛鼻甲（ethmoid turbinate）粘连确实也会发生。
诊断建议
粘连在对照动物中几乎从不见到，可作为坏死性、溃疡性或炎症性上皮病变慢性程度的指标，因此只要观察到即应诊断。粘连不应进行分级。任何伴随病变，如炎症、纤维化或上皮溃疡、变性或坏死，应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Turbinate synechia is diagnosed when there is adhesion of one turbinate to another turbinate ( Figure 1 , Figure 2 , and Figure 3 ), to another part of the same turbinate, to the lateral wall ( Figure 4 ), or, less commonly, to the nasal septum. Synechia is typically a sequela to chronic nasal lesions with epithelial ulceration or other mucosal inflammatory, degenerative/necrotic, regenerative/hyperplastic, or metaplastic lesions. Most synechiae tend to involve the maxilloturbinates and nasoturbinates, but synechia of the ethmoid turbinates does occur.
Recommendation
Synechiae are almost never seen in control animals and can be an indicator of the chronicity of necrotic, ulcerative, or inflammatory epithelial lesions and should therefore be diagnosed whenever they are observed. Synechiae should not be graded. Any accompanying lesions, such as inflammation, fibrosis, or epithelial ulceration, degeneration, or necrosis, should be diagnosed separately.
鼻甲萎缩Turbinate Atrophy 鼻萎缩
描述（中文）
鼻甲萎缩（Figure 2、Figure 4；与Figure 1、Figure 3所示的对照相比）可在暴露于高刺激性物质后发生，最常见于慢性吸入研究中。它通常伴随或先于上皮性病变出现，如坏死或炎症。它可能伴有其他骨骼病变，如骨质增生（骨量增加）、鼻甲骨坏死或鼻中隔穿孔。炎症和上皮性病变也可能存在。鼻甲萎缩的发病机制尚未阐明，但据推测，慢性炎症期间上皮细胞和/或炎症细胞释放的细胞因子使骨吸收与新骨生成之间的平衡向破骨细胞活性方向偏移（可能还伴有成骨细胞活性降低），导致骨量净丢失。据报道，雄性比雌性更易发生鼻甲萎缩。
诊断建议
鼻甲萎缩只要存在就应诊断，并赋予严重程度分级。其他病变，包括鼻中隔穿孔和骨质增生，当其显著程度或严重程度足以支持时，应单独诊断。相关链接：鼻－嗅上皮－萎缩
参考切片图（2 张）
查看英文原文
Comment
Atrophy of the turbinats ( Figure 2 and Figure 4 ; compare with controls shown in Figure 1 and Figure 3 ) can occur after exposure to highly irritating agents and is most commonly seen in chronic inhalation studies. It is typically accompanied or preceded by epithelial lesions, such as necrosis or inflammation. It may be accompanied by other bone lesions, such as hyperostosis (increased bone), necrosis of the turbinate bone, or perforation of the nasal septum. Inflammation and epithelial lesions may also be present. The pathogenesis of turbinate atrophy has not been elucidated, but it has been hypothesized that cytokines released by epithelial cells and/or inflammatory cells during chronic inflammation shift the balance between bone resorption and new bone production toward osteoclastic activity (and perhaps decreased osteoblastic activity, as well), resulting in a net loss of bone. Males are reported to be more susceptible to atrophy of the turbinates than are females.
Recommendation
Atrophy of the turbinates should be diagnosed whenever present and assigned a severity grade. Other lesions, including perforation of the nasal septum and hyperostosis, should be diagnosed separately when warranted by their prominence or severity. Related Links: Nose - Olfactory Epithelium - Atrophy
鼻甲骨质增生Turbinate Hyperostosis 鼻其他
描述（中文）
骨肥厚（hyperostosis）是骨量增加导致解剖结构增厚的表现（Figure 1、Figure 2、Figure 3、Figure 4）。骨肥厚可能是一种全身性病变，颅骨骨骼增厚也可能出现。在鼻腔中，骨肥厚常与鼻黏膜萎缩相关，更常见于鼻甲骨，但也发生于鼻中隔（Figure 3）。推测的发病机制涉及因破骨细胞功能受损而导致的骨吸收减少。在某些病例中，可能出现部分鼻甲萎缩而另一些鼻甲骨肥厚的情况（Figure 4）。
诊断建议
骨肥厚只要存在就应诊断，并赋予严重程度分级。所有伴随病变，如炎症、鼻甲萎缩和嗅上皮萎缩，均应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Hyperostosis is an increase in the amount of bone resulting in a thickened anatomic structure ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Hyperostosis may be a systemic condition, and thickening of the bones of the skull may also be present. In the nose, it is often associated with atrophy of the nasal mucosa and is more commonly seen in turbinate bone, but it also occurs in the nasal septum ( Figure 3 ). The proposed pathogenesis involves decreased bone resorption due to impaired osteoclast function. In some cases, there may be atrophy of some turbinates and hyperostosis of others ( Figure 4 ).
Recommendation
Hyperostosis should be diagnosed whenever present and assigned a severity grade. All accompanying lesions, such as inflammation, turbinate atrophy, and olfactory epithelial atrophy, should be diagnosed separately.
囊肿Cyst 肾脏囊肿
描述（中文）
在啮齿类动物肾脏中可见多种肾囊肿（renal cyst）。囊肿可为先天性、获得性，或与慢性进行性肾病（慢性（chronic） progressive nephropathy）或化学物给药相关，也可能在其他肾脏病理改变缺如的情况下作为孤立性所见被注意到（Figure 1、Figure 2）。囊肿可为单发或多发，可发生于肾实质的任何部位，包括皮质、髓质或乳头。囊肿可起源于肾小管或肾小球（Figure 3）。部分囊肿可能由进行性扩张所致，而另一些则被推测起源于正在发生上皮细胞增殖的肾小管。大多数囊肿内衬扁平至立方上皮，外观空虚，或可含有嗜酸性或双嗜性均匀液体。较大的囊肿可伴有囊周和/或肾小管间质炎症及纤维化。囊肿可由化学物给药引起（Figure 4）。以多囊肾为表现形式的遗传性疾病已在大鼠和小鼠中有报道（Figure 5）。
诊断建议
原发性肾囊肿应予以诊断。其部位应在诊断中以部位修饰词标明（例如肾小管、肾小球）。囊肿无需给出严重程度分级，除非分级有助于突出毒性效应。作为继发性改变、与原发性病变（如慢性进行性肾病、间质纤维化和/或反流性肾病严重程度不断增加）相关的囊肿无需单独记录。然而，对作为继发机制出现的囊肿，需结合化学物给药情况仔细判读，并在适当时予以诊断。与肾囊肿相关的炎症，若其严重程度足以需要记录，或病理学家认为该炎症反应对全面理解囊性改变具有重要意义，则应予以记录。相关链接：肾脏 - 肾小管 - 扩张
参考切片图（2 张）
查看英文原文
Comment
A variety of renal cysts can be seen in rodent kidneys. Cysts may be congenital, acquired, or associated with chronic progressive nephropathy or chemical administration and may be noted as isolated findings in the absence of other renal pathology ( Figure 1 and Figure 2 ). They can be solitary or multiple and can occur anywhere in the renal parenchyma, cortex, medulla, or papilla. Cysts can arise from tubules or glomeruli ( Figure 3 ). Some cysts may arise from progressive dilation, whereas others have been postulated to arise from tubules undergoing epithelial cell proliferation. Most cysts are lined by flattened to cuboidal epithelium and appear empty or may contain eosinophilic or amphophilic homogeneous fluid. Larger cysts may be associated with pericystic and/or tubulointerstitial inflammation and fibrosis. Cysts may arise from chemical administration ( Figure 4 ). Hereditary conditions manifesting as polycystic kidneys have been reported in rats and mice ( Figure 5 ).
Recommendation
Primary renal cysts should be diagnosed. Their location should be indicated in the diagnosis with a site modifier (e.g., renal tubule, glomerulus). Cysts need not be given a severity grade unless grading would highlight a toxic effect. Cysts arising as secondary changes associated with a primary lesion such as with increasing severities of chronic progressive nephropathy, interstitial fibrosis, and/or retrograde nephropathy need not be recorded separately. However, the presence of cysts arising as a secondary mechanism needs to be carefully interpreted and diagnosed when appropriate with respect to chemical administration. Inflammation associated with renal cysts should be recorded if warranted by severity or if the pathologist deems the inflammatory reaction important to the overall understanding of the cystic change. Related Links: Kidney - Renal Tubule - Dilation
尿路上皮增生Urothelium Hyperplasia 肾脏增生
描述（中文）
肾盂（与肾乳头相对或位于肾穹窿处；Figure 1）的尿路上皮增生（urothelial hyperplasia）可作为化学诱导性病变观察到，也可作为与炎症相关的再生性病变（Figure 2）或继发于尿路上皮损伤的病变观察到。增生灶可为局灶性（focal）、多灶性（multifocal）或弥漫性（diffuse）。
诊断建议
尿路上皮增生应当被诊断并给予严重程度分级。在炎症区域或存在结石的情况下，病理学家应运用其判断来决定继发性尿路上皮增生是否显著到足以需要单独诊断。相关链接：肾脏 - 结石；肾脏 - 乳头，上皮 - 增生
参考切片图（2 张）
查看英文原文
Comment
Urothelial hyperplasia in the renal pelvis (opposite the renal papilla or in the renal fornices; Figure 1 ) may be observed as a chemically induced lesion or as a regenerative lesion associated with inflammation ( Figure 2 ) or secondary to an injury to the urothelium. Hyperplastic foci can be focal, multifocal, or diffuse.
Recommendation
Urothelial hyperplasia should be diagnosed and given a severity grade. In areas of inflammation or with the presence of calculi, the pathologist should use his or her judgment in deciding whether secondary urothelial hyperplasia is prominent enough to warrant a separate diagnosis. Related Links: Kidney - Calculus Kidney - Papilla, Epithelium - Hyperplasia
异位组织Ectopic Tissue 肾脏其他
描述（中文）
在罕见情况下，肾脏中可见各种肾外组织灶，尤其是靠近被膜处。已有报道发现肝组织和肾上腺组织（Figure 1、Figure 2）。这些异位组织为自发性发生，无病理学或毒理学意义。必须将其与原发或转移性肿瘤的存在相鉴别。
诊断建议
异位组织存在时应予以诊断，但不应进行分级。诊断应注明组织来源加以修饰（例如，肾脏 - 异位组织，肝）。相关链接：肾脏 - 化生，骨性
参考切片图（2 张）
查看英文原文
Comment
In rare cases, various foci of extrarenal tissue can be noted in the kidney, particularly near the capsule. Liver tissue and adrenal tissue have been reported ( Figure 1 and Figure 2 ). These ectopic tissues occur spontaneously with no pathologic or toxicologic significance. They must be differentiated from the presence of either primary or metastatic neoplasia.
Recommendation
Ectopic tissues should be diagnosed when present but should not be graded. The diagnosis should be modified with the tissue of origin (e.g., Kidney - Ectopic tissue, Liver). Related Links: Kidney - Metaplasia, Osseous
慢性进行性肾病Nephropathy Chronic Progressive 肾脏其他
描述（中文）
慢性进行性肾病（慢性（chronic） progressive nephropathy，CPN）是大鼠和小鼠最常见的自发病变之一，也是最重要的单一肾脏疾病。CPN的病因尚不清楚，但品系、性别、年龄、饮食和激素等因素可能影响其发生率和严重程度。CPN的发生率和严重程度通常在大鼠中高于小鼠，且雄性大鼠比雌性大鼠受累更严重。肾病既是一种退行性疾病，也是一种再生性疾病，具有特征性的形态学表现，且呈年龄依赖性。它是一种进行性疾病，可导致慢性肾衰竭和死亡。早期病变可见于2至3月龄动物；至90天研究结束时，几乎所有雄性大鼠中均常见该病变。早期病变由局灶性（focal）至多灶性（multifocal）的肾小管嗜碱性、细胞核拥挤、肾小管周围基底膜增厚以及程度不等的单核炎症细胞浸润灶组成（Figure 1）。随着疾病进展，受累肾实质的范围增大，CPN的各个组成部分变得更加严重，并出现明显的透明管型（Figure 2、Figure 3）。同时，肾小球改变可能明显可见，如毛细血管丛增厚、肾小球上皮与鲍曼囊之间的粘连以及肾小球硬化。CPN可进展为终末期肾病，导致动物死亡（Figure 4）。CPN常可因化学物给药而加重。CPN的发生率和严重程度通常在小鼠中低于大鼠（Figure 5）。CPN常伴有肾乳头被覆上皮的增生。需要了解的是，在CPN晚期，近端小管增生性病变的发生率可能出现幅度虽小但具有显著意义的升高。肾病为双侧性病变，两肾之间肾病严重程度不同的情况罕见。
诊断建议
CPN应当根据病变的范围和严重程度进行诊断和分级。目前，对于CPN严重程度分级的判定尚无普遍接受的建议。然而，已有一些已发表的指南可供参考，每位病理学家可根据自身的训练和经验采用自己的标准，以实现分级的一致性。但是，如果CPN作为可能与处理相关的发现被报告，则病理学家应在病理学叙述中明确界定其严重程度及严重程度分级。不推荐对肾病的各个独立组成部分分别进行分级。相关链接：肾脏 - 肾小球肾炎；肾脏 - 肾小球硬化
参考切片图（2 张）
查看英文原文
Comment
Chronic progressive nephropathy, or CPN, is one of the most common spontaneous lesions and the single most important renal disease in rats and mice. The etiology of CPN is unknown, but factors such as strain, sex, age, diet, and hormones may modulate its occurrence and severity. The incidence and severity of CPN are generally greater in rats than in mice, and male rats are more severely affected than female rats. Nephropathy is both a degenerative and regenerative disease with characteristic morphology that is age dependent. It is a progressive disease and can lead to chronic renal failure and death. Early lesions can be seen in 2- to 3-month-old animals; by the end of 90-day studies, it is commonly observed in nearly all male rats. Early lesions consist of focal to multifocal foci of tubule basophilia, nuclear crowding, peritubular basement membrane thickening, and variable infiltration by mononuclear inflammatory cells ( Figure 1 ). As the disease progresses, the amount of affected renal parenchyma increases, individual components of CPN become more severe, and hyaline casts are prominent ( Figure 2 and Figure 3 ). At the same time, glomerular changes, such as capillary tuft thickening, adhesions between the glomerular epithelium and Bowman’s capsule, and glomerulosclerosis, may be evident. CPN may progress to end-stage kidney disease, resulting in the death of the animal ( Figure 4 ). CPN can often be exacerbated by chemical administration. The incidence and severity of CPN are generally less in the mouse than in the rat ( Figure 5 ). CPN is often accompanied by hyperplasia of the lining epithelium of the renal papilla. It is important to know that in advanced stages of CPN, there may be a small but significant increase in the incidence of proliferative lesions of the proximal tubule. Nephropathy is a bilateral lesion and differing severities of nephropathy between the two kidneys is rarely noted.
Recommendation
CPN should be diagnosed and graded according to the extent and severity of the lesion. Currently, there are no universally accepted recommendations for assigning a severity grade to CPN. However, some published guidelines have been reported, and each pathologist may use his or her own criteria, based on training and experience, to achieve consistent grading. However, if CPN is reported as a potential treatment-related finding, then the pathologist should clearly define the severity and severity grading in the pathology narrative. It is not recommended to grade the separate components of nephropathy. Related Links: Kidney - Glomerulonephritis Kidney - Glomerulosclerosis
核增大Karyomegaly 肾脏其他
描述（中文）
核巨大化（karyomegaly）推测源于核酸复制而核未分裂。其特征为细胞核显著增大，主要见于近端曲小管细胞（Figure 1）。受累细胞核常染色质深染并伴多个核仁（Figure 2）。核巨大化与化学物给药相关。一般认为是肿瘤前病变，在慢性研究中可导致肾小管肿瘤。
诊断建议
核巨大化一旦出现即应诊断并给出严重程度分级。核巨大化的细节应在病理学描述中讨论（例如受累的肾小管节段）。
参考切片图（2 张）
查看英文原文
Comment
Karyomegaly is presumed to result from nucleic acid replication without nuclear division. It is characterized by marked enlargement of nuclei observed predominantly in the proximal convoluted tubule cells ( Figure 1 ). Affected nuclei are often hyperchromatic with multiple nucleoli ( Figure 2 ). Karyomegaly has been associated with chemical administration. It is generally considered preneoplastic, leading to tubule neoplasia in chronic studies.
Recommendation
Karyomegaly should be diagnosed and given a severity grade whenever present. Details of the karyomegaly should be discussed in the pathology narrative (e.g., the tubular segment affected).
梗死Infarct 肾脏其他
描述（中文）
肾梗死通常表现为边界清晰、楔形或三角形的凝固性坏死区，从被膜表面延伸至髓质。这种特征性形状源于肾脏独特的血液供应。梗死可由多种损害血液供应的原因自发产生，例如肿瘤性浸润或肾毒性物质。急性梗死具有中心坏死区，周围炎症轻微（Figure 1）。随着病变进展，坏死区附近出现明显的中性粒细胞至单核细胞浸润（Figure 2）。慢性梗死的特征是肾实质间质纤维化和被膜表面凹陷（Figure 3）。然而，将所有皮质凹陷和纤维化区域都归因于梗死可能并不恰当，因为其中一些可能代表正在消退的既往间质炎症区域。
诊断建议
梗死应诊断为梗死，而不是诊断其各个组成部分（例如，坏死、炎症、纤维化）。应根据肾脏受累范围进行分级。在病理学描述中，梗死应标明为急性或慢性，如有可能，应确定梗死的原因。相关链接：肾脏 - 纤维化 肾脏 - 炎症
参考切片图（2 张）
查看英文原文
Comment
Renal infarcts usually appear as well-demarcated, wedge-shaped or triangular areas of coagulative necrosis that extend from the capsular surface into the medulla. The characteristic shape results from the kidney’s unique vascular supply. Infarcts can arise spontaneously from a number of causes that compromise the vascular supply, such as neoplastic infiltrates or nephrotoxicants. Acute infarcts have a central area of necrosis with little peripheral inflammation ( Figure 1 ). As the lesion progresses, neutrophilic to mononuclear infiltrates become evident near the area of necrosis ( Figure 2 ). Chronic infarcts are characterized by renal parenchymal interstitial fibrosis and capsule surface depression ( Figure 3 ). However, ascribing an infarct to all areas with cortical depression and fibrosis may not be warranted since some might represent areas of previous interstitial inflammation that are resolving.
Recommendation
Infarcts should be diagnosed as infarcts rather than diagnosing the individual components (e.g., necrosis, inflammation, fibrosis). They should be graded according to the extent of renal involvement. In the pathology narrative, infarcts should be designated as either acute or chronic, and if possible, the cause of the infarct should be identified. Related Links: Kidney - Fibrosis Kidney - Inflammation
淀粉样物质Amyloid 肾脏其他
描述（中文）
淀粉样物质沉积（amyloid deposition）是一种自发性的、与年龄相关的疾病，偶尔可能与受试物给药有关。该病变在小鼠的某些品系中常见，尤其是 CD-1 小鼠，但在大鼠中罕有报道或观察到。淀粉样物质最常见的表现是肾小球内出现淡染、均质、略嗜酸性的细胞外沉积物（Figure 1、Figure 2、Figure 3）。然而，淀粉样物质也可在小管周围间质间隙中被识别。常使用特殊染色来鉴定淀粉样物质，包括刚果红（Congo red）染色阳性并在偏振光下呈现苹果绿双折射（Figure 4、Figure 5、Figure 6），以及过碘酸-雪夫（PAS）染色阴性。与其他物种相比，小鼠的淀粉样物质沉积在刚果红染色下似乎呈弱阳性，而其他物种的苹果绿双折射更为明显。淀粉样物质必须与透明样肾小球病（hyaline glomerulopathy）相鉴别，后者是一种形态学相似的小鼠疾病，但发病机制和染色模式不同（见肾脏 - 透明样肾小球病）。淀粉样物质可导致乳头坏死（papillary necrosis）。同时，淀粉样物质沉积可存在于其他器官，如脾脏、肝脏和胃肠道。
诊断建议
淀粉样物质应当被诊断并分级。应使用部位修饰词在诊断中指明淀粉样物质沉积的位置。任何继发性病变，如坏死或变性，除非因严重程度而有必要，否则不应单独诊断。然而，继发性病变应在病理学描述中予以描述。相关链接：肾脏 - 透明样肾小球病 肾脏 - 肾小球肾炎 肾脏 - 肾小球硬化 肾脏 - 乳头 - 坏死
参考切片图（2 张）
查看英文原文
Comment
Amyloid deposition is a spontaneous and age-related disease that occasionally can be related to test item administration. It is commonly noted in some strains of mouse, particularly the CD-1 mouse, but is rarely reported or observed in the rat. Amyloid is most commonly noted as an extracellular deposition of pale, homogeneous, slightly eosinophilic material in renal glomeruli ( Figure 1 , Figure 2 , and Figure 3 ). However, amyloid may also be identified in peritubular interstitial spaces. Special stains are often used to identify amyloid, including Congo red positivity with apple green birefringence when polarized ( Figure 4 , Figure 5 , and Figure 6 ) and periodic acid-Schiff negativity. Amyloid deposits in mice seem to be faintly positive with Congo red compared with other species, where apple green birefringence is more pronounced. Amyloid must be distinguished from hyaline glomerulopathy, a morphologically similar disease of mice with a different pathogenesis and staining pattern (see Kidney - Hyaline Glomerulopathy ). Amyloid may result in papillary necrosis. Concurrently, amyloid deposits may be present in other organs, such as the spleen, liver, and gastrointestinal tract.
Recommendation
Amyloid should be diagnosed and graded. The location of the amyloid deposits should be indicated in the diagnosis by using a site modifier. Any secondary lesions, such as necrosis or degeneration, should not be diagnosed separately unless warranted by severity. Secondary lesions should, however, be described in the pathology narrative. Related Links: Kidney - Hyaline Glomerulopathy Kidney - Glomerulonephritis Kidney - Glomerulosclerosis Kidney - Papilla - Necrosis
炎症Inflammation 肾脏炎症
描述（中文）
在NTP研究中，根据存在的优势炎症细胞类型，炎症分为五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在肾脏-肾小球肾炎中。肾小管炎症（肾小管炎）（Figure 1、Figure 2）可能与多种原因有关，这些原因可能包括晶体沉积、下尿路延伸（肾盂肾炎）、感染过程、慢性进行性肾病、既往梗死或直接化学物质给药。肾小管炎症的特征是肾小管腔、上皮或两者内存在炎症细胞。炎症也可局限于肾盂（Figure 3、Figure 4、Figure 5、Figure 6）或间质（Figure 7、Figure 8）。肾盂炎症通常源于与局部感染相关的状况，这些感染从下尿路上升并延伸至肾乳头、髓质和皮质。然而，也可能见到无下尿路受累的肾盂炎症。炎症可能有多种原因。肾盂炎症通常为急性或化脓性，在肾盂周围组织中可见更慢性的病变。病理学家偶尔用于描述类似状况的另一个诊断术语是“肾盂肾炎”，其强调肾脏受累以及肾盂炎症。在显著（marked）病例中可能注意到微脓肿，这是由于上行感染或同时发生的败血症性感染。肾乳头溃疡和/或坏死可能作为肾盂炎症的结果而发生。在更慢性的病例中，常注意到反应性尿路上皮和/或乳头状上皮增生。间质炎症，即对多种原因所致组织损伤的细胞反应，在啮齿类动物的肾脏中可能频繁观察到。慢性间质炎症常被视为慢性进行性肾病的一个组成部分（见Kidney - Nephropathy, 慢性 Progressive）。
诊断建议
当肾脏炎症是原发性病变或严重到足以需要单独诊断时，应进行诊断并分级。诊断应包括部位修饰词（例如，间质、肾小管、肾小球）和炎症类型（例如，急性、慢性、慢性活动性）。肾小球中的炎症反应应诊断为肾小球肾炎，并在单独的文件中涵盖（见Kidney - Glomerulonephritis）。病理学家应运用其判断来决定与炎症相关的坏死或出血等继发性病变是否足够显著以需要单独诊断。作为慢性进行性肾病组成部分的炎症不应单独诊断。相关链接：Kidney - Fibrosis Kidney - Glomerulonephritis Kidney - Infarct Kidney - Nephropathy, 慢性（chronic） Progressive
参考切片图（2 张）
查看英文原文
Comment
In NTP studies, there are five standard categories of inflammation, according to the predominant inflammatory cell type present: acute, suppurative, chronic, chronic active, and granulomatous. In Kidney - Glomerulonephritis ). Renal tubule inflammation (tubulitis) ( Figure 1 and Figure 2 ) may be associated with a number of causes that may include the deposition of crystals, extension from the lower urinary tract (pyelonephritis), infectious processes, chronic progressive nephropathy, previous infarction, or direct chemical administration. Tubule inflammation is characterized by the presence of inflammatory cells within the tubule lumen, epithelium, or both. Inflammation can also be localized to the renal pelvis ( Figure 3 , Figure 4 , Figure 5 , and Figure 6 ) or the interstitium ( Figure 7 and Figure 8 ). Renal pelvis inflammation usually arises from conditions related to localized infections, which ascend from the lower urinary tract and extend into the renal papilla, medulla, and cortex. However, renal pelvis inflammation without lower urinary tract involvement may also be seen. There may be a number of causes for inflammation. Renal pelvis inflammation typically is acute or suppurative, with more chronic lesions noted in peripelvic tissues. Another diagnostic term occasionally used by pathologists to describe a similar condition is "pyelonephritis," which emphasizes renal involvement along with pelvis inflammation. Microabscesses may be noted in marked cases, due to either an ascending infection or a coinciding septicemic infection. Renal papillary ulceration and/or necrosis may occur as a result of renal pelvis inflammation. Reactive urothelial and/or papillary epithelial hyperplasia are often noted in more chronic cases. Interstitial inflammation, a cellular reaction to tissue injury from a variety of causes, may be observed frequently in the kidney of rodents. Chronic interstitial inflammation is often seen as a component of chronic progressive nephropathy (see Kidney - Nephropathy, Chronic Progressive ).
Recommendation
Inflammation in the kidney should be diagnosed and graded when it is a primary lesion or is severe enough to warrant a separate diagnosis. The diagnosis should include a site modifier (e.g., interstitium, renal tubule, glomerulus) and the type of inflammation (e.g., acute, chronic, chronic active). Inflammatory reactions in the glomerulus should be diagnosed as glomerulonephritis and are covered in a separate document (see Kidney - Glomerulonephritis ). The pathologist should use his or her judgment in deciding whether or not secondary lesions such as necrosis or hemorrhage associated with inflammation are prominent enough to warrant a separate diagnosis. Inflammation as a component of chronic progressive nephropathy should not be diagnosed separately. Related Links: Kidney - Fibrosis Kidney - Glomerulonephritis Kidney - Infarct Kidney - Nephropathy, Chronic Progressive
矿化Mineralization 肾脏矿化
描述（中文）
矿化更常与大鼠和小鼠肾皮质、髓质或肾乳头中嗜碱性沉积物的自发性、微小背景性病变相关（Figure 1）。一般而言，这些沉积物无病理学意义。然而，矿化也可见于变性和坏死的继发结果。矿化可由化学物、激素或饮食诱导。矿化沉积物通常累及肾小管上皮，但也可能累及间质。茜素红S（Alizarin red S）或von Kossa特殊染色用于在组织学切片中显示矿物质。矿化沉积物尤其见于雌性大鼠，位于外髓外带与外髓内带交界处附近的直部（pars recta）和Henle细环（Figure 2）。肾乳头矿化的线性沉积是诱导α2u-球蛋白肾病（α2u-globulin nephropathy）的慢性化学物给药的特征性表现（Figure 3）。外皮质有时可见人为假象性矿化。这种矿化的原因通常无法确定。
诊断建议
矿化应当诊断并分级。如果小的局灶性（focal）矿化沉积物被认定为自发性背景性病变，则无需诊断，病理学家应运用其判断来决定这些沉积物是否足够显著而值得诊断。当进行诊断时，矿化的模式（例如，线性肾乳头矿化、局灶性髓质矿化）应在病理学描述中予以描述。相关链接：肾脏-结石 肾脏-结晶
参考切片图（2 张）
查看英文原文
Comment
Mineralization is more commonly associated with spontaneous and minute background findings of basophilic deposits in the renal cortex, medulla,or papilla of rats and mice ( Figure 1 ). In general, these depositshave no pathologic significance. However, mineralization may also be seen as a consequence to degeneration and necrosis. Mineralization may be induced by chemicals, hormones, or diet. Mineralized deposits usually involve tubule epithelia but may also involve the interstitium. Alizarin red S or von Kossa’s special stains are used to demonstrate mineral in histologic sections. Mineralized deposits seen particularly in female rats are noted in the pars recta and thin loops of Henle near the junction of the outer stripe of the outer medulla and the inner stripe of the outer medulla ( Figure 2 ). Linear deposits of papillary mineralization are characteristic of chronic chemical administration that induces α2u-globulin nephropathy ( Figure 3 ). Artifactual mineralization is sometimes encountered in the outer cortex. The cause of this mineralization often cannot be identified.
Recommendation
Mineralization should be diagnosed and graded. If small deposits of focal mineralization are recognized as a spontaneous background finding, they need not be diagnosed and the pathologist should use his or her judgment in deciding whether or not they are prominent enough to warrant diagnosis. When diagnosed, the pattern of the mineralization (e.g., linear papillary mineralization, focal medullary mineralization) should be described in the pathology narrative. Related Links: Kidney - Calculus Kidney - Crystals
纤维化Fibrosis 肾脏纤维化
描述（中文）
肾（间质）纤维化与肾实质既往或持续存在的损伤有关，例如与慢性间质性炎症相关的损伤。纤维化的程度取决于诱发因素、肾实质损伤的程度以及病变的慢性程度。纤维化源于复杂的相互作用，涉及炎症细胞释放的细胞因子、肾小管上皮-间质转化尚有争议的影响，以及由于胶原溶解酶受抑制而导致的胶原清除减少。纤维化在间质中表现为略呈纤维状的嗜酸性物质（Figure 1、Figure 2）。纤维化可导致受累区域肾单位进行性萎缩和/或肾小管及鲍曼氏囊扩张。
诊断建议
如果纤维化是原发性改变，或伴有轻微炎症或无炎症，则应作出诊断并给出严重程度分级。当纤维化继发于另一过程（如炎症），且两者同时存在时，病理学家应运用其判断来决定纤维化是否足够显著而需要单独诊断。相关链接：肾脏 - 梗死 肾脏 - 炎症
参考切片图（2 张）
查看英文原文
Comment
Renal (interstitial) fibrosis is associated with previous or ongoing injury to the renal parenchyma,such as that associated with chronic interstitial inflammation. The amount of fibrosis dependson the inciting condition, the amount of damage to the renal parenchyma, and the chronicity of the lesion. Fibrosis results from a complex interaction involving cytokines released by inflammatory cells, thedebatable influence of tubule epithelial-mesenchyme transition, and decreased removal of collagen due to inhibition of collagenolytic enzymes. Fibrosis appears as a slightly fibrillar, eosinophilic material in the interstitium ( Figure 1 and Figure 2 ). Fibrosis may result in progressive atrophy of the nephron in affected areas and/or dilation of renal tubules and Bowman’s space.
Recommendation
If fibrosis is a primary change or is present with little or no inflammation, then it should be diagnosed and given a severity grade. When fibrosis is secondary to another process, such as inflammation, and both are present concurrently, the pathologist should use his or her judgment in deciding whether or not the fibrosis is prominent enough to warrant a separate diagnosis. Related Links: Kidney - Infarct Kidney - Inflammation
结晶Crystals 肾脏其他
描述（中文）
结晶可出现在肾小管的任何节段或肾盂（Figure 1、Figure 2）。在常规光学显微镜下，结晶往往难以发现，因为它们在组织处理过程中常被洗脱，或在光学上不明显。结晶的存在用偏振光可能更好地显示，因为它们常具有双折射性。另一方面，矿化不具有双折射性。由化学物质和/或代谢产物给药所致的结晶，可因尿滤液的浓度和pH值而在肾单位的任何节段沉淀。此外，某些化学物质在肾脏存在特定条件时是不溶的。许多结晶具有高度刺激性，取决于其大小和形状，并可能导致肾小管变性和/或坏死，以及随后的急性至慢性炎症或肾盂肾炎（见肾脏 - 肾病，梗阻性）。偶尔，结晶可在巨噬细胞或多核巨细胞内被识别（Figure 3）。
诊断建议
结晶只要存在就应诊断并给出严重程度分级。结晶的位置应作为部位修饰词纳入诊断（例如，肾小管或肾盂）。结晶的特征应在病理学描述中讨论。继发性病变，如炎症，除非严重程度足以需要，否则不应单独诊断，但应在病理学描述中描述。相关链接：肾脏 - 结石 肾脏 - 矿化 肾脏 - 肾病，梗阻性
参考切片图（2 张）
查看英文原文
Comment
Crystals can occur in any of the renal tubule segments or renal pelvis ( Figure 1 and Figure 2 ). Crystals are often difficult to find with routine light microscopy because they are often washed out in tissue processing or are optically inapparent. The presence of crystals may be better visualized with polarized light as they are often birefringent. Mineralization, on the other hand, is not birefringent. Crystals resulting from the administration of chemical and/or metabolites may precipitate in any segment of the nephron because of the concentration and pH of the urine filtrate. In addition, a number of chemicals are insoluble when certain conditions are present in the kidney. Many crystals are highly irritating, depending on their size and shape, and may result in tubule degeneration and/or necrosis and subsequent acute to chronic inflammation or pyelonephritis (see Kidney - Nephropathy, Obstructive ). Occasionally, crystals may be identified within macrophages or multinucleated giant cells ( Figure 3 ).
Recommendation
Crystals should be diagnosed and given a severity grade whenever present. The location of the crystals should be included in the diagnosis as a site modifier (e.g., renal tubule or pelvis). The features of the crystals should be discussed in the pathology narrative. Secondary lesions, such as inflammation, should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative. Related Links: Kidney - Calculus Kidney - Mineralization Kidney - Nephropathy, Obstructive
结石Calculus 肾脏其他
描述（中文）
结石（calculi）的自发病例在啮齿类动物的肾盂中偶见。结石也可能与外源性物质（xenobiotic）给药相关，甚至可能含有所给予的化学物质或化合物。结石倾向于为大小不等的嗜碱性凝结物（basophilic concretions），可引起炎症、阻塞或尿路上皮增生（urothelial hyperplasia）（Figure 1、Figure 2）。结石可与矿化（mineralization）相鉴别，因为结石一般游离于泌尿腔隙内，而矿化发生于组织中。小结石常见于肾穹窿（renal fornices），在那里它们通常不引起任何继发性改变（Figure 3）。
诊断建议
结石应当被诊断并给予严重程度分级。病理学家应运用其判断力来决定：肾盂或肾盂穹窿中无其他继发性改变的小结石是否足够显著而值得作出诊断，或者结石所致的继发性改变（如炎症或上皮增生）是否足够显著而值得单独作出诊断。相关链接：肾脏 - 结晶（Kidney - Crystals） 肾脏 - 矿化（Kidney - Mineralization） 肾脏 - 尿路上皮 - 增生（Kidney - Urothelium - Hyperplasia）
参考切片图（2 张）
查看英文原文
Comment
Spontaneous cases of calculi are sporadically seen in the renal pelvis of rodents. Calculi may also be associated with xenobiotic administration and may even contain the administered chemical or compound. Calculi tend to be basophilic concretions of variable size, which may result in inflammation, obstruction, or urothelial hyperplasia ( Figure 1 and Figure 2 ). Calculi can be differentiated from mineralization in that calculi are generally free within the urinary space whereas mineralization occurs in tissue. Small calculi are often observed in the renal fornices, where they often do not result in any secondary changes ( Figure 3 ).
Recommendation
Calculi should be diagnosed and given a severity grade. The pathologist shoulduse his or her judgment in deciding if small calculi in the renal pelvis or pelvic fornices without other secondary changes are prominent enough to warrant a diagnosis, or if changes secondary to the calculi, such as inflammation or epithelial hyperplasia, are prominent enough to warrant a separate diagnosis. Related Links: Kidney - Crystals Kidney - Mineralization Kidney - Urothelium - Hyperplasia
肾乳头上皮增生Papilla Epithelium Hyperplasia 肾脏增生
描述（中文）
肾乳头表面上皮增生（hyperplasia of the surface epithelium of the renal papilla）的范围可从上皮增厚（Figure 1，箭头）到上皮大小不等的向外生长并伴有细胞间透亮间隙（Figure 2）。有时，这些间隙含有嗜酸性物质或细胞。该病变常见于晚期慢性进行性肾病（参见肾脏 - 肾病，慢性进行性）。
诊断建议
肾乳头上皮增生一经出现即应诊断并给出严重程度分级。相关链接：肾脏 - 尿路上皮 - 增生
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of the surface epithelium of the renal papilla can range from thickening of the epithelium ( Figure 1 , arrows) to variably sized outgrowths of the epithelium with clear spaces amid the cells ( Figure 2 ). Sometimes, these spaces contain eosinophilic material or cells. This lesion is commonly observed with advanced chronic progressive nephropathy (see Kidney - Nephropathy, Chronic Progressive ).
Recommendation
Hyperplasia of the renal papillary epithelium should be diagnosed and given a severity grade whenever present. Related Links: Kidney - Urothelium - Hyperplasia
肾乳头坏死Papilla Necrosis 肾脏坏死
描述（中文）
肾乳头坏死是一种累及肾乳头尖端的特定病变。早期阶段表现为乳头尖端区域细胞轮廓丧失和染色亲和力丧失（Figure 1）。更严重的病例可能累及整个肾乳头坏死（Figure 2）。根据病变的慢性程度，可能可见尿路上皮增生、出血、水肿、炎症和矿化。坏死的乳头常脱落入肾盂并导致梗阻（Figure 3）。在脱落区域可能观察到再上皮化。炎症常见于坏死区域邻近，肾盂肾炎也可能与乳头坏死相关（Figure 4）。乳头坏死在化学物给药情况下报道较其他原因更为常见。在大鼠和小鼠中自发病例不常见。
诊断建议
肾乳头坏死应当诊断并给出严重程度分级。研究病理学家应运用其判断来决定与乳头坏死相关的继发性病变（如炎症）是否足够显著以需要单独诊断。相关链接：肾脏 - 梗死 肾脏 - 炎症
参考切片图（2 张）
查看英文原文
Comment
Renal papillary necrosis is a specific entity involving the tip of the renal papilla. Early stages involve loss of cellular definition and loss of staining affinity in the area of the papillary tip ( Figure 1 ). More severe cases may involve necrosis of the entire renal papilla ( Figure 2 ). Depending on the chronicity of the lesion, urothelial hyperplasia, hemorrhage, edema, inflammation, and mineralization may be evident. Often the necrotic papilla will slough off into the renal pelvis and result in obstruction ( Figure 3 ). Re-epithelialization may be observed in sloughed areas. Inflammation is commonly observed adjacent to necrotic areas, and pyelonephritis may also be associated with papillary necrosis ( Figure 4 ). Papillary necrosis is more commonly reported with chemical administration than from other causes. Spontaneous cases are uncommon in the rat and mouse.
Recommendation
Necrosis of the renal papilla should be diagnosed and given a severity grade. The study pathologist should use his or her judgment in deciding whether or not secondary lesions, such as inflammation, associated with papillary necrosis are prominent enough to warrant a separate diagnosis. Related Links: Kidney - Infarct Kidney - Inflammation
肾小球化生Glomerulus Metaplasia 肾脏化生
描述（中文）
在小鼠中，Bowman囊的肾小球壁层上皮存在性别二态性。雌性壁层上皮细胞通常呈扁平状（Figure 1），而雄性壁层上皮既可呈立方状也可呈扁平状。在由某些雄激素类化合物给药所致的肾小球化生中，雌性壁层上皮变为立方状，或呈雄性样（Figure 2）。
诊断建议
Bowman囊的肾小球化生应当诊断并给出严重程度分级。相关链接：肾脏 - 肾小管 - 肥大
参考切片图（2 张）
查看英文原文
Comment
In the mouse, sexual dimorphism of the glomerular parietal epithelium of Bowman’s capsule exists. The female parietal epithelial cells are typically flattened ( Figure 1 ) and the male parietalepithelium can be both cuboidal and flattened. In glomerular metaplasia, caused by administration of some androgenic compounds, the female parietal epithelium becomes cuboidal, or male-like ( Figure 2 ).
Recommendation
Glomerular metaplasia of Bowman’s capsule should be diagnosed and given a severity grade. Related Links: Kidney - Renal Tubule - Hypertrophy
肾小球硬化Glomerulosclerosis 肾脏其他
描述（中文）
肾小球硬化（glomerulosclerosis）是肾小球慢性退行性改变的结果，在 NTP 研究中很少作为原发性病变观察到。其特征性表现包括肾小球血管丛皱缩和收缩，以及系膜被纤维化取代（Figure 1、Figure 2）。由于形态学特征相似，必须排除淀粉样物沉积的存在。肾小球硬化可为 局灶性（focal）、segmental 或 global。
诊断建议
原发性肾小球硬化应予以诊断并给出严重程度分级。当肾小球硬化是慢性进行性肾病相关病变谱系的一个组成部分，或是对其他某种原发性肾脏疾病的继发性反应的一部分时，不应单独诊断，而应在病理学描述中予以描述。相关链接：肾脏 - 淀粉样物；肾脏 - 肾小球肾炎；肾脏 - 透明性肾小球病；肾脏 - 炎症；肾脏 - 肾病，慢性进行性
参考切片图（2 张）
查看英文原文
Comment
Glomerulosclerosis is a consequence of chronic degenerative changes in the glomerulus and is rarely observed as a primary lesion in NTP studies. Characteristic features include shrinkage and contraction of the glomerular tuft and replacement of the mesangium by fibrosis ( Figure 1 and Figure 2 ). The presence of amyloid deposits must be ruled out because of similar morphologic features. Glomerulosclerosis may be focal, segmental, or global.
Recommendation
Primary glomerulosclerosis should be diagnosed and given a severity grade. When a component of the spectrum of changes associated with chronic progressive nephropathy or part of a secondary response to some other primary renal disease, glomerulosclerosis should not be diagnosed separately but should be described in the pathology narrative. Related Links: Kidney - Amyloid Kidney - Glomerulonephritis Kidney - Hyaline Glomerulopathy Kidney - Inflammation Kidney - Nephropathy, Chronic Progressive
肾小球肾炎Glomerulonephritis 肾脏其他
描述（中文）
肾小球肾炎（glomerulonephritis，GN）由急性至慢性肾小球损伤所致，导致肾小球表现为增大、细胞增多，并伴有系膜基质（mesangial matrix）增加（Figure 1、Figure 2、Figure 3）。原发性 GN 在常规啮齿类动物研究中不常见。GN 存在多种形态学亚型，这些亚型具有某些组织学特征，可能提示潜在的发病机制。这些形态学亚型通常分类为增生性（proliferative）、膜增生性（membranoproliferative）、系膜增生性（mesangioproliferative）或新月体性（crescentic）。增生性 GN 表现为细胞增多，但未进一步明确细胞增多或基底膜增厚。膜增生性 GN 的特征为基底膜增厚，可为均匀或不规则，可通过过碘酸-雪夫（periodic acid-Schiff）染色或银染（silver stains）显示。系膜增生性 GN 的特征为系膜细胞数量增加。在新月体性 GN 中，脏层或壁层细胞的节段性区域相互形成粘连，并使鲍曼氏囊（Bowman’s space）缩小。此外，还可应用“弥漫性（diffuse）”和“segmental”等修饰词进一步描述肾小球内的病变特征。
诊断建议
肾小球肾炎应当作出诊断并给出严重程度分级。肾小球肾炎的类型和范围应在病理学描述中指明。相关链接：肾脏 - 淀粉样变（Kidney - Amyloid）；肾脏 - 肾小球硬化（Kidney - Glomerulosclerosis）；肾脏 - 玻璃样肾小球病（Kidney - Hyaline Glomerulopathy）；肾脏 - 肾病，慢性进展性（Kidney - Nephropathy, 慢性（chronic） Progressive）
参考切片图（2 张）
查看英文原文
Comment
Glomerulonephritis (GN) results from acute to chronic glomerular injury resulting in glomeruli that appear enlarged and hypercellular with an increase in mesangial matrix ( Figure 1 , Figure 2 , and Figure 3 ). Primary GN is not commonly observed in routine rodent studies. There are morphologic subtypes of GN, which have certain histologic features that may indicate an underlying pathogenesis. These morphologic subtypes are often classified as proliferative, membranoproliferative, mesangioproliferative, or crescentic. Proliferative GN appears hypercellular without further identification of increased cells or basement membrane thickening. Membranoproliferative GN is characterized by basement membrane thickening, either uniform or irregular, which can be demonstrated by periodic acid-Schiff or silver stains. Mesangioproliferative GN is characterized by an increase in the number of mesangial cells. In crescentic GN, segmental areas of visceral or parietal cells form adhesions to one another and reduce Bowman’s space. In addition, modifiers such as "diffuse" and "segmental" can also be applied to further characterize the change within glomeruli.
Recommendation
Glomerulonephritis should be diagnosed and given a severity grade. The type and extent of glomerulonephritis should be indicated in the pathology narrative. Related Links: Kidney - Amyloid Kidney - Glomerulosclerosis Kidney - Hyaline Glomerulopathy Kidney - Nephropathy, Chronic Progressive
肾小管再生Renal Tubule Regeneration 肾脏其他
描述（中文）
肾小管再生是对既往肾小管上皮变性和/或坏死的修复性反应。它是肾脏中最常见的受试物相关病变之一。再生的特征是一系列组织学改变，包括细胞质嗜碱性（cytoplasmic basophilia）、核增大（karyomegaly）以及受累肾小管节段核拥挤（nuclear crowding）（Figure 1、Figure 2）。与慢性进行性肾病（慢性（chronic） progressive nephropathy，CPN）不同，化学性损伤和再生一般不以基底膜增厚为特征。核分裂象（mitotic figures）多少不定。然而，化学性介导再生的判定可因CPN的存在而受到干扰，毒理病理学家可能难以区分。
诊断建议
再生应当诊断并给出严重程度分级。伴随CPN相关再生的肾小管再生不应单独诊断，而应纳入CPN的诊断中。如果坏死显著，可同时诊断。增生与再生之间的区别可能存在问题，病理学家必须运用其判断来区分这些病变。相关链接：肾脏 - 肾小管 - 变性；肾脏 - 肾小管 - 坏死
参考切片图（2 张）
查看英文原文
Comment
Renal tubule regeneration occurs as a reparative response to previous degeneration and/or necrosis of renal tubular epithelium. It is one of the most common test-article-related lesions observed in the kidney. Regeneration is characterized by a spectrum of histologic changes, including cytoplasmic basophilia, karyomegaly, and nuclear crowding along the affected tubule segment ( Figure 1 and Figure 2 ). In contrast to chronic progressive nephropathy (CPN), thickened basement membranes are generally not a feature with chemically induced injury and regeneration. Mitotic figures are variable. However, the determination of chemically mediated regeneration can be confounded by the presence of CPN and may be difficult for the toxicologic pathologist to distinguish.
Recommendation
Regeneration should be diagnosed and given a severity grade. Tubule regeneration accompanying CPN-related regeneration should not be diagnosed separately but should be included in the diagnosis of CPN. If necrosis is significant, it may be diagnosed concurrently. The difference between hyperplasia and regeneration can be problematic, and the pathologist must use his or her judgment in differentiating these lesions. Related Links: Kidney - Renal Tubule - Degeneration Kidney - Renal Tubule - Necrosis
肾小管变性Renal Tubule Degeneration 肾脏变性
描述（中文）
变性（degeneration）是一种非特异性病变，可由任何多种干扰细胞功能的病因引起，并且常常是坏死的早期指征。在某些情况下，变性之前会出现空泡化（vacuolation）（Figure 1）。一般来说，变性的特征是若干形态学和可变的细胞特征，例如细胞肿胀伴或不伴细胞质空泡化，以及细胞质淡染和碎裂（Figure 2）。变性必须与凋亡（apoptosis）相鉴别，凋亡代表肾脏中细胞更新的正常过程。坏死（necrosis）一般包括细胞肿胀、核固缩（pyknosis）和/或核碎裂（karyorrhexis）以及细胞脱落。变性可以是可逆的或不可逆的。
诊断建议
变性应当诊断并分级。如适用，应将受累肾小管的部位作为部位修饰词纳入诊断。相关病变，如炎症或再生，除非严重程度确有必要，否则不应单独诊断，但应在病理学叙述中描述。相关链接：肾脏 - 肾小管 - 细胞质改变；肾脏 - 肾小管 - 坏死；肾脏 - 肾小管 - 再生
参考切片图（2 张）
查看英文原文
Comment
Degeneration is a nonspecific entity that can arise from any number of etiologies that perturb cell function and is often an early indicator of necrosis. Degeneration, in some cases, is preceded by vacuolation ( Figure 1 ). In general, degeneration is characterized by several morphologic and variable cell features, such as cell swelling with or without cytoplasmic vacuolation and pale-staining and fragmented cytoplasm ( Figure 2 ). Degeneration must be distinguished from apoptosis, which represents the normal process of cell turnover in the kidney. Necrosis generally includes cell swelling, nuclear pyknosis and/or karyorrhexis, and cellular sloughing. Degeneration may be either reversible or irreversible.
Recommendation
Degeneration should be diagnosed and graded. If applicable, the location of the affected tubule(s) should be included as a site modifier in the diagnosis. Associated lesions, such as inflammation or regeneration, should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative. Related Links: Kidney - Renal Tubule - Cytoplasmic Alteration Kidney - Renal Tubule - Necrosis Kidney - Renal Tubule - Regeneration
肾小管嗜双色性空泡性增生Renal Tubule Hyperplasia Amphophilic Vacuolar 肾脏增生
描述（中文）
嗜酸性空泡性（amphophilic-vacuolar，A-V）增生是一种小的增殖性病变，伴有程度不一的嗜酸性胞质染色及细胞内和/或细胞外空泡（Figure 1）。与非典型肾小管增生一样，在A-V增生中，增殖细胞被认为局限于单一肾小管范围内。如果细胞增殖超出单一肾小管的范围，则该病变被认为是肿瘤（腺瘤或癌）。A-V增生被推测为大鼠的一种家族性疾病，可能进展为肿瘤。
诊断建议
嗜酸性空泡性增生应诊断为“肾脏，肾小管 - 增生，嗜酸性空泡性”，并给出严重程度分级。相关链接：肾脏 - 肾小管 - 非典型肾小管增生；肾脏 - 肾小管 - 增生，嗜酸性细胞性
参考切片图（1 张）
查看英文原文
Comment
Amphophilic-vacuolar (A-V) hyperplasia is a small proliferative lesion associated with variable amphophilic cytoplasmic staining and intra- and/or extracellular vacuoles ( Figure 1 ). As with atypical tubule hyperplasia, in A-V hyperplasia the proliferating cells are considered to be within the confines of a single renal tubule. If the cells proliferate beyond the confines of a single tubule, the lesion is considered a neoplasm (adenoma or carcinoma). A-V hyperplasia has been postulated to be a familial condition in rats, which may progress to tumors.
Recommendation
Amphophilic-vacuolar hyperplasia should be diagnosed as "Kidney, Renal tubule - Hyperplasia, Amphophilic-vacuolar" and given a severity grade. Related Links: Kidney - Renal Tubule - Atypical Tubule Hyperplasia Kidney - Renal Tubule - Hyperplasia, Oncocytic
肾小管嗜酸性细胞性增生Renal Tubule Hyperplasia Oncocytic 肾脏增生
描述（中文）
嗜酸性细胞增生（oncocytic hyperplasia）的特征是肾小管细胞胞质淡染、呈细颗粒状，细胞核位于中央。嗜酸性细胞增生在大鼠和小鼠中是一种罕见的病变（Figure 1），据报道起源于集合管。超微结构上，嗜酸性细胞由非典型线粒体构成。嗜酸性细胞增生难以与嗜酸性细胞瘤（oncocytoma）区分，应与其他肾小管增生性病变分别评分。
诊断建议
嗜酸性细胞增生应作出诊断并给出严重程度分级。相关链接：肾脏 - 肾小管 - 增生，嗜两性-空泡性；肾脏 - 肾小管 - 非典型肾小管增生
参考切片图（1 张）
查看英文原文
Comment
Oncocytic hyperplasia is characterized by tubule cells having lightly staining and finely granular cytoplasm with centralized nuclei. Oncocytic hyperplasia is a rare lesion in the rat and mouse ( Figure 1 ) and reportedly originates in the collecting tubule. Ultrastructurally, oncocytes are composed of atypical mitochondria. Oncocytic hyperplasia is difficult to separate from oncocytoma and should be scored separately from other hyperplastic lesions of the renal tubule.
Recommendation
Oncocytic hyperplasia should be diagnosed and given a severity grade. Related Links: Kidney - Renal Tubule - Hyperplasia, Amphophilic-Vacuolar Kidney - Renal Tubule - Atypical Tubule Hyperplasia
肾小管坏死Renal Tubule Necrosis 肾脏坏死
描述（中文）
坏死的诊断涵盖单个细胞死亡、局灶性（focal）或多灶性（multifocal）的肾小管坏死区域，直至较大融合区域的肾实质坏死（Figure 1）。坏死可见于肾脏的任何部位。典型表现为细胞肿胀、细胞碎裂、胞质染色性改变和核碎裂（Figure 2）。坏死的肾小管细胞迅速脱落进入肾小管腔。肾小管内的颗粒管型是既往坏死的指示性表现。急性肾小管坏死时很少观察到炎症。
诊断建议
坏死应当被诊断并给予严重程度分级。与肿瘤存在相关的坏死不应被诊断，而应在病理学叙述中描述。继发性改变，如再生和炎症，不应单独诊断，除非严重程度足以支持，但应在叙述中描述。肾小管坏死必须与人为假象相鉴别。相关链接：肾脏 - 肾小管 - 变性；肾脏 - 肾小管 - 再生
参考切片图（2 张）
查看英文原文
Comment
The diagnosis of necrosis encompasses death of individual cells, to focal or multifocal areas of tubule necrosis, to larger confluent areas of renal parenchyma necrosis ( Figure 1 ). Necrosis may be seen anywhere in the kidney. Typically, it is characterized by cell swelling, cell fragmentation, cytoplasmic tinctorial changes, and karyorrhexis ( Figure 2 ). Necrotic renal tubule cells quickly slough off into the tubule lumens. Granular casts within renal tubules are indicators of previous necrosis. Inflammation is seldom observed in association with acute tubule necrosis.
Recommendation
Necrosis should be diagnosed and given a severity grade. Necrosis associated with the presence of a tumor should not be diagnosed but should be described in the pathology narrative. Secondary changes, such as regeneration and inflammation, should not be diagnosed separately, unless warranted by severity, but should be described in the narrative. Renal tubular necrosis must be differentiated from artifact. Related Links: Kidney - Renal Tubule - Degeneration Kidney - Renal Tubule - Regeneration
肾小管扩张Renal Tubule Dilation 肾脏扩张
描述（中文）
肾小管扩张可发生于肾单位或集合管系统的任何部位。它可呈局灶性（focal）区域分布，也可呈沿肾脏切片全长走行的条带（Figure 1）。肾小管扩张可由外源化学物给药、继发性机制或未知发病机制引起（见肾脏-肾病，梗阻性）（Figure 2）。扩张可由对肾小管上皮的直接毒性损伤干扰吸收和分泌所致（Figure 3）。它也可继发于肾缺血或与给药相关的长时间利尿。肾小管扩张的继发性机制可源于下尿路梗阻、肾小管结晶沉积、间质炎症和/或纤维化以及慢性进行性肾病（Figure 4）。少数扩张的肾小管可视为正常组织学变异。
诊断建议
肾小管扩张应予以诊断并给出严重程度分级。肾小管扩张的部位应作为部位修饰词纳入诊断。病理学家应运用其判断来决定继发性肾小管扩张是否显著到足以需要单独诊断。相关链接：肾脏-囊肿；肾脏-肾病，梗阻性
参考切片图（2 张）
查看英文原文
Comment
Renal tubule dilation may occur anywhere along the nephron or collecting duct system. It may occur in focal areas or as tracts running along the entire length of kidney sections ( Figure 1 ). Renal tubule dilation may occur from xenobiotic administration, secondary mechanisms, or an unknown pathogenesis (see Kidney - Nephropathy, Obstructive ) ( Figure 2 ). Dilation may result from direct toxic injury to the tubule epithelium interfering with absorption and secretion ( Figure 3 ). It may also occur secondary to renal ischemia or from prolonged diuresis related to drug administration. Secondary mechanisms of tubule dilation may result from lower urinary tract obstruction, the deposition of tubule crystals, interstitial inflammation and/or fibrosis, and chronic progressive nephropathy ( Figure 4 ). A few dilated tubules may be regarded as normal histologic variation.
Recommendation
Renal tubule dilation should be diagnosed and given a severity grade. The location of tubule dilation should be included in the diagnosis as a site modifier. The pathologist should use his or her judgment in deciding whether or not secondary tubule dilation is prominent enough to warrant a separate diagnosis. Related Links: Kidney - Cyst Kidney - Nephropathy, Obstructive
肾小管管型Renal Tubule Cast 肾脏其他
描述（中文）
管型（intratubular casts）可具有多种成分，并呈现不同的形态学和染色特征。透明管型（hyaline casts）和颗粒管型（granular casts）均可在多种肾脏疾病中观察到。常见的管型包括：与肾小球通透性增高（如慢性进行性肾病）相关的透明管型（嗜酸性、均质性蛋白性物质）（Figure 1），以及提示既往肾小管细胞坏死的颗粒管型（坏死细胞碎片），后者与诱导α2u-球蛋白肾病的化学物相关（Figure 2、Figure 3）。
诊断建议
肾小管管型应根据其形态学表现（颗粒性、透明性等）作出诊断，并给出严重程度分级。作为慢性进行性肾病组成部分观察到的透明管型不应单独诊断。管型的细节，例如在肾脏内的位置（如外髓内带与外带交界处，即α2u-球蛋白肾病相关管型的典型位置），应在病理学描述中讨论。相关链接：肾脏-肾小管-坏死
参考切片图（2 张）
查看英文原文
Comment
Intratubular casts may have various compositions with different morphologic and staining characteristics. Both hyaline and granular casts may be observed in a number of renal diseases. Commonly observed casts are hyaline (eosinophilic, homogeneous proteinaceous) casts associated with increased glomerular permeability such as with chronic progressive nephropathy ( Figure 1 ) and granular (necrotic cellular debris) casts indicative of previous tubule cell necrosis associated with chemicals that induce α2u-globulin nephropathy ( Figure 2 and Figure 3 ).
Recommendation
Tubule casts should be diagnosed according to their morphologic appearance (granular, hyaline, etc.) and given a severity grade. Hyaline casts observed as a component of chronic progressive nephropathy should not be diagnosed separately. Details of the casts, such as location within the kidney (e.g., the junction of the inner and outer stripes of the outer medulla, the typical location of casts associated with α2u-globulin nephropathy) should be discussed in the pathology narrative. Related Links: Kidney - Renal Tubule - Necrosis
肾小管细胞质改变Renal Tubule Cytoplasmic Alteration 肾脏其他
描述（中文）
在某些品系雄性小鼠的外皮质肾小管中，可变的细胞质空泡化是一种正常所见（Figure 1）。这些空泡被认为代表与这些细胞正常变性相关的自噬空泡（autophagic vacuole）。某些化学物质可能减少肾小管上皮中空泡的数量（Figure 2）。
诊断建议
作为雄性小鼠正常背景性所见而存在的细胞质空泡化不必诊断。如果在雄性小鼠中给予处理后（与对照相比）观察到细胞质空泡减少，则该所见应诊断为“细胞质改变（cytoplasmic alteration）”并给出严重程度分级。相关链接：肾脏 - 肾小管 - 空泡化，细胞质
参考切片图（2 张）
查看英文原文
Comment
Variable cytoplasmic vacuolation in outer cortical tubules of certain strains of male mice is a normal finding ( Figure 1 ). They are thought to represent autophagic vacuoles associated with the normal degeneration of these cells. Some chemicals may decrease the number of vacuoles in the renal tubular epithelium ( Figure 2 ).
Recommendation
Cytoplasmic vacuolation that is present as a normal background finding in male mice does not have to be diagnosed. If a decrease in cytoplasmic vacuoles is seen following treatment in male mice (compared with controls), then this finding should be diagnosed as "cytoplasmic alteration" and given a severity grade. Related Links: Kidney - Renal Tubule - Vacuolation, Cytoplasmic
肾小管细胞质空泡化Renal Tubule Vacuolation Cytoplasmic 肾脏空泡化
描述（中文）
细胞质空泡化（cytoplasmic vacuolation）的特征是肾小管上皮内出现透明空泡，而不伴有任何与变性相关的形态学改变（Figure 1）。在某些品系的雄性小鼠中，外层皮质肾小管通常存在细胞质空泡，但雌性小鼠或大鼠通常不存在。异常性或病理性空泡化可见于各肾小管节段和集合管的任何部位。更常见于近端曲小管上皮。空泡化可能与单个较大的囊泡（大囊泡性，macrovesicular）相关，也可能与数个较小的囊泡（微囊泡性，microvesicular）相关。具有渗透活性的化合物（如某些糖类）常导致“渗透性肾病（osmotic nephrosis）”，表现为细胞质空泡化。肾小管上皮的细胞质空泡化也可见于磷脂沉积诱导性化学物、环糊精（cyclodextrins）以及其他通过吞噬溶酶体（phagolysosomes）诱导空泡化的化学物。在大多数情况下，细胞质空泡化是可逆的。与自溶或固定不良相关的假性空泡化（artifactual vacuolation）常见于试验中死亡或濒死状态处死的动物。通常难以将肾小管毒性与假性改变区分开来。
诊断建议
正常情况下，雄性小鼠存在程度不等的皮质肾小管细胞质空泡化，不必作出诊断（见 Kidney - Renal Tubule - Cytoplasmic Alteration）。在雄性小鼠中，只有当空泡的数量和/或大小超过同期对照时，才应诊断细胞质空泡化。雌性小鼠以及雄性和雌性大鼠的细胞质空泡化，只要存在即应诊断。该诊断应仅限用于空泡存在而不伴有其他变性形态学特征的情况。应在病理学描述中说明受影响的肾小管部位及肾脏区域。凡作出该诊断时，均应对细胞质空泡化进行分级。假性空泡化不应诊断。相关链接：Kidney - Renal Tubule - Cytoplasmic Alteration
参考切片图（2 张）
查看英文原文
Comment
Cytoplasmic vacuolation is characterized by the presence of clear vacuoles in renal tubule epithelium in the absence of any morphologic changes associated with degeneration ( Figure 1 ). Cytoplasmic vacuoles are normally present in the outer cortical tubules of male mice in certain strains, but are not typically present in female mice or rats. Abnormal, or pathologic, vacuolation may be seen anywhere along the various tubule segments and collecting ducts. It is more commonly observed in the proximal convoluted tubule epithelium. Vacuolation may be associated with single, larger vesicles (macrovesicular) or may be associated with several smaller vesicles (microvesicular). Osmotically active compounds such as some sugars often result in "osmotic nephrosis," which appears as cytoplasmic vacuolation. Cytoplasmic vacuolation of renal tubule epithelium may also be seen with phospholipidosis-inducing chemicals, cyclodextrins, and other chemicals that induce vacuolation through phagolysosomes. Cytoplasmic vacuolation, in most cases, is reversible. Artifactual vacuolation, related to autolysis or poor fixation, is frequently observed in animals either dying on test or sacrificed in a moribund state. Often it becomes problematic to separate tubule toxicity from artifact.
Recommendation
Normally, male mice have variable cortical tubule cytoplasmic vacuolation and do not have to be diagnosed (see Kidney - Renal Tubule - Cytoplasmic Alteration ). In male mice, cytoplasmic vacuolation should be diagnosed only when the number and/or size of vacuoles is greater than that of the concurrent controls. Cytoplasmic vacuolation in female mice and male and female rats should be diagnosed whenever present. This diagnosis should be reserved for those cases where the vacuoles are present in the absence of other morphologic features of degeneration. The tubule location and portion of the kidney affected should be described in the pathology narrative. Whenever it is diagnosed, cytoplasmic vacuolation should be graded. Artifactual vacuolation should not be diagnosed. Related Links: Kidney - Renal Tubule - Cytoplasmic Alteration
肾小管肥大Renal Tubule Hypertrophy 肾脏肥大
描述（中文）
肾小管肥大（renal tubule hypertrophy）的特征是肾小管上皮细胞增大，染色特性不一。典型情况下，肾小管由单层上皮细胞衬覆，上皮细胞数量不增加。肥大细胞的细胞质通常无定形且呈明亮的嗜酸性，而细胞核显得小、圆且致密（Figure 1、Figure 2）。肾小管肥大的切向切片可能造成误导，看起来有些像增生。肥大常见于较严重的慢性进行性肾病（见 Kidney - Nephropathy, 慢性（chronic） Progressive），并被认为是与肾功能下降相关的代偿机制。它也可能由化学物给药引起。肥大不应被视为癌前病变。
诊断建议
肾小管肥大应予以诊断并给出严重程度分级。作为慢性进行性肾病组成部分的肥大不应单独诊断，而应视为慢性进行性肾病的一个组成部分。相关链接：Kidney - Glomerulus - Metaplasia；Kidney - Nephropathy, 慢性（chronic） Progressive
参考切片图（2 张）
查看英文原文
Comment
Renal tubule hypertrophy is characterized by enlarged tubule epithelial cells that have variable tinctorial staining. Typically, the tubule is lined by a single layer of epithelial cells, and the numbers of epithelial cells are not increased. The cytoplasm of hypertrophic cells is usually amorphous and brightly eosinophilic, while nuclei appear small, round and dense ( Figure 1 and Figure 2 ). Tangential sections through renal tubule hypertrophy may be misleading, appearing somewhat hyperplastic. Hypertrophy is often observed in more severe cases of chronic progressive nephropathy (see Kidney - Nephropathy, Chronic Progressive ) and is believed to be a compensatory mechanism related to a decline in renal function. It may also result from chemical administration. Hypertrophy should not be regarded as a preneoplastic condition.
Recommendation
Renal tubule hypertrophy should be diagnosed and given a severity grade. Hypertrophy as a component of chronic progressive nephropathy should not be diagnosed separately but should be considered a component of chronic progressive nephropathy. Related Links: Kidney - Glomerulus - Metaplasia Kidney - Nephropathy, Chronic Progressive
肾小管透明滴蓄积Renal Tubule Accumulation Hyaline Droplet 肾脏其他
描述（中文）
玻璃样滴（hyaline droplets）是嗜酸性均质细胞质滴，通常存在于年轻、成熟雄性大鼠近端肾小管上皮的P2段。这些滴代表隔离于次级溶酶体中的alpha 2u-globulin（Figure 1），Mallory-Heidenhain选择性染色可增强其可见性和细胞质分布（Figure 2、Figure 3）。“玻璃样滴积聚（Hyaline droplet accumulation）”可作为诊断术语，用于描述雄性和雌性啮齿动物中其他形态相似的嗜酸性滴。正常情况下，雌性大鼠及雄性和雌性小鼠的肾小管上皮细胞没有玻璃样滴。Alpha 2u-globulin肾病是一种雄性大鼠特有的综合征，导致形态学上多样的病变谱，通常包括玻璃样滴的存在、肾小管上皮细胞的变性/坏死和再生，以及亚慢性研究中髓质外层的颗粒管型存在。在慢性研究中，通常观察到慢性进行性肾病加重和线性乳头矿化。雄性NBR大鼠不发生alpha 2u-globulin肾病，在怀疑诱导该综合征的化学物的毒理学研究中用作阴性对照。在alpha 2u-globulin肾病中，玻璃样滴数量增加，其形态可能从球形变为结晶状多角形（Figure 4）。此外，Mallory-Heidenhain染色显示，随着滴数量增加及其形态变化，玻璃样滴的正常细胞质分布发生改变（Figure 5）。玻璃样滴通常不存在于慢性研究中。病理学家必须意识到，玻璃样滴的存在可能并不总是表明alpha 2u-globulin肾病的存在，因为其他情况如荷瘤动物也可能有玻璃样滴。这在 mice and rats 的组织细胞肉瘤中尤为如此。
诊断建议
由于玻璃样滴的存在是年轻雄性大鼠的正常现象，亚慢性研究中雄性大鼠玻璃样滴积聚的诊断应保留给那些玻璃样滴数量相对于对照组增加的情况。在雌性大鼠以及雄性和雌性小鼠中，只要存在玻璃样滴，就应诊断玻璃样滴积聚。玻璃样滴积聚一旦诊断，就应进行分级。同时见到和与玻璃样滴积聚相关的其他变化（例如颗粒管型形成、上皮细胞变性/坏死）应单独诊断。疑似发病机制（例如alpha 2U-globulin增加、与肿瘤形成的关联）应在病理学叙述中讨论。相关链接：肾脏 - 肾小管 - 变性
参考切片图（2 张）
查看英文原文
Comment
Hyaline droplets are eosinophilic homogeneous cytoplasmic droplets that are normally present in the P2 segment of proximal tubule epithelia of young, mature male rats. The droplets represent alpha 2u-globulin sequestered in secondary lysosomes ( Figure 1 ),and selective staining with Mallory-Heidenhain enhances their visibility and cytoplasmic distribution ( Figure 2 and Figure 3 ). "Hyaline droplet accumulation" may be used as a diagnostic term to describe other morphologically similar eosinophilic droplets in male and female rodents. Normally, renal tubule epithelial cells of female rats and male and female mice do not have hyaline droplets. Alpha 2u-globulin nephropathy comprises a male-rat-specific syndrome that results in a morphologically variable spectrum of lesions that generally includes the presence of hyaline droplets, degeneration/necrosis and regeneration of tubule epithelial cells, and the presence of granular casts in the outer medulla in subchronic studies. In chronic studies, exacerbation of chronic progressive nephropathy and linear papillary mineralization are generally observed. Male NBR rats do not develop alpha 2u-globulin nephropathy and are used as negative controlsin toxicology studies of chemicals suspected to induce this syndrome. In alpha 2u-globulin nephropathy, hyaline droplets increase in number,and their morphology may change from spherical to crystalloid polyangular shape ( Figure 4 ). In addition, Mallory-Heidenhain staining shows that as the number of droplets increasesand their morphology changes, the normal cytoplasmic distribution of the hyaline droplets becomes altered ( Figure 5 ). Hyaline droplets are usually not present in chronic studies. Pathologists must be aware that the presence of hyaline droplets may not always indicate the presence of alpha 2u-globulin nephropathy since other conditions such as tumor-bearing animals may have hyaline droplets. This is particularly true with histiocytic sarcoma in mice and rats.
Recommendation
Since the presence of hyaline droplets is a normal occurrence in younger male rats, the diagnosis of hyaline droplet accumulation in male rats in subchronic studies should be reserved for those cases in which there is an increase in the number of hyaline droplets relative to controls. In female rats, and male and female mice, hyaline droplet accumulation should be diagnosed whenever hyaline droplets are present. Hyaline droplet accumulation should be graded whenever it is diagnosed. Other changes seen concurrently and in association with hyaline droplet accumulation (e.g., granular cast formation, degeneration/necrosis of epithelial cells) should be diagnosed separately. The suspected pathogenesis (e.g., increased alpha 2U-globulin, association with neoplasia) should be discussed in the pathology narrative. Related Links: Kidney - Renal Tubule - Degeneration
肾小管非典型小管增生Renal Tubule Atypical Tubule Hyperplasia 肾脏增生
描述（中文）
非典型肾小管增生（非典型性（atypical） tubule hyperplasia，ATH）可自发发生，可与慢性进行性肾病相关，也可由化学物给药引起。ATH通常起源于近端曲小管，但也可能起源于远端小管或集合管。它被认为是一种推定的肿瘤前病变，是导致肿瘤形成的连续过程的一部分（Figure 1、Figure 2、Figure 3）。ATH的特征是在单个肾小管范围内上皮细胞数量增多，这与腺瘤不同，腺瘤中增殖的细胞不再局限于单个肾小管范围内。ATH中增殖的衬覆上皮超过两到三层细胞。增生的细胞显得增大，胞质呈轻度嗜碱性的“玻璃样”光泽。可能存在不同程度的细胞质和细胞核多形性。病变扩张的证据可通过病变周围成纤维细胞变扁平并边缘化来识别。肾小管腺瘤中可见的新血管形成在ATH中不明显。ATH不应与肾小管增生混淆，后者常见于晚期慢性进行性肾病的病灶中（见肾脏 - 肾病，慢性进行性），其特征为肾小管由单层数量增多的上皮细胞衬覆。这种形式的肾小管增生很少由化学物给药诱导，被认为代表一种再生形式。
诊断建议
由于非典型肾小管增生被推定为肿瘤前病变，因此只要存在就应作出诊断并给予严重程度分级。相关链接：肾脏 - 肾病，慢性进行性；肾脏 - 肾小管 - 增生，嗜酸性空泡性；肾脏 - 肾小管 - 增生，嗜酸性细胞性
参考切片图（2 张）
查看英文原文
Comment
Atypical tubule hyperplasia (ATH) may occur spontaneously, in association with chronic progressive nephropathy, or as a result of chemical administration. ATH usually arises from the proximal convoluted tubule, but a distal tubule or collecting duct origin is possible. It is considered a putative preneoplastic lesion that is part of the continuum leading to neoplasia ( Figure 1 , Figure 2 , and Figure 3 ). ATH is characterized by an increased number of epithelial cells within the confines of a single tubule, as opposed to an adenoma, in which the proliferating cells are no longer within the confines of a single tubule. The proliferative lining epithelium in ATH is greater than two or three cell layers. Hyperplastic cells appear enlarged with a slightly basophilic “glassy” cytoplasmic sheen. Variable degrees of cytoplasmic and nuclear pleomorphism may be present. Evidence of lesion expansion is identified by fibroblast flattening and margination around the lesion. Neovascularization noted in renal tubule adenomas is not apparent in ATH. ATH should not be confused with tubule hyperplasia, which is often observed in foci of advanced chronic progressive nephropathy (see Kidney - Nephropathy, Chronic Progressive ) and characterized as a tubule lined by a single layer of increased numbers of epithelial cells. This form of tubule hyperplasia is rarely induced by chemical administration and is considered to represent a form of regeneration.
Recommendation
Since atypical tubule hyperplasia is presumed to be a preneoplastic lesion, it should be diagnosed and given a severity grade whenever present. Related Links: Kidney - Nephropathy, Chronic Progressive Kidney - Renal Tubule - Hyperplasia, Amphophilic-Vacuolar Kidney - Renal Tubule - Hyperplasia, Oncocytic
肾母细胞瘤病Nephroblastematosis 肾脏其他
描述（中文）
肾母细胞瘤病（nephroblastematosis）可为自发性病变，是肾母细胞瘤（nephroblastoma）的假定前驱病变。低倍镜下，肾母细胞瘤病表现为细胞密集的嗜碱性区域（Figure 1、Figure 2）。高倍镜下，可见形态一致的细胞浸润于肾小管之间，其特征为细胞边界和胞质不清，细胞核呈圆形至卵圆形，染色质呈点状（Figure 3）。肾母细胞瘤病与肾母细胞瘤之间的区分在一定程度上是人为的，取决于是否分化形成任何器官样（小管、肾小球样）结构——该结构见于肾母细胞瘤病——以及病变的整体大小。与其他病变（如细胞浸润、炎症或淋巴瘤）的鉴别通常取决于是否存在细胞类型更为异质性的细胞群（常呈局灶性（focal）至多灶性（multifocal）血管周围分布）和/或病变内血管中是否存在相关细胞（Figure 4）。
诊断建议
肾母细胞瘤病一旦存在即应诊断，并给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Nephroblastematosis can be a spontaneous lesion and is the presumptive precursor lesion of nephroblastoma. On low power, nephroblastematosis appears as an area of densely basophilic cellularity ( Figure 1 and Figure 2 ). On higher magnification, uniform cells are seen infiltrating between renal tubules and are characterized by having indistinct cell margins and cytoplasm and round to oval nuclei with stippled chromatin ( Figure 3 ). The distinction between nephroblastematosis and nephroblastoma is somewhat arbitrary and depends on differentiation into any organoid (tubule, glomeruloid) structures, which is seen in nephroblastematosis, and the overall size of the lesion. Differentiation from other lesions such as cellular infiltrates, inflammation, or lymphoma usually depends on the presence of a more heterogeneous population of cell types, which often have a focal to multifocal perivascular distribution, and/or the presence of associated cells in blood vessels within the lesion ( Figure 4 ).
Recommendation
Nephroblastematosis should be diagnosed whenever present and given a severity grade.
肾盂扩张Pelvis Dilation 肾脏扩张
描述（中文）
肾盂扩张（dilation of the renal pelvis）优于“肾盂积水（hydronephrosis）”一词，后者既可指大体剖检所见，也可指显微镜下改变。扩张的特征为肾盂的膨胀与扩张，通常伴有肾乳头萎缩（Figure 1、Figure 2）。该病变可能是啮齿类动物研究中的常见所见，既可为原发性，也可继发于下尿路梗阻性病变。原发性病例常被认定为先天性，并且主要见于大鼠右肾。小鼠中不存在此种好发倾向。已有双侧病例的报道。多种病因与肾盂扩张相关，大多与下尿路梗阻有关。部分肾盂扩张病例可变得相当严重，导致肾脏大体上显著扩张、仅残留少量实质，甚至死亡。已通过产前暴露于某些化学物引起输尿管改变及随后的尿路阻塞，从而诱导出肾盂扩张。
诊断建议
肾盂扩张（dilatation of the renal pelvis）应当作出诊断并给出严重程度分级。若为双侧，应在诊断中将“双侧（bilateral）”一词作为修饰词纳入。肾盂扩张可在剖检时被注意到，因此常存在大体-显微镜下所见的相关性，应予以引用。如有可能，应确定扩张的原因并在病理学描述中加以描述。相关链接：肾脏 - 囊肿（Kidney - Cyst）
参考切片图（2 张）
查看英文原文
Comment
Dilation of the renal pelvis is preferred over the term “hydronephrosis,”which can denote either a gross necropsy or microscopic change. Dilation is characterized by distention and dilation of the renal pelvis,usually accompanied by renal papilla atrophy ( Figure 1 and Figure 2 ). This lesion may be a common finding in rodent studies and can be either primary or secondary to an obstructive lesion of the lower urinary tract. Primary cases are often noted as congenital and are noted predominately in the right kidney of rats. There is no such predilection in mice. Bilateral cases have been reported. Many etiologies are associated with renal pelvis dilation, mostly related to obstruction of the lower urinary tract. Some cases of renal pelvis dilation can become quite severe, resulting in a grossly dilated kidney with little parenchyma remaining,or even death. Dilation of the renal pelvis has been induced from prenatal exposure with some chemicals by causing ureteral changes and subsequent urinary blockage.
Recommendation
Dilatation of the renal pelvis should be diagnosed and given a severity grade. If bilateral, the term "bilateral" should be included as a modifier in the diagnosis. Renal pelvic dilation can be noted at necropsy, so there is often a gross-microscopic correlate that should be cited. If possible, the cause of the dilation should be identified and described in the pathology narrative. Related Links: Kidney - Cyst
透明性肾小球病Hyaline Glomerulopathy 肾脏其他
描述（中文）
透明样肾小球病（hyaline glomerulopathy）在B6C3F1小鼠中可作为自发性及/或治疗相关性疾病发生，在F344/N大鼠中则为治疗相关性疾病。其特征为多种肾小球改变，包括细胞外嗜酸性沉积物所致的弥漫性肾小球增大，伴有肾小球毛细血管丛细胞数量减少（Figure 1、Figure 2）。透明样肾小球病必须与淀粉样变性（amyloidosis）相鉴别。有助于将其与淀粉样物质区分开的特殊染色特性包括：过碘酸-雪夫染色（PAS）阴性（Figure 3）、刚果红（Congo red）染色阴性以及Masson三色染色（Masson’s trichrome）阳性。嗜酸性沉积物仅出现于肾小球内，不存在于其他器官。“透明样肾病（hyaline nephropathy）”一词用于描述一种特定的肾小球病变，但并不表明或界定所蓄积物质的成分。需要进行超出常规组织病理学评估范围的特殊研究。
诊断建议
透明样肾小球病只要存在即应作出诊断并进行分级。分级应基于受累肾小球的数量以及受累肾小球内物质的量。相关链接：肾脏 - 淀粉样变性 肾脏 - 肾小球肾炎 肾脏 - 肾小球硬化
参考切片图（2 张）
查看英文原文
Comment
Hyaline glomerulopathy may occur as a spontaneous and/or treatment-related condition in B6C3F1 mice and a treatment-related condition in F344/N rats. It is characterized by several glomerular changes that include diffuse glomerular enlargement by an extracellular eosinophilic deposit accompanied by a reduction in glomerular tuft cellularity ( Figure 1 and Figure 2 ). Hyaline glomerulopathy must be differentiated from amyloidosis. Special staining qualities, which help to distinguish it from amyloid, include period acid-Schiff negativity ( Figure 3 ), Congo red negativity, and Masson’s trichrome positivity. Eosinophilic deposits occur only within the glomerulus and are not present in other organs. The term "hyaline nephropathy" is used to describe a specific glomerular lesion but does not indicate or define the composition of the accumulated material. Special studies outside the scope of routine histopathologic evaluation would be warranted.
Recommendation
Hyaline glomerulopathy should be diagnosed and graded whenever present. Grading should be based on the number of glomeruli affected and the amount of material within the affected glomeruli. Related Links: Kidney - Amyloid Kidney - Glomerulonephritis Kidney - Glomerulosclerosis
间质细胞浸润Interstitium Infiltration Cellular 肾脏浸润
描述（中文）
在啮齿类动物的肾脏中，细胞浸润（cellular infiltration）是常规观察到的现象（Figure 1）。浸润细胞通常为淋巴样细胞或单核细胞，但其他炎症细胞类型也可能构成浸润。这些浸润一般随年龄增长而增加。在许多情况下，它们属于背景性发现，病理学意义很小。必须将细胞浸润与炎症（inflammation）相鉴别。一般而言，当炎症细胞数量相对较少且不伴有其他炎症指征（如水肿、出血、组织损伤）时，诊断为细胞浸润。
诊断建议
当细胞浸润与处理相关时，应予以诊断。若与处理无关，其诊断由病理学家自行决定。若予以诊断，应在诊断中以修饰词的形式标明细胞类型（例如，肾脏，间质 - 浸润，细胞性，淋巴细胞）。相关链接：肾脏 - 炎症
参考切片图（1 张）
查看英文原文
Comment
Cellular infiltrates are routinely observed in the kidneys of rodents ( Figure 1 ). The infiltrating cells are typically lymphoid or mononuclear cells, but other inflammatory cell types may comprise the infiltrates. These infiltrates generally increase with age. In many cases, they represent a background finding that has little pathologic significance. Cellular infiltration must be differentiated from inflammation. In general, cellular infiltration is diagnosed when the number of inflammatory cells is relatively low and no other indicators of inflammation (e.g., edema, hemorrhage, tissue damage) accompany the cells.
Recommendation
Cellular infiltration should be diagnosed when it is treatment related. If it is not treatment related, its diagnosis is left to the discretion of the pathologist. If diagnosed, the cell type should be indicated in the diagnosis as a modifier (e.g., Kidney, Interstitium - Infiltration, Cellular, Lymphocyte). Related Links: Kidney - Inflammation
阻塞性肾病Nephropathy Obstructive 肾脏其他
描述（中文）
梗阻性肾病（obstructive nephropathy）可能由与结晶沉积相关的炎症、逆行性肾病（retrograde nephropathy）或下尿路流出道阻塞引起。无论病因如何，均可观察到相似的形态学改变。逆行性（反流性）肾病是梗阻性肾病的一种形式，与一种反流现象有关，其特征为小簇状扩张的肾小管从肾乳头向皮质延伸，这是由于下尿路改变导致尿液反流增加所致（Figure 1、Figure 2）。导致梗阻性肾病的下尿路病变并非总能通过显微镜检出，因此其发病机制可能仍不明确。肾小管特征通常包括皮质嗜碱性肾小管灶或区域，伴有远端肾小管和集合管扩张（Figure 3、Figure 4）。管腔内炎症细胞或伴随的上行性肾盂肾炎可能存在，也可能不存在。消退中的病变可导致纤维化条带。
诊断建议
梗阻性肾病应当作出诊断并给出严重程度分级。相关病变如炎症和纤维化，仅当其为主要特征时才应单独记录。每当观察到梗阻性肾病时，均应检查下尿路以寻找病因。继发于肿瘤的梗阻性肾病不应单独诊断，而应在病理学描述中予以描述。相关链接：肾脏 - 结晶；肾脏 - 肾病，慢性进展性
参考切片图（2 张）
查看英文原文
Comment
Obstructive nephropathy may result from inflammation associated with deposition of crystals, retrograde nephropathy, or a lower urinary tract outflow blockage. Whatever the cause, similar morphologic changes can be observed. Retrograde (reflux) nephropathy, a form of obstructive nephropathy, is related to a backflow phenomenon characterized by small clusters of dilated tubules that ascend from the papilla to the cortex and are due to increased urine reflux resulting from changes in the lower urinary tract ( Figure 1 and Figure 2 ). Lesions of the lower urinary tract contributing to obstructive nephropathy may not always be detected microscopically,and thus the pathogenesis may remain unclear. Tubule features often include foci or areas of cortical basophilic tubules with distal tubule and collecting duct dilation ( Figure 3 and Figure 4 ). Intraluminal inflammatory cells or an accompanying ascending pyelonephritis may or may not be present. Resolving lesions may result in tracts of fibrosis.
Recommendation
Obstructive nephropathy should be diagnosed and given a severity grade. Associated lesions such as inflammation and fibrosis should be recorded separately only if they are very prominent features. Whenever obstructive nephropathy is observed, the lower urinary tract should be examined for the cause. Obstructive nephropathy secondary to a neoplasm should not be diagnosed separately but should be described in the pathology narrative. Related Links: Kidney - Crystals Kidney - Nephropathy, Chronic Progressive
骨性化生Metaplasia Osseous 肾脏化生
描述（中文）
骨化生（osseous metaplasia）的特征是肾实质内出现外观成熟的骨组织。通常表现为皮质内的局灶性（focal）病变，被视为无病理意义的自发性病变。骨化生的大小可能不一，较大的病变内可能出现造血细胞（Figure 1、Figure 2）。骨化生需与矿化（mineralization）相鉴别。
诊断建议
骨化生应当记录，但无需分级。相关链接：肾脏-异位组织
参考切片图（2 张）
查看英文原文
Comment
Osseous metaplasia is characterized by mature-appearing bone in the renal parenchyma. It is usually noted as a focal lesion in the cortex and is regarded as a spontaneous lesion of no pathologic significance. Osseous metaplasia may vary in size, and hematopoietic cells may be present in larger lesions ( Figure 1 and Figure 2 ). Osseous metaplasia needs to be distinguished from mineralization.
Recommendation
Osseous metaplasia should be recorded but need not be graded. Related Links: Kidney - Ectopic Tissue
出血Hemorrhage 膀胱出血
描述（中文）
出血可见于膀胱的任何部位。出血通常与炎症、结石或肿瘤的存在相关（Figure 1、Figure 2）。濒死期出血可通过缺乏任何伴发病变（如水肿、炎症或含铁血黄素）加以鉴别。
诊断建议
出血通常为继发性所见，除非它是整体病变的主要组成部分且在该病变的发病机制中具有重要意义，否则不应作出诊断。濒死期出血不应作出诊断。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage can be seen anywhere in the bladder. It is commonly associated with inflammation, calculi, or the presence of tumors ( Figure 1 and Figure 2 ). Perimortem hemorrhage can be differentiated by the lack of any concurrent lesions, such as edema, inflammation, or hemosiderin.
Recommendation
Hemorrhage is usually a secondary finding and should not be diagnosed unless it is a major component of the overall lesion and important in the pathogenesis of the lesion. Perimortem hemorrhage should not be diagnosed.
化生Metaplasia 膀胱化生
描述（中文）
尿路上皮化生（metaplasia）反映了尿路上皮在多种条件下发生化生性改变的能力。鳞状化生（squamous metaplasia），伴或不伴角化，是最常见的变异型（Figure 1、Figure 2、Figure 3）。黏液性、腺性或混合性化生性病变较少见（Figure 4）。
诊断建议
尿路上皮化生，特别是化生的类型，当它成为病变的主要部分时，例如与炎症或增生相关时，应当诊断并给出严重程度分级。当小病变或局灶性（focal）病变是原发性病变（如慢性炎症和/或增生）的一部分时，不应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Metaplasia of the urothelium reflects the potential of the urothelium to undergo a metaplastic change under a variety of conditions. Squamous metaplasia, with or without keratinization, is the most common variant observed ( Figure 1 , Figure 2 , and Figure 3 ). Mucinous, glandular, or mixtures of metaplastic lesions are less commonly observed ( Figure 4 ).
Recommendation
Urothelial metaplasia and, in particular, the type of metaplasia should be diagnosed and given a severity grade when it becomes a major part of a lesion, for instance, in association with inflammation or hyperplasia. Small or focal lesions, when part of a primary lesion such as chronic inflammation and/or hyperplasia, should not be diagnosed separately.
坏死Necrosis 膀胱坏死
描述（中文）
尿路上皮坏死可能由细胞毒性所致，包括直接给予化学物质或晶体和结石引起的刺激，并可能与溃疡和炎症相关。坏死通过细胞嗜酸性变和碎裂，以及核固缩和核碎裂来识别（Figure 1）。变性可能先于坏死发生，但单纯变性很少被诊断。既往坏死的区域可发生再生并愈合，或导致尿路上皮增生。
诊断建议
尿路上皮坏死应予以诊断并给出严重程度分级。病理学家应运用其判断来决定与坏死相关的继发性病变是否足够显著，以 warrant 单独诊断。相关链接：Urinary Bladder - Ulcer
参考切片图（1 张）
查看英文原文
Comment
Necrosis of the urothelium may be due to cytotoxicity, including direct chemical administration or irritation from crystals and calculi and may be associated with ulceration and inflammation. Necrosis is recognized by cellular eosinophilia and fragmentation, as well as nuclear pyknosis and karyorrhexis ( Figure 1 ). Degeneration may precede necrosis, but degeneration by itself is infrequently diagnosed. Areas of previous necrosis can undergo regeneration and heal or result in urothelial hyperplasia.
Recommendation
Necrosis of the urothelium should be diagnosed and given a severity grade. The pathologist should use his or her judgment in deciding whether or not secondary lesions associated with necrosis are prominent enough to warrant a separate diagnosis. Related Links: Urinary Bladder - Ulcer
尿路上皮增生Urothelium Hyperplasia 膀胱增生
描述（中文）
尿路上皮增生（urothelial hyperplasia）定义为上皮细胞数量增多，常见于炎症、结石存在时，或作为化学物质给药后的反应。一般而言，增生可为单纯性（simple）、结节性（nodular）或乳头状（papillary）（Figure 1、Figure 2、Figure 3、Figure 4），对于偶发性和自发性病例，诊断可能并不重要。大多数增生病例为局灶性（focal）至弥漫性（diffuse）。增生的细胞形态可正常或呈多形性，或（罕见）可有异型性。核分裂象数量不定。可观察到鳞状、腺状或混合细胞化生的化生灶。尿路上皮增生可能是可逆的，但也可能进展为肿瘤。增生在小鼠中较少见。极轻微（minimal）增生难以诊断，因为固定过程中膀胱外观存在变异性。
诊断建议
通常，超过正常3至4层细胞厚度的尿路上皮增多即构成增生的判定标准。然而，由于非充盈状态下膀胱衬里的折叠，切片制作也给极轻微（minimal）或交界性增生的判定带来困难。应注意不要将切向切片误判为增生。增生应予以诊断并给出严重程度分级。与化学物质暴露相关的增生修饰词如“simple”、“nodular”或“papillary”应在叙述性报告中讨论。
参考切片图（2 张）
查看英文原文
Comment
Urothelial hyperplasia, defined as an increased number of epithelial cells, is commonly observed with inflammation, with the presence of calculi, or as a response to chemical administration. In general, hyperplasia can either be simple, nodular, or papillary ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ), which may not be important to diagnose for occasional and spontaneous cases. Most cases of hyperplasia are focal to diffuse. Hyperplastic cells may be normal in appearance or pleomorphic, or (rarely) may have atypia. Mitotic figures are variable. Metaplastic foci of squamous, glandular, or mixtures of cell metaplasia may be noted. Urothelial hyperplasia may be reversible but may also progress to neoplasia. Hyperplasia is less commonly observed in the mouse. Minimal hyperplasia is difficult to diagnose because of the variability of the bladder appearance during fixation.
Recommendation
Usually a guideline of an increase above the normal 3- to 4-cell-thick urothelium constitutes hyperplasia. However, sectioning also poses a difficulty in determining minimal or borderline hyperplasias because of folding of the bladder lining in nondistended states. Care should be taken to not confuse tangential sectioning as hyperplasia. Hyperplasia should be diagnosed and given a severity grade. Hyperplastic modifiers such as “simple,” “nodular,” or “papillary” associated with chemical exposure should be discussed in the narrative report.
尿路上皮细胞质颗粒Urothelium Cytoplasmic Granules 膀胱其他
描述（中文）
在尿路上皮最表层的上皮“伞”细胞内可能观察到细胞质颗粒。它们很少出现在中间细胞或基底细胞中，通常呈深嗜酸性。这些颗粒可能代表多种已报道的成分，如降解产物、化学物质/代谢物或线粒体。细胞质颗粒的存在通常不引起细胞反应，且未与癌前病变或肿瘤形成相关联。
诊断建议
细胞质颗粒应予以诊断并给出严重程度分级。如果与处理相关，则应在叙述性报告中描述颗粒的任何独特特征。
参考切片图（2 张）
查看英文原文
Comment
Cytoplasmic granules may be observed within the most superficial epithelial “umbrella” cells of the urothelium. They rarely occur in the intermediate or basal cells and typically are deeply eosinophilic. The granules may represent a number of reported constituents, such as degradation products, chemicals/metabolites, or mitochondria. The presence of cytoplasmic granules usually elicits no cell response and has not been associated with either preneoplasia or neoplasia.
Recommendation
Cytoplasmic granules should be diagnosed and given a severity grade. If treatment related, any unique characteristics of the granules should be described in the narrative report.
扩张Dilation 膀胱扩张
描述（中文）
膀胱扩张（dilation of the urinary bladder）的特征是膀胱过度膨胀，尿路上皮变扁平（Figure 1）。这是一种常见的病变，可由多种病因引起。最常见的原因是梗阻。在病因不明显或与化学物给药相关的情况下，也可观察到膀胱扩张的病例。当未检查尿道时，膀胱扩张的病因可能被遗漏。雄性动物的鼠泌尿综合征（mouse urologic syndrome）是导致梗阻、膀胱扩张、炎症、发病和死亡的常见原因。结石也可能阻塞尿液流出，导致扩张。尽管在膀胱三角区可观察到蛋白性栓子（proteinaceous plugs），但这些栓子通常不会导致扩张，因为在大多数情况下它们代表濒死事件。通常推荐用福尔马林充盈膀胱，但可能发生过充和其他与充盈相关的伪影。
诊断建议
膀胱扩张应当被诊断并给出严重程度分级。如果扩张与受试物相关，应考虑确定其病因。如果能够确定病因，应单独诊断该病因，并在叙述中讨论其与膀胱扩张的关系。
参考切片图（2 张）
查看英文原文
Comment
Dilation of the urinary bladder is characterized by an overly distended bladder with flattened urothelium ( Figure 1 ). This is a commonly observed change, which can result from a number of etiologies. The most common cause is obstruction. Cases of urinary bladder dilation may be noted where the cause is not apparent or related to chemical administration. The etiology of bladder dilation may be missed when the urethra is not examined. Mouse urologic syndrome in male animals is a frequent cause of obstruction, bladder dilation, inflammation, morbidity, and death. Calculi may also block the outflow of urine, leading to dilation. Although proteinaceous plugs may be observed in the trigone region of the urinary bladder, these plugs usually do not contribute to dilation because in most cases they represent agonal events. Formalin inflation of the urinary bladder is usually recommended, but overinflation and other inflation-related artifacts may occur.
Recommendation
Dilation of the urinary bladder should be diagnosed and given a severity grade. Identification of cause should be considered if dilation is treatment related. If the cause can be identified, it should be diagnosed separately and its relationship to the urinary bladder dilation discussed in the narrative.
水肿Edema 膀胱水肿
描述（中文）
水肿通常与其他病变同时出现，尤其是炎症，典型表现为上皮下结缔组织中无定形、略呈嗜酸性（eosinophilic）的液体（Figure 1）。水肿必须与用固定液充盈膀胱所产生的伪影相鉴别（Figure 2）。
诊断建议
由于部分水肿与炎症性和/或血管性病变同时出现，除非水肿是病变的主要组成部分，否则不应诊断为水肿。
参考切片图（2 张）
查看英文原文
Comment
Edema is usually seen with other lesions, particularly inflammation, and is typically noted as an amorphous, slightly eosinophilic fluid in the subepithelial connective tissue ( Figure 1 ). Edema has to be differentiated from artifacts produced by inflation of the urinary bladder with fixative solutions ( Figure 2 ).
Recommendation
Since some edema is seen with inflammatory and/or vascular lesions, edema should not be diagnosed unless it is a major component of the lesion.
淋巴细胞细胞浸润Infiltration Cellular Lymphocyte 膀胱浸润
描述（中文）
细胞浸润，淋巴细胞性，通常表现为局灶性（focal）至多灶性（multifocal）、边界清楚的黏膜下浸润，以淋巴细胞为主（Figure 1、Figure 2）。浸润也可见于血管周围。大多数细胞浸润往往为自发性，见于其他方面正常的膀胱，几乎没有或没有病理学意义。
诊断建议
由于较小的浸润在啮齿类动物膀胱中常见，病理学家对这些浸润设定诊断阈值并不罕见。确定阈值并在整个研究过程中始终如一地维持该阈值是病理学家的责任。当作出诊断时，淋巴细胞浸润应给予严重程度评分。
参考切片图（2 张）
查看英文原文
Comment
Infiltration cellular, lymphocyte, usually involves a focal to multifocal, well-defined, suburothelial infiltration of predominantly lymphocytes ( Figure 1 and Figure 2 ). Infiltrates can also be seen around vessels. Most cellular infiltrates tend to be spontaneous, in an otherwise normal bladder, and with little or no pathologic significance.
Recommendation
Since smaller infiltrates are common in rodent bladders, it is not uncommon for pathologists to have a diagnostic threshold for diagnosing these infiltrates. It is the responsibility of the pathologist to determine the threshold and to consistently maintain that threshold throughout the study. When diagnosed, lymphoid infiltrates should be given a severity score.
溃疡Ulcer 膀胱溃疡
描述（中文）
溃疡可由多种病因引起，例如直接化学暴露，或作为与炎症、结石或肿瘤相关的继发性病变。溃疡通常由尿路上皮糜烂/坏死进展而来，并延伸贯穿尿路上皮全层，导致上皮下出血和炎症（Figure 1、Figure 2）。炎症的严重程度取决于溃疡的大小和慢性程度。急性溃疡可能迅速发生。慢性病例中可观察到再生性增生和/或纤维化。
诊断建议
溃疡应予以诊断并给出严重程度分级。炎症和/或再生性增生明显时，应连同溃疡一起诊断，作为病变慢性程度的指标。
参考切片图（2 张）
查看英文原文
Comment
Ulcers may result from a number of etiologies, such as direct chemical exposure or as secondary lesions associated with inflammation, calculi, or tumors. Ulcers usually progress from urothelial erosions/necrosis and extend through the width of the urothelium, resulting in subepithelial hemorrhage and inflammation ( Figure 1 and Figure 2 ). The severity of the inflammation depends on the size and the chronicity of the ulcer. Acute ulceration may develop rapidly. Regenerative hyperplasia and/or fibrosis may be observed in chronic cases.
Recommendation
Ulcers should be diagnosed and given a severity grade. Inflammation and/or regenerative hyperplasia, when significant, should be diagnosed along with ulceration as an indicator of the chronicity of the lesion.
炎症Inflammation 膀胱炎症
描述（中文）
炎症是膀胱最常被诊断的病变之一。根据主要细胞类型或所涉及的细胞反应，炎症可以是急性、化脓性、慢性、慢性活动性或肉芽肿性。在急性炎症（急性（acute） inflammation）中，主要浸润细胞是中性粒细胞，尽管也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿和充血的表现。中性粒细胞也是化脓性炎症（化脓性（suppurative） inflammation）中的主要细胞类型；然而，中性粒细胞聚集，且其中许多发生退变（化脓性渗出物）。淋巴细胞在慢性炎症（慢性（chronic） inflammation）中占主导；淋巴细胞在慢性活动性炎症（慢性活动性（chronic-active） inflammation）中也占主导，但也存在大量中性粒细胞——两种病变均含有巨噬细胞。肉芽肿性炎症（肉芽肿性（granulomatous） inflammation）是慢性炎症的另一种形式，其诊断需要存在大量聚集的、大的活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。炎症细胞可见于膀胱的任何部位，包括管腔、黏膜、黏膜下层和肌层（Figure 1）。根据病变不同，可能明显可见出血、坏死、尿路上皮增生和纤维化（Figure 2）。在大多数情况下，炎症源于细菌感染或结石的存在。炎症也可能是化学物质给药的直接结果。
诊断建议
炎症应根据细胞反应和膀胱内的位置进行诊断，并应给出严重程度分级。如果出血、坏死、尿路上皮增生和纤维化构成病变的重要组分，则可分别诊断。
参考切片图（2 张）
查看英文原文
Comment
Inflammation is one of the most frequently diagnosed lesions of the urinary bladder. Inflammation may be acute, suppurative, chronic, chronic-active, or granulomatous, depending on the predominant cell type or cell response involved. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema and hyperemia. The neutrophil is also the predominant cell type in suppurative inflammation ; however, the neutrophils are aggregated, and many of them are degenerative (suppurative exudate). Lymphocytes predominate in chronic inflammation ; lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils—both lesions contain macrophages. Diagnosis of granulomatous inflammation , another form of chronic inflammation, requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammatory cells can be seen anywhere in the bladder, including the lumen, mucosa, submucosa, and muscularis ( Figure 1 ). Hemorrhage, necrosis, urothelial hyperplasia, and fibrosis may be evident, depending on the lesion ( Figure 2 ). In most instances, inflammation arises from bacterial infections or the presence of calculi. Inflammation may also be a direct consequence of chemical administration.
Recommendation
Inflammation should be diagnosed according to the cell response and the location within the bladder and should be given a severity grade. Hemorrhage, necrosis, urothelial hyperplasia, and fibrosis may be diagnosed separately if they constitute a significant component of the lesion.
矿化Mineralization 膀胱矿化
描述（中文）
矿化表现为深嗜碱性、颗粒状物质（Figure 1、Figure 2）。它通常累及膀胱的肌壁。营养不良性矿化（dystrophic mineralization）可继发于多种原因，尤其是在坏死区域。转移性矿化（metastatic mineralization）在啮齿类动物的膀胱中不常见。
诊断建议
当矿化在其他病变缺失的情况下出现（例如转移性矿化），或者当其继发于另一过程（例如营养不良性矿化）但构成病变的重要组分时，应当对其作出诊断并给出严重程度分级。相关链接：Urinary Bladder - Calculus/Crystal
参考切片图（2 张）
查看英文原文
Comment
Mineralization occurs as densely basophilic, granular material ( Figure 1 and Figure 2 ). It usually involves the muscle wall of the urinary bladder. Dystrophic mineralization may be seen secondary to a variety of causes, especially in areas of necrosis. Metastatic mineralization is uncommon in the rodent bladder.
Recommendation
Mineralization should be diagnosed and given a severity grade when seen in the absence of other lesions (e.g., metastatic mineralization) or, if it is secondary to another process (e.g., dystrophic mineralization), when it is a significant component of the lesion. Related Links: Urinary Bladder - Calculus/Crystal
细胞质空泡化Vacuolation Cytoplasmic 膀胱空泡化
描述（中文）
尿路上皮细胞的细胞质空泡化被视为一种非特异性病变，可能继发于多种膀胱毒物或致癌物所致的细胞损伤。它可能与变性有关，也可能无关。空泡化通常见于“伞”细胞或更表浅的尿路上皮细胞（Figure 1、Figure 2）。均匀一致的尿路上皮细胞空泡化（通常位于基底细胞层内）可能是自溶所致的伪影（Figure 3）。
诊断建议
细胞质空泡化应当被诊断并给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Cytoplasmic vacuolation of urothelial cells is regarded as a nonspecific lesion that may occur secondary to cell injury by a variety of bladder toxicants or carcinogens. It may or may not be related to degeneration. Vacuolation is usually noted in “umbrella” cells or more superficial urothelial cells ( Figure 1 and Figure 2 ). Uniform urothelial cell vacuolation (typically within the basal cell layer) may be an artifact resulting from autolysis ( Figure 3 ).
Recommendation
Cytoplasmic vacuolation should be diagnosed and given a severity grade.
色素Pigment 膀胱色素沉着
描述（中文）
啮齿类动物膀胱中色素沉积罕见报道。最常见的色素是含铁血黄素（hemosiderin）（Figure 1）。给予染料化合物后可见尿路上皮色素沉着。
诊断建议
色素沉积应当诊断并给出严重程度分级。除用于含铁血黄素的普鲁士蓝（Prussian blue）染色外，即使使用一系列特殊染色，在组织学切片中明确鉴定色素类型通常也很困难。因此，推荐诊断为“色素沉积”（而非诊断色素类型，例如含铁血黄素或脂褐素）更为恰当。病理学描述应描述色素的形态学特征。
参考切片图（1 张）
查看英文原文
Comment
Pigment is rarely reported in urinary bladders of rodents. The most common pigment is hemosiderin ( Figure 1 ). Pigmentation of urothelium has been observed with administered dye compounds.
Recommendation
Pigment should be diagnosed and given a severity grade. With the exception of Prussian blue staining for hemosiderin, definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, it is recommended that a diagnosis of “pigment” (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is more appropriate. The pathology narrative should describe the morphologic features of the pigment.
蛋白性栓Proteinaceous Plug 膀胱其他
描述（中文）
蛋白性栓子通常被认为是濒死期安乐死过程中附属性腺分泌物濒死性分泌所致的死后变化。蛋白性栓子大小不一，但可很大，充满膀胱（Figure 1、Figure 2）。显微镜下，栓子由无定形嗜酸性物质混合构成，有时含有脱落的上皮细胞和精子。蛋白性栓子本身无毒性学意义，也不是结石的前体。栓子可见于与细菌性炎症相关的梗阻综合征。必须与结石相鉴别。
诊断建议
单独发生且不与任何病理病变相关的蛋白性栓子应被认定为人为假象，不应作出诊断。偶尔，蛋白性栓子可在肉眼检查中被识别，病理学家应运用其判断力将肉眼病变与人为蛋白性栓子相关联。
参考切片图（2 张）
查看英文原文
Comment
Proteinaceous plugs are commonly noted as a postmortem change resulting from an agonal secretion of accessory sex gland fluids during euthanasia. Proteinaceous plugs vary in size but can be large, filling the urinary bladder ( Figure 1 and Figure 2 ). Microscopically, the plug is composed of a mixture of an amorphous eosinophilic material, sometimes containing desquamated epithelial cells and spermatozoa. Proteinaceous plugs by themselves have no toxicologic importance and are not precursors of calculi. Plugs may be seen with obstructive syndromes associated with bacterial inflammation. They must be differentiated from calculi.
Recommendation
Proteinaceous plugs occurring alone and not associated with any pathologic lesions should be recognized as an artifact and should not be diagnosed. Occasionally, proteinaceous plugs are recognized grossly, and the pathologist should use his or her judgment to correlate the gross lesion to an artifactual proteinaceous plug.
血管扩张Angiectasis 膀胱扩张
描述（中文）
膀胱内的局灶性（focal）血管扩张可诊断为血管扩张（angiectasis）（Figure 1、Figure 2）。这些病变通常报告为自发性病变，但也有报道与血管扩张性化学物质相关。血管扩张常见于黏膜下层，表现为局灶性或多灶性（multifocal）的病变，往往形态不规则且边界不清。血管扩张必须与血管瘤（hemangioma）相鉴别。两者的区分并不总是显而易见：血管瘤往往为边界清楚、无包膜的肿块，由紧密排列的扩张血管腔构成，每个血管腔由单层形态正常的内皮细胞围成并衬覆，内皮细胞排列于薄层胶原性间质上。
诊断建议
血管扩张应当诊断并给予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Focal blood vessel dilation in the urinary bladder may be diagnosed as angiectasis ( Figure 1 and Figure 2 ). These lesions are typically reported as spontaneous lesions but have been reported with vasodilating chemicals. Angiectasis is commonly noted in the submucosa as a focal or multifocal finding that tends to be irregular and not well circumscribed Angiectasis must be differentiated from hemangioma. The distinction is not always obvious: hemangiomas tend to be well circumscribed, unencapsulated masses composed of tightly packed dilated vascular spaces, each enclosed and lined by a single layer of normal-appearing endothelial cells aligned on a thin collagenous stroma.
Recommendation
Angiectasis should be diagnosed and given a severity grade.
扩张Dilation 输尿管扩张
描述（中文）
输尿管扩张（同义词：肾盂积水/输尿管积水，hydroureter）最常与梗阻性病变相关。肉眼观察时，常可见其与膀胱扩张及肾盂扩张同时存在。该病变可为单侧或双侧（Figure 1）。在大鼠中，先天性病例以右侧更为多见。已培育出具有自发性输尿管积水与肾积水的NON/Shi小鼠品系及SD/cShi大鼠品系，并可诱导其发生肾盂尿路上皮的增殖性病变。
诊断建议
输尿管扩张应予以诊断并评定严重程度分级。若输尿管扩张与受试物相关，研究病理学家应描述该病变为单侧还是双侧。
参考切片图（1 张）
查看英文原文
Comment
Dilation of the ureter (synonym: hydroureter) is most commonly associated with cases of obstruction. Often it can be seen grossly with dilation of the urinary bladder and renal pelvis. It can be either unilateral or bilateral ( Figure 1 ). In rats, congenital cases are more prevalent on the right side. A strain of mouse (NON/Shi) and a strain of rat (SD/cShi) have been developed that have spontaneous hydroureter and hydronephrosis and can be induced to develop proliferative lesions of the renal pelvic urothelium.
Recommendation
Dilation of the ureter should be diagnosed and assigned a severity grade. If ureter dilation is treatment related, the study pathologist should describe whether the lesion is unilateral or bilateral.
上皮变性Epithelium Degeneration 前胃变性
描述（中文）
细胞质空泡化（cytoplasmic vacuolization）、囊性变性（cystic degeneration）和水疱/大疱形成（vesicle/bulla formation）是鳞状上皮变性的几种形式，可发生于体内任何鳞状上皮。鳞状上皮的空泡化表现为表面上皮细胞染色浅淡、细胞质空泡化。相关黏膜可能发生溃疡，上皮细胞可能变性或坏死。下方组织有不同程度的炎症细胞浸润。此变化可能代表较坏死更轻微的改变，可见于采用灌胃方法的研究中。此病变也可能由致溃疡性或抗炎性化合物引起。囊性变性的特征为上皮细胞空泡化和气球样肿胀，导致细胞膜破裂，在上皮内形成不规则间隙，可能进而形成水疱或大疱。相关黏膜可能发生溃疡，上皮细胞可能变性或坏死。下方组织有不同程度的炎症细胞浸润。此变化可能代表空泡变性的进展，可见于采用灌胃方法的研究中。此病变也可能由致溃疡性或抗炎性化合物引起。大疱的特征为上皮层内或上皮层下局限性的液体积聚。水疱<1 cm，大疱≥1.0 cm。大疱可由棘层松解（acantholysis）、表皮或真皮水肿、基底细胞和角质形成细胞变性，或其他过程（如摩擦性创伤和烧伤导致细胞间黏附丧失）所形成。大疱可导致糜烂和溃疡。
诊断建议
当变性作为原发性病变存在时，应当诊断并分级。当变性作为继发性病变存在时（例如继发于炎症时），不应诊断，但应在病理学描述中予以描述。如果变性是病变的显著特征但不被视为原发性病变，若病理学家认为有正当理由，可将其与原发性病变同时诊断。分级应基于细胞肿胀的程度以及受累区域的范围和数量。如果变性和坏死同时存在，两者均应诊断并分级。炎症不应单独诊断，除非它是病变的显著特征。
参考切片图（2 张）
查看英文原文
Comment
Cytoplasmic vacuolization, cystic degeneration, and vesicle/bulla formation are forms of degeneration of the squamous epithelium that can occur in any squamous epithelium in the body. Vacuolization of the squamous epithelium is characterized by superficial epithelial cells with a pale staining and vacuolated cytoplasm. Associated mucosa may be ulcerated, and epithelial cells may be degenerate or necrotic. Subjacent tissue is variably infiltrated by inflammatory cells. This change may represent a milder change than necrosis and can be observed in studies involving gavage methods. This lesion may also be due to ulcerogenic or anti-inflammatory compounds. Cystic degeneration is characterized by vacuolization and ballooning swelling of epithelial cells, resulting in rupture of cell membranes to form irregular spaces in the epithelium, potentially leading to development of vesicles or bulla. Associated mucosa may be ulcerated, and epithelial cells may be degenerate or necrotic. Subjacent tissue is variably infiltrated by inflammatory cells. This change may represent a progression of vacuolar degeneration and can be observed in studies involving gavage methods. This lesion may also be due to ulcerogenic or anti-inflammatory compounds. Bulla are characterized as a localized collection of fluid in or beneath the epithelial layer. Vesicles are <1 cm and bulla are ≥ 1.0 cm. Bulla can form as the result of acantholysis, epidermal or dermal edema, degeneration of basal cells and keratinocytes, or other processes, such as frictional trauma and burns that cause a lack of cohesion between cells. Bulla can lead to erosions and ulceration.
Recommendation
Degeneration should be diagnosed and graded when present as a primary lesion. When degeneration is present as a secondary lesion (e.g., when secondary to inflammation) it should not be diagnosed but should be described in the pathology narrative. If the degeneration is a prominent feature of the lesion but is not considered the primary lesion, it may be diagnosed concurrently the primary lesion if the pathologist feels it is warranted. Grading should be based on the degree of cellular swelling and extent and number of areas affected. If both degeneration and necrosis are present, both should be diagnosed and graded. Inflammation should not be diagnosed separately, unless it is a prominent feature of the lesion.
上皮增生（局灶性/弥漫性）Epithelium Hyperplasia[Focal Diffuse] 前胃增生
描述（中文）
增生（hyperplasia）被定义为上皮一层或多层（基底层、棘层或颗粒层）中细胞数量的增加。当黏膜存在增生时，常可见角化过度（hyperkeratosis，即角质层厚度增加）。增生可为弥漫性（弥漫性（diffuse））（Figure 1、Figure 6、Figure 7、Figure 8）或局灶性（局灶性（focal））（Figure 2、Figure 3、Figure 4），并导致非腺性胃黏膜厚度增加。增生也可见于界嵴（limiting ridge）（Figure 6；与Figure 5中的正常界嵴相比较）。非腺性胃的增生通常表现为上皮各层均匀增厚，而无向上或向下的突起。然而，在更严重的病例中，上皮出现卷曲，并伴有网状钉突样结构（rete peg-like structures）的向下突起。基底细胞可能发生增殖，并可延伸至黏膜下层（Figure 7、Figure 8）。在局灶性增生较严重的病例中，可能出现向管腔内向上增殖、类似乳头状瘤（papilloma）的病变，在描述中可称为乳头状增生（papillary hyperplasia）。缺乏含血管的分支状结缔组织核心以及黏膜肌层完整，可将这种形式的增生与真性乳头状瘤区分开来。增生时，仍保留一定程度的有序成熟。
诊断建议
增生一经出现即应作出诊断并分级。应尽可能使用修饰词“局灶性（focal）”和“弥漫性（diffuse）”。分级应基于病变大小、分布范围及上皮厚度。多灶性病变不记录为“多灶性（multifocal）”，但应给予比单发病变更高的严重程度分级。若存在异型性特征，如角化不良（diskeratinization）、结构紊乱（disorganization）或存在非典型细胞，则应诊断为非典型增生（非典型性（atypical） hyperplasia）（见 Stomach, Forestomach - Epithelium - Hyperplasia, 非典型性）。若病理学家认为存在两种不同的增生过程（例如弥漫性和非典型性），则两者均应作出诊断，并在病理学描述中详尽描述。与增生相关的角化过度通常不作为独立病变诊断，除非它是病变的显著组成部分，但应在病理学描述中予以描述。相关链接：Stomach, Forestomach - Epithelium - Hyperplasia, 非典型性
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia is defined as an increase in the number of cells in one or more epithelial strata (basal, spinous, or granulosum). Hyperkeratosis (increased thickness of the stratum corneum) is often seen when hyperplasia of the mucosa is present. Hyperplasia may be diffuse ( Figure 1 , Figure 6 , Figure 7 , and Figure 8 ) or focal ( Figure 2 , Figure 3 , and Figure 4 ) and results in an increased thickness of the non-glandular stomach mucosa. Hyperplasia may also be seen at the limiting ridge ( Figure 6 ; compare with normal limiting ridge in Figure 5 ). Hyperplasia of the nonglandular stomach is often characterized as a uniform thickening of all layers of the epithelium without upward or downward projections. However, in more severe cases there are convolutions of the epithelium with downward projections of rete peg-like structures. There may be proliferation of the basal cells, which can extend into the submucosa ( Figure 7 and Figure 8 ). Focal upward proliferation into the lumen mimicking papilloma may be present in more severe cases of focal hyperplasia and may be described as papillary hyperplasia in the narrative. The absence of a branching connective tissue core containing blood vessels and the presence of an intact muscularis mucosa distinguish this form of hyperplasia from a true papilloma. With hyperplasia, there remains some degree of orderly maturation.
Recommendation
Hyperplasia should be diagnosed and graded whenever present. The modifiers "focal" and "diffuse" should be used whenever possible. Grading should be based on the size, extent of distribution, and thickness of the epithelium. Multifocal lesions are not recorded as "multifocal" but are given a higher severity grade than single lesions. If there are features of atypia, such as diskeratinization, disorganization, or the presence of atypical cells, then atypical hyperplasia should be diagnosed (see Stomach, Forestomach - Epithelium - Hyperplasia, Atypical ). If the pathologist feels that two distinct hyperplastic processes are present (e.g., diffuse and atypical), then both should be diagnosed and thoroughly described in the pathology narrative. Hyperkeratosis associated with hyperplasia is usually not diagnosed as a separate entity, unless it is a prominent component of the lesion, but it should be described in the pathology narrative. Related Links: Stomach, Forestomach - Epithelium - Hyperplasia, Atypical
上皮非典型增生Epithelium Hyperplasia Atypical 前胃增生
描述（中文）
某些化学物质可引起前胃的非典型性增生（非典型性（atypical） hyperplasia），其特征为增生和结构紊乱、异常角化或存在异常细胞（Figure 1、Figure 2）。早期鳞状细胞癌与局灶性（focal）非典型性增生之间的区分往往很困难。非典型性增生中没有超越基底膜的浸润，而癌则有不规则的细胞索或细胞簇向黏膜下层深部延伸。对于增生，即使病变深部有明显的异型性，仍保留一定程度的有序成熟过程。
诊断建议
非典型性增生一旦出现即应作出诊断并分级。如果存在异型性特征，如角化异常、结构紊乱或存在异常细胞，则应诊断为非典型性增生。如果病理学家认为存在两种不同的增生过程（例如弥漫性（diffuse）和非典型性（atypical）），则两者均应作出诊断并在病理学叙述中详细描述。应尽可能使用修饰词“局灶性（focal）”和“弥漫性”。分级应基于病变的大小、分布范围和上皮厚度。多灶性（multifocal）病变不记录为“多灶性”，而是给予比单个病变更高的严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Some chemicals cause atypical hyperplasia of the forestomach that is characterized by hyperplasia and disorganization, abnormal keratinization, or the presence of abnormal cells ( Figure 1 and Figure 2 ). The distinction between early squamous cell carcinomas and focal atypical hyperplasia can often be difficult. In atypical hyperplasia there is no invasion beyond the basement membrane, whereas carcinomas have irregular cords or clusters of cells that extend deeper into the submucosa. With hyperplasia, even with marked atypia at the deep aspect of the lesions, there remains some degree of orderly maturation.
Recommendation
Atypical hyperplasia should be diagnosed and graded whenever present. If there are features of atypia, such as diskeratinization, disorganization, or the presence of atypical cells, then atypical hyperplasia should be diagnosed. If the pathologist feels that two distinct hyperplastic processes are present (e.g., diffuse and atypical), then both should be diagnosed and thoroughly described in the pathology narrative. The modifiers "focal" and "diffuse" should be used whenever possible. Grading should be based on the size, extent of distribution, and thickness of the epithelium. Multifocal lesions are not recorded as "multifocal" but are given a higher severity grade than single lesions.
出血Hemorrhage 前胃出血
描述（中文）
前胃（forestomach）出血（Figure 1）可能为自发性（特发性）、与灌胃操作有关，或由直接/间接化学毒性所致。出血常与炎症相关。
诊断建议
出血应当依据病变范围进行诊断和分级。当出血是溃疡形成、坏死或炎症等其他过程的次要成分时，不单独诊断，除非出血是该病变的显著组成部分。
参考切片图（1 张）
查看英文原文
Comment
Hemorrhage in the forestomach ( Figure 1 ) may be spontaneous (idiopathic), related to the gavage procedure, or due to direct/indirect chemical toxicity. It is often associated with inflammation.
Recommendation
Hemorrhage should be diagnosed and graded based on the extent of the lesion. Hemorrhage that is a minor component of another process such as ulceration, necrosis, or inflammation is not diagnosed separately unless the hemorrhage is a prominent component of the lesion.
囊肿Cyst 前胃囊肿
描述（中文）
囊肿（包括角化囊肿和上皮包涵囊肿）可发生于食管或靠近限界嵴的前胃及胃窦黏膜。非腺性胃中的囊肿通常衬覆角化复层鳞状上皮，较少由黏液细胞衬覆。通常囊肿被视为偶然性发现。
诊断建议
囊肿应当予以诊断，并在病理学叙述中加以描述。在NTP研究中，囊肿不予分级，除非病理学家认为囊肿与受试物相关且严重程度分级能够揭示处理效应。
参考切片图（2 张）
查看英文原文
Comment
Cysts (including keratin cysts and epithelial inclusion cysts) can occur in the esophagus or forestomach near the limiting ridge and antral mucosa. Cysts in the nonglandular stomach are usually lined by keratinized stratified squamous epithelium and less frequently by mucous cells. Usually cysts are considered incidental findings.
Recommendation
Cysts should be diagnosed and described in the pathology narrative. Cysts are not graded in NTP studies unless the pathologist feels the cysts are treatment related and severity grading would reveal a treatment effect.
坏死Necrosis 前胃坏死
描述（中文）
坏死的特征性表现为核固缩（pyknosis）、核碎裂（karyorrhexis）、核溶解（karyolysis）等核改变，或核溶解后期细胞核消失。早期坏死时，H&E切片中细胞质呈均质粉红色。细胞质蛋白降解最终使坏死细胞呈苍白、鬼影状外观。坏死细胞通常失去与基底膜及邻近细胞的黏附。细胞破裂、细胞完整性丧失是细胞死亡最明显的证据。除染毒大鼠外，前胃黏膜坏死罕见。如Figure 1、Figure 2、Figure 3、Figure 4所示，小鼠和大鼠前胃的化学相关病变包括坏死和溃疡。在大鼠中，前胃坏死在灌胃研究中比在掺食或吸入研究中更常见。血栓形成可导致胃坏死（梗死）（Figure 4，箭头）。
诊断建议
如果坏死上皮仍然存在且至少部分附着于其下的固有层，或者坏死并非特别以erv前胃上皮为中心（即主要累及胃壁），则应诊断上皮坏死，而不是糜烂和溃疡。如果坏死符合继发于血栓形成的缺血（梗死），则叙述中应说明这一点，即使血栓不在切片平面内。严重程度分级取决于病变的总体大小和受累区域的数量。虽然出血、水肿、纤维化或炎症可能与坏死相关，但这些通常不单独记录，但可在叙述中描述。如果它们是坏死病变的显著组成部分，则应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Necrosis is characterized by nuclear changes of pyknosis, karyorrhexis, karyolysis, or absence of nucleus in the later stage of karyolysis. The cytoplasm in early necrosis is homogenous pink in H&E sections. Degradation of cytoplasmic proteins eventually gives the necrotic cell a pale, ghostlike appearance. Necrotic cells usually lose their adherence to basement membranes and neighboring cells. Rupture of cells with loss of cell integrity is the most obvious evidence of cell death. Necrosis of the forestomach mucosa is rarely seen except in treated rats. As shown in Figure 1 , Figure 2 , Figure 3 , and Figure 4 , chemical-related lesions in the forestomach of mice and rats include necrosis and ulceration. Necrosis of the forestomach is more frequent in gavage studies than in dosed-feed or inhalation studies in rats. Thrombosis can result in necrosis (infarction) of the stomach ( Figure 4 , arrow).
Recommendation
Necrosis of epithelium is diagnosed instead of erosion and ulcer if the necrotic epithelium is still present and at least partially attached to the underlying lamina propria or if the necrosis is not particularly centered on the epithelium of the forestomach (i.e., involves the wall primarily). If the necrosis is consistent with ischemia secondary to thrombosis (infarction), the narrative should state this, even if the thrombus is not in the plane of the section. Severity grading would depend on the overall size of the lesion and number of areas affected. While hemorrhage, edema, fibrosis, or inflammation may be associated with necrosis, these are usually not recorded separately but can be described in the narrative. If they are a prominent component of a necrotic lesion, they should be diagnosed separately.
寄生虫后生动物Parasite Metazoan 前胃其他
描述（中文）
由于现行的饲养管理方式，线虫感染较为罕见。然而，在大鼠的前胃中曾观察到筒线虫（Gongylonema spp.）。筒线虫是后生动物寄生虫，最常发现于上消化道的上皮，包括食管、舌、口腔和前胃（Figure 1、Figure 2）。在某些动物的气管、支气管和肺中也曾观察到该虫。前胃中未见其他线虫属。线虫可能对宿主几乎不引起反应。多种筒线虫见于灵长类动物、大鼠、小鼠及其他啮齿动物，以及多种野生动物。其生活史通常需要节肢动物宿主（常见为蟑螂和甲虫）摄入其虫卵。群体环境中存在节肢动物媒介可能导致该寄生虫在群体内传播。
诊断建议
线虫应诊断为“寄生虫，后生动物”，但不进行分级。如果能够鉴定到属种，应在病理学描述中注明。伴随的炎症或其他相关病变不应单独诊断，除非病理学家认为其由不同的病理过程所致，或严重程度足以需要单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Because of current husbandry practices, nematode infections are rare. However, Gongylonema spp. have been seen in the forestomach of rats. Gongylonema nematodes are metazoan parasites most frequently found in the epithelium of the upper gastrointestinal tract, including the esophagus, tongue, buccal cavity, and forestomach ( Figure 1 and Figure 2 ). They have also been observed in the trachea, bronchi, and lungs of some animals. Other nematode genera have not been seen in the forestomach. Nematodes may elicit little response in the host. Various species occur in primates, rats, mice, and other rodents, plus a wide variety of wild animals. Their life cycle typically requires that an arthropod host, commonly cockroaches and beetles, ingest their ova. The presence of the arthropod vectors in a colony environment may result in transmission of this parasite within the colony.
Recommendation
Nematodes are to be diagnosed as "parasite, metazoan" but not graded. If the genus species can be identified it should be noted in the pathology narrative. Accompanying inflammation or other associated lesions should not be diagnosed separately unless the pathologist feels it is due to a different pathologic process or it is severe enough to warrant a separate diagnosis.
异位组织Ectopic Tissue 前胃其他
描述（中文）
异位组织可存在于前胃的固有层（主要）、黏膜下层或浆膜下层。异位组织可为任何类型，但胰腺（Figure 1、Figure 2）、肝脏（Figure 3、Figure 4）和肠（Figure 5）常见。在某些情况下，它可与覆盖其上的鳞状上皮增生相关联。对于异位肠，肠道相关淋巴组织的存在不应被误认为炎症。异位组织被视为偶发性发现。
诊断建议
无论何时出现，异位组织都应被诊断，但不进行分级。诊断应随其来源组织加以修饰。
参考切片图（2 张）
查看英文原文
Comment
Ectopic tissue can be present in the lamina propria (primarily), submucosa, or subserosa of the forestomach. Ectopic tissue can be of any type, but pancreas ( Figure 1 and Figure 2 ), liver ( Figure 3 and Figure 4 ), and intestine ( Figure 5 ) are common. In some cases, it can be associated with hyperplasia of the overlying squamous epithelium. With ectopic intestine, the presence of gut-associated lymphoid tissue should not be mistaken for inflammation. Ectopic tissue is considered an incidental finding.
Recommendation
Whenever present, ectopic tissue should be diagnosed but not graded. The diagnosis should be modified with the tissue of origin.
异物Foreign Body 前胃其他
描述（中文）
毛发或饲料物质可继发于灌胃操作造成的损伤或外源性化学物引起的溃疡，嵌入前胃壁内。在 Figure 1、Figure 2 中，黏膜下层可见一个中央含有毛干（箭头）的小型肉芽肿；其上方黏膜已从先前损伤中愈合。这被认为是对照动物中的一个小型偶发性病变，可能继发于先前的灌胃创伤。
诊断建议
原发性异物应当诊断，但不进行分级。如果异物引起显著的炎症反应，则异物和炎症均予诊断。诸如毛发或饲料物质等被被动推入溃疡区域的异物，不应单独诊断，但可在叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Hair or feed material can become embedded in the wall of the forestomach secondary to injury from a gavage procedure or ulceration from xenobiotics. In Figure 1 and Figure 2 , a small granuloma with a central hair shaft (arrow) is in the submucosa; the overlying mucosa has healed from a previous injury. This is considered a small incidental lesion in a control animal that may have occurred secondary to previous gavage trauma.
Recommendation
A primary foreign body should be diagnosed but not graded. If a foreign body causes a significant inflammatory response, then both the foreign body and inflammation are diagnosed. A foreign body such as hairs or feed material that has been passively pushed into an ulcerated area should not be diagnosed separately but can be described in the narrative.
憩室Diverticulum 前胃其他
描述（中文）
憩室（diverticulum）在前胃比在腺胃更常见，但可发生于从食管到结肠的任何部位。憩室是先天性缺陷，其特征为部分胃壁向外膨出，膨出部分具有正常的细胞类型。憩室的壁和腔与前胃的壁和腔相连续（Figure 1、Figure 2），尽管二者之间的连通并不总是可见（Figure 2）。憩室偶尔会被误诊为腺瘤（adenoma），但憩室缺乏肿瘤的许多特征，如细胞呈肿块样增生、细胞异型性和正常结构丧失。憩室可能被食物嵌塞、发生溃疡、出现局部炎症，并最终穿孔，导致脓肿形成。憩室被视为偶发性病变。
诊断建议
憩室应予以诊断，但不进行分级。相关病变，如炎症或溃疡，若其严重程度足以需要，可单独诊断，但病理学家应在病理描述中明确说明其与憩室的关联。
参考切片图（2 张）
查看英文原文
Comment
Diverticula are more common in the forestomach than in the glandular stomach but can occur from the esophagus to the colon. Diverticula are congenital defects characterized by out-pouchings of a portion of the wall in which the normal cell types are present. The wall and lumen of a diverticulum are continuous with the wall and lumen of the forestomach ( Figure 1 and Figure 2 ), although the communication between them is not always visible ( Figure 2 ). Diverticula are occasionally misdiagnosed as a adenomas, but diverticula lack many of the features of neoplasms, such as a mass-like proliferation of cells, cellular atypia, and loss of normal architecture. Diverticula may become impacted with food, ulcerate, become locally inflamed, and eventually perforate, leading to abscess formation. Diverticula are considered incidental lesions.
Recommendation
Diverticulum should be diagnosed but not graded. Associated lesions, such as inflammation or ulcer, may be diagnosed separately if warranted by severity, but the pathologist should make the association with the diverticulum clear in the pathology narrative.
水肿Edema 前胃水肿
描述（中文）
水肿液在制片过程中常丢失，表现为组织中的空白区域（Figure 1、Figure 2），尽管蛋白含量较高的水肿液在切片中呈更强的嗜酸性。水肿是调节血浆、间质和细胞之间正常液体分布的任一因素发生改变的结果，例如血管通透性增加、血管内静水压升高、血管内渗透压降低和淋巴引流减少。
诊断建议
当水肿在没有其他病变的情况下出现时，应当记录并分级。然而，水肿通常是另一过程的组成部分，例如急性炎症，因此通常不单独记录。如果水肿是病变的重要组成部分，则可在原发病变之外另行记录。
参考切片图（2 张）
查看英文原文
Comment
Edema fluid is often lost at processing and appears as clear spaces in tissues ( Figure 1 and Figure 2 ), although edema fluid with a higher protein content will be more eosinophilic in sections. Edema is the result of alteration in any of the factors that regulate normal fluid distribution among the plasma, interstitium, and cells, such as increased vascular permeability, increased intravascular hydrostatic pressure, decreased intravascular osmotic pressure, and decreased lymphatic drainage.
Recommendation
When edema is seen in the absence of other lesions, it should be recorded and graded. However, edema is typically a component of another process, such as acute inflammation, so it is not typically recorded separately. If it is a significant component of the lesion, it may be recorded in addition to the primary lesion.
溃疡Ulcer 前胃溃疡
描述（中文）
溃疡（ulcer，Figure 1、Figure 2、Figure 3、Figure 4、Figure 5）定义为全部上皮细胞层缺失并延伸至黏膜下层，而糜烂（erosion）是黏膜浅层上皮层的缺失。溃疡底部及邻近组织中的炎症以及邻近上皮的增生是非常常见的伴随所见。前胃溃疡形成是一种常见的背景性所见。前胃是溃疡最常见的发生部位，但溃疡可发生于整个胃肠道。前胃溃疡形成可由灌胃事故引起，也可能与受试物相关（尤其是当受试物为刺激性物质时）。然而，在许多情况下，溃疡的确切原因并不清楚。
诊断建议
前胃溃疡只要存在即应诊断。应根据病变的范围、数量和深度进行分级。继发性病变，如水肿、炎症和邻近上皮的增生，除非是病变的显著组成部分或被认为是原发性病变（例如，增生先于溃疡发生），否则不单独诊断。如果坏死上皮仍然存在并附着于其下方的固有层，则诊断上皮坏死而非溃疡（见 Stomach, Forestomach - Necrosis）。相关链接：Stomach, Forestomach - Necrosis
参考切片图（2 张）
查看英文原文
Comment
An ulcer ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , and Figure 5 ) is defined as the loss of all epithelial cell layers extending through to the submucosa, whereas an erosion is the loss of superficial epithelial layers of the mucosa. Inflammation at the base of an ulcer and in adjacent tissue and hyperplasia of the adjacent epithelium are very common associated findings. Forestomach ulceration is a common background finding. The forestomach is the most common location for ulcers, but they may occur throughout the gastrointestinal tract. Ulceration of the forestomach can be caused by gavage accidents, or they may be treatment related (especially when the test article is an irritant). However, in many cases the exact cause of ulcers is not known.
Recommendation
Ulcers of the forestomach should be diagnosed whenever present. They should be graded based on the extent, number, and depth of the lesions. Secondary lesions, such as edema, inflammation, and hyperplasia of the adjacent epithelium, are not diagnosed separately unless they are prominent components of the lesion or they are considered a primary lesion (e.g., the hyperplasia occurred prior to the ulcer). Necrosis of the epithelium is diagnosed instead of ulcer if the necrotic epithelium is still present and attached to the underlying lamina propria (see Stomach, Forestomach - Necrosis ). Related Links: Stomach, Forestomach - Necrosis
炎症Inflammation 前胃炎症
描述（中文）
炎症可发生于前胃，如同在胃肠道其他部位一样。病变可为自发性（特发性）、与灌胃操作相关，或由直接/间接化学毒性所致。前胃炎症最常伴随上皮增生、溃疡或糜烂发生。炎症可诊断为急性、化脓性、慢性、慢性活动性或肉芽肿性。在急性炎症中，主要浸润细胞为中性粒细胞，尽管也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型（Figure 1），但中性粒细胞聚集，且其中许多发生退变（化脓性渗出物）。渗出物还可能含有细胞碎片，既来自 resident 细胞群体，也来自浸润的白细胞；含纤维蛋白的蛋白性液体；较少的巨噬细胞；偶见的淋巴细胞或浆细胞；以及可能的感染因子。肉眼观察，这些病变将以脓液存在为特征。在渗出物周围组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导（Figure 2）。淋巴细胞在慢性活动性炎症中也占主导（Figure 3、Figure 4），但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大的、活化的巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
炎症应予以诊断，并给出严重程度分级以及指示炎症持续时间或类型的修饰词（即 急性（acute）、化脓性（suppurative）、慢性（chronic）、慢性 active 或 肉芽肿性（granulomatous））。严重程度分级取决于前胃受累面积的范围和细胞浸润的密度。符合脓肿的病变诊断为化脓性炎症。增生、糜烂或溃疡区域内的炎症一般不记录，除非炎症的严重程度需要单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Inflammation can occur in the forestomach as elsewhere in the gastrointestinal tract. Lesions can be spontaneous (idiopathic), related to gavage procedure, or due to direct/indirect chemical toxicity. Inflammation in the forestomach most often occurs in association with epithelial hyperplasia, ulcer, or erosion. Inflammation can be diagnosed as acute, suppurative, chronic, chronic active, or granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation ( Figure 1 ), but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate). The exudate may also contain cell debris, both from the resident cell populations and from infiltrating leukocytes; proteinaceous fluid containing fibrin; fewer macrophages; occasional lymphocytes or plasma cells; and, possibly, an infectious agent. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation ( Figure 2 ). Lymphocytes also predominate in chronic active inflammation ( Figure 3 and Figure 4 ), but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
Inflammation should be diagnosed and given a severity grade and a modifier that indicates the duration or type of inflammation (i.e., acute, suppurative, chronic, chronic active, or granulomatous). The severity grade depends on the extent of area of forestomach affected and the density of the cellular infiltrate. Lesions consistent with an abscess are diagnosed as suppurative inflammation. Inflammation in areas of hyperplasia, erosion, or ulcer is not generally recorded unless the severity of the inflammation warrants a separate diagnosis.
矿化Mineralization 前胃矿化
描述（中文）
前胃的矿化通常累及黏膜下层，常沿基底膜（Figure 1）和肌层（Figure 2）分布。镜下，矿化表现为组织中界限清楚的结晶状嗜碱性物质。前胃矿化通常由钙磷代谢改变及甲状旁腺功能亢进所致，后者与终末期慢性进行性肾病继发的尿毒症相关。
诊断建议
应根据矿化范围对矿化进行诊断和分级。相关链接：肾脏 - 肾病，慢性进行性
参考切片图（2 张）
查看英文原文
Comment
Mineralization of the forestomach usually involves the submucosa, often along the basement membrane ( Figure 1 ), and tunica muscularis ( Figure 2 ). Microscopically, mineralization appears as distinct, crystalline, basophilic material in the tissue. Mineralization in the forestomach usually results from altered calcium-phosphorus metabolism and hyperparathyroidism associated with uremia secondary to end-stage chronic progressive nephropathy.
Recommendation
Mineralization should be diagnosed and graded based on the extent of the mineralization. Related Links: Kidney - Nephropathy, Chronic Progressive
穿孔Perforation 前胃其他
描述（中文）
穿孔（perforation，Figure 1）是胃壁上的一个孔洞。胃内容物可由此进入腹腔，通常会引起显著（marked）炎症反应。较大的穿孔若持续一段时间，胃与邻近器官或腹壁之间可能发生粘连。穿孔常由灌胃事故引起，或由大的、侵袭性溃疡穿透黏膜下层、肌层和浆膜所致。
诊断建议
前胃穿孔只要存在就应诊断，但不必给出严重程度分级。继发性病变，如炎症、纤维化或粘连，一般不应单独诊断，除非它们是病变的显著组成部分。若穿孔继发于异物，异物应单独诊断。
参考切片图（1 张）
查看英文原文
Comment
A perforation ( Figure 1 ) is a hole in the stomach. The contents of the stomach have access to the peritoneal cavity and generally incite a marked inflammatory response. Adhesions between the stomach and adjacent organs or the abdominal wall may occur with larger perforations that persist for some time. Perforations are often caused by gavage accident or by large, aggressive ulcers that progress through the submucosa, muscularis, and serosa.
Recommendation
Perforation of the forestomach should be diagnosed whenever present, but it is not necessary to assign a severity grade. Secondary lesions, such as inflammation, fibrosis, or adhesions, should generally not be diagnosed separately unless they are prominent components of the lesion. If a perforation is secondary to a foreign body, the foreign body should be diagnosed separately.
糜烂Erosion 前胃其他
描述（中文）
糜烂（erosion，Figure 1、Figure 2）的定义是黏膜表面上皮层缺失，而溃疡（ulcer）则是全部上皮细胞层缺失，并延伸至黏膜下层。糜烂可发生于胃肠道任何部位，但前胃是相对常见的部位。糜烂常发生于先前已存在上皮增生的区域。反之，糜烂的存在可诱导上皮细胞增殖（作为愈合反应），从而导致上皮增生。糜烂周围组织常见炎症。前胃糜烂可为自发性、继发于灌胃操作或与受试物相关（尤其是当受试物为刺激性物质时），但在许多情况下，糜烂的确切原因不明。
诊断建议
前胃糜烂只要存在即应诊断。糜烂应根据病变的范围、数量和深度进行分级。继发性病变，如水肿、炎症及邻近上皮的增生，不应单独诊断，除非它们是病变的显著组成部分或被认为是原发病变（例如，增生先于糜烂发生）。如果坏死上皮仍然存在并附着于其下的固有层，则应诊断上皮坏死而非糜烂（见 Stomach, Forestomach - Necrosis）。相关链接：Stomach, Forestomach - Necrosis
参考切片图（2 张）
查看英文原文
Comment
An erosion ( Figure 1 and Figure 2 ) is defined as the loss of superficial epithelial layers of the mucosa, whereas an ulcer is the loss of all epithelial cell layers, extending through to the submucosa. Erosions can occur anywhere in the gastrointestinal tract, but the forestomach is a relatively common location. Erosions often occur in areas of preexisting epithelial hyperplasia. Alternatively, the presence of an erosion can induce epithelial cell proliferation (as a healing response), which can result in epithelial hyperplasia. Inflammation is common in tissues around erosions. Erosion of the forestomach can be spontaneous, secondary to the gavage procedure, or treatment related (especially when the test article is an irritant), but in many cases, the exact cause of erosions is not known.
Recommendation
Erosion of the forestomach should be diagnosed whenever present. Erosions should be graded based on the extent, number, and depth of the lesions. Secondary lesions, such as edema, inflammation, and hyperplasia of the adjacent epithelium, should not be diagnosed separately unless they are prominent components of the lesion or they are considered a primary lesion (e.g., the hyperplasia occurred prior to the erosion). Necrosis of the epithelium is diagnosed instead of erosion if the necrotic epithelium is still present and attached to the underlying lamina propria (see Stomach, Forestomach - Necrosis ). Related Links: Stomach, Forestomach - Necrosis
纤维化Fibrosis 前胃纤维化
描述（中文）
纤维化（fibrosis）（Figure 1、Figure 2）通常发生在支持实质成分的结缔组织框架受到损伤时。在 Forestomach 中，鳞状上皮溃疡使下方黏膜下层暴露于胃内容物，胃内容物可损伤结缔组织成分并导致纤维化。严重或慢性炎症也可导致纤维化。坏死组织被含有许多新生毛细血管和成纤维细胞的纤维血管组织（肉芽组织）所取代，产生不成熟的胶原基质。随着纤维化成熟，其血管减少、胶原增多，直至最终基本无血管，主要由致密胶原束和相对少量的成纤维细胞组成。
诊断建议
当纤维化是唯一病变时，应诊断并分级。纤维化作为另一原发过程（如炎症、溃疡或肿瘤）的次要成分时，一般不应单独诊断，除非它是该病变的显著特征。
参考切片图（2 张）
查看英文原文
Comment
Fibrosis ( Figure 1 and Figure 2 ) generally occurs when there is damage to the connective tissue framework that supports the parechymal elements. In the forestomach, ulceration of the squamous epithelium exposes the underlying submucosa to gastric contents, which can damage the connective tissue elements and result in fibrosis. Severe or chronic inflammation can also lead to fibrosis. Necrotic tissue is replaced with fibrovascular tissue that contains many newly formed capillaries and fibroblasts (granulation tissue), producing an immature collagenous matrix. As fibrosis matures, it becomes less vascular and more collagenous until eventually it is fairly avascular and consists of primarily dense bundles of collagen and relatively low numbers of fibroblasts.
Recommendation
Whenever it is the sole lesion, fibrosis should be diagnosed and graded. Fibrosis as a minor component of another primary process such as inflammation, ulceration, or neoplasia should generally not be diagnosed separately unless it is a prominent feature of the lesion.
血管扩张Angiectasis 前胃扩张
描述（中文）
血管扩张（angiectasis，血管扩张症）主要是一种自发性的、与年龄相关的病变。病因通常未知，但偶尔可能是对化学性损伤的反应。血管扩张由广泛扩张的血管腔隙构成，尤其是毛细血管（或血窦）和小静脉，其内衬为无明显异常的内皮细胞。血管数量无明显增多，器官的间质未发生改变。应尝试对血管扩张与血管瘤进行鉴别，尽管血管扩张与血管瘤之间的差异往往并不明确。血管瘤倾向于为边界清楚、无包膜的肿块，由紧密排列的扩张血管腔隙构成。每个血管腔隙均由单层外观正常的内皮细胞围成并衬覆，这些内皮细胞排列于胶原性间隔上，间隔通常较薄，尽管有些具有宽阔的胶原性间质。血管扩张通常不表现为边界清楚的肿块，因为扩张的血管通道常不规则地穿行于结缔组织中。
诊断建议
血管扩张应予以诊断，并根据病变的范围给予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Angiectasis (vascular ectasia) is primarily a spontaneous, age-related lesion. The cause is generally not known but occasionally can be a response to chemical injury. Angiectasis consists of widely dilated vascular spaces, especially capillaries (or sinusoids) and venules, that are lined by unremarkable endothelial cells. There is no apparent increase in numbers of vessels, and the stroma of the organ is unaltered. A differentiation between angiectasis and hemangioma should be attempted, although the difference between angiectasis and hemangioma often is not clear. Hemangiomas tend to be well-circumscribed unencapsulated masses composed of tightly packed dilated vascular spaces. Each vascular space is enclosed and lined by a single layer of normal-appearing endothelial cells aligned on collagenous septa, which are usually thin, although some have broad collagenous stromata. Angiectasis does not usually present as a well-circumscribed mass because the dilated vascular channels are often irregularly coursing through connective.
Recommendation
Angiectasis should be diagnosed and given a severity grade based on the extent of the lesion.
角化过度Hyperkeratosis 前胃其他
描述（中文）
角化过度（hyperkeratosis）是指角质层增厚。其有两种形式：正角化性角化过度（orthokeratotic hyperkeratosis）或角化不全性角化过度（parakeratotic hyperkeratosis）。在正角化性角化过度（又称正角化，orthokeratosis）中，鳞状上皮细胞无核，而在角化不全性角化过度（又称角化不全，parakeratosis）中，鳞状上皮细胞保留固缩的细胞核。角化过度常伴随增生（hyperplasia）（Figure 1、Figure 2）。无增生伴随的角化过度应当诊断。它是厌食啮齿类动物中常见的特征，其解释意义与作为上皮增殖增强过程一部分而发生的角化过度不同。在厌食啮齿类动物中，过多的角质推测是由于食物通过所致的机械性去除减少所致。在与厌食相关的 fore stomach 角化过度病例中，角化过度通常也存在于食管。
诊断建议
如果角化过度存在而无上皮增生，则应当诊断角化过度并分级。严重程度分级应基于角质层的厚度和受累表面积的大小。如果角化过度伴随上皮增生，除非角化过度是病变的显著组成部分，否则不单独诊断角化过度。如果角化过度不单独诊断，则应在病理描述中描述。诊断中不将角化过度细分为正角化或角化不全，但应在描述中充分描述该病变。
参考切片图（2 张）
查看英文原文
Comment
Hyperkeratosis is defined as thickening of the stratum corneum. It occurs in two forms: orthokeratotic or parakeratotic hyperkeratosis. In orthokeratotic hyperkeratosis (also referred to as orthokeratosis squamous epithelial cells are anuclear, whereas in parakeratotic hyperkeratosis (also referred to as parakeratosis) the squamous epithelial cells have retained pyknotic nuclei. Hyperkeratosis frequently accompanies hyperplasia ( Figure 1 and Figure 2 ). Hyperkeratosis in the absence of hyperplasia should be diagnosed. It is a feature commonly present in anorectic rodents and has interpretative implications different from those of hyperkeratosis occurring as part of the process of enhanced epithelial proliferation. In the anorectic rodent, the excess keratin is presumably the result of reduced mechanical removal by the passage of food. In cases of hyperkeratosis in the forestomach associated with anorexia, hyperkeratosis is usually also present in the esophagus.
Recommendation
If hyperkeratosis is present without epithelial hyperplasia, then the hyperkeratosis should be diagnosed and graded. The severity grade should be based on the thickness of the keratin layer and the amount of surface area involved. If the hyperkeratosis accompanies epithelial hyperplasia, the hyperkeratosis is not diagnosed separately unless it is a prominent component of the lesion. If the hyperkeratosis is not diagnosed separately, it should be described in the pathology narrative. Hyperkeratosis is not subdivided into orthokeratosis or parakeratosis in the diagnosis, but the lesion should be well described in the narrative.
坏死Necrosis 口腔黏膜坏死
描述（中文）
口腔黏膜坏死可能是与处理相关的影响，但更常见是由灌胃操作和/或异物（毛干、食物残渣）存在所致的创伤引起。受创伤区域可发生坏死和溃疡，导致化脓性或慢性活动性炎症及肉芽组织形成。如果坏死位于表面深部且不像是溃疡的一部分，或者没有上皮细胞丢失，则该病变被认为是坏死而非糜烂或溃疡。Actinomyces 属感染可导致深部感染和坏死。切牙周围也可能发生牙龈的炎症和坏死。
诊断建议
如果坏死上皮仍然存在且至少部分附着于其下的固有层，或者坏死不仅累及上皮（即还累及或主要累及其下的结缔组织或骨），则诊断上皮坏死而非糜烂或溃疡。如果坏死符合继发于血栓形成的缺血（梗死），叙述中应如此说明，即使血栓不在切片平面内。严重程度分级将取决于病变的总体大小和受累区域的数量。虽然出血、水肿、纤维化或炎症可能与坏死相关，但只有当它们是坏死病变的显著组成部分时才单独记录，不过它们可以在叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Mucosal necrosis in the oral cavity can be a treatment-related effect but is more commonly caused by trauma due to the gavage procedure and/or the presence of foreign bodies (hair shafts, food material). The traumatized area can undergo necrosis and ulceration, resulting in suppurative or chronic active inflammation and granulation tissue formation. If the necrosis is deep to the surface and does not appear to be part of an ulcer, or there is no loss of epithelial cells, then the lesion is considered necrosis rather than an erosion or an ulcer. Infection with Actinomyces species can result in deep infection and necrosis. Inflammation and necrosis of gingiva may also occur around the incisor teeth.
Recommendation
Necrosis of epithelium is diagnosed instead of erosion or ulcer if the necrotic epithelium is still present and at least partially attached to the underlying lamina propria or if the necrosis involves more than just the epithelium (i.e., also or primarily involves the underlying connective tissue or bone). If the necrosis is consistent with ischemia secondary to thrombosis (infarction), the narrative should so state, even if the thrombus is not in the plane of the section. Severity grading would depend on the overall size of the lesion and number of areas affected. While hemorrhage, edema, fibrosis, or inflammation may be associated with necrosis, these are recorded separately only if they are a prominent component of a necrotic lesion, but they can be described in the narrative.
异物Foreign Body 口腔黏膜其他
描述（中文）
异物最常见的是来自垫料或饲料的植物性物质（Figure 1、Figure 2、Figure 3、Figure 4）或毛干（Figure 5、Figure 6、Figure 7、Figure 8）。异物可以是原发性的或继发性的。伴有溃疡形成的炎症可由创伤、感染或毒性化学物质引起，并可导致异物继发性地穿入口腔较深的组织。根据存在的异物类型和持续时间，异物周围可见任何类型的炎症，但化脓性炎症最为常见。日粮类型及其稠度可影响所观察到的口腔病变的发生频率和类型。饲喂含食物纤维的粉状日粮后，可发生牙周炎和瘘管。受累牙齿周围可出现伴有纤维化的局部肉芽肿性炎症。牙周沟处可形成牙周袋，且常是异物和炎性渗出物通过的途径。口腔、咽和鼻上皮内异物引起的慢性刺激和炎症可导致鳞状细胞癌的形成。
诊断建议
异物应当诊断，但不进行分级。如果存在炎症且炎症是病变的重要组成部分，则应单独诊断并分级，分级依据炎性细胞浸润的密度和范围。如果异物局限于牙周袋内且未穿入组织，则不诊断异物，该病变记录为“牙齿-牙周袋”（参见相应文件）。
参考切片图（2 张）
查看英文原文
Comment
Foreign bodies are most frequently plant material from the bedding or feed ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) or hair shafts ( Figure 5 , Figure 6 , Figure 7 , and Figure 8 ). Foreign bodies can be primary or secondary. Inflammation with ulceration can result from trauma, infection, or toxic chemicals and can result in foreign material secondarily penetrating the deeper tissues of the oral cavity. Depending on the type of foreign material present and the duration, any type of inflammation can be seen around a foreign body, but suppurative inflammation is the most common. The type of diet and its consistency can influence the frequency and types of oral cavity lesions observed. Periodontitis and fistulas can occur following the feeding of powdered diets that contain food fibers. Localized granulomatous inflammation with fibrosis can be present around the affected tooth. A periodontal pocket may form at the dental sulcus and is often the route of passage for foreign material and inflammatory exudates. Chronic irritation and inflammation induced by foreign bodies in the epithelium of the mouth, pharynx, and nose can lead to formation of squamous cell carcinoma.
Recommendation
A foreign body should be diagnosed but not graded. If inflammation is present and is a significant component of the lesion, it should be diagnosed and graded separately, with the grading based on the density and extent of inflammatory cell infiltration. If foreign material is confined to a periodontal pocket and has not penetrated into the tissue, then foreign body is not diagnosed and the lesion is recorded as "tooth - periodontal pocket" (see appropriate document).
溃疡Ulcer 口腔黏膜溃疡
描述（中文）
与黏膜坏死一样，口腔内的黏膜溃疡（Figure 1、Figure 2、Figure 3、Figure 4）可能是与处理相关的作用，但更常见是由灌胃操作和/或异物（毛干、食物残渣）存在所致的创伤引起。溃疡区域可伴有慢性活动性炎症（Figure 3、Figure 4）和肉芽组织。然而，由于口腔上皮的增殖能力，轻微的创伤性病变通常在数日内愈合。啮齿类动物口腔内鳞状上皮的角化通常使其对外源性化学物质直接毒性的易感性低于人类口腔，后者主要衬以非角化上皮。
诊断建议
溃疡应当根据病变的范围和数量进行诊断和分级。与溃疡相关的炎症和上皮增生通常不单独诊断，除非它是病变的重要组成部分。如果黏膜上皮细胞缺失但基底层仍存在并覆盖黏膜下层，则可诊断为糜烂（erosion）。当一部分上皮缺失或未附着于黏膜下层时，诊断为溃疡（ulcer）。如果上皮已坏死但仍存在并附着于黏膜下层，则诊断为坏死（necrosis）。
参考切片图（2 张）
查看英文原文
Comment
As with mucosal necrosis, mucosal ulceration in the oral cavity ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) can be a treatment-related effect but is more commonly caused by trauma due to the gavage procedure and/or the presence of foreign bodies (hair shafts, food material). Areas of ulceration can be accompanied by chronic active inflammation ( Figure 3 and Figure 4 ) and granulation tissue. However, because of the proliferative capacity of the oral epithelium, minor traumatic lesions are usually healed in a few days. Keratinization of the squamous epithelium in the rodent oral cavity generally makes it less susceptible to direct toxicity from xenobiotics than the human oral cavity, which is lined primarily by a nonkeratinizing epithelium.
Recommendation
Ulcers should be diagnosed and graded based on the extent and number of lesions. Inflammation and epithelial hyperplasia associated with ulcers is usually not diagnosed separately unless it is a significant component of the lesion. If epithelial cells are missing from the mucosa but the basal layers are still present and covering the submucosa, then erosion may be diagnosed. Ulcers are diagnosed when a portion of the epithelium is absent or not attached to the submucosa. If the epithelium is necrotic but is still present and attached to the submucosa, then necrosis is diagnosed.
炎症Inflammation 口腔黏膜炎症
描述（中文）
口腔内的炎症通常继发于异物或灌胃操作造成的创伤性损伤，或继发于化学物质引起的坏死。病变内可能可见感染性病原体，通常为细菌和真菌等机会性微生物（Figure 1、Figure 2）。在NTP研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））（Figure 1、Figure 2）、慢性（慢性（chronic））、慢性活动性（慢性 active）（Figure 3、Figure 4）和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症（急性 inflammation）中，主要浸润细胞为中性粒细胞（neutrophil），但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症（化脓性 inflammation）中的主要浸润细胞类型，但中性粒细胞聚集，且其中许多已变性（化脓性渗出物）。渗出物中还可能存在细胞碎片（来自 resident 细胞群和浸润白细胞）、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染性病原体。肉眼观察，这些病变的特征为脓液的存在。渗出物周围的组织可能含有成纤维细胞、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。慢性炎症（慢性 inflammation）中以淋巴细胞为主。慢性活动性炎症（慢性 active inflammation）中也以淋巴细胞为主，但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症（肉芽肿性 inflammation）是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大型、活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
炎症无论何时出现，均应予以诊断、分级，并给出一个修饰词以指明炎症的持续时间或类型（即 急性（acute）、化脓性（suppurative）、慢性（chronic）、慢性 active 或 肉芽肿性（granulomatous））。严重程度分级取决于受累区域的范围和细胞浸润的密度。符合脓肿的病变诊断为化脓性炎症。继发于其他病变（如溃疡、糜烂或坏死）的炎症不应单独诊断，除非严重程度足以支持单独诊断。然而，如果炎症被认为是原发病变并且是相关病变（溃疡、糜烂、坏死等）的原因，则应诊断炎症并在叙述中描述继发病变。细菌、真菌或其他机会性微生物不单独诊断。病变内的异物仅在被认为是原发病变（即炎症的原因）时才应诊断。如果病理学家认为异物是在炎症之后引入的，则应在病理学叙述中描述异物，但不单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Inflammation in the oral cavity is often secondary to traumatic injury from foreign bodies or gavage procedure or to necrosis from chemical agents. Infectious agents, usually opportunistic organisms such as bacteria and fungi, may be seen within the lesion ( Figure 1 and Figure 2 ). In NTP studies, there are five standard categories of inflammation: acute, suppurative ( Figure 1 and Figure 2 ), chronic, chronic active ( Figure 3 and Figure 4 ), and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate). Cell debris, both from the resident cell populations and from infiltrating leukocytes; proteinaceous fluid containing fibrin; fewer macrophages; occasional lymphocytes or plasma cells; and, possibly, an infectious agent may also be present in within the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may contain fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
Whenever present, inflammation should be diagnosed, graded, and given a modifier that indicates the duration or type of inflammation (i.e., acute, suppurative, chronic, chronic active, or granulomatous). The severity grade depends on the extent of the area affected and the density of the cellular infiltrate. Lesions consistent with an abscess are diagnosed as suppurative inflammation. Inflammation that is secondary to another lesion, such as ulcer, erosion, or necrosis, should not be diagnosed separately unless warranted by severity. If, however, the inflammation is considered the primary lesion and is the cause of the associated lesions (ulcer, erosion, necrosis, etc.), then the inflammation should be diagnosed and the secondary lesions described in the narrative. Bacteria, fungi, or other opportunistic organisms are not diagnosed separately. Foreign material within the lesion should be diagnosed only if it considered the primary lesion (i.e., the cause of the inflammation). If the pathologist feels the foreign material was introduced subsequent to the inflammation, then the foreign material should be described in the pathology narrative but not diagnosed separately.
牙龈异位组织Gingiva Ectopic Tissue 口腔黏膜其他
描述（中文）
口腔内的异位皮脂腺（ectopic sebaceous glands）也称为福代斯颗粒（Fordyce’s granules）。组织学上，这些是未与毛囊相关的皮脂腺集合（Figure 1、Figure 2、Figure 3、Figure 4）。磨牙牙龈中的腺体常伴有充满皮脂的囊性扩张导管。在一项检查734只雄性 and 722只雌性F344大鼠的NTP研究中，福代斯颗粒在雄性上切牙正中矢状牙龈中非常常见，且发生率随年龄增长而增加（26周、65周和2年研究中分别为34.2%、50%和56.3%）。异位皮脂腺在雌性中罕见（26周、65周和2年研究中分别为0%、0%和2.8%）。磨牙牙龈的异位皮脂腺在雌雄两性中均非常罕见。异位皮脂腺在大体检查中常不明显，被视为偶然发现。
诊断建议
该发现应诊断为“口腔黏膜，牙龈 - 异位组织，皮脂腺”。无需分级。
参考切片图（2 张）
查看英文原文
Comment
Ectopic sebaceous glands in the oral cavity are also known as Fordyce’s granules. Histologically, these are a collection of sebaceous glands unassociated with hair follicles ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). The glands in the molar gingiva are often associated with cystically dilated ducts filled with sebum. In one NTP study examining 734 male and 722 female F344 rats, Fordyce’s granules were very common in the midsagittal gingiva of the upper incisor in males and increased in incidence with age (34.2%, 50%, and 56.3% in 26-week, 65-week, and 2-year studies, respectively). Ectopic sebaceous glands were rare in females (0%, 0%, and 2.8% in 26-week, 65-week, and 2-year studies, respectively). Ectopic sebaceous glands of the molar gingiva were very rare in both sexes. Ectopic sebaceous glands are often not noticeable on gross examination and are considered an incidental finding.
Recommendation
This finding should be diagnosed as "Oral mucosa, gingiva - ectopic tissue, sebaceous gland." No grade is necessary.
角化性囊性增生Hyperplasia Cystic Keratinizing 口腔黏膜增生
描述（中文）
囊性角化性增生（cystic keratinizing hyperplasia）的特征是牙龈区域上皮显著增生，并呈乳头状皱褶隆起，在牙龈及邻近组织中形成充满角蛋白的囊样腔隙。部分此类病变为孤立性发生，而另一些则与黏膜的弥漫性（diffuse）增生病灶相伴发生。腔隙的数量可从单个至多个不等，使病变呈现多房外观。通常可见囊性结构与上覆的牙龈口腔黏膜之间存在连接，提示囊性角化性增生可能起源于鳞状上皮增生。该病变的鉴别诊断包括鳞状囊肿（squamous cyst，见口腔黏膜－囊肿，鳞状）和牙周袋（periodontal pocket，见牙齿－牙周袋）。鳞状囊肿和牙周袋通常为单房结构，衬以相当薄的、外观良性的鳞状上皮，且似乎并非起源于增生的牙龈黏膜。鳞状囊肿的囊壁鳞状上皮中可能存在毛囊。牙周袋是啮齿类动物常见的背景性改变，局限于牙齿周围的牙周组织，尤其是磨牙。牙周袋代表异常加深的牙龈沟，衬以角化的鳞状上皮，其腔内可能含有毛发、饲料、垫料和角蛋白。囊性角化性增生还必须与早期鳞状细胞癌相鉴别，后者的细胞呈多形性或非典型性，且鳞状细胞成熟紊乱。囊性角化性增生可能处于增生与鳞状细胞癌的连续谱系上，因为在一项研究中观察到该病变，同时该研究中牙龈鳞状细胞癌也显著增加。
诊断建议
无论何时出现，囊性角化性增生均应予以诊断，并根据充满角蛋白的囊样区域的数量和大小进行分级。继发性病变，如炎症或骨重塑，除非是病变的重要组成部分，否则不应单独诊断。相关链接：口腔黏膜－囊肿，鳞状；牙齿－牙周袋
参考切片图（2 张）
查看英文原文
Comment
Cystic keratinizing hyperplasia is characterized by areas in the gingiva in which the epithelium is markedly hyperplastic and raised in papillary folds forming cyst-like spaces filled with keratin in the gingival and adjacent tissues. Some of these lesions occur in isolation, whereas others occur in association with diffuse hyperplastic lesions of the mucosa. The number of cavities can vary from one to multiple, giving the lesion a multilocular appearance. Generally, a connection can be seen between the cystic structure and the overlying gingival oral mucosa, suggesting the cystic keratinizing hyperplasia may have arisen from squamous hyperplasia. A differential diagnosis for this lesion is a squamous cyst (see Oral Mucosa - Cyst, Squamous ) and periodontal pocket (see Tooth - Periodontal Pocket ). Squamous cysts and periodontal pockets tend to be unilocular structures lined by a fairly thin, benign-appearing squamous epithelium and do not appear to be arising from a hyperplastic gingival mucosa. Squamous cysts may have hair follicles in the squamous epithelium lining the cyst. Periodontal pockets are common background alterations in rodents restricted to the periodontal tissues surrounding the teeth, especially molars. The pockets represent an abnormally deepened gingival sulcus that is lined by keratinized squamous epithelium, and the lumen may contain hair, feed, bedding material, and keratin. Cystic keratinizing hyperplasia must also be differentiated from early squamous cell carcinoma, in which the cells are pleomorphic or atypical and there is disorderly maturation of the squamous cells. Cystic keratinizing hyperplasia may be on a continuum with hyperplasia and squamous cell carcinoma as this lesion was seen in a study in which there was also a significant increase in gingival squamous cell carcinomas.
Recommendation
Whenever present, cystic keratinizing hyperplasia should be diagnosed and graded based on the number and size of cyst-like areas filled with keratin. Secondary lesions, such as inflammation or bone remodeling, should not be diagnosed separately unless they are a significant component of the lesion. Related Links: Oral Mucosa - Cyst, Squamous Tooth - Periodontal Pocket
鳞状囊肿Cyst Squamous 口腔黏膜囊肿
描述（中文）
鳞状囊肿（Squamous cyst）（Figure 1、Figure 2、Figure 3）由分化良好的角化鳞状上皮衬覆，囊腔内通常含有角蛋白。鳞状囊肿属于先天性异常，因此被视为偶发性病变。它们通常为单房结构，衬覆囊肿的鳞状上皮中可能存在毛囊。该病变的可能鉴别诊断包括牙龈囊性角化性增生（cystic keratinizing hyperplasia）、牙周袋（periodontal pocket）和鳞状细胞癌（squamous cell carcinoma）。囊性角化性增生的特征是牙龈区域上皮显著增生并呈乳头状皱褶隆起，形成充满角蛋白的囊样腔隙。该病变与囊性区域相邻或附近的增生性牙龈上皮区域相关，而鳞状囊肿往往为单个、孤立性病变，与口腔内上皮增生区域无关。牙周袋与鳞状囊肿相似，但牙周袋始终位于牙周围，因为它代表异常加深的牙龈沟。牙周袋衬覆的鳞状上皮中无毛囊。鳞状细胞癌具有侵袭性，细胞多形性且非典型，不表现出有序的成熟过程。（见口腔黏膜－增生，囊性，角化性及牙－牙周袋）。
诊断建议
鳞状囊肿被视为偶发性背景病变，但为完整性起见，当存在时应予以诊断。在 NTP 研究中，囊肿通常不分级。相关链接：口腔黏膜－增生，囊性，角化性；牙－牙周袋
参考切片图（2 张）
查看英文原文
Comment
Squamous cysts ( Figure 1 , Figure 2 , and Figure 3 ) are lined by well-differentiated, keratinized squamous epithelium, and the lumen usually contains keratin. Squamous cysts are congenital anomalies and therefore are considered incidental lesions. They are usually unilocular structures that may have hair follicles in the squamous epithelium lining the cyst. Possible differentials for this lesion are cystic keratinizing hyperplasia of the gingiva, periodontal pockets, and squamous cell carcinoma. Cystic keratinizing hyperplasia is characterized by areas in the gingiva in which the epithelium is markedly hyperplastic and raised in papillary folds, forming cyst-like spaces filled with keratin. The lesion is associated with areas of hyperplastic gingival epithelium adjacent to or near the cystic areas, whereas squamous cysts tend to be a single, isolated lesions with no association to areas of epithelial hyperplasia in the oral cavity. Periodontal pockets are similar to squamous cysts, but they are always located around the tooth, as they represent an abnormally deepened gingival sulcus. Periodontal pockets do not have hair follicles in the squamous epithelium lining the pocket. Squamous cell carcinomas are invasive, and the cells are pleomorphic and atypical and do not exhibit orderly maturation. (See Oral Mucosa - Hyperplasia, Cystic, Keratinizing and Tooth - Periodontal Pocket ).
Recommendation
Squamous cysts are considered incidental background lesions but should be diagnosed when present for completeness sake. Cysts are generally not graded in NTP studies. Related Links: Oral Mucosa - Hyperplasia, Cystic, Keratinizing Tooth - Periodontal Pocket
鳞状增生Hyperplasia Squamous 口腔黏膜增生
描述（中文）
口腔黏膜的鳞状细胞增生（squamous hyperplasia）通常见于腭部（Figure 1、Figure 2、Figure 3）或牙龈（Figure 4）。鳞状细胞增生的特征是鳞状细胞数量增多，导致鳞状上皮厚度增加，可呈弥漫性（diffuse）或斑块状，或形成钝的乳头状突起。角化过度（hyperkeratosis）常与鳞状细胞增生同时出现。这些病变可能发生溃疡，通常归因于机械性摩擦。鳞状上皮的增生性病变被认为是一个连续的过程，从局灶性（focal）增生进展为乳头状瘤（papilloma），再进展为浸润性鳞状细胞癌（squamous cell carcinoma），尽管乳头状瘤阶段可能被跳过，直接从局灶性增生进展为鳞状细胞癌。乳头状瘤是表浅肿瘤，具有显著（marked）棘层肥厚（acanthosis）、角化过度和乳头状结构。乳头状瘤通常呈外生性（exophytic），但内翻性乳头状瘤（inverted papilloma）呈杯状向下方间质内生长。外生性乳头状瘤具有由结缔组织构成的血管化核心，从黏膜下层延伸（形成蒂样结构），表面覆盖增生的鳞状上皮细胞，这些细胞常发生角化。无蒂形态（sessile shape）、细胞分化良好的外观以及缺乏显著的间质成分，是区分增生与乳头状瘤的重要依据。鳞状细胞癌与增生的区别在于，鳞状细胞癌的肿瘤细胞通常为异型细胞，伴有核增大（karyomegaly）、核极性丧失、核仁增大显著以及核分裂象增多。肿瘤性鳞状细胞突破基底膜浸润，肿瘤性上皮细胞以岛状、索状和梁状延伸至下方间质。
诊断建议
鳞状细胞增生应当被诊断，并根据增生区域的大小、厚度和数量进行分级。病变的位置（例如牙龈、腭部）应在病理描述中注明。相关病变，如炎症，除非严重程度需要，否则不应单独诊断。与增生相关的角化过度或溃疡不应单独诊断，而应作为病理描述中病变描述的一部分。
参考切片图（2 张）
查看英文原文
Comment
Squamous hyperplasia of the oral mucosa is usually seen on the palate ( Figure 1 , Figure 2 , and Figure 3 ) or gingiva ( Figure 4 ). Squamous hyperplasia is characterized by increased numbers of squamous cells resulting in increased thickness of the squamous epithelium, which may be diffuse or plaque-like or form blunt papillary projections. Hyperkeratosis is frequently seen with squamous cell hyperplasia. Ulceration of the these lesions may be seen and is usually attributed to mechanical abrasion. Proliferative lesions of the squamous epithelium are thought to be on a continuum, progressing from focal hyperplasia to papilloma to invasive squamous cell carcinoma, although the papilloma stage may be skipped, with progress directly from focal hyperplasia to squamous cell carcinoma. Papillomas are superficial tumors with marked acanthosis, hyperkeratosis, and papillary patterns. Papillomas are usually exophytic, although the inverted papilloma grows in a cuplike shape into the underlying stroma. Exophytic papillomas have a vascularized inner core of connective tissue extending from the submucosa (forming a stalklike structure) that is covered by proliferating squamous epithelial cells, which are often keratinized. The sessile shape, well-differentiated appearance of cells, and absence of a prominent stromal component are important in distinguishing hyperplasia from papilloma. Squamous cell carcinomas can be differentiated from hyperplasia in that the neoplastic cells of a squamous cell carcinoma generally have atypical cells with karyomegaly, loss of nuclear polarity, enlarged prominent nucleoli, and increased mitotic figures. Neoplastic squamous cells invade beyond the basement membrane, with islands, cords, and trabeculae of neoplastic epithelial cells extending into the underlying stroma.
Recommendation
Squamous hyperplasia should be diagnosed and graded based on the size, thickness, and number of hyperplastic areas. The location of the lesion (e.g., gingival, palatal) should be noted in the pathology narrative. Associated lesions, such as inflammation, should not be diagnosed separately unless warranted by severity. Hyperkeratosis or ulceration associated with hyperplasia should not be diagnosed separately but should be a part of the lesion description in the pathology narrative.
下颌下腺分泌耗竭Submandibular Secretory Depletion 唾液腺其他
描述（中文）
分泌产物减少偶尔可见，且通常是一种细微的变化，需要仔细检查并与对照组比较才能发现。受累细胞的细胞质染色一般较浅，且由于细胞质数量减少，细胞往往较小。在小管细胞中，嗜酸性细胞质颗粒的数量常减少。分泌耗竭与萎缩的不同之处在于，分泌耗竭是一种轻微的、弥漫性的变化，不伴有小管、间质组织或炎症细胞浸润的增加。分泌耗竭可同时发生于腺泡细胞和小管细胞（Figure 2）。
诊断建议
无论何时出现，分泌耗竭均应作出诊断，并根据细胞中分泌产物减少的程度和受累细胞的数量进行分级。迂曲管中的分泌耗竭根据嗜酸性胞质内颗粒耗竭的程度和受累迂曲（颗粒）管的数量进行分级。如果分泌耗竭仅限于腺泡细胞，则无需部位修饰词（诊断为“salivary gland, submandibular - secretory depletion”）。如果该变化仅限于小管，则诊断为“salivary gland, submandibular, duct - secretory depletion”。如果该变化同时存在于腺泡细胞和小管细胞中，则同时作出上述两项诊断。
参考切片图（2 张）
查看英文原文
Comment
A decrease in secretory product is seen occasionally and is often a subtle change requiring careful examination and comparison with controls to be detected. The cytoplasm of affected cells generally stains less intensely, and the cells are often smaller because of decreased amounts of cytoplasm. In the ductular cells, there is frequently a decrease in the number of eosinophilic, cytoplasmic granules. Secretory depletion differs from atrophy in that secretory depletion is a slight, diffuse change without an accompanying increase in ducts, interstitial tissue, or inflammatory cell infiltrate. Secretory depletion can occur in the acinar and ductular cells concurrently ( Figure 2 ).
Recommendation
Whenever present, secretory depletion should be diagnosed and graded based on the degree of decrease in secretory product in cells and number of cells involved. Secretory depletion in the convoluted ducts is based on degree of depletion of eosinophilic intracytoplasmic granules and number of convoluted (granular) ducts involved. If the secretory depletion is limited to the acinar cells, then no site modifier is necessary ("salivary gland, submandibular - secretory depletion" is diagnosed). If the change is limited to the ducts, then "salivary gland, submandibular, duct - secretory depletion" is diagnosed. If the change is present in both the acinar and ductal cells, then both diagnoses are made.
下颌下腺导管细胞质改变Submandibular Duct Cytoplasmic Alteration 唾液腺其他
描述（中文）
关于啮齿类动物唾液腺性别二态性的讨论，请参见本章引言。此处提供正常雌性（Figure 1）和雄性（Figure 2）唾液腺导管的示例以供比较。在雌性中，下颌下唾液腺的细胞质改变表现为迂曲（颗粒）导管颗粒性增加（Figure 3），使其看起来类似于正常雄性唾液腺导管。这种改变是由某些化学物质或激素的雄性化效应所致。在雌性小鼠暴露于雄性化剂时，还可同时发生肾脏鲍曼囊（Bowman’s capsule）壁层上皮由扁平向立方形的化生。细胞质改变通常是一种细微的变化，需要仔细审视。
诊断建议
细胞质改变应当予以诊断，并根据嗜酸性胞质内颗粒增加的程度以及受累迂曲（颗粒）导管的数量进行分级。
参考切片图（2 张）
查看英文原文
Comment
For a discussion on the sexual dimorphism of the salivary gland in rodents, please see the Introduction for this chapter. Examples of the normal female ( Figure 1 ) and male ( Figure 2 ) salivary gland ducts are provided here for comparison. In females, cytoplasmic alteration of the submandibular salivary gland is characterized by an increase in granularity of the convoluted (granular) ducts ( Figure 3 ), such that it appears similar to the normal male salivary gland ducts ( Figure 2 ). This change is due to a masculinizing effect of certain chemicals or hormones. A concomitant metaplasia of the parietal epithelium of Bowman’s capsule in the kidneys from flattened to cuboidal can also occur in the female mouse when exposed to masculinizing agents. Cytoplasmic alteration is often a subtle change requiring careful scrutiny.
Recommendation
Cytoplasmic alteration should be diagnosed and graded based on the degree of increase in eosinophilic intracytoplasmic granules and number of convoluted (granular) ducts affected.
出血Hemorrhage 唾液腺出血
描述（中文）
出血可继发于创伤、血管炎症或化学毒性所致的血管损伤。出血常见于坏死区域。出血应与血管扩张（angiectasis）相鉴别。对于血管扩张，仔细查找可确认血液实际上位于由内皮细胞衬覆的腔隙内。
诊断建议
出血应予以诊断，并根据累及范围和区域数量进行分级。如果出血是其他病变（例如坏死、炎症或肿瘤）的一部分，则不应单独诊断，除非其严重程度足以支持单独诊断，但应在叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage can occur secondary to trauma, inflammation of vessels, or vascular damage secondary to chemical toxicity. Hemorrhage is frequently seen in areas of necrosis. Hemorrhage should be differentiated from angiectasis. With angiectasis, a careful search will confirm that the blood is actually contained within spaces lined with endothelial cells.
Recommendation
Hemorrhage should be diagnosed and graded based on the extent and number of areas involved. If hemorrhage is a part of another lesion (e.g., necrosis, inflammation, or neoplasia), it should not be diagnosed separately unless warranted by severity but should be described in the narrative.
坏死Necrosis 唾液腺坏死
描述（中文）
坏死可表现为散在的单个细胞坏死，也可表现为累及相邻细胞或结构的局部广泛坏死区。单个细胞坏死可表现为细胞皱缩、核染色质与细胞质浓缩、细胞轮廓扭曲以及凋亡小体形成。腺泡坏死可表现为局灶性（focal）至多灶性（multifocal）区域，其特征为组织较周围存活组织苍白，由肿胀细胞构成，细胞呈现不同程度的嗜酸性、细胞质玻璃样变、细胞质空泡化、核固缩、核溶解和/或核碎裂，并伴有相关细胞碎片（Figure 1、Figure 2）。继发性炎症常见。梗死（Figure 3、Figure 4）的特征为局灶性至focally extensive的唾液腺坏死区。大鼠唾液腺坏死、炎症和萎缩的原因之一是活动性涎泪腺炎病毒（sialodacryoadenitis virus）感染，但该病毒不累及小鼠唾液腺。
诊断建议
坏死一旦出现即应作出诊断，并根据坏死范围进行分级。继发性病变，如炎症或出血，除非其严重程度足以需要单独诊断，否则不单独诊断。梗死应诊断为坏死，但病理描述中应说明该病变符合梗死。
参考切片图（2 张）
查看英文原文
Comment
Necrosis may be characterized either by scattered single-cell necrosis or by locally extensive areas of necrosis involving contiguous cells or structures. Single-cell necrosis can present as cell shrinkage, condensation of nuclear chromatin and cytoplasm, convolution of the cell, and the presence of apoptotic bodies. Acinar necrosis can present as focal to multifocal areas characterized by tissue that is paler than the surrounding viable tissue, consisting of swollen cells with variable degrees of eosinophilia, hyalinized cytoplasm, vacuolated cytoplasm, nuclear pyknosis, karyolysis, and/or karyorrhexis with associated cellular debris ( Figure 1 and Figure 2 ). Secondary inflammation is common. Infarction ( Figure 3 and Figure 4 ) is characterized by a focal to focally extensive area of salivary gland necrosis. One cause of necrosis, inflammation, and atrophy of the salivary gland in the rat is an active sialodacryoadenitis virus infection, but this virus does not affect the mouse salivary gland.
Recommendation
Whenever present, necrosis should be diagnosed and graded based on the extent of the necrosis. Secondary lesions, such as inflammation or hemorrhage, are not diagnosed separately unless warranted by severity. Infarcts should be diagnosed as necrosis, but the pathology narrative should state that the lesion is consistent with an infarct.
增生Hyperplasia 唾液腺增生
描述（中文）
唾液腺增生（hyperplasia）可为腺泡性（acinar）、导管性（ductal）（Figure 2、Figure 4、Figure 5、Figure 6），或两者兼有。腺泡增生导致单个腺泡单位增多，但导管不增多；而导管增生则描述为导管增多，不伴有腺泡结构的同时增多。导管增生常发生于已遭受组织损伤的唾液腺，并表现为一种再生过程（Figure 5、Figure 6）。它是啮齿类动物、犬、猴及人类唾液腺多种炎症性和反应性病变的共同特征，并可与导管系统内结石和结石（calculi）的存在相关。导管上皮的再生性增生见于感染涎泪腺炎病毒（sialodacryoadenitis virus）的大鼠。唾液腺导管增生也可发生于 Wistar 大鼠舌下腺的导管中，而无明显的涎泪腺炎或任何特定疾病的证据。
诊断建议
唾液腺增生一经出现即应诊断并分级。若增生仅限于导管或仅限于腺泡，则诊断中应包含相应的部位修饰词（duct 或 acinus）。若导管和腺泡均增生，则不应使用部位修饰词，但应在病理描述中明确说明两种成分均受累。当增生发生于腺体已有组织损伤的区域时，可在增生诊断中加用修饰词“regenerative”。严重程度分级依据腺体（小叶）的大小或受累的增生腺体或导管的数量。相关病变如炎症、纤维化或坏死不应单独诊断，除非其严重程度足以支持单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of the salivary gland can be acinar, ductal ( Figure 2 , Figure 4 , Figure 5 , and Figure 6 ), or both. Hyperplasia of acini results in an increase in individual acinar units but not in ducts, whereas hyperplasia of the ducts is described as an increase in ducts without a concomitant increase in acinar structures. Often duct hyperplasia occurs in a salivary gland that has undergone tissue damage and appears to be a regenerative process ( Figure 5 and Figure 6 ). It is a common feature of many inflammatory and reactive conditions in the salivary glands of rodents, dogs, monkeys, and humans and can be associated with the presence of stones and calculi within the duct system. Regenerative hyperplasia of the ductal epithelium occurs in rats infected with the sialodacryoadenitis virus. Salivary duct hyperplasia can also be located in the ducts of the sublingual glands in the Wistar rat in the absence of obvious sialodacryoadenitis or evidence of any specific disease.
Recommendation
Hyperplasia of the salivary gland should be diagnosed and graded whenever present. If the hyperplasia is limited to the ducts or to the acini, then the appropriate site modifier (duct or acinus) should be included in the diagnosis. If both the ducts and acini are hyperplastic, then no site modifier should be used, but it should be made clear in the pathology narrative that both components are affected. The modifier "regenerative" can be added to the hyperplasia diagnosis when the hyperplasia is occurring in areas of the gland in which there has been tissue damage. Severity grading is based on the size of the gland (lobules) or number of hyperplastic glands or ducts affected. Associated lesions such as inflammation, fibrosis, or necrosis should not be diagnosed separately unless warranted by severity.
导管凝结物Duct Concretion 唾液腺其他
描述（中文）
凝结物（导管腔内物质的矿化）不常发生，但最常见于年龄较大的动物，作为背景性病变。它们可能与萎缩同时出现。凝结物或异物可导致导管扩张、炎症和纤维化。
诊断建议
唾液腺导管中的凝结物只要存在就应诊断。除非分级能揭示处理效应，否则无需分级。继发性病变，如扩张、炎症和纤维化，除非严重程度需要，否则无需单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Concretions (mineralization of material in the ductular lumen) occur infrequently but are most commonly seen in older animals as a background lesion. They may be seen with atrophy. Concretions or foreign bodies can lead to duct dilation, inflammation, and fibrosis.
Recommendation
A concretion in a salivary duct should be diagnosed whenever present. They need not be graded unless grading would divulge a treatment effect. Secondary lesions, such as dilation, inflammation, and fibrosis, need not be diagnosed separately unless warranted by severity.
导管囊肿Duct Cyst 唾液腺囊肿
描述（中文）
唾液腺导管囊肿（salivary gland duct cyst）往往累及一条或少数几条导管，通常呈圆形轮廓（Figure 1），而唾液腺的导管扩张（ductular dilation）通常更为弥漫（累及多条导管），且导管往往呈不规则轮廓（见 Salivary Gland - Duct - Dilation）。囊肿可能由结石、创伤或异物阻塞导管所致。导管扩张和导管囊肿在 NTP 啮齿类动物研究中不常见。
诊断建议
导管囊肿应当诊断，但一般不进行分级，除非囊肿大小存在与处理相关的影响。如果存在导管上皮的鳞状化生（squamous metaplasia），应当单独诊断并分级。相关链接：Salivary Gland - Duct - Dilation
参考切片图（1 张）
查看英文原文
Comment
Salivary gland duct cysts tend to involve one or a few ducts and usually have a circular profile ( Figure 1 ), whereas ductular dilation of salivary glands is typically more generalized (involving multiple ducts), and the ducts tend to have an irregular profile (see Salivary Gland - Duct - Dilation ). Cysts may be caused by obstruction of a duct by calculi, trauma, or foreign body. Ductular dilation and ductular cysts are not common in NTP rodent studies.
Recommendation
Duct cysts should be diagnosed but are generally not graded unless there is a treatment-related effect on the size of the cysts. If squamous metaplasia of the ductal epithelium is present, it should be diagnosed and graded separately. Related Links: Salivary Gland - Duct - Dilation
导管扩张Duct Dilation 唾液腺扩张
描述（中文）
唾液腺导管扩张通常更为弥漫（累及多个导管），且导管轮廓往往不规则（Figure 1、Figure 2），而唾液腺导管囊肿往往累及一个或少数几个导管，且通常呈圆形轮廓（见 Salivary Gland - Duct - Cyst）。导管扩张有时伴有导管上皮的鳞状化生（squamous metaplasia）。导管扩张和导管囊肿在 NTP 啮齿类动物研究中不常见。
诊断建议
只要存在，导管扩张就应诊断，并根据受累导管的数量和扩张导管的大小进行分级。如果存在导管上皮的鳞状化生，应单独诊断并分级。相关链接：Salivary Gland - Duct - Cyst
参考切片图（2 张）
查看英文原文
Comment
Ductular dilation of salivary glands is typically more generalized (involving multiple ducts), and the ducts tend to have an irregular profile ( Figure 1 and Figure 2 ), whereas salivary gland duct cysts tend to involve one or a few ducts and usually have a circular profile (see Salivary Gland - Duct - Cyst ). Ductular dilation is sometimes associated with squamous metaplasia of the duct epithelium. Ductular dilation and ductular cysts are not common in NTP rodent studies.
Recommendation
Whenever present, ductular dilation should be diagnosed and graded based on the number of ducts involved and size of the dilated ducts. If squamous metaplasia of the ductal epithelium is present, it should be diagnosed and graded separately. Related Links: Salivary Gland - Duct - Cyst
导管鳞状化生Duct Metaplasia Squamous 唾液腺化生
描述（中文）
化生（metaplasia）是一种终末分化细胞类型被同一胚层的另一种细胞类型所取代的改变。通常，一种特化的上皮类型被分化程度较低的上皮类型所取代。化生常常（但并非总是）是响应反复上皮损伤而发生的适应性改变，因此常伴有其他病变，如炎症或坏死。如果去除病因，鳞状化生（squamous metaplasia）可能是可逆的。鳞状化生是化生的一种常见形式，推测是因为鳞状上皮比其他形式的上皮更能抵抗损伤。鳞状化生通常是慢性刺激的结果，但也可能有其他原因（例如维生素A缺乏症）。在唾液腺导管中，已观察到正常立方导管上皮在化学物质、电离辐射、病毒感染、维生素A缺乏以及唾液腺结石阻塞导管的作用下发生化为复层鳞状上皮。导管上皮的鳞状化生可能是进展为鳞状细胞癌的癌前病变。
诊断建议
唾液腺导管的鳞状化生应当根据受累区域的数量和鳞状上皮的厚度进行诊断和分级。相关病变，如炎症、坏死或变性，应当单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Metaplasia is a change in which one terminally differentiated cell type is replaced by another cell type of the same germ line. Usually, a specialized type of epithelium is replaced by less specialized type of epithelium. Metaplasia is often, but not always, an adaptive change that occurs in response to repeated epithelial damage and is therefore often accompanied by other lesions such as inflammation or necrosis. Squamous metaplasia may be reversible if the cause is removed. Squamous metaplasia is a common form of metaplasia, presumably because squamous epithelium is more resistant to damage than other forms of epithelia. Squamous metaplasia is usually the result of chronic irritation, but it can have other causes (e.g., hypovitamnosis A). In the salivary ducts, metaplasia of the normally cuboidal ductal epithelium to stratified squamous epithelium has been seen in response to chemicals, ionizing radiation, viral infections, vitamin A deficiency, and blockage of ducts by salivary calculi. Squamous metaplasia of the ductular epithelium may be a preneoplastic lesion progressing to squamous cell carcinoma.
Recommendation
Squamous metaplasia of the salivary duct should be diagnosed and graded based on the number of areas involved and the thickness of the squamous epithelium. Associated lesions, such as inflammation, necrosis, or degeneration, should be diagnosed separately.
核增大Karyomegaly 唾液腺其他
描述（中文）
核增大（karyomegaly，即细胞核增大）在 NTP 研究中是一种不常见的所见。增大的细胞核可使整个细胞显得增大。在 NTP 研究中，唾液腺的核增大见于对照和染毒的 F344/N 大鼠、Osborne Mendel 大鼠以及单只 B6C3F1 小鼠（Figure 1、Figure 2）。增大的细胞核也可见于嗜碱性肥大性灶（basophilic hypertrophic foci），尽管其可能被嗜碱性胞质所掩盖。
诊断建议
只要存在，该病变即应诊断，并根据细胞核的大小和受累细胞核的数量进行分级。位于嗜碱性肥大性灶内或增殖性病变内的核增大不应单独诊断。如果整个细胞增大（包括细胞核），病理学家必须自行判断核增大或肥大（或两者）中哪一个是最合适的诊断。
参考切片图（2 张）
查看英文原文
Comment
Karyomegaly (enlarged nuclei) is an uncommon finding in NTP studies. The enlarged nuclei may make the entire cell appear to be enlarged. In NTP studies, karyomegaly in the salivary glands has been seen in control and treated F344/N and Osborne Mendel rats and a single B6C3F1 mouse ( Figure 1 and Figure 2 ). Enlarged nuclei can also be seen in basophilic hypertrophic foci, although they may be obscured by the basophilic cytoplasm.
Recommendation
Whenever present, this change should be diagnosed and graded based on the size of the nuclei and the number of nuclei affected. Karyomegaly within basophilic hypertrophic foci or within proliferative lesions should not be diagnosed separately. If the entire cell is enlarged (including the nucleus), the pathologist will have to use his or her judgment as to whether kayromegaly or hypertrophy (or both) would be most appropriate diagnosis.
水肿Edema 唾液腺水肿
描述（中文）
唾液腺水肿的特征是腺组织被清亮间隙或嗜酸性液体分隔。水肿液在制片过程中常丢失，因此在组织中表现为清亮间隙（Figure 1、Figure 2）。如果水肿液未被洗脱，则会在间质中表现为均质嗜酸性物质。水肿是调节血浆、间质和细胞之间正常液体分布的任一因素发生改变的结果，例如血管通透性增加、血管内静水压升高、血管内渗透压降低和淋巴引流减少。有观点认为，将受试物机械性注入唾液腺可能引起局部组织损伤、水肿和唾液流出障碍，进而导致继发性炎症和偶发的继发性细菌感染（来自口腔常驻细菌）。另一种可能性是唾液流出减少导致唾液蛋白水解酶间质渗漏并引起局部组织损伤。
诊断建议
在没有其他炎症证据的情况下发生的水肿，应根据水肿液分隔实质的程度以及病变在唾液腺内的范围进行诊断和分级。当水肿是炎症过程的一部分时，不应单独诊断，而应在病理学描述中作为炎症的组成部分加以描述。
参考切片图（2 张）
查看英文原文
Comment
Edema in the salivary gland is characterized by separation of the glandular tissue by clear space or eosinophilic fluid. Edema fluid is often lost at processing and therefore appears as clear spaces in tissues ( Figure 1 and Figure 2 ). If the edema fluid is not washed out, it will appear as homogenous eosinophilic material in the interstitium. Edema is the result of alteration in any of the factors that regulate normal fluid distribution between the plasma, interstitium, and cells such as increased vascular permeability, increased intravascular hydrostatic pressure, decreased intravascular osmotic pressure, and decreased lymphatic drainage. It has been suggested that the mechanical administration of test materials into the salivary gland may provoke local tissue damage, edema, and deranged salivary outflow leading to secondary inflammation and occasional secondary bacterial infection (from resident oral bacteria). Another possibility is that a decreased salivary outflow results in interstitial leakage of salivary proteolytic enzymes and causes local tissue damage.
Recommendation
Edema occurring in the absence of other evidence of inflammation should be diagnosed and graded based on degree of separation of parenchyma by edema fluid and extent of the lesion within the salivary gland. When edema is part of an inflammatory process, it should not be diagnosed separately but should be described in the pathology narrative as a component of the inflammation.
淀粉样物质Amyloid 唾液腺其他
描述（中文）
组织中的淀粉样物质沉积（淀粉样变性（amyloidosis））是一种全身性疾病，在B6C3F1、BALB/c和C3H小鼠中罕见，但在CD-1、A、Swiss Webster、SJL和B6小鼠中常见，并且可以是死亡的原因。其发生率可因群养雄性动物间的打斗以及外寄生虫感染而升高。淀粉样物质表现为无定形、嗜酸性、玻璃样、细胞外物质，随着其进行性蓄积，导致邻近细胞和组织萎缩。在唾液腺中，淀粉样物质可导致唾液腺腺泡萎缩（Figure 1、Figure 2）。在食管和小肠中，该病似乎始于淀粉样物质在黏膜下层的沉积。肾脏肾小球中的淀粉样物质沉积通常是死于淀粉样变性动物的死亡原因。刚果红（Congo red）将淀粉样物质染成橙色至橙红色，在偏振光下呈现浅绿色，即所谓的苹果绿荧光。
诊断建议
无论何时出现，唾液腺中的淀粉样物质沉积都应诊断为“淀粉样物质（amyloid）”，并根据淀粉样物质沉积的范围进行分级。相关的组织萎缩无需单独诊断，但可在叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Amyloid deposition in tissues (amyloidosis) is a systemic disease that is rare in B6C3F1, BALB/c, and C3H mice but common in CD-1, A, Swiss Webster, SJL, and B6 mice and can be a cause of death. The incidence can be increased in association with fighting among group-housed males and with ectoparasitism. Amyloid appears as an amorphous, eosinophilic, hyaline, extracellular substance that, with progressive accumulation, results in atrophy of adjacent cells and tissue. In the salivary gland, the amyloid can cause atrophy of the salivary gland acini ( Figure 1 and Figure 2 ). In the esophagus and small intestine, the disease appears to begin as a deposition of amyloid in the submucosa. Amyloid deposits in the glomeruli of the kidney are usually the cause of death in animals that die with amyloidosis. Congo red stains amyloid orange to orange red and under polarized light imparts a light green, so-called apple green, fluorescence.
Recommendation
Whenever present, amyloid deposits in the salivary gland should be diagnosed as "amyloid" and graded based on the extent of the amyloid deposits. Associated atrophy of the tissues need not be diagnosed separately but can be described in the narrative.
炎症Inflammation 唾液腺炎症
描述（中文）
在NTP研究中，炎症有五种标准分类：急性（Figure 1、Figure 2）、化脓性（Figure 3、Figure 4）、慢性、慢性活动性和肉芽肿性（Figure 5、Figure 6）。在急性炎症中，主要浸润细胞是中性粒细胞，尽管也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但中性粒细胞聚集，且其中许多发生退变（化脓性渗出物）。渗出物可能含有细胞碎片，既来自 resident 细胞群体，也来自浸润的白细胞；含纤维蛋白的蛋白性液体；较少的巨噬细胞；偶见的淋巴细胞或浆细胞；以及可能的感染因子。肉眼上，这些病变以脓液存在为特征。渗出物周围组织可能含有成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大型、活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。慢性炎症可见于感染涎泪腺炎冠状病毒的大鼠、产气克雷伯菌的慢性感染以及小鼠的免疫介导性涎腺炎。涎泪腺炎病毒（一种冠状病毒）是影响大鼠唾液腺的最重要感染因子（小鼠不敏感），因为它有可能影响毒理学研究的解释。该病毒主要影响下颌下腺和腮腺唾液腺，引起腺体肉眼增大、腺泡和导管上皮坏死以及显著炎症。舌下唾液腺通常不受影响。在急性期，中性粒细胞浸润与坏死相关，但后期浸润主要由单核细胞组成（慢性炎症）。
诊断建议
无论何时出现，炎症均应诊断并给出严重程度分级。诊断中应包含指示炎症持续时间或类型的修饰词（即急性、化脓性、慢性、慢性活动性或肉芽肿性）。严重程度分级取决于受影响唾液腺区域的范围和细胞浸润的密度。符合脓肿的病变诊断为化脓性炎症。相关病变，如纤维化、坏死、水肿和出血，除非严重程度需要，否则不应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
In NTP studies, there are five standard categories of inflammation: acute ( Figure 1 and Figure 2 ), suppurative ( Figure 3 and Figure 4 ), chronic, chronic active, and granulomatous ( Figure 5 and Figure 6 ). In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate). The exudate may contain cell debris, both from the resident cell populations and from infiltrating leukocytes; proteinaceous fluid containing fibrin; fewer macrophages; occasional lymphocytes or plasma cells; and, possibly, an infectious agent. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may contain fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Chronic inflammation can be seen in rats infected with sialodacryoadenitis corona virus, chronic infections with Klebsiella aerogenes , and immune-mediated sialoadenitis in mice. Sialodacryoadenitis virus (a corona virus) is the most important infectious agent affecting the salivary glands of rats (mice are not susceptible) because of its potential to compromise the interpretation of toxicologic studies. The virus, which mainly affects the submandibular and parotid salivary glands, causes gross enlargement of the glands, necrosis of both acinar and ductular epithelium, and marked inflammation. The sublingual salivary glands are not generally affected. In the acute phase, a neutrophilic infiltrate is associated with the necrosis, but later the infiltrates consist predominantly of mononuclear cells (chronic inflammation).
Recommendation
Whenever present, inflammation should be diagnosed and given a severity grade. A modifier indicating the duration or type of inflammation (i.e., acute, suppurative, chronic, chronic active, or granulomatous) should be included in the diagnosis. The severity grade depends on the extent of area of salivary gland affected and the density of the cellular infiltrate. Lesions consistent with an abscess are diagnosed as suppurative inflammation. Associated lesions, such as fibrosis, necrosis, edema, and hemorrhage, should not be diagnosed separately unless warranted by severity.
纤维化Fibrosis 唾液腺纤维化
描述（中文）
纤维化可见于唾液腺内及周围（Figure 1、Figure 2），且常取代腺体组织。它可与严重炎症和坏死同时出现。在某些慢性病例中，炎症和坏死已消退，纤维化表现为基本无细胞的嗜酸性组织。此类情况下，受累腺体或小叶可能较小，且腺泡可能发生萎缩。
诊断建议
凡纤维化作为唯一病变存在时，均应诊断并分级。然而，除非是病变的终末期，纤维化很少在没有同时存在的组织损伤或炎症的情况下出现。凡纤维化是退行性、坏死性或炎症性病变的重要组成成分时，均应诊断并分级。被认为继发于纤维化的腺体组织萎缩不应单独诊断，除非它是病变的显著组成成分。继发性病变应在病理学描述中记述。
参考切片图（2 张）
查看英文原文
Comment
Fibrosis can be found in and around the salivary glands ( Figure 1 and Figure 2 ) and often replaces glandular tissue. It may be seen concurrently with severe inflammation and necrosis. In some chronic cases, the inflammation and necrosis have resolved and the fibrosis appears as largely acellular, eosinophilic tissue. In such cases, the affected gland or lobule may be small, and there may be atrophy of the glandular acini.
Recommendation
Whenever present as the sole lesion, fibrosis should be diagnosed and graded. However, unless it is the end stage of a lesion, fibrosis is rarely seen without concurrent tissue damage or inflammation. Whenever it is a significant component of a degenerative, necrotic, or inflammatory lesion, fibrosis should be diagnosed and graded. Atrophy of glandular tissue that is considered secondary to fibrosis should not be diagnosed separately unless it is a prominent component of the lesion. Secondary lesions should be described in the pathology narrative.
细胞浸润Infiltration Cellular 唾液腺浸润
描述（中文）
唾液腺中的浸润细胞可包括小型成熟淋巴细胞、嗜酸性粒细胞（eosinophil）、肥大细胞、组织细胞和未退变的粒细胞。单核细胞浸润，主要为淋巴细胞，有时混有少量浆细胞，在B6C3F1小鼠的唾液腺中常见（Figure 1、Figure 2），如同在B6C3F1小鼠的其他器官中一样。这些浸润在唾液腺中的意义尚不清楚。浸润可由单个或多个细胞簇组成，通常在雌性中较大且更频繁。它们一般始于血管周围间隙，但可能增大至浸润并取代腺实质。在发生年龄相关唾液腺萎缩的老年大鼠中，可能存在淋巴细胞或浆细胞灶。有必要将显著（marked）淋巴细胞浸润与慢性炎症和淋巴瘤区分开来。慢性炎症还会伴有坏死和组织损伤，而这些在细胞浸润中未见。淋巴瘤预期会导致唾液腺结构消失，并存在于其他器官，因为淋巴瘤罕见于唾液腺原发。
诊断建议
无论何时出现，唾液腺中的细胞浸润应诊断为记录为“infiltration, cellular”，并指明适当的细胞类型（即淋巴细胞、嗜酸性粒细胞、组织细胞等）。严重程度分级基于浸润唾液腺的细胞数量。如果淋巴细胞（或其他浸润细胞）被认为是萎缩的组成部分，则不应诊断，而应在叙述中随萎缩一起描述。
参考切片图（2 张）
查看英文原文
Comment
Infiltrates in the salivary gland can include small mature lymphocytes, eosinophils, mast cells, histiocytes, and nondegenerate granulocytes. Infiltrates of mononuclear cells, primarily lymphocytes, sometimes admixed with a few plasma cells, occur commonly in the salivary glands of B6C3F1 mice ( Figure 1 and Figure 2 ), as in other organs in the B6C3F1 mouse. The significance of these infiltrates in the salivary gland is unclear. The infiltrates may consist of a single or multiple clusters and are usually larger and more frequent in females. They generally begin in the perivascular space but may increase in size so as to infiltrate and displace glandular parenchyma. Foci of lymphocytes or plasma cells may be present in older rats undergoing age-related atrophy of the salivary glands. It is necessary to differentiate marked lymphocyte infiltrate from chronic inflammation and lymphoma. Chronic inflammation will also have necrosis and tissue damage, which are not noted with cellular infiltrates. Lymphoma would be expected to result in effacement of salivary gland architecture and to be present in other organs, as lymphoma is rarely primary to the salivary gland.
Recommendation
Whenever present, an infiltrate of cells in the salivary gland should be diagnosed as recorded as "infiltration, cellular" with the appropriate cell type indicated (i.e., lymphocyte, eosinophil, histiocyte, etc.). Severity grading is based on the number of cells infiltrating the salivary gland. If lymphocytes (or other infiltrating cells) are considered a component of atrophy, they should not be diagnosed but should be described in the narrative with the atrophy.
细胞质空泡化Vacuolation Cytoplasmic 唾液腺空泡化
描述（中文）
细胞质空泡化通常被认为是变性的一种早期形式。细胞质空泡化（Figure 1、Figure 2）表现为细胞因液体超负荷而导致的细胞大小和体积增加，这是由于细胞未能维持正常稳态并调节液体的进入和排出所致。组织学上，细胞增大，受累细胞的细胞质内含有半透明空泡。这些空泡可能代表扩张的内质网或高尔基体，或肿胀的线粒体，提示细胞损伤。在某些情况下，空泡可能代表小脂滴。需要电子显微镜才能明确鉴定空泡的真实性质。
诊断建议
无论何时出现，细胞质空泡化均应予以诊断，并根据空泡的数量和大小进行分级。如果有证据表明细胞损伤超出细胞质空泡化但无显著坏死，则可以使用“变性”一词。如果炎症是病变的显著组成部分，则应单独诊断和分级。
参考切片图（2 张）
查看英文原文
Comment
Cytoplasmic vacuolation is generally considered to be an early form of degeneration. Cytoplasmic vacuolization ( Figure 1 and Figure 2 ) manifests as increased cell size and volume resulting from an overload of fluid caused by a failure of the cell to maintain normal homeostasis and regulate the ingress and excretion of fluid. Histologically, cells are enlarged and the cytoplasm of affected cells contains translucent vacuoles. The vacuoles may represent distended endoplasmic reticulum or Golgi or swollen mitochondria, indicative of cell injury. In some cases, the vacuoles may represent small lipid droplets. Electron microscopy is required to definitively identify the true nature of the vacuoles.
Recommendation
Whenever present, cytoplasmic vacuolation should be diagnosed and graded based on the number and size of vacuoles. The term "degeneration" can be used if there is evidence of cell damage beyond cytoplasmic vacuolation but no significant necrosis. If inflammation is a prominent component of the lesion, it should be diagnosed and graded separately.
腮腺嗜碱性肥大灶Parotid Basophilic Hypertrophic Focus 唾液腺坏死灶
描述（中文）
唾液腺的嗜碱性肥大灶（basophilic hypertrophic foci）在小鼠和大鼠中仅见于腮腺，通常为单个发生（Figure 1、Figure 2），尽管也可能观察到多个病灶（Figure 3、Figure 4、Figure 5）。这些病灶由增大的腺泡细胞呈局灶性（focal）簇状聚集构成，细胞内胞质增多，有时细胞核也增大。顶端胞质通常呈空泡化且淡染，而基底部胞质呈深嗜碱性。该变化偶尔可见于未处理的 rat，但包括多西拉敏（doxylamine）在内的化学物质已在 F344 rat 的腮腺中诱导出该变化。该变化不被认为是肿瘤前病变。
诊断建议
当存在单个病灶时，应诊断为“嗜碱性肥大灶（basophilic hypertrophic focus）”。多个病灶应诊断为“嗜碱性肥大灶，multiple”。不必进行严重程度分级，但如果病灶大小或数量的增加与化学物质暴露相关，则应采用兼顾每只动物病灶大小和数量的分级标准。
参考切片图（2 张）
查看英文原文
Comment
Basophilic hypertrophic foci of the salivary glands have been found only in the parotid gland in mice and rats and usually occur singly ( Figure 1 and Figure 2 ), although multiple foci may be observed ( Figure 3 , Figure 4 , and Figure 5 ). The foci consist of focal clusters of enlarged acinar cells that contain increased amounts of cytoplasm and, sometimes, enlarged nuclei. The apical cytoplasm is usually vacuolated and pale, while the basilar cytoplasm is deeply basophilic. This change may be seen occasionally in untreated rats, but chemicals, including doxylamine, have produced this change in the parotid gland of F344 rats. This change is not thought to be preneoplastic.
Recommendation
When a single focus is present, it should be diagnosed as "basophilic hypertrophic focus." Multiple foci should be diagnosed as "basophilic hypertrophic focus, multiple." Severity grading is not necessary, but if an increase in size or number of foci is correlated with chemical exposure, a grading scale should be applied that takes into account both the size and number of foci in each animal.
腮腺腺泡肥大Parotid Acinus Hypertrophy 唾液腺肥大
描述（中文）
不伴嗜碱性灶的腮腺腺泡细胞弥漫性肥大在 NTP 研究中罕见。同样，下颌下腺和舌下腺的腺泡细胞弥漫性肥大在 B6C3F1 小鼠和 Fischer 344 大鼠中罕见。腺泡细胞肥大（Figure 2）的特征是细胞体积增大，主要由于细胞质增多，尽管肥大细胞的细胞核通常也较大。肥大性嗜碱性灶所见的强烈嗜碱性并不存在，且细胞通常没有那么大。腺泡细胞的弥漫性肥大往往可能是细微变化，需要与对照动物仔细比较。
诊断建议
唾液腺腺泡肥大应根据腺泡细胞体积增大的程度和受累细胞的数量进行诊断和分级。多灶性（multifocal） 肥大应给予比 局灶性（focal） 肥大更高的严重程度等级。如果肥大遍及整个腺体，则应在诊断中加上修饰词“弥漫性（diffuse）”。
参考切片图（2 张）
查看英文原文
Comment
Diffuse hypertrophy of parotid salivary gland acinar cells not associated with basophilic foci is rare in NTP studies. Likewise, diffuse acinar cell hypertrophy of the submandibular and sublingual salivary glands is rare in B6C3F1 mice and Fischer 344 rats. Acinar cell hypertrophy ( Figure 2 ) is characterized by increased cell size primarily due to an increase in cytoplasm, although the nuclei are also usually larger in hypertrophied cells. The intense basophilia seen with hypertrophic basophilic foci is not present, and the cells are typically not as large. Diffuse hypertrophy of acinus cells often can be a subtle change requiring close comparison with control animals.
Recommendation
Salivary gland acinar hypertrophy should be diagnosed and graded based on the degree of increase in acinar cell size and number of cells affected. Multifocal hypertrophy would be assigned a higher severity grade than focal hypertrophy. If the hypertrophy is diffuse throughout the gland, then the modifier "diffuse" should be added to the diagnosis.
萎缩Atrophy 唾液腺萎缩
描述（中文）
唾液腺萎缩（Figure 1、Figure 2）常见于老年F344/N大鼠。与许多其他腺体器官一样，分泌腺的大小对功能需求具有应答性，并受年龄相关变化的影响。在老龄大鼠中，颗粒（卷曲）管的数量和上皮高度以及成熟分泌颗粒的数量已被证明随年龄增长而减少。间质纤维结缔组织可能轻度增多，并可能有慢性炎性细胞浸润。有时在小叶和腺泡之间可见局灶性脂肪细胞聚集，类似于胰腺和胸腺的退行性变化。也可能存在少数单个腺泡细胞的坏死。其他品系大鼠中可见与F344大鼠相似的年龄相关萎缩性或退行性变化。萎缩可能是毒性的结果，但常见与唾液腺肿瘤或炎性病变相关。当细胞体积减小呈弥漫性时，萎缩可能很轻微且易被忽视。萎缩、坏死和炎症通常见于活动性涎泪腺炎病毒（sialodacryoadenitis virus）感染。萎缩也可见于单核细胞白血病浸润唾液腺或面神经分支起源的神经鞘瘤局部侵袭时。导管腔内物质的矿化不常发生，并可与萎缩同时出现。去神经支配、肾上腺素能拮抗剂、导管结扎或流质饮食可导致唾液腺萎缩。饮食因素影响唾液腺大小。食物摄入减少或蛋白质饥饿可降低大鼠唾液腺重量。黏液腺和浆液腺的皱缩及酶原颗粒的丢失与RNA减少但DNA含量不变相关，归因于蛋白质合成需求降低。由于唾液腺功能对肾上腺素能刺激具有应答性，因此肾上腺素能阻断后发生萎缩并不令人意外。小鼠颌下腺重量在给予β-肾上腺素能阻断剂普萘洛尔（propranolol）后显示下降。这与可染性中性黏蛋白减少及腺泡细胞厚度减小相关，使腺腔显得比正常更大。唾液腺萎缩偶尔发生于老龄B6C3F1小鼠。萎缩一般累及单个小叶，其特征为腺泡和腺泡上皮细胞体积减小，可伴有慢性炎性细胞浸润及间质结缔组织和/或腺管数量增加。颌下腺和腮腺比舌下腺更常受累。
诊断建议
无论何时出现，萎缩均应予以诊断，并根据导管/腺泡细胞萎缩的程度及唾液腺内受累范围进行分级。与年龄相关萎缩有关的炎症和纤维化不单独诊断，除非其严重程度足以支持单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Atrophy of the salivary glands ( Figure 1 and Figure 2 ) occurs commonly in older F344/N rats. As is the case with many other glandular organs, the size of the secretory glands is responsive to functional demand and is subject to age-related changes. In aging rats, the number and epithelial height of granular (convoluted) ducts and the number of mature secretory granules have been shown to decrease with age. There may be a slight increase in stromal fibrous connective tissue, and there may be an infiltrate of chronic inflammatory cells. Focal aggregates of adipocytes are sometimes seen between lobules and acini, similar to involutional changes in the pancreas and thymus. Necrosis of a few individual acinar cells may also be present. Age-associated atrophic or degenerative changes similar to those in the F344 rat are seen in other strains of rats. Atrophy may be the result of toxicity, but it is commonly seen in association with neoplasia or inflammatory lesions in the salivary gland. Atrophy can be subtle and can be overlooked when the decrease in cell size is diffuse. Atrophy, necrosis, and inflammation are typically seen with active sialodacryoadenitis virus infection. Atrophy is also seen with mononuclear cell leukemia infiltration of the salivary gland or local invasion by a schwannoma arising in branches of the facial nerve. Mineralization of material in the ductular lumen occurs infrequently and may be seen with atrophy. Denervation, adrenergic antagonists, duct ligation, or liquid diets can result in salivary gland atrophy. Dietary factors influence salivary gland size. Decreased food consumption or protein starvation can reduce the weight of salivary glands in rats. Shrinking of mucous and serous glands and loss of zymogen granules are associated with decreased RNA but unchanged DNA content, attributable to the reduced requirements for protein synthesis. As salivary gland function is responsive to adrenergic stimulation, it is not surprising that atrophy occurs following adrenergic blockage. The weights of the submandibular gland in mice were shown to decrease after administration of the B-adrenergic blocking agent propranolol. This was associated with a reduction in stainable neutral mucins and a decrease in the thickness of the acinar cells, making the gland lumens appear larger than normal. Salivary gland atrophy occurs occasionally in aging B6C3F1 mice. The atrophy generally affects individual lobules and is characterized by a decrease in the size of acini and acinar epithelial cells, which may be accompanied by an infiltrate of chronic inflammatory cells and an increase in interstitial connective tissue and/or in the number of glandular ducts. The submandibular and parotid glands tend to be involved more commonly than the sublingual gland.
Recommendation
Whenever present, atrophy should be diagnosed and graded based on the degree of ductal/acinar cell atrophy and the extent of involvement within the salivary gland. Inflammation and fibrosis associated with age related atrophy are not diagnosed separately unless warranted by severity.
切牙变性Incisor Degeneration 牙齿变性
描述（中文）
门齿的退行性改变在NTP研究中不常见。门齿退行性变包括一组病变，这些病变可能不会同时出现。早期病变包括牙髓内局灶性（focal）间充质细胞空泡化和骨牙本质形成。更严重的病变包括局灶性或多灶性（multifocal）成牙本质细胞退行性变伴牙本质龛形成（Figure 1、Figure 2）、牙本质基质排列异常以及基质染色改变（Figure 3、Figure 4）。严重病变中可见牙本质层断裂。门齿退行性变可能由化学物质诱导，并且至少在大鼠的一个案例中，有研究提示其继发于选择性前成牙本质细胞群损伤。
诊断建议
牙齿，门齿 - 退行性变：只要存在即应诊断并分级。如果牙本质层外观正常而仅成牙本质细胞发生退行性变或坏死，则应诊断为“牙齿，成牙本质细胞 - 退行性变”或“牙齿，成牙本质细胞 - 坏死”。
参考切片图（2 张）
查看英文原文
Comment
Degenerative changes of the incisors are uncommon in NTP studies. Incisor degeneration comprises a set of lesions that may not all be present concurrently. Early lesions include focal mesenchymal cell vacuolation and osteodentin formation within the pulp. More severe lesions include focal or multifocal odontoblast degeneration with dentin niche formation ( Figure 1 and Figure 2 ), abnormal organization of the dentin matrix, and altered matrix staining ( Figure 3 and Figure 4 ). Breaks in the dentin layer may be seen with severe lesions. Incisor degeneration may be chemically induced and, at least in one case in rats, has been suggested to be secondary to injury to a selective population of preodontoblasts.
Recommendation
Tooth, Incisor - Degeneration should be diagnosed and graded whenever present. If the dentin layer appears normal and the odontoblasts only are undergoing degeneration or necrosis, then "tooth, odontoblast - degeneration" or "tooth, odontoblast - necrosis" should be diagnosed.
坏死Necrosis 牙齿坏死
描述（中文）
牙髓中的细菌感染及其他损伤会诱发炎症反应，但与脑组织被颅骨包绕类似，牙髓被牙本质包绕限制了肿胀的程度。炎症时发生的肿胀可导致牙髓内压力显著升高，从而抑制血流。此外，由于牙根尖是血管的唯一入口，牙髓内 collateral 血管的形成受到抑制。牙髓内压力升高或血管闭塞（如血栓形成）所致的血流减少，通常导致牙髓缺血性坏死和牙齿死亡。
诊断建议
当牙齿的大部分受累且牙内多个组织发生坏死时，应诊断牙齿坏死并分级。若牙内1或2个特定部位受累（如成釉细胞、成牙本质细胞、牙髓），而牙齿的大部分未受累，则应在诊断中注明受累部位。任何伴随的炎症，仅当其被认为与坏死无关（即属于原发性病变）或其严重程度足以需要单独诊断时，才应予以诊断。
参考切片图（2 张）
查看英文原文
Comment
Bacterial infection and other injuries in the tooth pulp induce an inflammatory response, but similar to the brain’s enclosure within the calvarium, the tooth pulp’s enclosure within the dentin limits the amount of swelling. The swelling that occurs with inflammation can result in markedly increased pressure in the tooth pulp, which inhibits blood flow. Additionally, the intrapulpal formation of collateral blood vessels is inhibited because the apex of the tooth is the sole entry point for blood vessels. The decreased blood flow due to increased intrapulpal pressure or vascular occlusion (e.g., thrombosis) generally results in ischemic necrosis of the pulp and death of the tooth.
Recommendation
Necrosis of the teeth should be diagnosed and graded if the majority of a tooth is affected and multiple tissues within the tooth are necrotic. If 1 or 2 particular sites in the tooth are affected (e.g., ameloblast, odontoblast, pulp), and the majority of the tooth is unaffected, then the site(s) should be included in the diagnosis. Any associated inflammation should be diagnosed only if it is considered to be unrelated to the necrosis (i.e., is a primary lesion) or if it is severe enough to warrant a separate diagnosis.
成牙本质细胞变性Odontoblast Degeneration 牙齿变性
描述（中文）
氟化物毒性是成牙本质细胞变性（odontoblast degeneration）最具特征性的原因（Figure 1、Figure 2，箭头）。成牙本质细胞变性的特征为细胞质减少、细胞数量减少、上皮细胞层排列紊乱以及细胞核极性丧失。该病变可为局灶性（focal）或弥漫性（diffuse）。成牙本质细胞变性会影响其产生牙本质的能力，并可能导致局灶性至弥漫性的牙本质发育不全或发育缺失，从而引起牙本质厚度的变化。已发表的关于小鼠此类效应的报道并不常见。
诊断建议
成牙本质细胞变性应当根据变性程度和受累成牙本质细胞的数量进行诊断和分级。
参考切片图（2 张）
查看英文原文
Comment
Fluoride toxicity is the most well characterized cause of odontoblast degeneration ( Figure 1 and Figure 2 , arrows). Odontoblast degeneration is characterized by decreased amounts of cytoplasm, decreased cell numbers, disorganization of the epithelial cell layers and lack of nuclear polarity in cells. It may be focal or diffuse. Degeneration of the odontoblasts affects their ability to produce dentin and may result in focal to diffuse dentin hypoplasia or aplasia, which causes variations in the thickness of the dentin. Published reports of such effects in mice are uncommon.
Recommendation
Odontoblast degeneration should be diagnosed and graded based on the degree of degeneration and the number of odontoblasts affected.
成牙本质细胞坏死Odontoblast Necrosis 牙齿坏死
描述（中文）
成牙本质细胞坏死（Odontoblast necrosis）的特征是成牙本质细胞丢失，以及成牙本质细胞胞质呈强嗜酸性、细胞核皱缩和/或淡染（Figure 1、Figure 2、Figure 3、Figure 4，箭头）。NTP 研究中已观察到化学暴露所致的成牙本质细胞坏死。所提出的坏死机制为牙髓血管血栓形成继发的梗死。牙髓内的炎症也可导致缺血性坏死，原因是牙本质限制范围内组织肿胀使牙髓内压力升高，而牙本质限制了可发生的肿胀程度。此外，牙髓内 collateral 血供的发育受限，因为供应牙髓的血管必须经牙根尖进入牙齿。伴有成牙本质细胞坏死的牙髓炎症在啮齿类动物中可为偶发性病变。
诊断建议
成牙本质细胞坏死应当根据病变范围进行诊断和分级。如果成牙本质细胞坏死继发于牙髓血管血栓形成，应当诊断坏死（而非梗死），并应在病理学描述中充分讨论可疑的发病机制。相关炎症不应单独诊断，除非其严重程度足以需要单独诊断。如果炎症是原发病变且为成牙本质细胞坏死的原因，应当诊断炎症，病理学家需运用其判断力决定是否也应诊断成牙本质细胞坏死。如果未诊断成牙本质细胞坏死，则应在病理学描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Odontoblast necrosis is characterized by loss of odontoblasts and odontoblasts with highly eosinophilic cytoplasm and shrunken and/or faded nuclei ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 , arrows). Odontoblast necrosis due to chemical exposure has been observed in NTP studies. The proposed mechanism of necrosis was infarction secondary to thrombosis of pulp vessels. Inflammation in the pulp can also result in ischemic necrosis due to increased pressure in the tooth pulp from tissue swelling within the confines of the dentin, which limits the degree of swelling that can occur. In addition, the development of collateral blood supply within the pulp is limited because blood vessels supplying the pulp must enter the tooth through the apex of the tooth. Inflammation of the tooth pulp with odontoblast necrosis can be an incidental lesion in rodents.
Recommendation
Odontoblast necrosis should be diagnosed and graded based on the extent of the lesion. If the odontoblast necrosis is secondary to thrombosis of vessels in the tooth pulp, necrosis should be diagnosed (as opposed to infarct), and the suspected pathogenesis should be thoroughly discussed in the pathology narrative. Associated inflammation should not be diagnosed separately unless it is severe enough to warrant a separate diagnosis. If the inflammation is the primary lesion and the cause of the odontoblast necrosis, the inflammation should be diagnosed, and the pathologist will need to use his or her judgment in determining whether the odontoblast necrosis should also be diagnosed. If the odontoblast necrosis is not diagnosed, it should be described in the pathology narrative.
成釉细胞萎缩Ameloblast Atrophy 牙齿萎缩
描述（中文）
成釉细胞（ameloblast）（Figure 1、Figure 3，箭头）是负责釉质生成的细胞。成釉细胞的局灶性（focal）萎缩可导致釉质发育不全，但由于组织切片制备中的釉质脱钙会去除釉质，因此难以评估。釉质缺失在受累牙齿的大体检查中可能呈现特征性的褐色变色。成釉细胞萎缩（Figure 2、Figure 4，箭头）可由化学暴露引起，最显著的是氟化物毒性。成牙本质细胞也可受累，但成釉细胞似乎更为敏感。萎缩的特征是单个成釉细胞因细胞质减少和细胞核变小而缩短（Figure 4，箭头）。萎缩可导致成釉细胞鳞状化生，其特征为成釉细胞柱状层丧失并被鳞状上皮取代（见 Tooth - Ameloblast - Metaplasia, Squamous）。
诊断建议
无论何时出现，成釉细胞萎缩均应作出诊断，并根据细胞萎缩程度和受累成釉细胞数量进行分级。相关链接：Tooth - Ameloblast - Metaplasia, Squamous
参考切片图（2 张）
查看英文原文
Comment
Ameloblasts ( Figure 1 and Figure 3 , arrows) are the cells responsible for enamel production. Focal atrophy of ameloblasts can lead to enamel hypoplasia, which is difficult to assess because enamel decalcification removes the enamel in tissue sections. The loss of enamel may impart a characteristic brownish discoloration on gross examination in affected teeth. Ameloblast atrophy ( Figure 2 and Figure 4 , arrows) can be caused by chemical exposure, most notably fluoride toxicity. Odontoblasts can also be affected, but ameloblasts appear to be more sensitive. Atrophy is characterized by shortening of individual ameloblasts ( Figure 4 , arrow) due to decreased amounts of cytoplasm and smaller nuclei. Atrophy can lead to squamous metaplasia of ameloblasts, characterized by loss of the columnar layer of ameloblasts with replacement by squamous epithelium (see Tooth - Ameloblast - Metaplasia, Squamous ).
Recommendation
Whenever present, ameloblast atrophy should be diagnosed and graded based on the degree of cellular atrophy and the number of ameloblasts affected. Related Links: Tooth - Ameloblast - Metaplasia, Squamous
成釉细胞鳞状化生Ameloblast Metaplasia Squamous 牙齿化生
描述（中文）
成釉细胞损伤后可出现鳞状化生（squamous metaplasia）。萎缩以细胞质减少（单个成釉细胞变短）为特征，而鳞状化生以成釉细胞柱状层丧失并被鳞状上皮取代为特征（Figure 2、Figure 4，箭头）。
诊断建议
成釉细胞鳞状化生一旦出现即应诊断并分级。鳞状化生的严重程度分级基于病变范围及病变中鳞状细胞的层数。
参考切片图（2 张）
查看英文原文
Comment
Squamous metaplasia can be seen following injury to the ameloblasts. While atrophy is characterized by decreased cytoplasm (shortening of individual ameloblasts), squamous metaplasia is characterized by loss of the columnar layer of ameloblasts and replacement by squamous epithelium ( Figure 2 and Figure 4 , arrows).
Recommendation
Squamous metaplasia of the ameloblasts should be diagnosed and graded whenever present. Severity grading for squamous metaplasia is based on the extent of the lesion and the number of layers of squamous cells in the lesion.
炎症Inflammation 牙齿炎症
描述（中文）
在NTP研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞是中性粒细胞（neutrophil），尽管也可能存在较少的巨噬细胞（macrophage）和淋巴细胞（lymphocyte）。还可能有水肿或充血（hyperemia）的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但中性粒细胞聚集，且其中许多发生变性（化脓性渗出物，化脓性 exudate）。渗出物还可能含有细胞碎片，既来自驻留细胞群，也来自浸润的白细胞；含纤维蛋白（fibrin）的蛋白性液体；较少的巨噬细胞；偶见的淋巴细胞或浆细胞（plasma cell）；以及可能的感染因子。肉眼上，这些病变以脓液存在为特征。取决于病变的慢性程度，渗出物周围组织中可能存在成纤维细胞（fibroblast）、纤维结缔组织和混合性炎症细胞。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大型、活化巨噬细胞、上皮样巨噬细胞（epithelioid macrophage）或多核巨细胞（multinucleated giant cell）。牙齿炎症可累及牙髓（pulp）、牙骨质（cementum）、牙本质（dentin）或这些的任何组合，并可延伸至牙周组织。慢性牙齿炎症可导致牙齿吸收（tooth resorption）。牙齿炎症最常由细菌引起，但也可能是口腔内异物所致。如果细菌感染进入牙本质小管，它可扩散穿过牙本质并进入牙髓。由于牙髓被封闭在牙本质内，炎症引起的牙髓肿胀可导致髓内压升高、血流减少和缺血（ischemia）。龋齿（caries）是牙齿钙化部分炎症的肉眼术语。龋齿在小鼠或大鼠中不常见，但饮食中高水平的碳水化合物（例如蔗糖或木糖醇）可诱导其形成。牙齿炎症在伴有牙齿损伤的动物中可能是背景性发现。
诊断建议
每当存在时，牙齿炎症应当被诊断，并根据牙齿受累范围、炎症浸润的密度和受累牙齿的数量进行分级。炎症类型（例如急性、化脓性、慢性活动性）应作为修饰词纳入诊断。如果仅累及牙髓，应将术语“牙髓（pulp）”作为部位修饰词加入诊断（即“牙齿，牙髓 - 炎症”）。如果炎症累及牙本质和/或牙骨质，或者如果除牙髓外还累及牙本质和/或牙骨质，诊断应为“牙齿 - 炎症”。相关坏死不应单独诊断，除非它被认为是原发性病变（而非继发于炎症），或者其严重程度足以需要单独诊断。
参考切片图（2 张）
查看英文原文
Comment
In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate). The exudate may also contain cell debris, both from the resident cell populations and from infiltrating leukocytes; proteinaceous fluid containing fibrin; fewer macrophages; occasional lymphocytes or plasma cells; and, possibly, an infectious agent. Grossly, these lesions would be characterized by the presence of pus. Fibroblasts, fibrous connective tissue, and mixed inflammatory cells may be present in the tissue surrounding the exudate, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammation of the tooth can involve the pulp, the cementum, the dentin, or any combination of these and can extend to the periodontal tissues. Chronic tooth inflammation can result in tooth resorption. Tooth inflammation is most often caused by bacteria but can be the result of foreign bodies in the oral cavity. If a bacterial infection gains access to the dentin tubules, it can spread throughout the dentin and into the tooth pulp. Because of its enclosure within the dentin, swelling of the tooth pulp due to inflammation can result in increased intrapulpal pressure, decreased blood flow, and ischemia. Caries is a gross term for inflammation of the calcified portions of the tooth. Dental caries are not common in mice or rats, but high levels of carbohydrates (e.g., sucrose or xylitol) in the diet can induce their formation. Tooth inflammation can be a background finding in animals with dental injury.
Recommendation
Whenever present, inflammation of the teeth should be diagnosed and graded based on the extent of tooth involvement, the density of the inflammatory infiltrate, and the number of teeth affected. The type of inflammation (e.g., acute, suppurative, chronic active) should be included in the diagnosis as a modifier. If the tooth pulp only is involved, the term "pulp" should be added to the diagnosis as a site modifier (i.e., "tooth, pulp - inflammation"). If the inflammation involves the dentin and/or cementum, or if the dentin and/or cementum is involved in addition to the pulp, the diagnosis should be "tooth – inflammation." Associated necrosis should not be diagnosed separately unless it is considered to be a primary lesion (not secondary to the inflammation) or if it is severe enough to warrant a separate diagnosis.
牙周袋Periodontal Pocket 牙齿其他
描述（中文）
牙周袋（periodontal pocket）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6、Figure 7、Figure 8）是啮齿类动物常见的背景性病变。它们见于牙齿周围的牙周组织，尤其是磨牙周围。牙周袋表现为异常加深的牙龈沟，其内衬为角化的鳞状上皮，且常继发于毛发（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6）、饲料（Figure 7、Figure 8）或垫料的嵌塞。另外，细菌性牙周炎可导致牙周膜纤维的脱离和吸收，并形成牙周袋，异物可在其中被包裹。嵌塞的毛发、饲料或垫料可穿透周围组织，导致慢性炎症和纤维化（Figure 4、Figure 5、Figure 6）。牙周袋内衬为鳞状上皮，该上皮常发生角化。牙周袋的鉴别诊断包括鳞状囊肿和囊性角化增生。囊性角化增生被认为处于从增生到鳞状细胞癌的连续谱上。相比之下，牙周袋往往是由正常鳞状上皮衬覆的单房结构。鳞状囊肿在形态学上与牙周袋相似，但它们不一定位于牙齿邻近部位，且不与口腔黏膜相通。理想情况下，在牙周袋病变中可以看到与口腔的相通，但由于切面原因，开口可能不明显。
诊断建议
牙周袋应当诊断，但不进行分级。牙周袋内的异物（如毛干、垫料、饲料）不应单独诊断，而应在病理描述中加以描述。然而，在牙周袋周围组织内发现的异物应记录为“异物”。相关的炎症和纤维化不应单独诊断，除非其严重程度足以需要单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Periodontal pockets ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 , Figure 7 , and Figure 8 ) are common background findings in rodents. They are found in the periodontal tissues surrounding the teeth, especially the molars. The pockets represent an abnormally deepened gingival sulcus that is lined by keratinized squamous epithelium and are frequently secondary to the impaction of hair ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ), feed ( Figure 7 and Figure 8 ), or bedding material. Alternatively, bacterial periodontitis can result in detachment and resorption of periodontal ligament fibers and the formation of a periodontal pocket in which foreign bodies can become entrapped. Impacted hair, feed, or bedding may penetrate the surrounding tissues, resulting in chronic inflammation and fibrosis ( Figure 4 , Figure 5 , and Figure 6 ). They are lined by squamous epithelium that is often keratinized. Differential diagnoses for periodontal pocket include squamous cyst and cystic keratinizing hyperplasia. Cystic keratinizing hyperplasia is thought to be on a continuum from hyperplasia to squamous cell carcinoma. In comparison, periodontal pockets tend to be unilocular structures lined by normal squamous epithelium. Squamous cysts are similar to periodontal pockets morphologically, but they are not necessarily located adjacent to a tooth and do not communicate with the oral mucosa. Ideally, the communication to the oral cavity can be seen in a periodontal pocket lesion, but the opening may not be apparent because of the plane of section.
Recommendation
Periodontal pockets should be diagnosed but not graded. Foreign material (e.g., hair shafts, bedding, feed) within the pocket should not be diagnosed separately but should be described in the pathology narrative. However, foreign material found in the tissue surrounding the pocket should be recorded as "foreign body." Associated inflammation and fibrosis should not be diagnosed separately unless warranted by severity.
牙本质嗜碱性颗粒Dentin Basophilic Granules 牙齿其他
描述（中文）
牙本质中的嗜碱性颗粒（Figure 1、Figure 2）在NTP研究中罕见。它们是小而圆的嗜碱性球状物，在牙本质层内呈线性排列。在暴露于氟化钠2年的F344大鼠的predentin和dentin中曾见到此类颗粒。据报道，类似的沉积物代表牙齿/骨骼标本脱钙过程中形成的氟化钙结晶。
诊断建议
嗜碱性颗粒一旦出现即应诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Basophilic granules in the dentin ( Figure 1 and Figure 2 ) are rarely seen in the NTP studies. They are small, round, basophilic globules that occur in a linear pattern within the dentin layer. They have been seen in the predentin and dentin in F344 rats exposed to sodium fluoride for 2 years. Similar deposits are reported to represent calcium fluoride crystal formation that occurs during decalcification of tooth/bone specimens.
Recommendation
Basophilic granules should be diagnosed and graded whenever present.
牙本质小体Denticle 牙齿其他
描述（中文）
在对照和处理小鼠的上颌切牙中，常可见单个或多个牙本质小体（denticle）（Figure 1、Figure 2、Figure 3、Figure 4）。组织学上，牙本质小体呈圆形至卵圆形，中央有腔，周围环绕管状牙本质。未成熟牙本质小体的中央腔内可含有上皮细胞，而成熟牙本质小体则无细胞或含有细胞碎片。牙本质小体起源于牙髓，但可部分或完全并入牙本质层。牙本质小体起源于紧邻髓腔的上皮鞘发出的小芽状突起。一层柱状成牙本质细胞围绕髓内牙本质小体的外表面，不过在牙本质内或紧密贴附的牙本质小体中通常难以辨认成牙本质细胞。髓内牙本质小体的形成可能通过干扰正常牙齿发育、使受累牙齿易发生畸形及生物力学失效和折断，从而促进小鼠牙发育不良的发生。
诊断建议
由于牙本质小体是常见的背景性病变，除非其发生明显与处理相关，否则无需诊断。若进行诊断，则应分级。
参考切片图（2 张）
查看英文原文
Comment
Single or multiple denticles ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) are often seen in the maxillary incisors of control and treated mice. Histologically, denticles are round to ovoid in shape with a central cavity surrounded by tubular dentin. Immature denticles can contain epithelial cells within the central cavity, whereas mature denticles either are devoid of cells or contain cell fragments. Denticles originate in the tooth pulp but can become partly or entirely incorporated into the dentin layer. Denticles originate from small budlike projections emanating from the epithelial sheath, immediately adjacent to the pulp chamber. A layer of columnar odontoblasts surrounds the outer surface of intrapulpal denticles, although odontoblasts are not usually appreciated in denticles found within the tooth dentin or in closely apposed denticles. Intrapulpal denticle formation may contribute to the development of dental dysplasia in mice by interfering with normal tooth development and predisposing affected teeth to malformation and biomechanical failure and fracture.
Recommendation
Since they are common background findings, denticles need not be diagnosed unless their occurrence is clearly treatment related. If they are diagnosed, they should be graded.
牙髓血栓Pulp Thrombus 牙齿血栓
描述（中文）
牙髓内血管的血栓形成（thrombosis）（Figure 1、Figure 2，箭头）可导致牙髓梗死（infarction）、成牙本质细胞变性（odontoblast degeneration）（Figure 1，箭头所指）及坏死（necrosis）。牙髓内血管的特异性血栓形成在NTP研究中尚未见报道，但在化学物诱导的播散性血栓形成中可见，此时在多个器官中可识别出栓子。化学物诱导血栓形成发病机制中可能涉及的机制包括血管损伤和血流障碍。血管闭塞通常导致牙髓缺血性坏死和牙齿死亡。
诊断建议
牙髓内血管血栓应予以诊断，并根据其大小和数量进行分级。相关的梗死或坏死，或成牙本质细胞或其他细胞的变性，应分别予以诊断和分级。牙齿坏死/变性成分与血栓之间的关系应在病理学描述中明确说明。
参考切片图（2 张）
查看英文原文
Comment
Thrombosis of vessels in the tooth pulp ( Figure 1 and Figure 2 , arrows) can result in infarction of the pulp and odontoblast degeneration ( Figure 1 , arrowhead) and necrosis. Thrombosis specifically of vessels in the tooth pulp has not been seen in NTP studies, but it has been seen with disseminated, chemically induced thrombosis in which thrombi were identified in multiple organs. Mechanisms that may be involved in the pathogenesis of chemically induced thrombosis include vascular damage and disturbance of blood flow. Vascular occlusion generally results in ischemic necrosis of the pulp and death of the tooth.
Recommendation
Vascular thrombi in the tooth pulp should be diagnosed and graded based on their size and number. Associated infarction or necrosis or degeneration of the odontoblasts or other cells should be diagnosed and graded separately. The relationship between the necrosis/degeneration components of the tooth and the thrombi should be made clear in the pathology narrative.
牙髓骨性牙本质Pulp Osteodentin 牙齿其他
描述（中文）
骨样牙本质（osteodentin）在牙髓受损或成牙本质细胞移位后形成。若牙齿发生折断，髓腔会被这种物质填充以将其封闭。此类反应也可作为一种继发性修复反应发生，以增加生长/萌出发生改变或中断的牙齿和/或处于改变了的生物力学应力下的牙齿的强度。骨样牙本质沉积的速率取决于刺激的强度和持续时间；刺激/损伤越严重，骨样牙本质沉积的速率越快。刺激的类型对骨样牙本质的结构和构造有影响。若刺激为龋损，由于细菌代谢产物和毒素的弥散，牙本质发生广泛破坏，牙髓受到损伤。因此，骨样牙本质快速沉积，呈稀疏而不规则的管状模式并伴有一些细胞包涵物。快速沉积后，成牙本质细胞被困于新形成的基质中，管状模式变得模糊或扭曲。形成可为孤立性（Figure 1、Figure 2，箭头）、多发性或弥漫性（Figure 3、Figure 4，箭头）。某些受试物可直接或间接引起细胞丰富区内的未分化牙髓间充质细胞终末分化为成牙本质细胞样细胞，并在牙髓内沉积骨样牙本质。骨样牙本质沉积物在髓腔内可类似于骨、骨样组织、前牙本质或牙本质。
诊断建议
骨样牙本质应根据骨样牙本质形成区域的数量和大小进行诊断和分级。牙齿或成牙本质细胞的任何损伤（若存在）应单独诊断和分级，并应在病理学描述中明确两者之间的关联。
参考切片图（2 张）
查看英文原文
Comment
Osteodentin is formed after injury to the pulp or displacement of odontoblasts. If a tooth fractures, the pulp chamber will fill with this material in order to seal it off. This type of reaction can also occur as a secondary reparative response to add strength to teeth with altered or disrupted growth/eruption and/or teeth under altered biomechanical stress. The rate of osteodentin deposition depends on the intensity and duration of the stimulus; the more severe the stimulus/injury, the more rapid the rate of osteodentin deposition. The type of stimulus has an effect on the architecture and structure of the osteodentin. If the stimulus is a carious lesion, there is extensive destruction of dentin and damage to the pulp, due to the differentiation of bacterial metabolites and toxins. Thus, osteodentin is deposited rapidly, with a sparse and irregular tubular pattern and some cellular inclusions. After rapid deposition, odontoblasts become trapped in the newly formed matrix, and the tubular pattern becomes obscured or distorted. Formation may be solitary ( Figure 1 and Figure 2 , arrows), multiple, or diffuse ( Figure 3 and Figure 4 , arrows). Some test articles can directly or indirectly cause undifferentiated pulp mesenchymal cells within the cell-rich zone to terminally differentiate into odontoblast-like cells and deposit osteodentin within the pulp. Osteodentin deposits may resemble bone, osteoid, predentin, or dentin in the pulp cavity.
Recommendation
Osteodentin should be diagnosed and graded based on the number and size of areas of osteodentin formation. Any damage to the tooth or odontoblasts, if present, should be diagnosed and graded separately, and the association between the two should be made clear in the pathology narrative.
牙齿发育不良Dental Dysplasia 牙齿其他
描述（中文）
牙齿发育不良（dental dysplasia）（Figure 1、Figure 2、Figure 3、Figure 4）是一种常见的牙齿慢性退行性改变，主要累及切齿，可发生于创伤或炎症之后。它代表受损或移位牙源性组织的异常发育，其特征为牙本质、牙骨质和类骨质（来自牙槽骨）的异常沉积。它可以是单侧或双侧的。具有高冠齿列（hypsodont dentition）的物种，其切齿特别容易发生发育不良性改变，因为形成器官在动物整个生命周期中持续存在。啮齿类的上切齿比下齿更易遭受创伤性损伤，因为颅骨为牙齿提供的支持基础较不稳定。上颌切齿正常功能所需的背侧骨性支持是坚固的，但牙齿的侧方支持主要来自软组织，易受创伤性损伤和移位。当切齿受伤时，牙器官的残余部分可能继续尝试形成牙齿，尽管由于细胞或组织移位而表现异常。此外，通常还存在类似骨折愈合的一般性愈合反应，这常常解释此类病变中骨、牙本质或骨牙本质（osteodentin）的增多。在某些动物中，发育不良的牙齿物质在正常牙齿位置邻近形成大的实性团块。牙本质、牙骨质和类骨质并不总能轻易相互区分。在牙齿团块相关部位观察到牙周脓肿，部分伴有向鼻腔的穿孔和严重鼻炎。饲喂粉状饲料（减少了切齿的正常磨损）以及反复修剪过度生长的切齿，被认为促成了该病症的发生率。牙齿发育不良必须与牙瘤（odontoma）相鉴别。“牙瘤”一词指的是大多数权威认为的类似肿瘤的错构瘤性畸形。牙瘤的特征是牙器官的增生性冗余，进展至釉质和牙本质形成的阶段。大小和细胞密度/增殖活性是区分牙瘤与牙齿发育不良的标准。一般而言，牙齿发育不良类似于尝试性修复（令人联想到伴有大量致密骨/骨牙本质的骨折骨痂），并带有一些残留的活跃牙器官组织。“牙瘤”的诊断保留用于较大、细胞更丰富的团块，这些团块似乎增殖超出了发育中牙齿或牙齿骨折尝试性修复的预期范围。由于膨胀，牙瘤可以是破坏性团块。
诊断建议
牙齿发育不良应当根据发育不良牙齿的数量和大小进行诊断和分级。
参考切片图（2 张）
查看英文原文
Comment
Dental dysplasia ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is a common, chronic, degenerative change of the teeth, mainly the incisors, that can occur after trauma or inflammation. It represents abnormal development of injured or displaced odontogenic tissues and is characterized by abnormal deposits of dentin, cementum, and osteoid (from the alveolar bone). It can be unilateral or bilateral. The incisors of species with hypsodont dentition are particularly prone to dysplastic changes because of the persistence of the formative organ throughout the animal’s life. The upper incisors of rodents are more susceptible to traumatic injury than the lower teeth because the bones of the skull provide a less stable base of support. The dorsal bony support of the maxillary incisors, which is needed for normal function, is solid, but the lateral support of the teeth is derived mainly from the soft tissue and is susceptible to traumatic injury and displacement. When an incisor is injured, what remains of the dental organ may continue to attempt tooth formation, although it is abnormal because of cell or tissue displacement. In addition, there is often a general healing response, similar to fracture healing, and this often accounts for the increased bone, dentin, or osteodentin in these lesions. In some animals, dysplastic dental material forms large solid masses adjacent to the normal tooth position. Dentin, cementum, and osteoid cannot always be readily distinguished from one another. Periodontal abscesses, some with perforation into the nasal cavities and severe rhinitis, were observed in association with the dental masses. Feeding powdered ration, which reduced the normal wearing of the incisors, and repeated clipping of overgrown incisors were believed to contribute to the incidence of this condition. Dental dysplasia must be differentiated from odontoma. The term "odontoma" refers to what most authorities consider a hamartomatous malformation that resembles a neoplasm. Odontomas are characterized by proliferative redundancies of the dental organ that progress to the stage of both enamel and dentin formation. Size and cellularity/proliferative activity are criteria for differentiating odontomas from dental dysplasia. In general, dental dysplasia resembles attempted repair (reminiscent of a fracture callus with abundant dense bone/osteodentin) with some residual active dental organ tissue. The diagnosis of "odontoma" is reserved for larger, more cellular masses that appear to be proliferating beyond what one would expect for a developing tooth or attempted repair of a tooth fracture. Because of expansion, odontomas can be destructive masses.
Recommendation
Dental dysplasia should be diagnosed and graded based on the number and size of the dysplastic teeth.
纤维化Fibrosis 牙齿纤维化
描述（中文）
肺泡内的纤维化（Figure 1、Figure 2、Figure 3、Figure 4）可能是影响切牙或磨牙牙根的吸收所致。吸收可由错位咬合、感染或创伤（包括医源性骨折）引发。吸收可进展至牙齿完全缺失，并由纤维结缔组织和/或骨替代。炎症可伴随纤维化出现（Figure 3、Figure 4）。
诊断建议
当纤维化在病变中显著，或已进展至纤维化为唯一现存病变的程度时，应当对其进行诊断并分级。若纤维化仅为炎症的次要成分，则不必单独诊断，但应在病理描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Fibrosis within the alveolus ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) may be the result of resorption affecting the incisor or molar roots. Resorption may be initiated by malocclusion, infection, or trauma (including iatrogenic fracture). Resorption may progress to complete loss of the tooth and replacement with fibrous connective tissue and/or bone. Inflammation may accompany the fibrosis ( Figure 3 and Figure 4 ).
Recommendation
Fibrosis should be diagnosed and graded when it is prominent in a lesion or if it has progressed to the point that fibrosis is the only lesion present. If fibrosis is a minor component of inflammation, it is not necessary to diagnose it separately, though it should be described in the pathology narrative.
血管扩张Angiectasis 牙齿扩张
描述（中文）
牙髓位于牙髓腔内，由纤细的结缔组织构成，其间散布小血管、淋巴管、感觉神经和原始结缔组织细胞。牙齿的血管扩张（angiectasis，血管扩张症）表现为牙髓腔内大小不一、扩张的血管腔隙，内衬单层分化良好的内皮（Figure 1、Figure 2）。血管数量无明显增多，器官间质未发生改变。牙髓血管扩张是一种常见的偶然性发现。血管扩张与血管瘤之间的区别可能并不明确。血管瘤往往呈边界清楚、无包膜的肿块，由紧密排列的扩张血管腔隙构成。每个血管腔隙均被单层外观正常的内皮细胞所包绕并衬覆，这些内皮细胞排列于胶原性间隔上，间隔通常较薄，但部分具有宽阔的胶原性间质。血管扩张通常不表现为边界清楚的肿块，因为扩张的血管通道常不规则地穿行于结缔组织之中。
诊断建议
血管扩张一旦出现即应作出诊断并给予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
The dental pulp is located in the pulp cavity and is composed of delicate connective tissue interspersed with small blood vessels, lymphatics, sensory nerves, and primitive connective tissue cells. Angiectasis (vascular ectasia) of the tooth consists of variable-sized, dilated vascular spaces lined by a single layer of well-differentiated endothelium ( Figure 1 and Figure 2 ) in the pulp cavity. There is no apparent increase in numbers of vessels, and the stroma of the organ is unaltered. Angiectasis in the pulp is a common incidental finding. The difference between angiectasis and hemangioma can be unclear. Hemangiomas tend to be well-circumscribed unencapsulated masses composed of tightly packed dilated vascular spaces. Each vascular space is enclosed and lined by a single layer of normal-appearing endothelial cells aligned on collagenous septa, which are usually thin, although some have broad collagenous stroma. Angiectasis does not usually present as a well-circumscribed mass, as the dilated vascular channels often course irregularly through connective tissue.
Recommendation
Angiectasis should be diagnosed and given a severity grade whenever present.
上皮增生Epithelium Hyperplasia 腺胃增生
描述（中文）
在NTP小鼠研究中，腺胃病变相当罕见。腺胃黏膜增生在对照组中不常见，但可见于再生性增生，例如溃疡或糜烂边缘处。腺体增生的特征为黏膜内腺体密度增加。在大鼠中，增生可能是癌前病变。小鼠中偶见局灶性（focal）增生。然而，在小鼠中这不被视为癌前改变；在伴有腺胃癌的研究中其发生率并未增加，且尚未观察到从局灶性增生进展为腺癌。
诊断建议
腺胃增生的诊断和分级基于病变范围及胃腺内细胞数量。当诊断为非典型性（atypical）增生时，应在病理描述中清楚描述其非典型性特征（见胃，腺胃－上皮－增生，非典型性）。相关病变，如坏死和炎症，应单独诊断。如果认为增生继发于坏死或炎症（例如再生性），应在病理描述中明确说明。相关链接：胃，腺胃－上皮－增生，非典型性
参考切片图（2 张）
查看英文原文
Comment
Glandular stomach lesions are quite rare in NTP mouse studies. Hyperplasia of the glandular stomach mucosa is not common in controls but may be seen in regenerative hyperplasia, such as at the margin of an ulcer or erosion. Glandular hyperplasia is characterized by an increase in density of glands within the mucosa. In rats, hyperplasia may be a preneoplastic lesion. Focal hyperplasia is seen occasionally in mice. However, in mice this is not considered to be a preneoplastic change; the incidence is not increased in studies with adenocarcinomas of the glandular stomach, and progression from focal hyperplasia to adenocarcinoma has not been observed.
Recommendation
Hyperplasia of the glandular stomach is diagnosed and graded based on the extent of the lesion and the number of cells within the gastric glands. When atypical hyperplasia is diagnosed, the atypical features should be clearly described in the pathology narrative (see Stomach, Glandular Stomach - Epithelium - Hyperplasia, Atypical ). Associated lesions, such as necrosis and inflammation, should be diagnosed separately. If the hyperplasia is thought to be secondary to necrosis or inflammation (e.g., regenerative), it should be made clear in the pathology narrative. Related Links: Stomach, Glandular Stomach - Epithelium - Hyperplasia, Atypical
上皮细胞质空泡化Epithelium Vacuolation Cytoplasmic 腺胃空泡化
描述（中文）
细胞质空泡化通常被认为是变性的一种早期形式。细胞质空泡化（Figure 1、Figure 2）表现为细胞因液体超载而导致的细胞大小和体积增加，这种液体超载是由于细胞未能维持正常稳态并调节液体的进入和排出所致。在组织学上，细胞增大，受累细胞的细胞质内含有半透明空泡。这些空泡可能代表扩张的内质网或高尔基体，或肿胀的线粒体，提示细胞损伤。在某些情况下，空泡可能代表小脂滴。需要电子显微镜才能明确鉴定空泡的真实性质。
诊断建议
无论何时出现，该变化都应诊断为“腺胃，上皮——空泡化，细胞质”，并根据细胞肿胀程度以及受累区域的范围和数量进行分级。如果存在其他变性证据（例如细胞脱落或丢失，或核改变），该病变可诊断为变性。如果两个或多个病变（例如细胞质空泡化、囊泡、大疱、坏死、溃疡、炎症）被认为是同一病变的不同表现，研究病理学家应在叙述中详细说明。如果炎症是病变的显著组成部分，则应单独诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Cytoplasmic vacuolation is generally considered to be an early form of degeneration. Cytoplasmic vacuolization ( Figure 1 and Figure 2 ) manifests as increased cell size and volume resulting from an overload of fluid caused by a failure of the cell to maintain normal homeostasis and regulate the ingress and excretion of fluid. Histologically, cells are enlarged, and the cytoplasm of affected cells contains translucent vacuoles. The vacuoles may represent distended endoplasmic reticulum or Golgi or swollen mitochondria, indicative of cell injury. In some cases, the vacuoles may represent small lipid droplets. Electron microscopy is required to definitively identify the true nature of the vacuoles.
Recommendation
Whenever present, this change should be diagnosed as "glandular stomach, epithelium - vacuolation, cytoplasmic" and graded based on the degree of cellular swelling and extent and number of areas affected. If there is other evidence of degeneration (e.g., sloughing or loss of cells, or nuclear changes), the lesion may be diagnosed as degeneration. If two or more lesions (e.g., cytoplasmic vacuolation, vesicles, bulla, necrosis, ulcers, inflammation) are considered different manifestations of the same lesion, the study pathologist should explain this in detail in the narrative. If inflammation is a prominent component of the lesion, then it should be diagnosed and graded separately.
上皮非典型增生Epithelium Hyperplasia Atypical 腺胃增生
描述（中文）
在 NTP 小鼠研究中，腺胃病变相当罕见。在胃中，非典型增生（非典型性（atypical） hyperplasia）的主要特征包括细胞异型性（cellular atypia）、异常分化（abnormal differentiation）和黏膜结构紊乱（disorganized mucosal architecture）。细胞异型性的特征为核多形性、核深染和核层叠、核质比增高以及细胞和核极性的丧失。异常分化的特征为黏膜正常分泌产物减少或改变。黏膜结构紊乱的特征包括隐窝结构不规则、腺体“背靠背”（back-to-back）、隐窝出芽和分支以及腔内和表面乳头状生长。在接受致癌物处理的大鼠腺胃中可见非典型增生。
诊断建议
非典型增生的诊断和分级基于腺上皮细胞的增殖程度、结构紊乱程度和异型性程度。当诊断为非典型增生时，应在病理描述中清楚描述其非典型特征。相关病变，如坏死和炎症，应单独诊断。如果认为增生继发于坏死或炎症（例如再生性），则应在病理描述中明确说明。
参考切片图（2 张）
查看英文原文
Comment
Glandular stomach lesions are quite rare in NTP mouse studies. In the stomach, the principal features of atypical hyperplasia include cellular atypia, abnormal differentiation, and disorganized mucosal architecture. Cellular atypia is characterized by nuclear pleomorphism, hyperchromasia and stratification of nuclei, increased nuclear-cytoplasmic ratio, and loss of cellular and nuclear polarity. Abnormal differentiation is distinguished by reduction or alteration in the normal secretory products of the mucosa. The features of disorganized mucosal architecture include irregularity of crypt structure, "back-to-back" glands, budding and branching of crypts and intraluminal, and surface papillary growths. Atypical hyperplasia can be found in the glandular stomach of rats treated with carcinogens.
Recommendation
Atypical hyperplasia is diagnosed and graded based on the degree of proliferation, disorganization, and atypia of the glandular epithelial cells. When atypical hyperplasia is diagnosed, the atypical features should be clearly described in the pathology narrative. Associated lesions, such as necrosis and inflammation, should be diagnosed separately. If the hyperplasia is thought to be secondary to necrosis or inflammation (e.g., regenerative), this should be made clear in the pathology narrative.
出血Hemorrhage 腺胃出血
描述（中文）
以固有层（Figure 1）、黏膜下层（Figure 2）或胃壁肌层内游离红细胞为特征的出血（hemorrhage）不常见，通常继发于与处理相关的炎症（inflammation）、糜烂（erosion）、溃疡（ulceration）、坏死（necrosis）或血栓形成（thrombosis）（Figure 3、Figure 4，箭头）。
诊断建议
出血（hemorrhage）应予以诊断并分级。坏死或炎症区域内的出血通常不单独诊断，除非它是病变的显著组成部分，但应在病理学描述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage characterized by free red blood cells in the lamina propria ( Figure 1 ), submucosa ( Figure 2 ) or muscular wall of the stomach is uncommon and usually secondary to treatment-related inflammation, erosion, ulceration, necrosis, or thrombosis ( Figure 3 and Figure 4 , arrows).
Recommendation
Hemorrhage should be diagnosed and graded. Hemorrhage in an area of necrosis or inflammation is usually not diagnosed separately, unless it is a prominent component of the lesion, but should be described in the pathology narrative.
囊肿Cyst 腺胃囊肿
描述（中文）
腺胃囊肿通常见于幽门窦，可延伸至黏膜下层，内衬分化良好的上皮细胞。胃底腺囊肿的发生率随动物年龄增长而升高，几乎所有15月龄以上的大鼠均存在。囊肿内衬立方至扁平的主细胞、壁细胞或黏液细胞。囊腔内含黏液或混合性炎性渗出物。偶见囊肿周围纤维化及慢性炎性细胞浸润。老年大鼠的腺囊肿常伴有矿物质沉积。腺囊肿与腺体扩张的鉴别在于：囊肿通常为单发、体积较大，内衬变薄的上皮；而腺体扩张通常累及多个腺体，扩张的轮廓常不规则，即不具有界限清楚的圆形结构（见胃，腺胃-腺体-扩张）。与腺体扩张相比，囊肿与处理因素相关的可能性较小。
诊断建议
囊肿应予以诊断，但通常不分级。相关链接：胃，腺胃-腺体-扩张
参考切片图（1 张）
查看英文原文
Comment
Cysts in the glandular stomach are usually found in the pyloric antrum, extend into the submucosa, and are lined by well-differentiated epithelial cells. Glandular cysts in the fundus occur with increased frequency as the animal ages and are present in virtually all rats older than 15 months. The cysts are lined by cuboidal to flattened chief, parietal, or mucous cells. The lumen contains mucus or mixed inflammatory exudates. Occasionally cysts are surrounded by fibrosis and chronic inflammatory infiltrates. Glandular cysts are frequently associated with mineralized deposits in aged rats. Glandular cysts are differentiated from glandular dilation, as the cysts are usually solitary, larger, and lined by attenuated epithelium, whereas glandular dilation usually involves multiple glands and the dilatation is often irregular in profile, that is, does not have a well-circumscribed circular structure (see Stomach, Glandular Stomach - Glands - Dilation ). Cysts are less likely to be associated with treatment than is glandular dilation.
Recommendation
Cysts should be diagnosed but typically are not graded. Related Links: Stomach, Glandular Stomach - Glands - Dilation
坏死Necrosis 腺胃坏死
描述（中文）
坏死的特征性表现为核的改变，包括核固缩（pyknosis）、核碎裂（karyorrhexis）、核溶解（karyolysis），或核溶解后期核消失。在H&E切片中，早期坏死细胞的胞质呈均质粉红色。胞质蛋白的降解最终使坏死细胞呈现苍白、鬼影样外观。坏死细胞通常失去与基底膜及邻近细胞的黏附。细胞破裂、细胞完整性丧失是细胞死亡最明显的证据。坏死可表现为散在分布于整个黏膜的坏死细胞（Figure 1、Figure 2，箭头），或累及黏膜和/或肌壁的局灶性（focal）区域。血栓形成（thrombosis）（Figure 3、Figure 4，箭头）可导致胃黏膜坏死（Figure 3）或胃黏膜及胃壁均发生坏死（Figure 4）。
诊断建议
如果坏死上皮仍然存在且至少部分附着于其下方的固有层，或者坏死并非特别以腺胃上皮为中心（即主要累及胃壁），则应诊断上皮坏死，而非糜烂和溃疡。如果坏死符合继发于血栓形成的缺血（梗死），则应诊断坏死（而非梗死），但描述中应说明该病变符合梗死，即使血栓不在切片平面内。严重程度分级取决于病变的总体大小和受累区域的数量。继发性病变，如出血、水肿、纤维化或炎症，通常不单独诊断，除非它们是病变的显著组成部分。但应在描述中予以记述。
参考切片图（2 张）
查看英文原文
Comment
Necrosis is characterized by nuclear changes of pyknosis, karyorrhexis, karyolysis, or absence of nucleus in the later stage of karyolysis. The cytoplasm in early necrosis is homogeneous pink in H&E sections. Degradation of cytoplasmic proteins eventually gives the necrotic cell a pale, ghostlike appearance. Necrotic cells usually lose their adherence to basement membranes and neighboring cells. Rupture of cells with loss of cell integrity is the most obvious evidence of cell death. Necrosis can involve scattered necrotic cells throughout the mucosa ( Figure 1 and Figure 2 , arrows) or a focal area involving the mucosa and/or muscular wall. Thrombosis ( Figure 3 and Figure 4 , arrows) can result in necrosis of the stomach mucosa ( Figure 3 ) or both the mucosa and the wall of the stomach ( Figure 4 ).
Recommendation
Necrosis of epithelium is diagnosed instead of erosion and ulcer if the necrotic epithelium is still present and at least partially attached to the underlying lamina propria or if the necrosis is not particularly centered on the epithelium of the glandular stomach (i.e., involves the wall primarily). If the necrosis is consistent with ischemia secondary to thrombosis (infarction), necrosis should be diagnosed (rather than infarct), but the narrative should state that the lesion is consistent with an infarct, even if the thrombus is not in the plane of the section. Severity grading would depend on the overall size of the lesion and number of areas affected. Secondary lesions, such as hemorrhage, edema, fibrosis, or inflammation, are usually not diagnosed separately unless they are prominent components of the lesion. They should, however, be described in the narrative.
异位组织Ectopic Tissue 腺胃其他
描述（中文）
异位胰腺（Figure 1、Figure 2）、肝脏（Figure 3、Figure 4）或肠（Figure 5、Figure 6）罕见发生于腺胃的黏膜下层。腺胃黏膜下层/固有层中出现肝细胞在B6C3F1小鼠及其他小鼠品系中已有报道，属罕见现象。在对照组和给药组、雌雄两性小鼠中均发现胃内肝细胞。该病变可能源于原胃细胞类型的化生，但更可能是发育缺陷的结果，被视为偶发性发现。所有病例均须排除肝脏肿瘤的侵袭或转移，即使细胞不呈现肿瘤性外观。由腺泡和导管细胞构成的异位胰腺组织也曾在小鼠胃黏膜下层中被描述。肠组织灶可发生于腺胃（Figure 5、Figure 6）。这被视为与胃内肝/胰腺异位灶类似的偶发性先天性病变。其与肠化生的鉴别在于其发生于黏膜上皮之外，且不伴有上皮的其他改变，如增生、非典型改变（异型增生）或胃癌。
诊断建议
异位组织无论何时出现，均应诊断但不进行分级。诊断应注明异位组织的类型。
参考切片图（2 张）
查看英文原文
Comment
Ectopic pancreas ( Figure 1 and Figure 2 ), liver ( Figure 3 and Figure 4 ) or intestines ( Figure 5 and Figure 6 ) occur rarely in the submucosa of the glandular stomach. Hepatocytes in the submucosa/lamina propria of the glandular stomach have been reported as a rare occurrence in the B6C3F1 mouse, as well as other mouse strains. Mice from control and treatment groups and both sexes have been found with gastric hepatocytes. This condition may arise from metaplasia of a primary stomach cell type but more likely is the result of a developmental defect and is considered an incidental finding. Invasion or metastasis from a liver neoplasm must be ruled out in all cases, even if the cells do not appear neoplastic. Ectopic pancreatic tissue, composed of acinar and ductal cells, has also been described in the submucosa of the mouse stomach. Foci of intestinal tissue can occur in the glandular stomach ( Figure 5 and Figure 6 ). This is considered an incidental congenital lesion similar to hepatic/pancreatic ectopic foci in the stomach. It is differentiated from intestinal metaplasia by occurrence outside of the mucosal epithelium and a lack of association with other changes in the epithelium, such as hyperplasia, atypical changes (dysplasia), or gastric carcinoma.
Recommendation
Whenever present, ectopic tissue should be diagnosed but not graded. The diagnosis should be modified with the type of ectopic tissue.
异物Foreignbody 腺胃其他
描述（中文）
毛发（Figure 1、Figure 2，箭头）或饲料物质可继发于灌胃操作所致的损伤或外源性化学物所致的溃疡形成而嵌入腺胃壁。溃疡形成过程使下方的固有层和肌层暴露于胃内容物，并使毛发和食物物质得以穿透进入溃疡下方形成的肉芽组织。
诊断建议
原发性异物应当诊断，但不进行分级。如果异物引起了显著的炎症反应，则异物和炎症两者均予诊断。在上述所示病例中，异物（毛发）和炎症（肉芽肿性）两者均应诊断。诸如毛发或饲料物质等被动附着于溃疡表面的异物不应单独诊断；可在叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Hair ( Figure 1 and Figure 2 , arrows) or feed material can become embedded in the wall of the glandular stomach secondary to injury from a gavage procedure or ulceration from xenobiotics. The process of ulceration exposes the underlying propria and muscular wall to gastric contents and allows hair and food material to penetrate into the granulation tissue, which forms beneath the ulcer.
Recommendation
A primary foreign body should be diagnosed but not graded. If a foreign body causing a significant inflammatory response, then both the foreign body and inflammation are diagnosed. In the case illustrated above, both the foreign body (hair) and the inflammation (granulomatous) should be diagnosed. A foreign body such as hair or feed material that is passively adhered to an ulcerated surface should not be diagnosed separately; it can be described in the narrative.
扩张Dilation 腺胃扩张
描述（中文）
扩张的腺体通常累及胃腺的基底部至中部，可因清亮液体、分泌物或细胞碎片而膨胀（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6）。这通常以局灶性（focal）或多灶性（multifocal）的形式发生，在大鼠中可能被视为一种衰老性改变。腺体扩张通常累及多个腺体，且扩张的轮廓常不规则（即不是界限清楚的圆形结构）。腺体囊肿（见 Stomach, Glandular Stomach - Glands - Cyst）通常为单发、较大，并由变薄的皮细胞被覆。
诊断建议
只要存在，腺体扩张就应诊断并分级；分级依据为扩张腺体的数量和大小以及受累黏膜的总面积。相关链接：Stomach, Glandular Stomach - Glands - Cyst
参考切片图（2 张）
查看英文原文
Comment
Dilated glands usually involve the basal to midportion of the gastric glands, which may become distended with clear fluid, secretion, or cellular debris ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ). This usually occurs as a focal or multifocal event and may be seen as an aging change in rats. Glandular dilation usually involves multiple glands, and the dilatation is often irregular in profile (i.e., not a well-circumscribed circular structure). Glandular cysts (see Stomach, Glandular Stomach - Glands - Cyst ) are usually solitary, larger, and lined by attenuated epithelium.
Recommendation
Whenever present, glandular dilation should be diagnosed and graded; grading is based on the number and size of dilated glands and total area of mucosa affected. Related Links: Stomach, Glandular Stomach - Glands - Cyst
水肿Edema 腺胃水肿
描述（中文）
水肿液（Edema fluid）在制片过程中常丢失，表现为组织中的透亮空隙，尽管蛋白含量较高的水肿液在切片中呈较强的嗜酸性。水肿是调节血浆、间质和细胞之间正常液体分布的任一因素发生改变的结果，例如血管通透性增加、血管内流体静压升高、血管内渗透压降低和淋巴引流减少。因此，任何引起上述改变的化学物均可导致水肿。水肿常是炎症的早期组成部分。
诊断建议
每当水肿作为其本身的显著病变存在时，应当对其进行诊断和分级。严重程度分级取决于水肿液分离组织的范围及受累组织的总量。与炎症相关的轻微水肿不单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Edema fluid is often lost in processing and appears as clear spaces in tissues, although edema fluid with a higher protein content will be more eosinophilic in sections. Edema is the result of alteration in any of the factors that regulate normal fluid distribution among the plasma, interstitium, and cells, such as increased vascular permeability, increased intravascular hydrostatic pressure, decreased intravascular osmotic pressure, and decreased lymphatic drainage. Therefore, any chemical resulting in the above changes can cause edema. Edema is often an early component of inflammation.
Recommendation
Whenever present as a prominent finding of its own, edema should be diagnosed and graded. Severity grade depends on the extent of separation of the tissues by the edema fluid and overall amount of tissue affected. Minor edema associated with inflammation is not diagnosed separately.
淀粉样物质Amyloid 腺胃其他
描述（中文）
淀粉样物质沉积（淀粉样变性（amyloidosis））是一种全身性疾病，在B6C3F1、BALB/c和C3H小鼠中罕见，但在CD-1、A、Swiss Webster、SJL和B6小鼠中常见，并且可以是死亡的原因。其发生率可因群养雄性动物间的打斗以及外寄生虫感染而升高。淀粉样物质表现为无定形、嗜酸性、玻璃样、细胞外物质，随着其进行性蓄积，导致邻近细胞和组织的压迫性萎缩。全身性（系统性）淀粉样物质沉积可见于许多组织，包括胃肠道、脾、肝、肾、舌和肠系膜淋巴结。腺胃中的淀粉样物质沉积（Figure 1、Figure 2）通常发生于固有层和黏膜下层。肾小球中的淀粉样物质沉积通常是伴有淀粉样变性的动物死亡的原因。刚果红（Congo red）将淀粉样物质染成橙色至橙红色，在偏振光下呈现浅绿色，即所谓的苹果绿荧光。
诊断建议
无论何时出现，淀粉样物质沉积均应诊断为“amyloid”，并根据淀粉样物质沉积的范围进行分级。继发于淀粉样物质沉积的细胞丢失不应单独诊断，而应在叙述性描述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Amyloid deposition (amyloidosis) is a systemic disease that is rare in B6C3F1 BALB/c, and C3H mice but common in CD-1, A, Swiss Webster, SJL, and B6 mice and can be a cause of death. The incidence can be increased in association with fighting among group-housed males and with ectoparasitism. Amyloid appears as an amorphous, eosinophilic, hyaline, extracellular substance that, with progressive accumulation, results in pressure atrophy of adjacent cells and tissue. Generalized (systemic) amyloid deposition can be seen in many tissues, including gastrointestinal tract, spleen, liver, kidney, tongue, and mesenteric lymph node. Amyloid deposition in the glandular stomach ( Figure 1 and Figure 2 ) generally occurs in the lamina propria and submucosa. Amyloid deposits in the glomeruli of the kidney are usually the cause of death in animals that die with amyloidosis. Congo red stains amyloid orange to orange red and under polarized light imparts a light green, so-called apple green fluorescence.
Recommendation
Whenever present, amyloid deposits should be diagnosed as "amyloid" and graded based on the extent of the amyloid deposits. The loss of cells secondary to amyloid deposition should not be diagnosed separately but should be described in the narrative.
溃疡Ulcer 腺胃溃疡
描述（中文）
在小鼠和F344/N大鼠的NTP研究中，腺胃溃疡的自发性发生并不常见。溃疡主要见于受处理的大鼠，并已被实验性诱导作为人类溃疡的模型。溃疡（Figure 1、Figure 2）定义为整个上皮层厚度丧失，深达或穿透基底膜和黏膜肌层，而糜烂（见Stomach, Glandular Stomach - Erosion）为上皮的部分厚度丧失。相比之下，如果坏死上皮仍然存在且至少部分附着于其下的固有层，则诊断为上皮坏死而非溃疡。细菌感染可继发于糜烂或溃疡，原因包括灌胃操作造成的局部创伤或坏死/缺血。大鼠胃内的固有细菌通常仅见于附着于最靠近管腔的黏膜表面，而不见于胃小凹内。发生糜烂/溃疡后，细菌可进入黏膜和胃壁的更深部位。产生糜烂和溃疡的化合物可通过影响黏膜血流、黏膜细胞动力学、黏液或酸/碳酸氢盐分泌，或维持黏液屏障而发挥作用。高脂饮食、慢性泛酸缺乏、生糖氨基酸缺乏、血小板活化因子、胆汁盐反流增加以及外分泌胰腺功能降低与溃疡发生相关，但仅在迷走神经支配完整时如此。溃疡的介质可能是花生四烯酸代谢的脂氧合酶途径的代谢产物。白三烯阻断剂类药物可预防某些致溃疡物引起的溃疡。
诊断建议
腺胃溃疡应根据病变的范围和分布进行诊断和分级。水肿、炎症和邻近上皮的增生不应单独诊断，除非它们是病变的显著组成部分。如果坏死上皮仍然存在且至少部分附着于其下的固有层，则诊断为上皮坏死而非溃疡。相关链接：Stomach, Glandular Stomach - Erosion
参考切片图（2 张）
查看英文原文
Comment
Spontaneous occurrence of ulceration of the glandular stomach is uncommon in NTP studies in mice and F344/N rats. Ulceration is seen primarily in treated rats and has been experimentally induced as a model for ulcer in humans. An ulcer ( Figure 1 and Figure 2 ) is defined as the loss of the entire epithelial thickness down to or through the basement membrane and muscularis mucosa, whereas an erosion (see Stomach, Glandular Stomach - Erosion ) is a partial thickness loss of epithelium. In comparison, necrosis of epithelium is diagnosed instead of ulceration if the necrotic epithelium is still present and at least partially attached to the underlying lamina propria. Bacterial infections can occur secondary to erosion or ulceration due to local trauma from a gavage procedure or necrosis/ischemia. Indigenous bacteria in the stomach of the rat are normally found adherent to only the most luminal mucosa but not in the gastric pits. Following erosion/ulceration, bacteria can gain access to deeper portions of the mucosa and stomach wall. Compounds that produce erosions and ulcers can act via effects on mucosal blood flow, mucosal cell kinetics, mucus or acid/bicarbonate secretion, or maintenance of the mucus barrier. High-fat diets, chronic pantothenic acid deficiency, deficiency of gluconeogenic amino acids, platelet-activating factor, increased reflux of bile salts, and reduced exocrine pancreatic function are associated with ulceration but only with intact vagal innervations. The mediators of ulceration may be metabolites of the lipooxygenase pathway of arachidonic acid metabolism. Pharmaceutical agents that are leukotriene blockers prevent ulceration by some ulcerogens.
Recommendation
Ulceration of the glandular stomach should be diagnosed and graded based upon the extent and distribution of the lesion. Edema, inflammation, and hyperplasia of the adjacent epithelium should not diagnosed separately unless they are a prominent component of the lesion. Necrosis of epithelium is diagnosed instead of ulceration if the necrotic epithelium is still present and at least partially attached to the underlying lamina propria. Related Links: Stomach, Glandular Stomach - Erosion
炎症Inflammation 腺胃炎症
描述（中文）
炎症（Figure 1、Figure 2、Figure 3、Figure 4）可发生于腺胃，如同在胃肠道其他部位一样。病变可为自发性（特发性）、与灌胃操作相关，或由直接/间接化学毒性所致。炎症可诊断为急性、化脓性、慢性、慢性活动性或肉芽肿性。在急性炎症中，主要浸润细胞为中性粒细胞，尽管也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但中性粒细胞聚集，且其中许多发生变性（化脓性渗出物）。渗出物还可能含有细胞碎片，既来自 resident 细胞群体，也来自浸润的白细胞；含纤维蛋白的蛋白性液体；较少的巨噬细胞；偶见的淋巴细胞或浆细胞；以及可能的感染因子。肉眼上，这些病变将以脓液的存在为特征。在渗出物周围的组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大的、活化的巨噬细胞、上皮样巨噬细胞或多核巨细胞。嗜酸性粒细胞性炎症（Figure 3、Figure 4）不属于NTP通常诊断的五种主要炎症类型之一，但如果炎症细胞主要为嗜酸性粒细胞，则可作出该诊断。只要在叙述中讨论了偏离的理由，病理学家可以偏离5种主要炎症诊断。
诊断建议
无论何时出现，炎症均应作出诊断，并给出严重程度分级和表明炎症持续时间或类型的修饰词（例如，急性（acute）、化脓性（suppurative）、慢性（chronic）、慢性 active或肉芽肿性（granulomatous））。严重程度分级取决于腺胃受累面积的范围、细胞浸润的密度以及组织改变的程度（例如，水肿、出血、变性、坏死）。与脓肿一致的病变诊断为化脓性炎症。偶尔，病理学家可能发现有必要使用不同于上述五种的修饰词。使用其他修饰词（如“eosinophilic”）的理由应在叙述中说明。糜烂或溃疡区域内的炎症通常不记录，除非炎症是病变的重要组成部分。
参考切片图（2 张）
查看英文原文
Comment
Inflammation ( Figure 1 , Figure 2 , Figure 3 and Figure 4 ) can occur in the glandular stomach as in elsewhere in the gastrointestinal tract. Lesions can be spontaneous (idiopathic), related to gavage procedure, or due to direct/indirect chemical toxicity. Inflammation can be diagnosed as acute, suppurative, chronic, chronic active, or granulomatous. In acute inflammation, the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate). The exudate may also contain cell debris, both from the resident cell populations and from infiltrating leukocytes; proteinaceous fluid containing fibrin; fewer macrophages; occasional lymphocytes or plasma cells; and, possibly, an infectious agent. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Eosinophilic inflammation ( Figure 3 and Figure 4 ) is not one of the five main types of inflammation ordinarily diagnosed by the NTP but may be diagnosed if the inflammatory cells are primarily eosinophils. The pathologist may deviate from the 5 main inflammation diagnoses as long as the reason for the deviation is discussed in the narrative.
Recommendation
Whenever present, inflammation should be diagnosed and given a severity grade and a modifier that indicates the duration or type of inflammation (e.g., acute, suppurative, chronic, chronic active, or granulomatous). The severity grade depends on the extent of area of glandular stomach affected, the density of the cellular infiltrate, and the extent of changes in the tissue (e.g., edema, hemorrhage, degeneration, necrosis). Lesions consistent with an abscess are diagnosed as suppurative inflammation. Occasionally, the pathologist may find it necessary to use different modifiers than the five stated above. The reasons for the use of other modifiers, such as "eosinophilic," should be explained in the narrative. Inflammation in areas of erosion or ulcer is not generally recorded unless the inflammation is a significant component of the lesion.
矿化Mineralization 腺胃矿化
描述（中文）
以局灶性聚集体或致密蓝染矿物质凝结物为特征的矿化，在老年大鼠胃的H&E染色切片中相当常见，此类矿化与胃腺的囊性扩张相关；小鼠和仓鼠偶尔也可见类似变化。当啮齿类动物存在矿物质代谢紊乱时，胃矿化可能变得显著（显著（marked）），尤其是在慢性进行性肾病和尿毒症时，这是由于钙磷代谢改变和甲状旁腺功能亢进所致。这些变化的特征为整个胃底、肌层和间质的血管发生矿化，呈与黏膜富含壁细胞区域平行的带状分布（Figure 1、Figure 2，箭头所示），但不累及贲门、胃窦或幽门。矿物质沉积物在环绕上皮和血管的基底膜周围形成。固有层因水肿而扩张，并出现间质纤维增生。胃腺扩张，伴壁细胞肿胀和变性以及主细胞萎缩。发生腺上皮糜烂伴出血。胃矿化常伴有黏液细胞增生。
诊断建议
应当诊断矿化并根据矿化范围进行分级。继发于矿化的相关病变，如炎症或胃上皮细胞变性，不应单独诊断，而应在叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Mineralization characterized by focal aggregates or concretions of densely blue-staining mineral is fairly common in the H&E-stained sections from the stomachs of aged rats, where they are associated with cystic dilation of the gastric glands; mice and hamsters occasionally show similar changes. Gastric mineralization may become marked in rodents when there is disturbance in mineral metabolism, particularly with chronic progressive renal disease and uremia due to altered calcium-phosphorus metabolism and hyperparathyroidism. These changes are characterized by mineralization of the vessels throughout the gastric fundus, muscular tunics, and interstitium in a band paralleling the parietal-cell-rich region of the mucosa ( Figure 1 and Figure 2 , arrows) but not the cardia, antrum, or pylorus. Mineral deposits develop around basement membranes surrounding epithelium and blood vessels. The lamina propria becomes expanded by edema, and fibroplasia of the interstitium develops. The gastric glands become dilated with swelling and degeneration of parietal cells and atrophy of chief cells. Erosion of the glandular epithelium with hemorrhage occurs. Gastric mineralization is frequently accompanied by mucous cell hyperplasia.
Recommendation
Mineralization should be diagnosed and graded depending on the extent of mineralization. Associated lesions, such as inflammation or degeneration of gastric epithelial cells, that are secondary to the mineralization should not be diagnosed separately but should be described in the narrative.
神经内分泌细胞增生Neuroendocrine Cell Hyperplasia 腺胃增生
描述（中文）
神经内分泌细胞增生（hyperplasia of the neuroendocrine cells）表现为黏膜内神经内分泌细胞数量增多。神经内分泌细胞附着于黏膜基底膜，并嵌于黏液细胞、壁细胞和主细胞之间；部分神经内分泌细胞具有可达黏膜腔的胞质突起。由于其附着于基底膜，增生主要见于黏膜下半部。神经内分泌细胞在H&E染色下难以识别，但可通过特殊嗜银染色（Grimelius、Sevier-Munger）、免疫组织化学或电子显微镜识别。嗜银染色可显示胞质内的小颗粒。嗜铬粒蛋白（chromogranins）是构成神经分泌颗粒主要成分的蛋白质，因此抗嗜铬粒蛋白A（Chromogranin A）抗体用于在组织切片中识别神经内分泌细胞。腺胃神经内分泌细胞增生可由组胺2受体拮抗剂或质子泵抑制剂诱导，并见于NTP甲基丁香酚（methyleugenol）灌胃慢性研究。此外，甲基丁香酚研究中的大鼠和小鼠腺胃神经内分泌肿瘤增多。腺胃神经内分泌细胞增生不视为背景性病变。
诊断建议
神经内分泌细胞增生只要存在即应诊断并分级。分级应基于增生的神经内分泌细胞数量。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of the neuroendocrine cells consists of increased numbers of neuroendocrine cells in the mucosa. The neuroendocrine cells are attached to the mucosa basement membrane and are wedged between the mucous, parietal, and chief cells; some neuroendocrine cells have cytoplasmic extensions that reach the mucosa lumen. Because of their attachment to the basement membrane, hyperplasia will be noted primarily in the lower half of the mucosa. Neuroendocrine cells are difficult to recognize with H&E stains but are identifiable with special argyrophilic stains (Grimelius, Sevier-Munger), immunohistochemistry, or electron microscopy. Argyrophilic stains reveal small granules in the cytoplasm. Chromagranins are proteins that represent the predominant constituent of neurosecretory granules, so antibodies to Chromagranin A are used to identify neuroendocrine cells in tissue sections. Hyperplasia of the neuroendocrine cells of the glandular stomach can be induced with histamine 2 blockers or proton pump inhibitors and was seen in the NTP chronic methyleugenol gavage study. In addition, rats and mice in the methyleugenol study had an increase in neuroendocrine tumors of the glandular stomach. Hyperplasia of the neuroendocrine cells of the glandular stomach is not seen as a background lesion.
Recommendation
Neuroendocrine hyperplasia should be diagnosed and graded whenever present. Grading should be based on the number of hyperplastic neuroendocrine cells present.
糜烂Erosion 腺胃其他
描述（中文）
在小鼠和F344/N大鼠的NTP研究中，腺胃糜烂的自发性发生不常见。糜烂主要见于处理组大鼠。糜烂（Figure 1、Figure 2）是部分厚度的上皮缺失，相比之下，溃疡（见Stomach, Glandular Stomach - Ulcer）则是整个上皮厚度缺失，深达或穿透基底膜和黏膜肌层。相比之下，如果上皮的坏死部分仍然存在并至少部分附着于其下方存活的上皮，则应诊断为上皮坏死而非糜烂。细菌感染可继发于糜烂或溃疡，原因包括灌胃操作造成的局部创伤或坏死/缺血。大鼠胃内的固有细菌通常仅见于附着于最靠近管腔的黏膜表面，而不存在于胃小凹中。发生糜烂/溃疡后，细菌可进入黏膜和胃壁的更深部位。产生糜烂和溃疡的化合物可通过影响黏膜血流、黏膜细胞动力学、黏液或酸/碳酸氢盐分泌，或维持黏液屏障而发挥作用。高脂饮食、慢性泛酸缺乏、生糖氨基酸缺乏、血小板活化因子、胆汁盐反流增加以及外分泌胰腺功能降低与溃疡形成相关，但仅在迷走神经支配完整时如此。溃疡形成的介质可能是花生四烯酸代谢的脂氧合酶途径的代谢产物。据报道，大鼠幼仔与母鼠分离的日龄会影响其对制动应激诱导的胃糜烂发生的易感性。
诊断建议
腺胃糜烂应予以诊断，并根据病变的范围和分布进行分级。水肿、炎症和邻近上皮的增生不应单独诊断，除非它们是病变的显著组成部分。如果坏死上皮仍然存在并至少部分附着于其下方存活的上皮，则应诊断为上皮坏死而非糜烂。相关链接：Stomach, Glandular Stomach - Ulcer
参考切片图（2 张）
查看英文原文
Comment
Spontaneous occurrence of erosion of the glandular stomach is uncommon in NTP studies in mice and F344/N rats. Erosions are seen primarily in treated rats. An erosion ( Figure 1 and Figure 2 ) is a partial thickness of epithelial loss, compared with an ulcer (see Stomach, Glandular Stomach - Ulcer ), in which the entire epithelial thickness has been lost down to or through the basement membrane and muscularis mucosa. In comparison, necrosis of epithelium is diagnosed instead of erosion if the necrotic portion of the epithelium is still present and at least partially attached to the underlying viable epithelium. Bacterial infections can occur secondary to erosion or ulceration due to local trauma from a gavage procedure or necrosis/ischemia. Indigenous bacteria in the stomach of the rat are normally found adherent to only the most luminal mucosa but not in the gastric pits. Following erosion/ulceration, bacteria can gain access to deeper portions of the mucosa and stomach wall. Compounds that produce erosions and ulcers can act via effects on mucosal blood flow, mucosal cell kinetics, mucus or acid/bicarbonate secretion, or maintenance of the mucus barrier. High-fat diets, chronic pantothenic acid deficiency, deficiency of gluconeogenic amino acids, platelet-activating factor, increased reflux of bile salts, and reduced exocrine pancreatic function are associated with ulceration but only with intact vagal innervations. The mediators of ulceration may be metabolites of the lipooxygenase pathway of arachidonic acid metabolism. Age of maternal separation of rat pups from their mothers has been reported to affect susceptibility to development of immobilization-induced gastric erosions.
Recommendation
Erosion of the glandular stomach should be diagnosed and graded based on the extent and distribution of the lesions. Edema, inflammation, and hyperplasia of the adjacent epithelium should not be diagnosed separately unless they are a prominent component of the lesion. Necrosis of epithelium is diagnosed instead of erosion if the necrotic epithelium is still present and at least partially attached to the underlying viable epithelium. Related Links: Stomach, Glandular Stomach - Ulcer
纤维化Fibrosis 腺胃纤维化
描述（中文）
纤维化（fibrosis）发生于胃部，是结缔组织和上皮细胞坏死的结果，这些细胞是再生组织实质成分所必需的。坏死之后，该空间被纤维血管组织填充，其中含有许多新形成的毛细血管和成纤维细胞，产生不成熟的胶原基质。随着纤维化成熟，其血管减少、胶原增多，直至最终基本无血管，主要由致密胶原束和相对少量的成纤维细胞构成。溃疡形成和/或严重炎症可导致纤维化并伴有腺体组织丧失。
诊断建议
纤维化一旦出现即应诊断，并根据病变范围进行分级。纤维化作为另一原发病变（如炎症、溃疡形成或肿瘤形成）的次要成分时，不单独记录。纤维化区域中可能存在的腺体黏膜萎缩和炎症细胞不应单独诊断，除非它们是病变的显著成分。
参考切片图（2 张）
查看英文原文
Comment
Fibrosis occurs in the stomach as the result of necrosis of the connective tissue and epithelial cells required to regenerate the parenchymatous elements of the tissue. Following necrosis, the space is filled with fibrovascular tissue, which contains many newly formed capillaries and fibroblasts, producing an immature collagenous matrix. As fibrosis matures, it becomes less vascular and more collagenous until eventually it is fairly avascular and consists primarily of dense bundles of collagen and relatively low numbers of fibroblasts. Ulceration and/or severe inflammation can result in fibrosis with loss of glandular tissue.
Recommendation
Whenever present, fibrosis should be diagnosed and graded based on the extent of the lesion. Fibrosis as a minor component of another primary process, such as inflammation, ulceration, or neoplasia, is not documented separately. Atrophy of glandular mucosa and inflammatory cells that may be present in areas of fibrosis should not be diagnosed separately unless they are a prominent component of the lesion.
细胞浸润Infiltration Cellular 腺胃浸润
描述（中文）
“细胞浸润（cellular infiltrate）”一词常用于描述炎症细胞的存在，而无其他炎症过程的证据（例如水肿、坏死或细胞变性、血管损伤的证据）。浸润通常由淋巴细胞、肥大细胞或嗜酸性粒细胞组成。腺胃中的淋巴细胞浸润可为偶然发现；它们通常出现在黏膜深层和黏膜下层。在图1（箭头）中，淋巴细胞浸润存在于腺胃深部黏膜和前胃固有层。嗜酸性粒细胞（图2和图3，箭头）在过敏性疾病和寄生虫病中存在的嗜酸性粒细胞趋化因子作用下从血流被募集到大多数器官，并提示超敏反应。胃黏膜下层偶可见肥大细胞的局灶性（focal）聚集。肥大细胞已被证明在急性过敏反应、迟发相反应和慢性过敏性炎症中起重要作用。胃肠道黏膜下层肥大细胞的局灶性聚集在NTP研究中通常被视为偶然性病变。此类聚集可能与肥大细胞瘤混淆。肥大细胞的局灶性聚集往往比肥大细胞瘤更小且边界更不清楚，并且浸润于结构之间而非压迫或取代邻近结构。
诊断建议
当炎症细胞存在而无其他炎症特征（例如水肿、出血、变性、坏死）时，应使用“infiltrate, cellular”一词。一般而言，炎症细胞浸润往往相当小，可能不足以作出诊断。当作出诊断时，应根据细胞数量和受累组织总面积对浸润进行分级。应使用修饰词指明具体的细胞类型（例如淋巴细胞、嗜酸性粒细胞、肥大细胞）。
参考切片图（2 张）
查看英文原文
Comment
The term "cellular infiltrate" is often used to describe the presence of inflammatory cells without other evidence of an inflammatory process (e.g., edema, necrosis or degeneration of cells, evidence of vascular injury). Infiltrates usually consist of lymphocytes, mast cells, or eosinophils. Lymphocytic infiltrates in the glandular stomach can be an incidental finding; they typically appear in the deep aspect of the mucosa and in the submucosa. In Figure 1 (arrow), lymphocytic infiltrates are present in the deep mucosa of the glandular stomach and in the propria of the forestomach. Eosinophils ( Figure 2 and Figure 3 , arrows) are recruited from the blood stream into most organs in response to eosinophil chemoattractants present in allergic and parasitic diseases and indicate a hypersensitivity reaction. Focal collections of mast cells can occasionally be found in the submucosa of the stomach. Mast cells have been shown to contribute importantly to acute allergic reactions, late-phase reactions, and chronic allergic inflammation. Focal accumulations of mast cells in the submucosa of the gastrointestinal tract are usually considered an incidental lesion in NTP studies. Such accumulations may be confused with mast cell tumor. Focal accumulations of mast cells tend to be smaller and less well circumscribed than mast cell tumors and infiltrate between structures rather than compressing or effacing adjacent structures.
Recommendation
The term "infiltrate, cellular" should be used when inflammatory cells are present with no other features of inflammation (e.g., edema, hemorrhage, degeneration, necrosis). Generally, infiltrates of inflammatory cells are often quite small and may not warrant a diagnosis. When diagnosed, infiltrates should be graded based on the number of cells and the total tissue area affected. A modifier should be used to indicate the specific type of cell (e.g., lymphocyte, eosinophil, mast cell).
肠化生Metaplasia Intestinal 腺胃化生
描述（中文）
肠上皮化生由形态学上与肠道相似的胃黏膜区域构成（Figure 1、Figure 2）。化生的黏膜衬里可有隐窝、不同程度发育的绒毛、杯状细胞（goblet cells）、潘氏细胞（paneth cells）和吸收细胞，并可能在酶学上与肠道相似。慢性炎症可导致胃小凹化生为黏液型增生性上皮，与肠道者相似。注意Figure 2中上皮细胞表面的微绒毛。在某些情况下，肠上皮化生可能与胃肿瘤形成相关。
诊断建议
无论何时出现，肠上皮化生均应予以诊断，并根据存在的化生腺体数量进行分级。
参考切片图（2 张）
查看英文原文
Comment
Intestinal metaplasia consists of areas of gastric mucosa morphologically similar to the intestine ( Figure 1 and Figure 2 ). The metaplastic mucosal lining may have crypts, variably developed villi, goblet cells, paneth cells, and absorptive cells and may be enzymatically similar to the intestine. Chronic inflammation can result in metaplasia of the gastric pitsto a mucus-type hyperplastic epithelium, similar to that of the intestine. Notice the microvilli on surface of epithelial cells in Figure 2 . In some cases, intestinal metaplasia may be associated with gastric neoplasia.
Recommendation
Whenever present, intestinal metaplasia should be diagnosed and graded based on the number of metaplastic glands present.
色素Pigment 腺胃色素沉着
描述（中文）
腺体黏膜上皮细胞中偶见局灶性（focal）至多灶性（multifocal）的色素蓄积区域（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6）。在某些情况下，其发生呈散发性且来源不明，被视为incidental或人为假象。色素性物质的示例包括血红蛋白的分解产物（hematin、类hematin、寄生虫hematin、hemosiderin）、lipofuscin以及受试物。Hemosiderin（金棕色色素）最常见，常位于巨噬细胞内。黏膜中出现类酸性hematin色素提示存在未切到组织学切片平面内的溃疡性或糜烂性病变。
诊断建议
无论何时出现，该变化均应诊断为“色素”并进行分级。严重程度分级取决于所存在色素区域的数量和大小以及色素蓄积的密度。除非使用特殊染色或其他方法作出明确诊断，否则诊断中不应指明色素性物质的具体类型。然而，在叙述性描述中，病理学家可对所存在色素的类型提供意见。
参考切片图（2 张）
查看英文原文
Comment
Focal to multifocal areas of pigment accumulation in epithelial cells of the glandular mucosa are occasionally noted ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 and Figure 6 ). In some cases the occurrence is sporadic and of unknown origin and is considered incidental or artifactual. Examples of pigmented material are breakdown products of hemoglobin (hematin, hematin-like, parasite hematin, hemosiderin), lipofuscin, and test article. Hemosiderin (golden-brown pigment), often within macrophages, is the most common. The presence of acid hematin-like pigment in the mucosa is suggestive of an ulcerative or erosive process not in the plane of histologic section.
Recommendation
Whenever present, this change should be diagnosed as "pigment" and graded. Severity grading depends on the number and size of pigmented areas present and on the density of pigment accumulation. The specific type of pigmented material should not be specified in the diagnosis unless special stains or other means are used for definitive diagnosis. However, in the narrative the pathologist may provide an opinion as to the type of pigment that is present.
萎缩Atrophy 腺胃萎缩
描述（中文）
腺胃病变在NTP小鼠中罕见。以黏膜上皮细胞体积减小和数量减少为特征的局灶性（focal）黏膜萎缩可能由溃疡、炎症、矿化或梗死引起。广泛性黏膜萎缩可如Figure 2、Figure 4所示由化学物质诱导。弥漫性（diffuse）萎缩也可为年龄相关变化，表现为黏膜高度弥漫性降低和黏膜纤维结缔组织增多。在老龄大鼠中，胃底腺可呈弥漫性萎缩，壁细胞和主细胞减少，并含有囊肿。腺体被纤维结缔组织取代，固有层和腺上皮内伴有局灶性淋巴细胞浸润，沿界嵴伴有混合性炎症细胞浸润。
诊断建议
萎缩应当诊断并分级。严重程度分级取决于病变范围及上皮细胞丢失/体积减小的程度。
参考切片图（2 张）
查看英文原文
Comment
Lesions of the glandular stomach are rare in NTP mice. Focal mucosal atrophy characterized by decreased size and number of mucosal epithelial cells may result from ulceration, inflammation, mineralization, or infarction. Generalized mucosal atrophy can be chemically induced as in Figure 2 and Figure 4 . Diffuse atrophy can also be an age-related change with a diffuse decrease of mucosal height and increased mucosal fibrous connective tissue. In the aged rat, fundic glands may be diffusely atrophic, with fewer parietal and chief cells, and contain cysts. Glands are replaced by fibrous connective tissue with focal lymphocytic infiltrates in the lamina propria and the glandular epithelium and a mixed inflammatory infiltrate along the limiting ridge.
Recommendation
Atrophy should be diagnosed and graded. Severity grade depends on the extent of the lesion and degree of loss/decreased size of epithelial cells.
血栓Thrombus 腺胃血栓
描述（中文）
供应胃壁的血管内血栓形成（Figure 2、Figure 4）可导致出血和坏死（Figure 1、Figure 3）。血栓可能起源于血管壁，也可能是来自其他部位（如心房或瓣膜）的血栓栓子所致。
诊断建议
无论何时出现，血栓均应诊断并分级。血栓的严重程度分级取决于发生血栓的血管数量及血栓大小。在炎症和坏死区域血管内发现的小血栓，若看来是局部炎症过程所致，通常不予记录。继发于血栓的坏死区域内的出血，除非是显著病变，通常不予记录。若血栓导致组织坏死（梗死），则血栓和坏死均予记录并分级。
参考切片图（2 张）
查看英文原文
Comment
Thrombosis in vessels ( Figure 2 and Figure 4 ) supplying the stomach wall can result in hemorrhage and necrosis ( Figure 1 and Figure 3 ). Thrombosis may originate in the vessel wall or may be the result of thromboemboli originating elsewhere, such as the atrium or valves.
Recommendation
Whenever present, thrombi should be diagnosed and graded. The severity grade for thrombi depends on the number of vessels thrombosed and the size of the thrombi. Small thrombi found in vessels in areas of inflammation and necrosis are not usually recorded if they appear to have formed as result of the local inflammatory process. Hemorrhage in an area of necrosis secondary to a thrombus is not usually recorded unless it is a prominent lesion. If a thrombus results in necrosis (infarction) of the tissue, both the thrombus and the necrosis are recorded and graded.
血管扩张Angiectasis 腺胃扩张
描述（中文）
血管扩张（angiectasis，血管扩张症）主要是一种自发性的年龄相关病变。病因通常未知，但偶尔可能是对化学损伤的反应。血管扩张由广泛扩张的血管腔隙构成，尤其是毛细血管（或血窦）和小静脉，其内衬为无明显异常的内皮细胞。血管数量无明显增多，器官的间质未发生改变。应尝试区分血管扩张与血管瘤（hemangioma），尽管血管扩张与血管瘤之间的差异有时并不明显。血管瘤往往为边界清楚、无包膜的肿块，由紧密排列的扩张血管腔隙构成。每个血管腔隙均由单层外观正常的内皮细胞围成并衬覆，这些内皮细胞排列于胶原性间隔上，间隔通常较薄，尽管有些具有宽阔的胶原性间质。血管扩张通常不表现为边界清楚的肿块，因为扩张的血管通道常不规则地穿行于结缔组织中。
诊断建议
血管扩张应当被诊断，并根据病变的范围给予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Angiectasis (vascular ectasia) is primarily a spontaneous age-related lesion. The cause is generally not known but occasionally can be a response to chemical injury. Angiectasis consists of widely dilated vascular spaces, especially capillaries (or sinusoids) and venules, that are lined by unremarkable endothelial cells. There is no apparent increase in numbers of vessels, and the stroma of the organ is unaltered. A distinction between angiectasis and hemangioma should be attempted, although the difference between angiectasis and hemangioma is sometimes not obvious. Hemangiomas tend to be well-circumscribed unencapsulated masses composed of tightly packed dilated vascular spaces. Each vascular space is enclosed and lined by a single layer of normal-appearing endothelial cells aligned on collagenous septa, which are usually thin, although some have broad collagenous stromata. Angiectasis does not usually present as a well-circumscribed mass as the dilated vascular channels are often irregularly coursing through connective tissue.
Recommendation
Angiectasis should be diagnosed and given a severity grade based on the extent of the lesion.
透明滴Hyaline Droplet 腺胃其他
描述（中文）
透明滴蓄积（hyaline droplet accumulation，既往称为“嗜酸性胞质改变”）由黏膜上皮细胞胞质内均质的球状透明物质组成。这些球状物可位于核下或核上位置。在晚期病例中，这些球状物可能伴有细胞内或细胞外嗜酸性蛋白性结晶。它们在H&E染色下呈明亮的嗜酸性，PAS染色呈阴性。该嗜酸性物质的组成尚不清楚，但在肺中，透明物质的蓄积和结晶的形成可诱发肺炎，结晶的主要成分已被鉴定为Ym1蛋白，属于几丁质酶样蛋白家族成员。蓄积倾向于在小鼠的心脏区更为常见，在大鼠则靠近界嵴。这与鼻上皮、下呼吸道和胰腺上皮细胞在轻度刺激下所见的物质蓄积相同。偶尔可见局灶性（focal）慢性炎症和隐窝脓肿，但通常透明滴蓄积不伴有炎症。
诊断建议
透明滴蓄积应当进行诊断，并根据受累腺体的数量以及腺体内透明滴蓄积的量进行分级。含有透明滴的细胞可能增大，但除非细胞增大并非由透明物质所致，否则不应诊断为肥大（hypertrophy）。如果同时存在细胞变性，变性应当单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Hyaline droplet accumulation (previously termed "eosinophilic cytoplasmic change") is composed of homogeneous globular hyaline material in the cytoplasm of the mucosal epithelial cells. The globules may be in sub- or supranuclear positions. In advanced cases, these globules may be associated with intra- or extracellular eosinophilic proteinaceous crystals. They stain brightly eosinophilic with H&E and negatively with periodic acid-Schiff. The composition of the eosinophilic material is unknown, but in the lung, where the accumulation of the hyaline material and formation of crystals induce pneumonia, the main component of the crystals has been identified as Ym1 protein, a member of the chitinase-like family of proteins. Accumulations tend to be more common in the cardiac region in mice and near the limiting ridge in rats. This is the same accumulation of material as seen in epithelial cells of the nasal epithelium, lower respiratory tract, and pancreas in response to minor irritation. Occasionally, focal chronic inflammation and crypt abscesses are seen, but usually hyaline droplet accumulation is present without inflammation.
Recommendation
Hyaline droplet accumulation should be diagnosed and graded based on the number of glands involved and the amount of hyaline droplet accumulation within glands. Cells containing hyaline droplets may be enlarged, but hypertrophy should not be diagnosed unless the cell enlargement is not due to the hyaline material. If there is concurrent degeneration of the cells, degeneration should be diagnosed separately.
鳞状化生Metaplasia Squamous 腺胃化生
描述（中文）
腺胃鳞状化生（squamous metaplasia）的特征是一种可逆性改变，即立方状或柱状黏膜上皮细胞被鳞状上皮细胞所取代（Figure 1、Figure 2，箭头）。鳞状化生常常（但并非总是）是对抗不良环境条件（如慢性刺激）的一种适应性改变，若去除病因则可逆转。腺胃鳞状化生最常发生于界限嵴（limiting ridge）（Figure 1、Figure 2，箭头）。它可以是偶然性发现，也可以是治疗相关病变。
诊断建议
无论何时出现，鳞状化生均应予以诊断，并根据化生区域的数量和大小进行分级。相关病变（如炎症）应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Squamous metaplasia of the glandular stomach is characterized by a reversible change in which cuboidal or columnar mucosal epithelial cells are replaced by squamous epithelial cells ( Figure 1 and Figure 2 , arrows). Squamous metaplasia is often but not always an adaptive change to withstand adverse environmental conditions, such as chronic irritation, and is reversible if the cause is removed. Squamous metaplasia of the glandular stomach most often occurs at the limiting ridge ( Figure 1 and Figure 2 , arrows). It can be an incidental finding or a treatment-related lesion.
Recommendation
Whenever present, squamous metaplasia should be diagnosed and graded based on the number and size of metaplastic areas. Associated lesions, such as inflammation, should be diagnosed separately.
上皮变性Epithelium Degeneration 舌变性
描述（中文）
细胞变性（degeneration）是细胞损伤的一种基本表现，被认为具有可逆性。其表现形式多样，包括细胞因无法维持正常稳态及调节水分的进入和排出而导致水分超负荷，进而引起细胞大小和体积增大。这也可能导致细胞质比未受损细胞显得更苍白（Figure 1、Figure 2）。受累细胞的细胞质内可含有半透明空泡，代表肿胀的线粒体以及扩张的高尔基体和内质网池。邻近组织可有不同程度的炎性细胞浸润。
诊断建议
变性一旦出现即应诊断并分级。若上皮已缺失、暴露出下方真皮，则诊断为“溃疡（ulcer）”。变性的严重程度分级依据细胞肿胀程度以及受累区域的范围和数量。相关病变如炎症，除非其严重程度足以需要诊断，否则不应诊断。
参考切片图（2 张）
查看英文原文
Comment
Degeneration of cells is a fundamental expression of cell injury that is considered to be reversible. It can manifest in many ways, including increased cell size and volume resulting from an overload of water caused by a failure of the cell to maintain normal homeostasis and regulate the ingress and excretion of water. This may also cause the cytoplasm to appear paler than that of undamaged cells ( Figure 1 and Figure 2 ). The cytoplasm of affected cells may contain translucent vacuoles that represent swollen mitochondria and dilated cisternae of the Golgi and endoplasmic reticulum. Subjacent tissue can be variably infiltrated with inflammatory cells.
Recommendation
Degeneration should be diagnosed and graded whenever present. If the epithelium has been lost, exposing the underlying dermis, then "ulcer" is diagnosed. The severity grade for degeneration is based on the degree of cellular swelling and extent and number of areas affected. Associated lesions, such as inflammation, should not be diagnosed unless warranted by severity.
上皮增生Epithelium Hyperplasia 舌增生
描述（中文）
口腔中的鳞状细胞增生（squamous cell hyperplasia）最常见于舌、腭和咽侧壁。鳞状细胞增生的特征是细胞数量增多，通常导致鳞状上皮厚度增加。鳞状增生可呈弥漫性（diffuse）或斑块状，或可形成钝的乳头状突起。局灶性（focal）增生可有多个指状突起，每个突起都有自己的固有层（Figure 1、Figure 2）。角化过度（hyperkeratosis）常与鳞状细胞增生同时出现，但通常不出现角化珠形成。大小、细胞分化良好的外观以及缺乏显著的间质成分对于区分增生与乳头状瘤（papilloma）很重要。乳头状瘤通常有一个单一的蒂状附着于舌，该附着可能不在切片平面内。累及鳞状上皮的增生性病变倾向于呈连续谱系，从局灶性增生进展为乳头状瘤再进展为鳞状细胞癌（squamous cell carcinoma）。然而，也有一些研究的例子显示乳头状瘤阶段明显被跳过，进展直接从局灶性增生到鳞状细胞癌。机械性损伤可导致增生上皮的溃疡或糜烂以及炎症。
诊断建议
鳞状细胞增生应当被诊断，并根据受影响区域的大小和数量以及上皮的厚度进行分级。相关的角化过度、溃疡或炎症不应单独诊断，除非其严重程度足以支持单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Squamous cell hyperplasia in the oral cavity is seen most commonly on the tongue, palate, and lateral wall of the pharynx. Squamous cell hyperplasia is characterized by increased cell numbers, which usually results in increased thickness of the squamous epithelium. Squamous hyperplasia may be diffuse or plaque-like or may form blunt papillary projections. Focal hyperplasia can have multiple finger-like projections, each with its own lamina propria ( Figure 1 and Figure 2 ). Hyperkeratosis is frequently seen with squamous cell hyperplasia, but usually keratin pearl formation is not present. Size, the well-differentiated appearance of cells, and the absence of a prominent stromal component are important in distinguishing hyperplasia from papilloma. Papillomas frequently will have a single stalklike attachment to the tongue, which may not be in the plane of section. Proliferative lesions involving squamous epithelium tend to be on a continuum, progressing from focal hyperplasia to papilloma to squamous cell carcinoma. There are, however, examples of studies in which the papilloma stage was apparently bypassed, and progression was directly from focal hyperplasia to squamous cell carcinoma. Mechanical damage can result in ulceration or erosion of the hyperplastic epithelium and inflammation.
Recommendation
Squamous hyperplasia should be diagnosed and graded based on the size and number of the areas affected and the thickness of the epithelium. Associated hyperkeratosis, ulceration, or inflammation should not be diagnosed separately unless warranted by severity.
出血Hemorrhage 舌出血
描述（中文）
出血（Figure 1、Figure 2）可由化学暴露、创伤或其他血管损伤引起，也可由干扰正常凝血所需因子的化学物质引起。它也可能是急性炎症的一个组成部分。
诊断建议
出血应当诊断并分级，除非它是继发于炎症或溃疡形成，在这种情况下不应单独诊断，而应在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage ( Figure 1 and Figure 2 ) can be due to chemical exposure, trauma, or other damage to blood vessels or due to a chemical that interferes with factors necessary for normal clotting. It may also be a component of acute inflammation.
Recommendation
Hemorrhage should be diagnosed and graded, unless it is secondary to inflammation or ulceration, in which case it should not be diagnosed separately but should be described in the pathology narrative.
坏死Necrosis 舌坏死
描述（中文）
坏死可继发于创伤、感染、血管炎或血栓形成，也可作为受试物的直接效应而发生（尤其是上皮坏死）。坏死与溃疡的鉴别在于，溃疡是鳞状上皮缺失的区域，且病变穿过基底膜，暴露出其下的固有层。而在坏死时，坏死上皮仍附着于基底膜。坏死可累及舌的全层（Figure 1、Figure 2、Figure 3、Figure 4），尤其当病因为血管性时。除肌肉坏死外（Figure 2、Figure 4、Figure 5、Figure 6，箭头），舌被覆的鳞状上皮也可发生坏死（Figure 2、Figure 3，箭头），这取决于坏死的部位和范围。炎症常伴随坏死出现，所呈现的炎症类型取决于病程的慢性程度和病因。在 NTP 研究中，舌肌肉的病变并不常见。
诊断建议
坏死应当被诊断并给予严重程度分级。如果坏死累及舌的肌肉或多个组织，则诊断为“舌——坏死”。然而，如果坏死仅限于舌的上皮，则诊断应为“舌，上皮——坏死”。继发性病变，如炎症或出血，一般不应单独诊断，除非它们是病变的显著组成部分。如果坏死性病变符合梗死，则应诊断为“坏死”，但病理学描述中应说明该病变符合梗死。
参考切片图（2 张）
查看英文原文
Comment
Necrosis can occur secondary to trauma, infection, vasculitis, or thrombosis or as a direct effect of a test agent (particularly epithelial necrosis). Necrosis is differentiated from ulcer in that an ulcer is an area of loss of squamous epithelium that extends through the basement membrane, exposing the underlying lamina propria. In necrosis, the necrotic epithelium remains attached to the basement membrane. Necrosis may involve the full thickness of the tongue ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ), particularly when the etiology is vascular. In addition to muscle necrosis ( Figure 2 , Figure 4 , Figure 5 , and Figure 6 , arrows), the overlying squamous epithelium of the tongue can also be necrotic ( Figure 2 and Figure 3 , arrows), depending on the location and extent of necrosis. Inflammation often accompanies the necrosis, and the type of inflammation present depends on the chronicity and the etiology. Lesions are not common in the muscle of the tongue in NTP studies.
Recommendation
Necrosis should be diagnosed and given a severity grade. If the necrosis involves muscle or multiple tissues in the tongue, then it is diagnosed as "tongue - necrosis." However, if the necrosis is limited to the epithelium of the tongue, the diagnosis should be "tongue, epithelium - necrosis." Secondary lesions, such as inflammation or hemorrhage, generally should not be diagnosed separately unless they are prominent components of the lesion. If the necrotic lesion is consistent with an infarct, it should be diagnosed as "necrosis," but the pathology narrative should state the lesion is consistent with an infarct.
水肿Edema 舌水肿
描述（中文）
与其他器官一样，水肿是调节血浆、间质和细胞之间正常液体分布的任一因素发生改变的结果，例如血管通透性增加、血管内静水压升高、血管内渗透压降低和淋巴引流减少。因此，任何影响这些因素的化学物均可引起水肿。水肿也可作为急性炎症的组成部分。水肿液在间质内表现为均质、淡染的嗜酸性物质，但在制片过程中常丢失，表现为清晰空隙（Figure 1、Figure 2）。
诊断建议
无明显炎症情况下发生的水肿，应根据水肿液分离舌组织的程度及组织累及的总范围进行诊断和分级。当水肿与炎症相关时，应单独诊断，除非水肿非常显著或严重程度不成比例，但应在病理学描述中将其作为炎症的组成部分加以描述。其他相关病变，如坏死，应单独诊断和分级。
参考切片图（2 张）
查看英文原文
Comment
As in other organs, edema is the result of alteration in any of the factors that regulate the normal fluid distribution between the plasma, interstitium, and cells, such as increased vascular permeability, increased intravascular hydrostatic pressure, decreased intravascular osmotic pressure, and decreased lymphatic drainage. Therefore, any chemical that affects any of these factors can cause edema. Edema can also be a component of acute inflammation. Edema fluid appears as homogeneous, pale, eosinophilic material within the interstitium but is often lost in processing and appears as clear spaces ( Figure 1 and Figure 2 ).
Recommendation
Edema occurring in the absence of obvious inflammation should be diagnosed and graded based on the degree of separation of the tongue tissues by edema fluid and the total extent of tissue involvement. When it is associated with inflammation, it should be diagnosed separately unless it is very prominent or disproportionately severe, but it should be described in the pathology narrative as a component of the inflammation. Other associated lesions, such as necrosis, should be diagnosed and graded separately.
溃疡Ulcer 舌溃疡
描述（中文）
溃疡和糜烂可发生于胃肠道任何部位，包括舌。糜烂指黏膜表面上皮的缺失，而溃疡（Figure 1、Figure 2）则涉及上皮细胞全层的缺失并延伸至固有层。溃疡形成和炎症可由自发性疾病或局部或全身性毒性损伤所致。舌部溃疡可由切牙过度生长导致的错颌引起，也可继发于尿毒症。它们通常伴有炎症，也可能伴有肌细胞变性。
诊断建议
舌的溃疡形成和糜烂应当诊断并分级。邻近上皮的水肿、炎症和增生一般不应单独诊断，除非它们是病变的显著组成部分。如果坏死上皮仍然存在并附着于其下的固有层，则应诊断上皮坏死而非糜烂或溃疡形成。
参考切片图（2 张）
查看英文原文
Comment
Ulcers and erosions can occur anywhere in the gastrointestinal tract, including the tongue. An erosion involves the loss of superficial epithelium of the mucosa, whereas an ulcer ( Figure 1 and Figure 2 ) involves loss of the full thickness of epithelial cells and extends to the lamina propria. Ulceration and inflammation can be the result of spontaneous disease or local or systemic toxic injury. Ulcers on the tongue can be caused by malocclusion with incisor overgrowth or can be secondary to uremia. They are typically accompanied by inflammation and may also be accompanied by myocyte degeneration.
Recommendation
Ulceration and erosion of the tongue should be diagnosed and graded. Edema, inflammation, and hyperplasia of the adjacent epithelium should not generally be diagnosed separately unless they are prominent components of the lesion. Necrosis of the epithelium is diagnosed instead of erosion or ulceration if the necrotic epithelium is still present and attached to the underlying lamina propria.
炎症Inflammation 舌炎症
描述（中文）
在NTP研究中，炎症有五种标准分类：急性（急性（acute））、化脓性（化脓性（suppurative））（Figure 3、Figure 4、Figure 5、Figure 6）、慢性（慢性（chronic））、慢性活动性（慢性 active）（Figure 1、Figure 2）以及肉芽肿性（肉芽肿性（granulomatous））（Figure 7、Figure 8、Figure 9、Figure 10）。在急性炎症（急性 inflammation）中，主要浸润细胞是中性粒细胞（neutrophil），但也可能存在少量巨噬细胞（macrophage）和淋巴细胞（lymphocyte）。还可能有水肿或充血（hyperemia）的证据。中性粒细胞也是化脓性炎症（化脓性 inflammation）中的主要浸润细胞类型，但中性粒细胞聚集，且其中许多发生退变（化脓性渗出物，化脓性 exudate）。渗出物可能含有细胞碎片，既来自 resident 细胞群体，也来自浸润的白细胞；含纤维蛋白（fibrin）的蛋白性液体；少量巨噬细胞；偶见淋巴细胞或浆细胞（plasma cell）；以及可能的感染因子。肉眼观察，这些病变以脓液存在为特征。渗出物周围组织可能含有成纤维细胞（fibroblast）、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。淋巴细胞在慢性炎症（慢性 inflammation）中占主导地位。淋巴细胞在慢性活动性炎症（慢性 active inflammation）中也占主导地位，但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症（肉芽肿性 inflammation）是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大型、活化巨噬细胞、上皮样巨噬细胞（epithelioid macrophage）或多核巨细胞（multinucleated giant cell）。炎症可以是治疗相关病变，但也可能作为自发性背景病变出现。化脓性炎症常由异物（foreign body）（Figure 6）或细菌感染引起。如果诱发因素持续存在（例如，异物未被移除），炎症反应可能变为肉芽肿性（Figure 9、Figure 10）。NTP对被认为是脓肿（abscess）的病变使用术语“化脓性炎症”。一般而言，脓肿是偶然发现；然而，对舌鳞状上皮（squamous epithelium）有毒性的药物可能导致治疗相关的发生率增加。
诊断建议
无论何时出现，炎症均应被诊断并给予严重程度分级。指示炎症持续时间或类型的适当修饰词（即 急性（acute）、化脓性（suppurative）、慢性（chronic）、慢性 active 或 肉芽肿性（granulomatous））应包含在诊断中。符合脓肿的病变诊断为化脓性炎症。如果异物是炎症的原因，应单独诊断（异物不分级）。如果存在细菌或真菌，不应单独诊断，而应在描述中描述。其他相关病变，如出血（hemorrhage）、水肿（edema）或坏死（necrosis），除非严重程度需要，否则不应单独诊断，而应在病理学描述中描述。
参考切片图（2 张）
查看英文原文
Comment
In NTP studies, there are five standard categories of inflammation: acute, suppurative ( Figure 3 , Figure 4 , Figure 5 , and Figure 6 ), chronic, chronic active ( Figure 1 and Figure 2 ), and granulomatous ( Figure 7 , Figure 8 , Figure 9 , and Figure 10 ). In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate). The exudate may contain cell debris, both from the resident cell populations and from infiltrating leukocytes; proteinaceous fluid containing fibrin; fewer macrophages; occasional lymphocytes or plasma cells; and, possibly, an infectious agent. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may contain fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammation can be a treatment-related lesion but can also occur as a spontaneous background lesion. Suppurative inflammation is often due to foreign bodies ( Figure 6 ) or bacterial infections. If the inciting agent persists (e.g., the foreign body is not removed), the inflammatory response may become granulomatous ( Figure 9 and Figure 10 ). The NTP uses the term "suppurative inflammation" for lesions that are considered abscesses. Generally, abscesses are incidental findings; however, a treatment-related increased incidence could occur with agents toxic to the squamous epithelium of the tongue.
Recommendation
Whenever present, inflammation should be diagnosed and given a severity grade. The appropriate modifier indicating the duration or type of inflammation (i.e., acute, suppurative, chronic, chronic active, or granulomatous) should be included in the diagnosis. Lesions consistent with an abscess are diagnosed as suppurative inflammation. If a foreign body is the cause of the inflammation, it should be diagnosed separately (foreign bodies are not graded). If bacteria or fungi are present, they should not be diagnosed separately but should be described in the narrative. Other associated lesions, such as hemorrhage, edema, or necrosis, should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative.
纤维化Fibrosis 舌纤维化
描述（中文）
纤维化（fibrosis）（Figure 1、Figure 2）的特征是成纤维细胞及相关胶原增多，通常为组织损伤的后遗症。当组织框架发生坏死且该空间被纤维血管组织（肉芽组织）填充，最终被成熟结缔组织取代形成瘢痕时，即形成纤维化。纤维化常伴有炎症，炎症在过程早期可能为慢性活动性，但通常为慢性。纤维化也见于脓肿，此时机体试图将致病因子包裹隔离。纤维化可能是与治疗相关的病变，但也可能是偶然发现。
诊断建议
当纤维化在没有其他病变的情况下发生时，应当诊断并分级。当纤维化是慢性炎症的组成部分时，不应单独诊断，除非其特别显著或相对于炎症的严重程度而言严重程度不成比例，或者病理学家认为它是需要突出显示的重要病变。相关病变如显著，应当单独诊断（例如坏死、炎症）。
参考切片图（2 张）
查看英文原文
Comment
Fibrosis ( Figure 1 and Figure 2 ) is characterized by an increase in fibroblasts and associated collagen and is usually a sequela of tissue damage. Fibrosis forms when there is necrosis of the tissue framework and the space is filled with fibrovascular tissue (granulation tissue), which is eventually replaced by mature connective tissue forming a scar. Fibrosis is often accompanied by inflammation, which may be chronic active early in the process but is often chronic. Fibrosis is also seen with abscesses where the body is attempting to wall off the inciting agent. Fibrosis may be a treatment-related lesion but can also be an incidental finding.
Recommendation
When it occurs in absence of other lesions, fibrosis should be diagnosed and graded. When it is a component of chronic inflammation, fibrosis should not be diagnosed separately unless it is particularly prominent or disproportionately severe relative to the severity of the inflammation, or if the pathologist feels it is an important lesion that needs to be highlighted. Associated lesions, if prominent, should be diagnosed separately (e.g., necrosis, inflammation).
腺体囊肿Glands Cyst 舌囊肿
描述（中文）
舌内的囊性唾液腺导管（也称为舌下囊肿）衬以低立方上皮，与唾液腺导管一致（不同于唾液腺黏液囊肿，后者为充满唾液分泌物的囊性腔隙，但无上皮衬覆）。唾液腺导管囊肿（Figure 1、Figure 2）可能充满淡嗜酸性液体，但该液体在制片过程中可能丢失，留下空囊肿。囊肿、扩张或黏液囊肿可能继发于创伤、唾液腺结石或小导管异物，被视为偶然发现。破裂的囊肿可能伴有炎症，常为肉芽肿性。它们在F344/N rat和B6C3F1 mouse中罕见。
诊断建议
舌内唾液腺导管囊肿和扩张无论何时出现均应诊断，但通常不分级。若病变小，诊断为扩张；较大的病变诊断为囊肿。若有相关炎症，除非炎症的严重程度需要，否则不单独记录炎症。
参考切片图（2 张）
查看英文原文
Comment
Cystic salivary ducts in the tongue (also known as ranulae) are lined by low cuboidal epithelium consistent with the salivary duct (as opposed to salivary mucoceles, which are cystic cavities filled with salivary secretions but not lined by an epithelium). Salivary gland duct cysts ( Figure 1 and Figure 2 ) may be filled with pale eosinophilic fluid, but the fluid can be lost in processing, leaving an empty cyst. Cysts, dilations, or mucoceles may occur secondary to trauma, salivary calculi, or ductular foreign bodies and are considered incidental findings. Ruptured cysts may be accompanied by inflammation, often granulomatous. They are rare in F344/N rats and B6C3F1 mice.
Recommendation
Whenever present, salivary duct cysts and dilations in the tongue should be diagnosed, but they are not generally graded. If the lesion is small, is diagnosed as dilation; larger lesions are diagnosed as cysts. If there is associated inflammation, the inflammation is not recorded separately unless warranted by severity.
血管扩张Angiectasis 舌扩张
描述（中文）
舌的血管性病变在NTP研究中很少见。血管扩张（angiectasis，血管扩张症）主要是一种自发性、与年龄相关的病变。其原因通常未知，但偶尔可能是对化学性损伤的反应。血管扩张由广泛扩张的血管腔隙构成，其内衬为无明显异常的内皮细胞（Figure 1、Figure 2）。血管数量无明显增加，器官的间质未发生改变。血管扩张应与血管瘤（hemangioma）相鉴别，但两者之间的区分往往并不明确。血管瘤倾向于为边界清楚、无包膜的肿块，由紧密排列的扩张血管腔隙构成。每个血管腔隙内衬单层外观正常的内皮细胞，这些细胞排列于胶原性间隔上，间隔通常较薄，尽管有些具有宽阔的胶原性间质。血管扩张通常不表现为边界清楚的肿块，因为扩张的血管通道常不规则地穿行于结缔组织之中。
诊断建议
血管扩张只要存在即应作出诊断，并给予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Vascular lesions of the tongue are rarely encountered in NTP studies. Angiectasis (vascular ectasia) is primarily a spontaneous age-related lesion. The cause is generally not known but occasionally can be a response to chemical injury. Angiectasis consists of widely dilated vascular spaces that are lined by unremarkable endothelial cells ( Figure 1 and Figure 2 ). There is no apparent increase in numbers of vessels, and the stroma of the organ is unaltered. Angiectasis should be distinguished from hemangioma, but the distinction often is not clear. Hemangiomas tend to be well-circumscribed unencapsulated masses composed of tightly packed dilated vascular spaces. Each vascular space is lined by a single layer of normal-appearing endothelial cells aligned on collagenous septa, which are usually thin, although some have broad collagenous stroma. Angiectasis does not usually present as a well-circumscribed mass, as the dilated vascular channels often course irregularly through connective tissue.
Recommendation
Angiectasis should be diagnosed whenever present and given a severity grade.
角化过度Hyperkeratosis 舌其他
描述（中文）
角化过度性病变虽然在前胃中非常常见，但在NTP研究的舌部却罕见。角化过度（角质层增厚）有两种形式：正角化性（Figure 1、Figure 2）或角化不全性角化过度。在正角化性角化过度（有时称为正角化）中，死亡的角质细胞无核，而在角化不全性角化过度（有时称为角化不全）中，死亡的角质细胞保留固缩的细胞核。角化过度常伴随鳞状上皮增生。
诊断建议
一般而言，与下方鳞状上皮增生相关的角化过度不单独诊断，而是在病理学描述中作为增生的一个组成部分加以描述。然而，如果角化过度显著，或与增生程度相比不成比例地增加，或在没有上皮增生的情况下发生，则应予以诊断并分级。分级应基于角蛋白的厚度和受累舌表面的范围。病理学家应运用其判断力决定是否应单独诊断角化过度。当进行诊断时，正角化性和角化不全性两种形式均应使用“角化过度（hyperkeratosis）”一词（即，不要使用角化不全（parakeratosis）一词）。
参考切片图（2 张）
查看英文原文
Comment
Hyperkeratotic lesions, although very common in the forestomach, are rare on the tongue in NTP studies. Hyperkeratosis (thickening of the stratum corneum) occurs in two forms: orthokeratotic ( Figure 1 and Figure 2 ) or parakeratotic hyperkeratosis. In orthokeratotic hyperkeratosis (sometimes referred to as orthokeratosis), the dead keratinocytes are anuclear, whereas in parakeratotic hyperkeratosis (sometimes referred to as parakeratosis), the dead keratinocytes have retained pyknotic nuclei. Hyperkeratosis often accompanies squamous epithelial hyperplasia.
Recommendation
In general, hyperkeratosis associated with hyperplasia of the underlying squamous epithelium is not diagnosed separately but is described in the pathology narrative as a component of the hyperplasia. However, if the hyperkeratosis is prominent or is disproportionately increased compared with the degree of hyperplasia, or if it occurs in the absence of epithelial hyperplasia, then it should be diagnosed and graded. Grading should be based on the thickness of the keratin and the amount of tongue surface affected. The pathologist should use his or her judgment in determining whether or not the hyperkeratosis should be diagnosed separately. When diagnosed, the term "hyperkeratosis" should be used for both the ortho- and parakeratotic forms (i.e., do not use the term parakeratosis).
鳞状囊肿Squamous Cyst 舌囊肿
描述（中文）
鳞状囊肿（squamous cyst）（Figure 1、Figure 2）可见于舌或牙龈，或可与牙齿相关。这些囊肿由角化鳞状上皮衬覆，囊腔内通常含有角化物质。在舌内，鳞状囊肿为良性先天性异常，被视为偶发性病变。
诊断建议
鳞状囊肿应予以诊断，但除非发生率与受试物相关，否则不应分级。
参考切片图（2 张）
查看英文原文
Comment
Squamous cysts ( Figure 1 and Figure 2 ) may be found in the tongue or gingiva or may be associated with the teeth. These cysts are lined by keratinized squamous epithelium, and the lumen usually contains keratinized material. In the tongue, squamous cysts are benign congenital anomalies and are considered incidental lesions.
Recommendation
Squamous cysts should be diagnosed but not graded unless the incidence is treatment related.
黏膜纤维上皮性息肉Mucosa Fibroepithelial Polyp 舌其他
描述（中文）
由分化良好的鳞状上皮（有时为增生性上皮）结节状生长、并由纤维性间质支撑的良性息肉样病变，偶见于啮齿类动物。这些病变与舌黏膜相连，尽管附着部位常不在切片平面内（Figure 1、Figure 2）。支撑上皮的固有层常发生矿化。这些病变必须与乳头状瘤相鉴别，后者被认为是良性肿瘤。乳头状瘤由鳞状上皮细胞构成，表现为显著（marked）棘层肥厚、角化过度和乳头状生长方式，而纤维上皮性息肉由无显著异常的纤维性间质构成，表面覆盖非乳头状的增生性鳞状上皮。鳞状乳头状瘤由三个区域组成：血管化的内层增殖性结缔组织核心；中层为增殖的复层鳞状上皮，基底细胞界限清楚；外层为角蛋白表面。与乳头状瘤一样，纤维上皮性息肉的附着部位常呈蒂状。间质矿化在纤维上皮性息肉中常见，而角化过度通常不是其显著特征。纤维上皮性息肉一般被认为是偶然发现，不是肿瘤性的。
诊断建议
纤维上皮性息肉无论何时出现，都应诊断，但不进行分级。任何伴随的炎症（如果存在）不应单独诊断，除非其异常严重并延伸至舌本身。任何矿化都不应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Benign polypoid lesions consisting of a nodular growth of well-differentiated squamous, sometimes hyperplastic, epithelium supported by fibrous stroma occasionally occur in rodents. These lesions are continuous with the tongue mucosa, although the attachment site is often not in the plane of section ( Figure 1 and Figure 2 ). The lamina propria supporting the epithelium is often mineralized. These lesions must be differentiated from papillomas, which are considered to be benign neoplasms. Papillomas are composed of squamous epithelial cells that exhibit marked acanthosis, hyperkeratosis, and a papillary growth pattern, whereas fibroepithelial polyps consist of an unremarkable fibrous stroma covered by a nonpapillary layer of hyperplastic squamous epithelium. Squamous papillomas consist of three zones: a vascularized, inner, proliferative connective tissue core; a middle area of proliferating stratified squamous epithelium with well-defined basal cells; and an outer surface of keratin. As with papillomas, the attachment site for fibroepithelial polyps frequently is stalklike. Mineralization of the stroma is common in fibroepithelial polyps, and hyperkeratosis is not typically a prominent feature. Fibroepithelial polyps are generally considered incidental findings and are not neoplastic.
Recommendation
Whenever present, fibroepithelial polyps should be diagnosed but not graded. Any associated inflammation, if present, should not be diagnosed separately unless it is unusually severe and extends into the tongue itself. Any mineralization should not be diagnosed separately.
出血Hemorrhage 食管出血
描述（中文）
出血（Figure 1、Figure 2）可发生于食管及胃肠道其他部位。若出血为慢性，还可能出现含铁血黄素分解产物和载含铁血黄素的巨噬细胞。在NTP研究中，化学物对食管的直接毒性作用罕见。灌胃操作造成的创伤是食管出血最常见的原因。出血时常可见水肿和炎症。
诊断建议
出血应作出诊断并分级。相关炎症应单独诊断。相关水肿若严重程度足以支持，可单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage ( Figure 1 and Figure 2 ) can occur in the esophagus and elsewhere in the gastrointestinal tract. If the hemorrhage is chronic, hemosiderin breakdown products and hemosiderin-laden macrophages may also be present. Direct toxic effects of chemicals on the esophagus are rare in NTP studies. Trauma from the gavage procedure is the most common cause of hemorrhage in the esophagus. Often edema and inflammation are noted in conjunction with the hemorrhage.
Recommendation
Hemorrhage should be diagnosed and graded. Associated inflammation should be diagnosed separately. Associated edema may be diagnosed separately if warranted by severity.
增生Hyperplasia 食管增生
描述（中文）
黏膜上皮增生（hyperplasia of the mucosal epithelium）的特征是上皮细胞数量增多且无异型性。上皮细胞可为一种或多种上皮细胞类型（基底细胞、棘细胞或颗粒细胞）。严重病例中，网嵴样结构可延伸至黏膜下层（Figure 1、Figure 2）。当黏膜增生存在时，常可见角化过度（hyperkeratosis，角质层增厚）。据报道，大鼠长期高剂量给予酒精等溶媒后，食管可出现鳞状黏膜增生伴角化过度。
诊断建议
上皮增生应予以诊断，并根据食管受累区域的大小及增生食管上皮的厚度进行分级。与增生相关的角化过度通常不作为一个独立病变诊断，但可在描述中提及。当角化过度存在而无增生时，或角化过度极为严重时，应将其与增生分开诊断并分级（见食管-角化过度（Esophagus - Hyperkeratosis）的描述）。相关链接：食管-角化过度
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of the mucosal epithelium is characterized by an increased number of epithelial cells and the absence of atypia. The epithelial cells may be of one or more epithelial cell types (basal, spinous, or granulosum). In severe cases, rete peg-like structures may extend into the submucosa ( Figure 1 and Figure 2 ). Hyperkeratosis (increased thickness of the stratum corneum) is often seen when hyperplasia of the mucosa is present. Hyperplasia of the squamous mucosa with hyperkeratosis has been reported in the esophagus of the rat following chronic high-dose administration of vehicles such as alcohol.
Recommendation
Epithelial hyperplasia should be diagnosed and graded based on the size of the area of esophagus affected and the thickness of the hyperplastic esophageal epithelium. Hyperkeratosis associated with hyperplasia is usually not diagnosed as a separate entity, although it may be mentioned in the narrative. When hyperkeratosis is present in the absence of hyperplasia or when the hyperkeratosis is extreme, it should be diagnosed and graded separately from the hyperplasia (see description of Esophagus - Hyperkeratosis ). Related Links: Esophagus - Hyperkeratosis
憩室Diverticulum 食管其他
描述（中文）
憩室（diverticulum）（Figure 1，箭头）可发生于消化道的任何部位。憩室是管壁薄弱部位向外膨出形成的与管腔相通的囊袋。憩室由与其起源器官相同类型的上皮衬覆，在食管即为鳞状上皮，且该上皮与器官的正常上皮相连续。由于切面原因，食管与憩室之间的开口并非总能见到。憩室偶尔会被误诊为腺瘤，但憩室上皮缺乏肿瘤的细胞学特征。憩室可被食物嵌塞、发生溃疡、出现局部炎症，并最终穿孔，导致脓肿形成。憩室被视为背景病变。
诊断建议
憩室一旦出现即应作出诊断，但无需对该病变进行严重程度分级。相关病变，如炎症或溃疡，若严重程度足以需要，可单独诊断，但应在病理学描述中明确说明这些病变与憩室相关。
参考切片图（1 张）
查看英文原文
Comment
Diverticula ( Figure 1 , arrow) may occur anywhere in the alimentary tract. They are a bulge in a weakened portion of the wall that forms a pocket that is continuous with the lumen. Diverticula are lined by the same type of epithelium as the organ in which they originate, which in the esophagus is squamous epithelium, and the epithelium is continuous with the normal epithelium of the organ. The aperture between the esophagus and the diverticulum is not always present due to the plane of section. Diverticula are occasionally misdiagnosed as adenomas, but the epithelia of diverticula lack the cellular features of neoplasms. Diverticula may become impacted with food, ulcerate, become locally inflamed, and eventually perforate, leading to abscess formation. Diverticula are considered background lesions.
Recommendation
Whenever present, diverticula should be diagnosed, but it is not necessary to give the lesion a severity grade. Associated lesions, such as inflammation or ulceration, may be diagnosed separately if warranted by severity, but it should be made clear in the pathology narrative that the lesions are associated with the diverticulum.
扩张Dilation 食管扩张
描述（中文）
食管扩张（esophageal dilation）的特征是食管腔扩大和食管壁变薄。慢性食管扩张还可能伴有食管壁肌肉和神经细胞的退行性变。饲料物质嵌塞在食管内是食管扩张（扩张、巨食管）的原因之一。在 NTP 研究中，食管扩张主要发生于饲喂粉状饲料的雌性 F344 大鼠。该病变可导致死亡、化脓性异物性肺炎或鼻炎。
诊断建议
食管扩张应当予以诊断，并根据扩张食管的整体大小进行分级。
参考切片图（2 张）
查看英文原文
Comment
Esophageal dilation is characterized by enlargement of the esophageal lumen and thinning of the esophageal wall. Chronic esophageal dilation may also have degeneration of the muscles and nerve cells in the wall of the esophagus. Feed material impacted in the esophagus is one cause of esophageal dilation (ectasia, megaesophagus). In NTP studies esophageal dilation has occurred primarily in female F344 rats administered a powdered diet. This lesion may result in mortality, suppurative foreign-body pneumonia, or rhinitis.
Recommendation
Esophageal dilation should be diagnosed and graded based on the overall size of the dilated esophagus.
水肿Edema 食管水肿
描述（中文）
水肿液，尤其蛋白质含量高的液体，在细胞外间隙表现为均质的嗜酸性物质。它在处理过程中常丢失，在组织中可能表现为空白区域（Figure 1、Figure 2）。水肿是调节血浆、间质和细胞之间正常液体分布的任一因素发生改变的结果，例如血管通透性增加、血管内静水压升高、血管内渗透压降低和淋巴引流减少。食管水肿的一个常见原因是灌胃继发的创伤。
诊断建议
水肿应诊断并分级。作为炎症过程（如急性炎症）一部分的水肿，通常不单独记录，除非它是病变的重要组成成分。
参考切片图（2 张）
查看英文原文
Comment
Edema fluid, particularly fluid with a high protein content, appears as homogeneous eosinophilic material in extracellular spaces. It is often lost at processing and may appear as clear spaces in tissues ( Figure 1 and Figure 2 ). Edema is the result of alteration in any of the factors that regulate normal fluid distribution among the plasma, interstitium, and cells, such as increased vascular permeability, increased intravascular hydrostatic pressure, decreased intravascular osmotic pressure, and decreased lymphatic drainage. One common cause of edema in the esophagus is trauma secondary to gavage.
Recommendation
Edema is diagnosed and graded. Edema as part of an inflammatory process, such as acute inflammation, is ordinarily not recorded separately unless it is a significant component of the lesion.
淀粉样物质Amyloid 食管其他
描述（中文）
淀粉样变性（amyloidosis）是一种全身性疾病，在B6C3F1小鼠、BALB/c小鼠和C3H小鼠中罕见，但在CD-1小鼠、A小鼠、Swiss Webster小鼠、SJL小鼠和B6小鼠中常见，并且可以是致死原因。其发生率可因群养雄性动物间的打斗以及体外寄生虫感染而升高。淀粉样物质表现为无定形、嗜酸性、玻璃样、细胞外物质（Figure 1，箭头），随着其进行性蓄积，会导致邻近细胞和组织的压迫性萎缩。可使用刚果红（Congo red）等特殊染色来确认该物质为淀粉样物质。刚果红将淀粉样物质染成橙色至橙红色，在偏振光下呈现特征性的浅绿色双折射，通常被称为苹果绿。在食管和小肠中，该病似乎以淀粉样物质在黏膜下层沉积开始。在全身性淀粉样变性中，如果在食管中发现淀粉样物质，则也很可能在脾、肝、肾、舌、小肠和肠系膜淋巴结中发现。肾小球中的淀粉样物质沉积通常是死于淀粉样变性动物的致死原因。
诊断建议
无论何时出现，淀粉样物质沉积都应诊断为“淀粉样物质”，并根据淀粉样物质沉积的范围进行分级。
参考切片图（1 张）
查看英文原文
Comment
Amyloidosis is a systemic disease that is rare in B6C3F1 mice, BALB/c and C3H mice but common in CD-1, A, Swiss Webster, SJL, and B6 mice and can be a cause of death. The incidence can be increased in association with fighting among group-housed males and with ectoparasitism. Amyloid appears as an amorphous, eosinophilic, hyaline, extracellular substance ( Figure 1 , arrow) that, with progressive accumulation, results in pressure atrophy of adjacent cells and tissue. Special stains such as Congo red can be used to confirm that the material is amyloid. Congo red stains amyloid orange to orange red and under polarized light imparts a characteristic light green birefringence that is often referred to as apple green. In the esophagus and small intestine, the disease appears to begin as a deposition of amyloid in the submucosa. In systemic amyloidosis, if amyloid is found in the esophagus, it is also likely to be found in spleen, liver, kidney, tongue, small intestine, and mesenteric lymph node. Amyloid deposits in the glomeruli of the kidney are usually the cause of death in animals that die with amyloidosis.
Recommendation
Whenever present, amyloid deposits should be diagnosed as "amyloid" and graded based on the extent of the amyloid deposits.
溃疡Ulcer 食管溃疡
描述（中文）
食管糜烂、溃疡和坏死常由灌胃操作失误所致。此类创伤可导致穿孔、食管周围脓肿和纤维化。糜烂（erosion）定义为黏膜层浅表部分（即基底膜浅表部分）的缺失，而溃疡（ulcer，Figure 1、Figure 2、Figure 3、Figure 4、Figure 5，箭头）则穿透基底膜，暴露出其下的固有层。若覆盖其上的上皮已坏死但仍保持完整，则该病变诊断为坏死。溃疡形成通常伴有炎症和上皮再生。
诊断建议
凡出现溃疡时，均应作出诊断，并根据病变范围和受累区域数量进行分级。若上皮病变未延伸至基底膜，则应诊断为糜烂。若糜烂与溃疡作为同一病变的组成部分同时存在，则仅诊断溃疡。溃疡边缘的黏膜上皮增生及与溃疡相关的炎症，除非构成病变的显著组成部分，通常不作诊断。病理学家应在叙述中注明其认为该病变系由化学物暴露所致还是由灌胃失误所致。
参考切片图（2 张）
查看英文原文
Comment
Esophageal erosions, ulcers, and necrosis are frequently the result of gavage accidents. Such trauma can lead to perforation, periesophageal abscesses, and fibrosis. An erosion is defined as loss of the superficial portion (i.e., superficial to the basement membrane) of the tunica mucosa, while an ulcer ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , and Figure 5 , arrows) extends through the basement membrane, exposing the underlying lamina propria. If the overlying epithelium is necrotic but still intact, the lesion is diagnosed as necrosis. Inflammation and regeneration of the epithelium typically accompany ulcerations.
Recommendation
Whenever present, ulcers should be diagnosed and graded based on the extent of the lesion and number of areas affected. If the epithelial lesion does not extend to the basement membrane, erosion should be diagnosed. If both erosion and ulcer are present concurrently as part of the same lesion, only ulcer is diagnosed. Mucosal epithelial hyperplasia at the edges of an ulcer and inflammation associated with an ulcer are not ordinarily diagnosed unless they are a prominent component of the lesion. It should be noted in the narrative whether the pathologist considers this lesion due to chemical exposure or a gavage error.
炎症Inflammation 食管炎症
描述（中文）
在 NTP 研究中，化学物质对食管的直接毒性作用罕见。啮齿类动物的食管炎症最常由灌胃创伤引起，并可伴有溃疡、坏死和穿孔。在 NTP 研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞是中性粒细胞（neutrophil），但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但中性粒细胞聚集，且其中许多发生变性（化脓性渗出物）。渗出物还可能含有细胞碎片，既来自 resident 细胞群体，也来自浸润的白细胞；含纤维蛋白的蛋白性液体；较少的巨噬细胞；偶见的淋巴细胞或浆细胞；以及可能的感染因子。肉眼观察，这些病变以脓液存在为特征。在渗出物周围组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大型、活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。因灌胃创伤继发细菌感染的化脓性炎症在食管中相对常见（Figure 1、Figure 2、Figure 3、Figure 4）。
诊断建议
无论何时出现，炎症均应予以诊断并分级。诊断应包括指明炎症持续时间或类型的修饰词（即 急性（acute）、化脓性（suppurative）、慢性（chronic）、慢性 active 或 肉芽肿性（granulomatous））。严重程度分级取决于食管中病变的范围和细胞浸润的密度。符合脓肿的病变诊断为化脓性炎症。相关坏死或炎症通常不予记录，除非炎症或坏死是病变的重要组成部分。
参考切片图（2 张）
查看英文原文
Comment
Direct toxic effects of chemicals on the esophagus are rare in NTP studies. Esophageal inflammation in rodents is most commonly caused by gavage trauma and can be associated with ulceration, necrosis, and perforation. In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate). The exudate may also contain cell debris, both from the resident cell populations and from infiltrating leukocytes; proteinaceous fluid containing fibrin; fewer macrophages; occasional lymphocytes or plasma cells; and, possibly, an infectious agent. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation , but a significant number of neutrophils are also present. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Suppurative inflammation with secondary bacterial infection due to gavage trauma is relatively common in the esophagus ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ).
Recommendation
Whenever present, inflammation should be diagnosed and graded. The diagnosis should include a modifier indicating the duration or type of inflammation (i.e., acute, suppurative, chronic, chronic active, or granulomatous). The severity grade depends on the extent of the lesion in the esophagus and the density of the cellular infiltrate. Lesions consistent with an abscess are diagnosed as suppurative inflammation. Associated necrosis or inflammation is not generally recorded unless the inflammation or necrosis is a significant component of the lesion.
肌层变性Muscularis Degeneration 食管变性
描述（中文）
变性（degeneration）的特征是纤维体积减小（Figure 1、Figure 2）、过度收缩、“纤维扭曲卷曲”、细胞质呈均质嗜酸性至颗粒状或絮状、横纹消失以及矿化。巨噬细胞（macrophage）（Figure 3、Figure 4）常见于肌肉变性和坏死区域。灌胃创伤可导致食管肌壁损伤，引起肌肉变性和坏死或穿孔。
诊断建议
只要存在，肌层（tunica muscularis）的变性即应诊断为“食管，肌层 - 变性”，并根据病变范围进行分级。病理学家认为该病变系化学暴露所致还是灌胃操作失误所致，应在文字描述中注明。
参考切片图（2 张）
查看英文原文
Comment
Degeneration is characterized by decreased fiber size ( Figure 1 and Figure 2 ), hypercontraction, "twisting and curling of fibers," homogeneous eosinophilic to granular or floccular cytoplasm, loss of striations, and mineralization. Macrophages ( Figure 3 and Figure 4 ) are frequently found in areas of muscle degeneration and necrosis. Gavage trauma can result in damage to the muscular wall of the esophagus, resulting in muscle degeneration and necrosis or perforation.
Recommendation
Whenever present, degeneration of the tunica muscularis should be diagnosed as "esophagus, muscularis - degeneration" and graded based upon the extent of the lesion. It should be noted in the narrative whether the pathologist considers this lesion to be due to chemical exposure or a gavage error.
血管扩张Angiectasis 食管扩张
描述（中文）
血管扩张（angiectasis，血管扩张症）主要是一种自发性的、与年龄相关的病变，也可作为对化学损伤的反应出现。血管扩张由广泛扩张的血管腔隙构成，尤其是毛细血管（或血窦）和小静脉，其内衬为无明显异常的内皮细胞。血管数量不发生改变，器官间质亦无变化。应尝试区分血管扩张与血管瘤（hemangioma），尽管两者之间的差异有时并不明显。血管瘤往往表现为边界清楚、无包膜的肿块，由紧密排列的扩张血管腔隙组成。每个血管腔隙均由单层外观正常的内皮细胞围成并衬覆，这些内皮细胞排列于胶原性间隔上，间隔通常较薄，但部分具有宽阔的胶原性间质。血管扩张通常不表现为边界清楚的肿块，因为扩张的血管通道常不规则地穿行于结缔组织之中。
诊断建议
血管扩张应当被诊断，并根据病变范围给予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Angiectasis (vascular ectasia) is primarily a spontaneous, age-related lesion that can also be a response to chemical injury. Angiectasis consists of widely dilated vascular spaces, especially capillaries (or sinusoids) and venules, that are lined by unremarkable endothelial cells. The number of vessels is not altered, and there are no changes in the stroma of the organ. A distinction between angiectasis and hemangioma should be attempted, although the difference between angiectasis and hemangioma is sometimes not obvious. Hemangiomas tend to be well-circumscribed unencapsulated masses composed of tightly packed dilated vascular spaces. Each vascular space is enclosed and lined by a single layer of normal-appearing endothelial cells aligned on collagenous septa, which are usually thin, although some have broad collagenous stromata. Angiectasis does not usually present as a well-circumscribed mass, as the dilated vascular channels are often irregularly coursing through connective tissue.
Recommendation
Angiectasis should be diagnosed and given a severity grade based on the extent of the lesion.
角化过度Hyperkeratosis 食管其他
描述（中文）
角化过度（hyperkeratosis）是食管常见的改变。角化过度（角质层增厚）有两种形式：正角化性角化过度（orthokeratotic hyperkeratosis）或角化不全性角化过度（parakeratotic hyperkeratosis）。在正角化性角化过度（有时称为正角化，orthokeratosis）中，鳞状上皮细胞无核，而在角化不全性角化过度（有时称为角化不全，parakeratosis）中，鳞状上皮细胞保留固缩的细胞核。角化过度常伴随增生。饮食成分影响角化，低纤维、低蛋白或液体饮食会导致角化上皮层厚度增加。此外，不进食的动物常出现食管角化过度而无相关增生。无增生的角化过度与作为上皮增殖增强过程一部分而发生的角化过度，在解释意义上有所不同。在厌食的啮齿类动物中，过多的角质推测是由于食物通过所致的机械性去除减少。在食管角化过度与厌食相关的情况下，前胃通常也出现角化过度。在这些情况下，将没有基底细胞层增殖反应增强的证据。另外，维生素失衡和锌缺乏可引起角化不全性角化过度及相关鳞状细胞增生。
诊断建议
当黏膜增生存在时，角化过度常可见到，通常不作为一个独立病变诊断，尽管可在叙述中增生的描述中提及。当角化过度存在而无增生，或角化过度极严重时，则应记录并分级。严重程度分级基于角质厚度程度和食管受累面积。诊断中角化过度不分为正角化和角化不全，但应在叙述中充分描述。
参考切片图（2 张）
查看英文原文
Comment
Hyperkeratosis is a common alteration of the esophagus. Hyperkeratosis (thickening of the stratum corneum) occurs in two forms: orthokeratotic or parakeratotic hyperkeratosis. In orthokeratotic hyperkeratosis (sometimes referred to as orthokeratosis squamous epithelial cells are anuclear, whereas in parakeratotic hyperkeratosis (sometimes referred to as parakeratosis) the squamous epithelial cells have retained pyknotic nuclei. Hyperkeratosis frequently accompanies hyperplasia. Dietary composition affects keratinization, with low-fiber, low-protein, or liquid diets resulting in increased thickness of the keratinized epithelial layer. Also, animals that are not eating will often have hyperkeratosis of the esophagus without associated hyperplasia. Hyperkeratosis in the absence of hyperplasia has interpretative implications different from those of hyperkeratosis occurring as part of the process of enhanced epithelial proliferation. In the anorectic rodent, the excess keratin is presumably the result of reduced mechanical removal by the passage of food. In cases of hyperkeratosis in the esophagus associated with anorexia, hyperkeratosis is usually also present in the forestomach. In these situations, there will be no evidence of an increased proliferative response in the basal layer. Alternatively, vitamin imbalance and zinc deficiency can cause parakeratotic hyperkeratosis and associated squamous cell hyperplasia.
Recommendation
Hyperkeratosis is often seen when hyperplasia of the mucosa is present and is usually not diagnosed as a separate entity, although it may be mentioned in the description of hyperplasia in the narrative. When hyperkeratosis is present in the absence of hyperplasia or when hyperkeratosis is extreme, then it should be documented and graded. The severity grade is based on the degree of thickness of the keratin and the area of the esophagus affected. Hyperkeratosis is not divided into orthokeratosis and parakeratosis in the diagnosis, but this should be well described in the narrative.
出血Hemorrhage 哈氏腺出血
描述（中文）
哈德氏腺出血（Harderian gland hemorrhage）表现为腺体间质和/或腺泡内数量不等的外渗血细胞（Figure 1、Figure 2）。常见原因是眶后采血操作造成的创伤。
诊断建议
哈德氏腺出血应作出诊断并评定严重程度分级。继发于其他病变（如炎症）的出血不应单独诊断，除非其严重程度足以支持单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Harderian gland hemorrhage consists of variable numbers of extravasated blood cells in the gland interstitium and/or alveoli ( Figure 1 and Figure 2 ). A common cause is trauma from retro-orbital bleeding procedures.
Recommendation
Harderian gland hemorrhage should be diagnosed with assignment of a severity grade. Hemorrhage secondary to other lesions (e.g., inflammation) should not be diagnosed separately unless warranted by severity.
单核细胞性细胞浸润Infiltration Cellular Mononuclear Cell 哈氏腺浸润
描述（中文）
大鼠和小鼠哈德氏腺（Harderian gland）间质内小而局限的炎性细胞簇是常见的偶然性所见。这些浸润细胞最常见为单核细胞（淋巴细胞）（Figure 1、Figure 2），但也可能存在其他炎性细胞。此类浸润的发生率和严重程度增加也可与多种病理状态相关。细胞浸润与炎症的鉴别在于是否存在炎症的其他特征，如组织破坏、出血、纤维化、水肿或额外类型的白细胞。
诊断建议
哈德氏腺浸润应予以诊断并赋予严重程度分级，尤其是当发生率或严重程度出现与处理相关增加时。诊断中应以修饰词标明所存在的主要细胞类型（例如，Harderian gland - Infiltration cellular, Mononuclear cell）。若细胞类型均匀混合（即无单一细胞类型占优势），可使用修饰词“mixed”。相关链接：Harderian Gland - Inflammation
参考切片图（2 张）
查看英文原文
Comment
Small focal clusters of inflammatory cells in the interstitium are common incidental findings in the Harderian gland of rats and mice. These infiltrates are most commonly mononuclear cells (lymphocytes) ( Figure 1 and Figure 2 ), but other inflammatory cells may also be present. Increased incidences and severity of such infiltrates can also be associated with various pathologic conditions. Cellular infiltrates can be distinguished from inflammation by the presence of other features of inflammation, such as tissue destruction, hemorrhage, fibrosis, edema, or additional types of leukocytes.
Recommendation
Harderian gland infiltrates should be diagnosed and assigned a severity grade, especially when there are treatment-related increases in incidence and/or severity. The predominant type of cell present should be indicated in the diagnosis as a modifier (e.g., Harderian gland - Infiltration cellular, Mononuclear cell). If there is an even mix of cell types (i.e., no one cell type predominates), the modifier "mixed" may be used. Related Links: Harderian Gland - Inflammation
囊肿Cyst 哈氏腺囊肿
描述（中文）
哈德氏腺囊肿（Harderian gland cysts）为体积较大、明显扩张的单房至多房性腔隙（Figure 1、Figure 2），内衬扁平上皮，腔内充满数量不等的淡染无定形分泌物。通常，囊肿的直径大于扩张的腺泡。哈德氏腺囊肿不常见。
诊断建议
哈德氏腺囊肿应诊断为存在（不进行严重程度分级）。继发性炎症不应单独诊断（除非其严重程度足以支持单独诊断）。
参考切片图（2 张）
查看英文原文
Comment
Harderian gland cysts are large, widely distended, single to multiloculated spaces ( Figure 1 and Figure 2 ) lined by flattened epithelium and filled with variable amounts of pale amorphous secretory material. Typically, cysts have greater diameter than dilated gland alveoli. Harderian gland cysts are uncommon.
Recommendation
Harderian gland cysts should be diagnosed as present (without assignment of a severity grade). Secondary inflammation should not be diagnosed separately (unless warranted by severity).
坏死Necrosis 哈氏腺坏死
描述（中文）
坏死（necrosis）的特征是细胞肿胀、核固缩（pyknosis）和/或核碎裂（karyorhexis），以及细胞与结构细节的丧失。广泛性组织坏死表现为正常结构被破坏，并由坏死细胞碎片取代（Figure 1、Figure 2）。坏死通常伴有炎症。也可能存在出血或其他组织改变，如矿化。与眼球后出血操作相关的创伤是哈氏腺（Harderian gland）坏死的常见原因。哈氏腺的坏死和变性也可由过度光照引起；作为大鼠涎泪腺炎病毒（sialodacyroadentis virus）感染的早期改变；或由眼球后间隙注射刺激性物质引起。
诊断建议
如果哈氏腺坏死是原发性改变（尤其是与处理相关时），应当予以诊断并赋予严重程度分级。如果坏死是其他病变（例如广泛性炎症）的特征之一，则不应单独诊断（除非严重程度确有必要），但应在病理学叙述中加以描述。相关病变，如炎症、出血或矿化，不应单独诊断，除非严重程度确有必要。
参考切片图（2 张）
查看英文原文
Comment
Necrosis is characterized by cell swelling, nuclear pyknosis and/or karyorhexis, and loss of cellular and architectural detail. Extensive tissue necrosis is characterized by effacement of the normal architecture and replacement by necrotic cell debris ( Figure 1 and Figure 2 ). Necrosis is typically accompanied by inflammation. Hemorrhage or other tissue changes, such as mineralization, may also be present. Trauma associated with retro-bulbar bleeding procedures is a common cause of Harderian gland necrosis. Necrosis and degeneration of the Harderian gland can also result from excessive exposure to light; as an early change in sialodacyroadentis virus infection in rats; or from injection of irritants in the retrobulbar space.
Recommendation
If Harderian gland necrosis is a primary change (especially if related to treatment), it should be diagnosed and assigned a severity grade. If necrosis is a feature of other lesions (e.g., extensive inflammation), it should not be diagnosed separately (unless warranted by severity), though it should be described in the pathology narrative. Associated lesions, such as inflammation, hemorrhage, or mineralization, should not be diagnosed separately, unless warranted by severity.
增生Hyperplasia 哈氏腺增生
描述（中文）
哈德氏腺增生（Harderian gland hyperplasia）（Figure 1、Figure 2、Figure 3、Figure 4）的特征为边界清楚但无压迫性的局灶性（focal）区域，其中腺泡内衬的大细胞数量增多，染色特性与周围正常细胞略有不同。细胞核通常与正常细胞相似，但在某些病例中，细胞核可能增大（Figure 1、Figure 2）。细胞数量增多可导致细胞拥挤和形成多层细胞（Figure 3、Figure 4），甚至形成小的乳头状突起。无压迫性或无明显核多形性有助于将哈德氏腺增生与腺瘤区分开来。哈德氏腺增生可作为变性和炎症的反应性后遗症发生，但也可能是原发性毒性效应和哈德氏腺肿瘤形成的前驱病变。
诊断建议
哈德氏腺增生应当被诊断并赋予严重程度分级。应在描述中注明该增生被视为原发性效应还是继发性反应性改变，尤其是在发病率或严重程度存在处理相关差异时。
参考切片图（2 张）
查看英文原文
Comment
Harderian gland hyperplasia ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is characterized as a well-demarcated but noncompressive focal area in which alveoli are lined by increased numbers of large cells with slightly different tinctorial quality than surrounding normal cells. Nuclei are often similar to those of normal cells, but in some cases, the nuclei may be enlarged ( Figure 1 and Figure 2 ). The increased cell numbers can result in crowding and multiple cell layers ( Figure 3 and Figure 4 ), and even formation of small papillary projections. The absence of compression or marked nuclear pleomorphism can help distinguish Harderian gland hyperplasia from adenoma. Harderian gland hyperplasia may occur as a reactive sequela to degeneration and inflammation but can also be a primary toxic effect and precursor to Harderian gland neoplasia.
Recommendation
Harderian gland hyperplasia should be diagnosed and assigned a severity grade. Whether the hyperplasia is considered a primary effect or a secondary reactive change should be noted in the narrative, especially if there are treatment-related differences in incidence and/or severity.
扩张Dilation 哈氏腺扩张
描述（中文）
哈德氏腺扩张（Harderian gland dilation）的特征是哈德氏腺腺泡呈局灶性（focal）簇状分布，腺腔扩张，内衬略扁平的上皮细胞（Figure 1、Figure 2）；相关间质纤维化即使存在也极少。部分扩张的腺泡还可见腔内卟啉色素聚集体。此种扩张是大鼠和小鼠哈德氏腺常见的自发性病变，但也可由给予各种化学剂诱导发生。
诊断建议
仅当发生率或严重程度（或两者）存在处理相关差异时，才应诊断哈德氏腺扩张。诊断时，应赋予严重程度分级。相关的卟啉色素不应单独诊断（除非严重程度需要），但应在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Harderian gland dilation is characterized by focal clusters of Harderian gland alveoli with dilated lumens lined by slightly flattened epithelial cells ( Figure 1 and Figure 2 ); there is little if any associated interstitial fibrosis. Some dilated gland alveoli also exhibit intraluminal porphyrin pigment aggregates. Such dilatation is a common spontaneous finding in the Harderian glands of rats and mice but can also be induced by administration of various chemical agents.
Recommendation
Harderian gland dilation should be diagnosed only if there are treatment-related differences in incidence and/or severity. When diagnosed, it should be assigned a severity grade. The associated porphyrin pigment should not be diagnosed separately (unless warranted by severity), but should be described in the pathology narrative.
炎症Inflammation 哈氏腺炎症
描述（中文）
哈德氏腺（Harderian gland）炎症可继发于球后采血操作造成的创伤，也可由其他原因引起，如感染性病原体（例如涎泪腺炎病毒，sialodacryoadenitis virus）、异物、过度光照以及某些营养缺乏。在 NTP 研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞是中性粒细胞（neutrophil），但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，然而，在化脓性炎症中，中性粒细胞聚集，其中许多发生退变（化脓性渗出物，化脓性 exudate）。渗出物中还可能存在细胞碎片（来自 resident 细胞群和浸润白细胞）、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染性病原体。大体上，这些病变以脓液存在为特征。在渗出物周围的组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但在慢性活动性炎症中，还存在大量中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的、活化的巨噬细胞、上皮样巨噬细胞（epithelioid macrophages）或多核巨细胞。炎症与细胞浸润的不同之处在于，炎症病变有组织损伤的证据，如水肿、出血、变性、坏死、再生等。
诊断建议
哈德氏腺炎症应当诊断并赋予严重程度分级。诊断中应当包括适当的类型修饰词（急性、慢性等）。哈德氏腺中的异物可以单独诊断为存在（不赋予严重程度分级）。相关病变（例如坏死）不应单独诊断（除非严重程度 warrant），但可在叙述中描述。相关链接：哈德氏腺 - 细胞浸润，单核细胞（Harderian Gland - Infiltration Cellular, Mononuclear Cell）
参考切片图（2 张）
查看英文原文
Comment
Harderian gland inflammation can be secondary to trauma from retrobulbar bleeding procedures and can be result from other causes, such as infectious agents (e.g., sialodacryoadenitis virus), foreign bodies, excessive exposure to light, and certain nutritional deficiencies. In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation, the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation, however, in suppurative inflammation, the neutrophils are aggregated and many of them are degenerate (suppurative exudate). Cell debris, both from the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation. Lymphocytes also predominate in chronic-active inflammation, but in chronic-active inflammation, there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammation differs from cellular infiltration in that inflammatory lesions have evidence of tissue damage, such as edema, hemorrhage, degeneration, necrosis, regeneration, etc.
Recommendation
Harderian gland inflammation should be diagnosed and assigned a severity grade. An appropriate type modifiers (acute, chronic, etc.) should be included in the diangosis. Foreign bodies in the Harderian gland can be diagnosed separately as present (without assignment of a severity grade). Associated lesions (e.g., necrosis) should not be diagnosed separately (unless warranted by severity), though they can be described in the narrative. Related Links: Harderian Gland - Infiltration Cellular, Mononuclear Cell
色素Pigment 哈氏腺色素沉着
描述（中文）
脂质是啮齿类动物眶外泪腺（Harderian gland）的主要分泌产物，但卟啉色素（porphyrin pigment）也会被合成并分泌。卟啉色素在腺泡腔内表现为金黄色至深棕色的无定形团块或层状凝结物（Figure 1、Figure 2）。卟啉分泌随年龄增长而增加，过度产生可导致“红泪”（chromodacyorrhea）。偶然发生的卟啉沉积通常在雌性大鼠和小鼠的眶外泪腺中更为显著。给予各种化学物质后，卟啉分泌增加也可能是与受试物相关的效应。
诊断建议
由于卟啉色素是啮齿类动物眶外泪腺中的正常所见，只有当发生率或严重程度存在与受试物相关的差异时，才应对色素作出诊断并赋予严重程度分级。如果病理学家认为该色素由卟啉以外的物质（例如含铁血黄素（hemosiderin）或脂褐素（lipofuscin））构成，也应当作出诊断。即使使用一系列特殊染色，在组织学切片中确定色素的种类通常仍很困难。因此，推荐作出“色素”的诊断（而非诊断色素的类型，例如含铁血黄素或脂褐素），这是最恰当的做法。病理学描述应描述色素沉着的形态学特征。并非所有色素都必须作出诊断，因为有些色素在老龄动物中普遍存在，或与其他某种疾病过程相关，而不具有毒理学意义。病理学家应运用其判断力，决定继发性色素沉积是否显著到足以需要单独作出诊断。
参考切片图（2 张）
查看英文原文
Comment
Lipids are the primary secretory products of the rodent Harderian gland, but porphyrin pigment is also synthesized and secreted. Porphyrin pigment occurs as golden to dark brown amorphous clumps or laminated concretions in the alveolar lumens ( Figure 1 and Figure 2 ). Porphyrin secretion increases with age, and excessive production results in "red tears" (chromodacyorrhea). Incidentally occurring porphyrin deposits are generally more prominent in the Harderian glands of female rats and mice. Increased porphyrin secretion can also be a treatment-related effect following administration of various chemical agents.
Recommendation
Since porphyrin pigment is a normal finding in rodent Harderian glands, pigment should be diagnosed and assigned a severity grade only if there are treatment-related differences in incidence and/or severity. It should also be diagnosed if the pathologists feels the pigment is composed of something other than porphyrin (e.g., hemosiderin or lipofuscin). Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, it is recommended that a diagnosis of pigment (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should describe the morphologic features of the pigmentation. Not all pigments have to be diagnosed, as some are ubiquitous in aging animals or related to some other disease process and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether or not secondary deposits of pigment are prominent enough to warrant a separate diagnosis.
萎缩Atrophy 哈氏腺萎缩
描述（中文）
哈德氏腺（Harderian gland）萎缩（伴或不伴纤维化）可由多种原因引起，包括眼球后出血操作所致创伤；基因突变；营养缺乏；对异物或过量卟啉分泌物质积聚的反应；或各种原因所致变性或炎症的继发结果。该病变的特征为腺泡皱缩至轻度扩张、迂曲，衬覆不同程度变扁平的上皮细胞（Figure 1、Figure 2）。萎缩常伴有间质纤维化。
诊断建议
哈德氏腺萎缩只要存在即应诊断并赋予严重程度分级。任何相关的反应性纤维化除非严重程度确有必要，否则不应单独诊断，但应在病理描述中予以描述。其他相关病变（如炎症）应单独诊断。如果萎缩是另一病变（如炎症或纤维化）的主要组成部分，则无需单独诊断（除非严重程度确有必要），但应在病理描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Harderian gland atrophy (with or without concurrent fibrosis) results from various causes, including trauma from retro-bulbar bleeding procedures; genetic mutations; nutritional deficiencies; as a reaction to foreign bodies or accretions of excess porphyrin secretory material; or as a sequel to degeneration or inflammation from various causes. The lesion is characterized by alveoli that are shrunken to slightly widened, tortuous, and lined by variably flattened epithelial cells ( Figure 1 and Figure 2 ). Atrophy is often accompanied by interstitial fibrosis.
Recommendation
Harderian gland atrophy should be diagnosed and assigned a severity grade whenever present. Any associated reactive fibrosis should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative. Other associated lesions (such as inflammation) should be diagnosed separately. If atrophy is a main component of another lesion (such as inflammation or fibrosis), it need not be diagnosed separately (unless warranted by severity), but should be described in the pathology narrative.
单核细胞性细胞浸润Infiltration Cellular Mononuclear Cell 泪腺浸润
描述（中文）
散在的、大小不一的单核细胞（通常为淋巴细胞）间质灶在大鼠和小鼠的泪腺中很常见（Figure 1、Figure 2），在老年动物中其发生率和严重程度往往增加。此类浸润的发生率和严重程度增加也可作为治疗相关的毒性效应或发生于其他病理状况中。
诊断建议
只有当发生率和/或严重程度存在治疗相关差异时，才应对泪腺单核细胞浸润作出诊断并赋予严重程度分级。单核细胞浸润可通过炎症的特征与炎症相区分，如组织破坏、出血、纤维化、水肿以及其他白细胞类型的存在。相关链接：泪腺 - 炎症
参考切片图（2 张）
查看英文原文
Comment
Scattered, variably sized interstitial foci of mononuclear cells (usually lymphocytes) are common in the lacrimal glands of rats and mice ( Figure 1 and Figure 2 ), often increasing in incidence and severity in older animals. Increased incidences and severity of such infiltrates can also occur as treatment-related toxic effects or in other pathologic conditions.
Recommendation
Lacrimal gland mononuclear cell infiltrates should be diagnosed and assigned a severity grade only if there are treatment-related differences in the incidence and/or severity. Mononuclear cell infiltrates can be distinguished from inflammation by features of inflammation such as tissue destruction, hemorrhage, fibrosis, edema, and the presence of other leukocyte types. Related Links: Lacrimal Gland - Inflammation
哈德氏腺化生Metaplasia Harderian 泪腺化生
描述（中文）
大鼠和小鼠的泪腺中可出现由立方上皮细胞衬覆的管状结构簇，其胞质呈淡染、泡沫状至空泡状（类似Harderian腺腺泡）（Figure 1、Figure 2）。这种“Harderian化（harderization）”在眶外泪腺（组织学检查通常采样的泪腺）中比在眶内泪腺中更为显著。该病变的发生率和严重程度随年龄增长而增加，且在雄性大鼠中比雌性大鼠更常见、范围更广。雄性大鼠泪腺中Harderian腺型结构发育较雌性增多，是该物种该组织显著性别二态性的特征之一。在小鼠中，该病变似乎雌性比雄性更常见。这些细胞的代谢和功能特征尚未被阐明，且尚不清楚这代表真正的化生性改变还是退行性改变。
诊断建议
该所见应诊断为“泪腺 - 化生，Harderian（lacrimal gland - metaplasia, Harderian）”并赋予严重程度分级。仅当发生率和/或严重程度存在与处理相关差异时才应诊断。“异位Harderian腺（Ectopic Harderian gland）”和“异位组织（ectopic tissue）”被认为是不恰当的术语，因为它们提示发育异常。
参考切片图（2 张）
查看英文原文
Comment
Clusters of tubules lined by cuboidal cells with pale, foamy to vacuolated cytoplasm (resembling Harderian gland alveoli) can occur in the lacrimal glands of rats and mice, especially rats ( Figure 1 and Figure 2 ). This “harderization” is more prominent in the exorbital lacrimal gland (the lacrimal gland usually sampled for histology) than in the intraorbital lacrimal gland. Incidence and severity of this change increase with age, and it is more common and extensive in male than in female rats. The increased Harderian gland–type development in the lacrimal glands of male versus female rats is one feature of the prominent sexual dimorphism of this tissue in this species. In mice, this change appears to be more frequent in females than in males. The metabolic and functional characteristics of these cells have not been characterized, and it is unknown whether this represents a true metaplastic or a degenerative change.
Recommendation
This finding should be diagnosed as "lacrimal gland - metaplasia, Harderian" and assigned a severity grade. It should be diagnosed only if there are treatment-related differences in incidence and/or severity. "Ectopic Harderian gland" and "ectopic tissue" are considered inappropriate terms because they suggest a developmental anomaly.
核增大Karyomegaly 泪腺其他
描述（中文）
泪腺核巨大症（lacrimal gland karyomegaly）的特征是泪腺腺泡细胞核增大，常呈多形性，核仁明显和/或多倍体化（Figure 3、Figure 4）。有时可见核内假包涵体（intranuclear pseudoinclusions）（Figure 3），最可能是胞质内陷。受累细胞一般表现为胞质体积增大（整体细胞巨大）。这一非常常见的改变发生于大鼠和小鼠（以大鼠更常受累），并倾向于随年龄增长而发病率和严重程度增加。雄性啮齿动物比雌性更常受累且病变范围更广，这促成了该器官在小鼠尤其是大鼠中的性二态性（整体泪腺相对较大）。
诊断建议
只有当泪腺核巨大症的发病率（incidence）和/或严重程度存在与处理相关的差异时，才应作出诊断。作出诊断时，应进行分级。
参考切片图（2 张）
查看英文原文
Comment
Lacrimal gland karyomegaly is characterized by lacrimal gland acinar cells with enlarged, often pleomorphic nuclei with prominent nucleoli and/or polyploidy ( Figure 3 and Figure 4 ). Intranuclear pseudoinclusions are sometimes present ( Figure 3 ) and are most likely cytoplasmic invaginations. Affected cells generally exhibit increased cytoplasmic volume (overall cytomegaly). This very common change occurs in rats and mice (with rats more frequently affected) and tends to increase in incidence and severity with age. Male rodents are more frequently and extensively affected than females, which contributes to the sexual dimorphism (overall relatively larger lacrimal glands) of this organ in mice and especially in rats.
Recommendation
Karyomegaly in the lacrimal gland should be diagnosed only if there are treatment-related differences in incidence and/or severity. When diagnosed, it should be graded.
炎症Inflammation 泪腺炎症
描述（中文）
大鼠和小鼠的泪腺炎症可由多种原因引起，包括球后出血性外伤、感染性病原体（如大鼠的涎泪腺炎病毒）以及自身免疫性疾病。在NTP研究中，炎症有五个标准类别：急性、化脓性、慢性、慢性活动性和肉芽肿性。在急性炎症（Figure 1、Figure 2）中，主要浸润细胞是中性粒细胞，尽管也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，然而，在化脓性炎症中，中性粒细胞聚集，其中许多发生变性（化脓性渗出物）。渗出物中还可能存在细胞碎片（来自 resident 细胞群和浸润白细胞）、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染性病原体。肉眼观察，这些病变将以脓液的存在为特征。在渗出物周围的组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症（Figure 3、Figure 4）中也占主导地位，但在慢性活动性炎症中，还存在大量中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。炎症与细胞浸润的区分在于是否存在其他变化，如水肿、出血、变性、坏死或其他组织损伤的证据。
诊断建议
泪腺炎症只要存在就应诊断并赋予严重程度分级。应在诊断中通过适当的修饰词（急性、慢性等）指明炎症类型。应在病理描述中指明炎症在腺体内的位置（腺泡或导管）。相关病变（如纤维化）除非严重程度需要，否则不应单独诊断，但应在病理描述中描述。相关链接：泪腺 - 细胞浸润，单核细胞
参考切片图（2 张）
查看英文原文
Comment
Lacrimal gland inflammation in rats and mice can result from various causes, including retrobulbar bleeding trauma, infectious agents such as sialodacryoadenitis virus in rats, and autoimmune disease. In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation ( Figure 1 and Figure 2 ), the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation, however, in suppurative inflammation, the neutrophils are aggregated and many of them are degenerate (suppurative exudate). Cell debris, both from the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation. Lymphocytes also predominate in chronic-active inflammation ( Figure 3 and Figure 4 ), but in chronic-active inflammation, there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammation is differentiated from cellular infiltrates by the presence of other changes, such as edema, hemorrhage, degeneration, necrosis, or other evidence of tissue damage.
Recommendation
Lacrimal gland inflammation should be diagnosed and assigned a severity grade whenever present. The type of inflammation should be indicated in the diagnosis with an appropriate modifier (acute, chronic, etc.). The location of the inflammation within the gland (acini or duct) should be indicated in the pathology narrative. Associated lesions (e.g., fibrosis) should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative. Related Links: Lacrimal Gland - Infiltration Cellular, Mononuclear Cell
萎缩Atrophy 泪腺萎缩
描述（中文）
泪腺萎缩（Figure 1、Figure 2）在大鼠和小鼠中常见，为自发性衰老性改变，也可作为创伤、炎症或其他原发性泪腺疾病的后遗症。其特征为局灶性（focal）至融合性分布的腺泡皱缩区，衬覆小而低至扁平的立方细胞，并由不同程度增多的纤维性间质支撑。
诊断建议
泪腺萎缩应当作出诊断并赋予严重程度分级。任何相关的反应性纤维化不应单独诊断，除非其严重程度足以支持单独诊断，但可在叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Lacrimal gland atrophy ( Figure 1 and Figure 2 ) occurs commonly in rats and mice as a spontaneous aging change and can also be a sequela of trauma, inflammation, or other primary lacrimal gland disease. It is characterized by focal to confluent areas of shrunken acini lined by small, low to flattened cuboidal cells and supported by variably increased fibrous stroma.
Recommendation
Lacrimal gland atrophy should be diagnosed and assigned a severity grade. Any associated reactive fibrosis should not be diagnosed separately, unless warranted by severity, but can be described in the narrative.
前房出血Anterior Chamber Hemorrhage 眼出血
描述（中文）
前房出血（anterior chamber hemorrhage）的特征是角膜与虹膜之间的间隙内出现外渗的血细胞（Figure 1、Figure 2）。临床上，此称为前房积血（hyphema）。在实验室大鼠和小鼠中，前房出血并不少见，可作为球后采血操作所致创伤的后遗症。它也可由虹膜或睫状血管的获得性损伤（如由炎症或代谢性疾病引起）或晶状体或虹膜周围持续存在的胚胎血管渗漏引起。感染涎泪腺炎病毒（sialodacryoadenitis virus）的大鼠除其他眼部病变外，也可表现出前房出血。前房内渗出的血细胞可阻塞虹膜角膜滤角通道和/或邻近的小梁网，阻碍房水的正常引流，从而导致眼内压升高。
诊断建议
前房出血应当被诊断并赋予严重程度分级。如果前房出血是眼部更弥漫性炎症过程的一部分，则无需单独诊断，除非其严重程度使其有必要单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage in the anterior chamber is characterized by extravasated blood cells in the space between the cornea and iris ( Figure 1 and Figure 2 ). Clinically, this is referred to as hyphema. In laboratory rats and mice, anterior chamber hemorrhage is not uncommon as a sequela to trauma from retrobulbar bleeding procedures. It can also result from acquired damage to iridial or ciliary blood vessels (as from inflammation or metabolic disease) or from leakage from persistent embryonic vessels around the lens or iris. Rats with sialodacryoadenitis virus infection can also exhibit anterior chamber hemorrhage, among other ocular lesions. Extravasated blood cells in the anterior chamber can occlude the iridocorneal filtration angle channels and/or the adjacent trabecular meshwork, impeding normal drainage of aqueous humor with resultant elevations in intraocular pressure.
Recommendation
Anterior chamber hemorrhage should be diagnosed and assigned a severity grade. If anterior chamber hemorrhage is part of a more dispersed inflammatory process in the eye, it need not be diagnosed separately unless warranted by its severity.
前房蛋白性液体Anterior Chamber Proteinaceous Fluid 眼其他
描述（中文）
前房蛋白性液体（anterior chamber proteinaceous fluid）的特征为前房内积聚均匀淡嗜酸性物质（常含纤维蛋白（fibrin）），其中炎性细胞极少甚至没有（Figure 1、Figure 2）。前房蛋白性液体可压迫虹膜角膜滤角通道和/或邻近小梁网（trabecular meshwork），阻碍房水（aqueous humor）的正常引流，从而导致眼内压升高。（Figure 1 和/或 Figure 2 中的其他眼部病变包括虹膜后粘连（posterior synechiae）、伴矿化的晶状体白内障（lens cataract with mineralization）和/或虹膜炎症（iridial inflammation）。）
诊断建议
前房中的蛋白性液体应诊断为“眼，前房 - 蛋白性液体”（Eye, Anterior chamber - Proteinaceous fluid），并赋予严重程度分级。如果前房蛋白性液体是眼内更弥漫性炎症过程的一部分，则无需单独诊断，但应在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Anterior chamber proteinaceous fluid is characterized by intracameral accumulations of homogeneous pale eosinophilic material (often including fibrin) that contains few if any inflammatory cells ( Figure 1 and Figure 2 ). Anterior chamber proteinaceous fluid can compress the iridocorneal filtration angle channels and/or the adjacent trabecular meshwork, impeding normal drainage of aqueous humor with resultant elevations in intraocular pressure. (Other ocular lesions in Figure 1 and/or Figure 2 include posterior synechiae, lens cataract with mineralization, and/or iridial inflammation.)
Recommendation
Proteinaceous fluid in the anterior chamber should be diagnosed as "Eye, Anterior chamber - Proteinaceous fluid" and assigned a severity grade. If anterior chamber proteinaceous fluid is part of a more dispersed inflammatory process in the eye, it need not be diagnosed separately but should be described in the pathology narrative.
巩膜骨性化生Sclera Metaplasia Osseous 眼化生
描述（中文）
巩膜骨性化生（osseous metaplasia）是一种随年龄增长而发生的偶然性改变，在Fischer 344/N大鼠中频繁发生，在其他常见大鼠品系中较少发生，而在小鼠中即使有也极为罕见。其表现为单个至多个、离散的、分化良好的矿化骨灶。偶尔可观察到类似的巩膜软骨灶（软骨性化生，cartilaginous metaplasia）。这些无害的结构不会引起巩膜或邻近组织的病理学改变。
诊断建议
巩膜骨性化生只有在与处理相关时才应诊断，但不需要严重程度分级（即应记录为“存在”）。
参考切片图（2 张）
查看英文原文
Comment
Osseous metaplasia of the sclera is an incidental aging change that occurs frequently in Fischer 344/N rats, less often in other common rat strains, and seldom if ever in mice. It consists of single to multiple, discrete foci of well-differentiated, mineralized bone. Occasionally, similar scleral foci of cartilage are observed (cartilaginous metaplasia). These innocuous structures do not incite pathologic changes in the sclera or adjacent tissues.
Recommendation
Scleral osseous metaplasia should be diagnosed only if treatment related, but it does not need a severity grade (i.e., it should be recorded as "present").
晶状体白内障Lens Cataract 眼其他
描述（中文）
白内障（cataract）是晶状体混浊（囊性、囊下、前皮质或后皮质或核性），可由任何原因引起，包括遗传、创伤、代谢性疾病、营养失衡、环境因素、眼内压升高、衰老以及过度暴露于电离辐射或环境光。白内障也可与其他眼部疾病并发或继发于其他眼部疾病，如严重炎症、虹膜粘连和/或视网膜变性。病因不明、偶然发生的自发性白内障在老龄大鼠和小鼠中并不少见。白内障的特征是晶状体纤维具有各种异常特征，包括分离、肿胀、颗粒化、浓缩、断裂和正常有序结构的破坏，以及数个肿胀晶状体纤维中晶状体纤维核的异常滞留（Figure 1、Figure 2）。伴有异常滞留核的肿胀晶状体纤维有时被称为“膀胱”细胞或“气球”细胞。白内障还可表现出其他特征，如囊膜增厚、皱褶和/或破裂（Figure 3）或晶状体纤维或囊膜矿化（Figure 4）。白内障晶状体的前上皮细胞也可在损伤刺激下发生增殖和纤维化生（上皮-间充质转化）。白内障晶状体中还可能有前囊下纤维化（Figure 5）（注意混杂的深嗜酸性、碎裂的晶状体纤维物质），以及前上皮增生（Figure 6）。增殖的前上皮还可延伸至晶状体弓后方（晶状体上皮后移）（Figure 6）。
诊断建议
白内障应被诊断并赋予严重程度分级。诊断中应包含部位修饰词“lens”（即 Eye, Lens - Cataract）。如果与治疗效应的特征描述相关，白内障的亚定位（囊下、皮质、核性等）应在病理学叙述中描述，但不应包含在诊断中。白内障的形态学特征（矿化、纤维化生、膀胱细胞等）不应单独诊断，但也应在叙述中描述。相关病变（如后粘连）应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
A cataract is a lens opacity (capsular, subcapsular, anterior or posterior cortical, or nuclear) resulting from any cause, including heredity, trauma, metabolic disease, nutritional imbalance, environmental factors, increased intraocular pressure, aging, and excessive exposure to ionizing radiation or ambient light. Cataracts can also be concurrent with or secondary to other ocular disease, such as severe inflammation, iridial synechiae, and/or retinal degeneration. Incidental, spontaneously occurring cataracts of uncertain etiology are not uncommon in aging rats and mice. Cataracts are characterized by lens fibers with various abnormal features, including separation, swelling, granularity, condensation, fragmentation, and disruption of the normally orderly configuration, as well as abnormal retention of lens fiber nuclei in several swollen lens fibers ( Figure 1 and Figure 2 ). Swollen lens fibers with abnormally retained nuclei are sometimes referred to as "bladder" or "balloon" cells. Cataracts can also exhibit additional features, such as capsular thickening, wrinkling, and/or rupture ( Figure 3 ) or lens fiber or capsular mineralization ( Figure 4 ). Anterior epithelial cells of cataractous lens can also undergo proliferation and fibrous metaplasia (epithelial-to-mesenchymal transition) in response to injury. There may also be anterior subcapsular fibrosis ( Figure 5 ) in a cataractous lens (note the intermixed dark eosinophilic, fragmented lens fiber material), as well as hyperplasia of the anterior epithelium of ( Figure 6 ). The proliferative anterior epithelium may also extend posterior to the lens bow (posterior migration of lens epithelium) ( Figure 6 ).
Recommendation
Cataracts should be diagnosed and assigned a severity grade. The site modifier "lens" should be included in the diagnosis (i.e., Eye, Lens - Cataract). If pertinent to the characterization of a treatment effect, the subtopographical localization of cataracts (subcapsular, cortical, nuclear, etc.) should be described in the pathology narrative but should not be included in the diagnosis. Morphologic features of cataracts (mineralization, fibrous metaplasia, bladder cells, etc.) should not be diagnosed separately, but should also be described in the narrative. Associated lesions (e.g., posterior synechia) should be diagnosed separately.
炎症Inflammation 眼炎症
描述（中文）
除角膜可能例外，眼部炎症是一种不常见的背景性病变。它可以发生在任何眼部结构中，并且常常同时出现于多个眼部结构。眼部炎症有多种原因，包括外伤（尤其是角膜）、化学刺激物和全身性毒素。角膜炎症可以是弥漫性的，也可以局限于特定区域，例如上皮或基质。除上述原因外，角膜炎症还可由泪液分泌不足、营养缺乏以及感染因子（如细菌、真菌和病毒）引起。由于角膜通常是无血管组织，基质新生血管形成是角膜炎症性病变的常见组成部分。上皮增生也是常见的表现（Figure 1、Figure 2）。在慢性病变中，可见基质纤维化。虽然完整的角膜对大多数细菌性病原体具有抵抗力，但上皮的任何破损（例如由擦伤、穿透性损伤或毒素诱导的坏死引起）都可能引入细菌，从而引发炎症反应。细菌还可继发性定植于原有的炎症区域（Figure 3、Figure 4）和/或溃疡区域。前房炎症可延伸至邻近的虹膜、睫状体和晶状体。前房中的炎症细胞可阻塞虹膜角膜滤角通道和/或邻近的小梁网，阻碍房水的正常引流，从而导致眼内压升高。临床上，前房内中性粒细胞积聚称为前房积脓（hypopyon）。前葡萄膜束（虹膜和睫状体）炎症可由多种原因引起，例如细菌和病毒等感染因子，以及免疫介导（过敏性）反应。虹膜和睫状体炎症（Figure 7、Figure 8, and Figure 9）常延伸至邻近的前房和后房、角膜和/或脉络膜。同样，脉络膜（后葡萄膜）炎症（Figure 10、Figure 11）常延伸至前葡萄膜束（睫状体和虹膜）和/或邻近的视网膜。玻璃体炎症（Figure 12、Figure 13）的特征是玻璃体内有明显的炎症细胞积聚。玻璃体炎症可由外伤（例如玻璃体内注射或其他穿透性损伤）引起，也可作为玻璃体内或全身给予毒素的原发效应而发生。它也可继发于其他眼部病变，如白内障和视网膜炎症。慢性炎症性浸润常伴有玻璃体纤维化。球后炎症（Figure 14、Figure 15）最常由球后出血性操作所致的外伤引起，通常为急性。它常伴有出血。在NTP研究中，炎症有五个标准类别：急性、化脓性、慢性、慢性活动性和肉芽肿性。在急性炎症中，主要浸润细胞是中性粒细胞，尽管也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，然而，在化脓性炎症中，中性粒细胞聚集，其中许多发生退变（化脓性渗出物）。渗出物中还可能存在来自驻留细胞群和浸润白细胞的细胞碎片、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子。肉眼上，这些病变的特征是存在脓液。在渗出物周围的组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但在慢性活动性炎症中，还有大量中性粒细胞。两种病变都可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的、活化的巨噬细胞、上皮样巨噬细胞或多核巨细胞。炎症与细胞性浸润的鉴别在于存在其他变化，如水肿、出血、变性、坏死或其他组织损伤的证据。
诊断建议
眼部炎症只要存在就应诊断并分级。炎症应对每个眼部结构（例如角膜、前房、虹膜、睫状体、视网膜）分别诊断。如果炎症位于球后间隙，应使用修饰词“retrobulbar”。诊断中应包含适当的类型修饰词（急性、慢性等）。两个或更多亚部位（例如睫状体和虹膜）不应在同一行条目诊断中使用。相关病变，如纤维化或新生血管形成，除非因严重程度而有必要，不应单独诊断，但应在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
With the possible exception of the cornea, ocular inflammation is an uncommon background lesion. It can occur in any of the ocular structures and often present in multiple ocular structures concurrently. Ocular inflammation has a number of causes, including trauma (especially the cornea), chemical irritants, and systemic toxins. Corneal inflammation can be diffuse or localized in particular zones, such as the epithelium or stroma. In addition to the causes listed above, corneal inflammation can also be caused by insufficient tear production, nutritional deficiencies, and infectious agents, such as bacteria, fungi, and viruses. Since the cornea is normally an avascular tissue, stromal neovascularization is a common component of corneal inflammatory lesions. Hyperplasia of the epithelium is also a frequent finding ( Figure 1 and Figure 2 ). In chronic lesions, stromal fibrosis may be seen. While the intact cornea is resistant to most bacterial pathogens, any breach in the epithelium (e.g., from abrasions, penetrating injury, or toxin-induced necrosis) can introduce bacteria, which incite an inflammatory response. Bacteria can also secondarily colonize preexisting areas of inflammation ( Figure 3 and Figure 4 ) and/or ulceration. Anterior chamber inflammation can extend into the adjacent iris, ciliary body, and lens. Inflammatory cells in the anterior chamber can occlude the iridocorneal filtration angle channels and/or the adjacent trabecular meshwork, impeding normal drainage of aqueous humor with resultant elevations in intraocular pressure. Clinically, intracameral accumulations of neutrophils are referred to as hypopyon. Anterior uveal tract (iris and ciliary body) inflammation can result from various causes, such as infectious agents such as bacteria and viruses, and immune-mediated (allergic) reactions. Iridial and ciliary body inflammation ( Figure 7 , Figure 8 , and Figure 9 ) often extends into the adjacent anterior and posterior chambers, cornea, and/or choroid. Likewise, inflammation of the choroid, or posterior uvea ( Figure 10 and Figure 11 ), often extends into the anterior uveal tract (ciliary body and iris) and/or into the adjacent retina. Vitreal inflammation ( Figure 12 and Figure 13 ) is characterized by prominent accumulations of inflammatory cells in the vitreous. Vitreal inflammation can result from trauma (e.g., from intravitreal injections or other penetrating injury) or as a primary effect of intravitreally or systemically administered toxins. It can also occur secondary to other ocular lesions, such as cataracts and retinal inflammation. Chronic inflammatory infiltrates are often accompanied by vitreal fibrosis. Retrobulbar inflammation ( Figure 14 and Figure 15 ) is most frequently caused by trauma due to retrobulbar bleeding procedures and is typically acute. It is often accompanied by hemorrhage. In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation, the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation, however, in suppurative inflammation, the neutrophils are aggregated and many of them are degenerate (suppurative exudate). Cell debris, both from the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation. Lymphocytes also predominate in chronic-active inflammation, but in chronic-active inflammation, there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammation is differentiated from cellular infiltrates by the presence of other changes, such as edema, hemorrhage, degeneration, necrosis, or other evidence of tissue damage.
Recommendation
Inflammation in the eye should be diagnosed and graded whenever present. Inflammation should be diagnosed separately for each ocular structure (e.g., cornea, anterior chamber, iris, ciliary body, retina). The modifier as "retrobulbar" should be used if the inflammation is in the retrobulbar space. An appropriate type modifier (acute, chronic, etc.) should be included in the diagnosis. Two or more subtopographies (e.g., ciliary body and iris) should not be used in the same line-entry diagnosis. Associated lesions, such as fibrosis or neovascularization should not be diagnosed separately, unless warranted by severity, but should be described in the pathology narrative.
玻璃体出血Vitreous Hemorrhage 眼出血
描述（中文）
玻璃体出血（vitreous hemorrhage）（Figure 1、Figure 2、Figure 3、Figure 4）的特征是玻璃体内出现外渗血液的积聚。常同时存在视网膜脱离和/或变性。玻璃体出血可源于持续性胎儿（玻璃体）血管或视网膜血管的渗漏，可继发于玻璃体内注射或眶后出血操作所致的创伤，也可继发于炎症。
诊断建议
玻璃体出血应当被诊断并赋予严重程度分级。如果玻璃体出血继发于其他病变（例如炎症），则不应单独诊断，除非严重程度确有必要，但应在病理学叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Vitreous hemorrhage ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is characterized by accumulations of extravasated blood in the vitreous. Retinal detachment and/or degeneration are often present concurrently. Vitreous hemorrhage can be due to leakage from persistent fetal (hyaloid) vessels or from retinal vessels, can follow trauma from intravitreal injections or retro-orbital bleeding procedures, or can be secondary to inflammation.
Recommendation
Vitreous hemorrhage should be diagnosed and assigned a severity grade. If vitreal hemorrhage is secondary to other lesions (e.g., inflammation), it should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative.
玻璃体纤维化Vitreous Fibrosis 眼纤维化
描述（中文）
玻璃体的各种损伤（穿透性损伤、炎症等）可导致反应性血管化和机化，并伴有玻璃体纤维结缔组织增生（玻璃体瘢痕或纤维膜形成）。在早期纤维化中，疏松的纤维结缔组织填充晶状体与视网膜之间的玻璃体空间（Figure 1、Figure 2）。更进展的纤维化（Figure 3、Figure 4）以致密的成熟纤维组织层为特征，取代正常玻璃体。玻璃体纤维化常伴有慢性炎症和/或色素性巨噬细胞聚集（Figure 1、Figure 2、Figure 3、Figure 4）。反应性视网膜色素上皮（retinal pigment epithelium，RPE）细胞可经视网膜迁移进入玻璃体（Figure 5），并沿视网膜内表面蔓延。此类迁移的 RPE 细胞可发生纤维性化生（上皮-间充质转化）而转变为成纤维细胞样细胞，并参与异常玻璃体纤维组织的形成，包括视网膜表面及其他眼后段结构上的纤维膜。参与玻璃体纤维化发生的其他细胞包括活化的常驻玻璃体透明细胞、视网膜 Müller 细胞和星形胶质细胞、移入的巨噬细胞以及巩膜成纤维细胞。晚期玻璃体纤维化中偶尔可形成软骨性或骨性化生（Figure 6）。
诊断建议
玻璃体纤维化应作出诊断并赋予严重程度分级。若与描述治疗相关效应有关，应在文字描述中描述纤维组织的形态和分布（例如视网膜前膜）。病理学家应自行判断在特定动物中是仅诊断玻璃体炎症还是玻璃体纤维化，抑或两者均诊断。RPE 细胞迁移以及软骨性和骨性化生等特征不应单独诊断，但可在病理学文字描述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Various insults to the vitreous (penetrating injury, inflammation, etc.) can result in reactive vascularization and organization with proliferation of vitreal fibrous connective tissue (vitreal scar or fibrous membrane formation). In early fibrosis, loose fibrous connective tissue fills the vitreous space ( Figure 1 and Figure 2 ) between the lens and retina. More advanced fibrosis ( Figure 3 and Figure 4 ) is characterized by dense sheets of mature fibrous tissue that replace the normal vitreous. Vitreous fibrosis is often associated with chronic inflammation and/or pigmented macrophage accumulations ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Reactive retinal pigment epithelium (RPE) cells may migrate transretinally into the vitreous ( Figure 5 ) and spreading along the inner surface of the retina. Such migrant RPE cells can undergo fibrous metaplasia (epithelial-to-mesenchymal transition) into fibroblast-like cells and participate in the formation of abnormal vitreal fibrous tissue, including fibrous membranes on the surface of the retina and other posterior ocular structures. Other cells that participate in development of vitreal fibrosis include activated resident vitreal hyalocytes, retinal Müller cells and astrocytes, immigrant macrophages, and scleral fibroblasts. Cartilaginous or osseous metaplasia can occasionally form in late-stage vitreal fibrosis ( Figure 6 ).
Recommendation
Vitreous fibrosis should be diagnosed and assigned a severity grade. If pertinent to the characterization of a treatment-related effect, the morphology and distribution of the fibrous tissue (e.g., epiretinal membranes) should be described in the narrative. The pathologist should exercise judgment in deciding whether to diagnose only vitreal inflammation or vitreal fibrosis in a given animal, or whether to diagnose both. Features such as RPE cell migration and cartilaginous and osseous metaplasia should not be diagnosed separately, though they can be described in the pathology narrative.
玻璃体蛋白性液体Vitreous Proteinaceous Fluid 眼其他
描述（中文）
玻璃体内蛋白质性液体（proteinaceous fluid）（Figure 1）的特征为玻璃体内积聚均匀、淡染、嗜酸性物质（与蛋白质性或纤维素性液体相符），其中无或极少炎性细胞。原因包括（但不限于）晶状体白内障及视网膜脱离和变性。当存在视网膜脱离时，视网膜下间隙可能有类似液体（Figure 1）。
诊断建议
玻璃体内蛋白质性液体无论何时出现均应诊断并赋予严重程度分级。相关病变（如晶状体白内障或视网膜脱离）应单独诊断。若液体中存在大量炎性细胞，炎症可能是更合适的诊断。
参考切片图（1 张）
查看英文原文
Comment
Proteinaceous fluid in the vitreous ( Figure 1 ) is characterized by accumulations of homogeneous, pale, eosinophilic material (consistent with proteinaceous or fibrinous fluid) with no or very few inflammatory cells in the vitreous. Causes include (but are not limited to) lens cataract and retinal detachment and degeneration. When there is retinal detachment, there may be similar fluid in the subretinal space ( Figure 1 ).
Recommendation
Intravitreal accumulations of proteinaceous fluid should be diagnosed whenever present and assigned a severity grade. Associated lesions (e.g., lens cataract or retinal detachment) should be diagnosed separately. If there are a significant number of inflammatory cells within the fluid, inflammation may be a more appropriate diagnosis.
球后出血Retrobulbar Hemorrhage 眼出血
描述（中文）
球后区域出血（Figure 1、Figure 2）的特征是外渗血液的积聚。球后和/或眼部炎症也可能存在。此类所见通常是眶后采血操作所致创伤的结果。
诊断建议
球后出血应当作出诊断并赋予严重程度分级。如果它是继发于另一病理过程（例如眶内肿瘤形成），则不应单独诊断，而应在病理学叙述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage of the retrobulbar region ( Figure 1 and Figure 2 ) is characterized by accumulations of extravasated blood. Retrobulbar and/or ocular inflammation may also be present. Such findings are generally the result of trauma from retro-orbital bleeding procedures.
Recommendation
Retrobulbar hemorrhage should be diagnosed and assigned a severity grade. If it is secondary to another pathologic process (e.g., intraorbital neoplasia), it should not be diagnosed separately, but should be described in the pathology narrative.
眼球萎缩Phthisis Bulbi 眼其他
描述（中文）
眼球痨（phthisis bulbi）（Figure 1、Figure 2、Figure 3、Figure 4）是用于描述“终末期”眼球形态的诊断术语，该形态由多种原因所致的严重损伤引起，例如创伤、炎症、电离辐射或环境光过度暴露，或眶内占位性肿块（如哈德氏腺肿瘤）的物理压迫（Figure 4）。眼球痨的特征是眼球显著皱缩，伴有眼结构的明显移位和结构紊乱。
诊断建议
眼球痨应诊断为存在，但不进行严重程度分级。眼部各亚部位的变化不应单独诊断，因为它们已包含在集合性诊断术语“眼球痨”中。如果存在诱发原因（例如异物），应单独诊断，并应在叙述中描述这两种病变之间的关联。
参考切片图（2 张）
查看英文原文
Comment
Phthisis bulbi ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is the diagnostic term used for the "end-stage" eye morphology resulting from severe injury from various causes, such as trauma, inflammation, excess exposure to ionizing radiation or ambient light, or physical compression by space-occupying orbital masses, such as neoplasms of the Harderian gland ( Figure 4 ). Phthisis bulbi is characterized by prominent shrinkage of the globe with marked displacement and disorganization of ocular structures.
Recommendation
Phthisis bulbi should be diagnosed as present without assignment of a severity grade. Changes in the various ocular subtopographies should not be diagnosed separately as they are included in the collective diagnostic term "phthisis bulbi." If an inciting cause (e.g., a foreign body) is present, it should be diagnosed separately, and the association between the two lesions should be described in the narrative.
结膜水肿Conjunctiva Edema 眼水肿
描述（中文）
球结膜水肿（Figure 1、Figure 2、Figure 3）的特征是清亮至淡嗜酸性液体积聚所致的弥漫性肿胀。临床上，结膜水肿称为 chemosis。它是一种非特异性病变，继发于局部刺激物、变应原、创伤和感染因子等原因。水肿区域可能存在炎性细胞。
诊断建议
结膜水肿应当被诊断并赋予严重程度分级。如果位于球结膜，水肿可在器官/亚部位“眼，结膜”下诊断。如果位于睑结膜，则可在“皮肤，眼睑”的器官/亚部位下诊断。如果继发于另一过程（例如炎症），结膜水肿不应单独诊断（除非严重程度确有必要），而应在叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Edema of the bulbar conjunctiva ( Figure 1 , Figure 2 , and Figure 3 ) is characterized by diffuse swelling due to accumulation of clear to pale eosinophilic fluid. Clinically, conjunctival edema is referred to as chemosis. It is a nonspecific finding secondary to such causes as topical irritants, allergens, trauma, and infectious agents. Inflammatory cells may be present in the edematous areas.
Recommendation
Conjunctival edema should be diagnosed and assigned a severity grade. If located in the bulbar conjunctiva, edema can be diagnosed under the organ/subtopography "eye, conjunctiva." If located in the palpebral conjunctiva, it can be diagnosed under the organ/subtopography of “skin, eyelid.” If secondary to another process (e.g., inflammation), conjunctival edema should not be diagnosed separately (unless warranted by severity) but should be described in the narrative.
虹膜粘连Iris Synechia 眼其他
描述（中文）
眼粘连（ocular synechiae）是指虹膜与其他眼部结构之间的异常粘连。其原因包括眼内炎症，尤其是虹膜和睫状体的炎症。粘连也可是多种眼部疾病的后遗症，如白内障、眼内压升高、压迫性或浸润性眼内肿瘤，以及由各种原因引起的炎症。前粘连（anterior synechia）（Figure 1、Figure 2、Figure 3、Figure 4）是由于异常纤维血管组织形成而导致的虹膜与角膜后表面的粘连。后粘连（posterior synechia）（Figure 3、Figure 4、Figure 5、Figure 6）是由于异常纤维血管组织形成而导致的虹膜与晶状体前囊和/或玻璃体的粘连。也可同时存在前粘连和后粘连（Figure 3、Figure 4）。相关病变包括葡萄肿（staphyloma，虹膜部分突入角膜基质）、葡萄膜内翻（entropion uveae，虹膜瞳孔缘向后翻转）、异常纤维血管膜导致瞳孔阻塞以及炎症等。
诊断建议
粘连只要存在即应诊断，但不应进行分级。诊断中应包含部位修饰词“iris”。诊断中还应包含指示粘连为前部或后部的修饰词。如果同时存在前粘连和后粘连，则不应使用修饰词，但应在病理描述中指明两者均存在。相关病变（如炎症）应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Ocular synechiae are abnormal adhesions of the iris to other ocular structures. Causes include intraocular inflammation, especially of the iris and ciliary body. Synechiae can also be sequelae of many ocular diseases, such as cataract, increased intraocular pressure, compressive or invasive intraocular neoplasms, and inflammation resulting from various causes. Anterior synechia ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is an adhesion of the iris to the posterior cornea due to abnormal fibrovascular tissue formation. Posterior synechia ( Figure 3 , Figure 4 , Figure 5 , and Figure 6 ) is an adhesion of the iris to the anterior lens capsule and/or vitreous due to abnormal fibrovascular tissue formation. There can also be concurrent anterior and posterior synechiae ( Figure 3 and Figure 4 ). Associated lesions include staphyloma (partial protrusion of the iris into the corneal stroma), entropion uveae (posterior inversion of the pupillary margin of the iris), occlusion of the pupil by an abnormal fibrovascular membrane, and inflammation, among others.
Recommendation
Synechiae should be diagnosed whenever present, but should not be graded. The site modifier "iris" should be included in the diagnosis. A modifier indicating whether the synechia is anterior or posterior should also be included in the diagnosis. If both anterior and posterior synechiae are present, no modifier should be used, but it should be indicated in the pathology narrative that both are present. Associated lesions (e.g., inflammation) should be diagnosed separately.
视神经变性Optic Nerve Degeneration 眼变性
描述（中文）
视神经变性（optic nerve degeneration）可由多种原因引起，包括眼内压升高、血管供应受损以及物理性创伤（例如来自眶后采血操作）。由于视神经由视网膜神经节细胞的轴突构成，视网膜的原发性病变（尤其是影响神经节细胞层和神经纤维层的病变）常导致并发的视神经病理改变，包括变性。由于视神经是脑的颅外白质束，视神经变性也可以是继发于脑部病变的“下行性”改变。尽管程度可随啮齿动物品系而异，视神经轴突变性和丢失也可以是大鼠和小鼠的年龄相关偶然性改变。病因不明的视神经变性也有报道为成年大鼠的自发性改变。视神经变性的特征可为散在的空泡（如 Figure 1、Figure 2 所示），其中常含有肿胀、淡染的嗜酸性粒细胞（eosinophil）碎片化轴突和/或髓鞘碎片。在更慢性的病例中，可出现轴突数量减少、残留轴突直径减小以及软膜隔增厚。轴突丢失可导致神经整体直径减小。可同时发生程度不等的胶质细胞增生和/或巨噬细胞浸润。
诊断建议
视神经变性应当诊断并赋予严重程度分级。视神经变性的存在应当促使仔细检查视网膜（尤其是神经节细胞层和神经纤维层）以发现并发病理改变。相关病变（例如炎症）应当单独诊断。相关链接：Eye - Optic Nerve - Gliosis
参考切片图（2 张）
查看英文原文
Comment
Optic nerve degeneration can result from various causes, including increased intraocular pressure, compromised vascular supply, and physical trauma (e.g., from retro-orbital bleeding procedures). Since the optic nerve is composed of the axons of retinal ganglion cells, primary lesions in the retina (especially those affecting the ganglion cell and nerve fiber layers) frequently result in concurrent optic nerve pathology, including degeneration. Since the optic nerve is an extracranial white matter tract of the brain, optic nerve degeneration can also be a "descending" change secondary to lesions in the brain. Although the extent can vary with rodent strain, optic nerve axonal degeneration and loss can also be an age-related incidental change in rats and mice. Optic nerve degeneration of uncertain etiology has also been reported as a spontaneous change in adult rats. Optic nerve degeneration can be characterized by scattered clear vacuoles (as in Figure 1 and Figure 2 ), which often contain swollen, pale eosinophilic fragmented axons and/or myelin debris. In more chronic cases, there can be decreased numbers of axons, decreased diameter of the remaining axons, and pial septa thickening. The loss of axons may lead to decreased overall diameter of the nerve. Variable glial cell proliferation and/or macrophage infiltration may occur concurrently.
Recommendation
Optic nerve degeneration should be diagnosed and assigned a severity grade. The presence of optic nerve degeneration should prompt careful examination of the retina (especially the ganglion cell and nerve fiber layers) for concurrent pathology. Associated lesions (e.g., inflammation) should be diagnosed separately. Related Links: Eye - Optic Nerve - Gliosis
视神经胶质增生Optic Nerve Gliosis 眼其他
描述（中文）
视神经中的胶质细胞增生和/或活化（胶质增生）通常作为与视神经变性相关的反应性改变而发生。其病因多样，如创伤或眼内压升高，其特征为胶质细胞数量呈局灶性（focal）至弥漫性（diffuse）性增加（Figure 1、Figure 2、Figure 3）。增加的胶质细胞群体可包括星形胶质细胞、少突胶质细胞和/或小胶质细胞。增生的星形胶质细胞可表现出反应性表型，胞质体积增大、细胞突起增粗、细胞核更大且更具囊泡状。其代谢活性亦增强。反应性少突胶质细胞和小胶质细胞同样发生形态学和代谢改变。反应性星形胶质细胞、结缔组织成分及其他胶质细胞的局灶性性聚集有时被称为“胶质瘢痕”。
诊断建议
视神经胶质增生应当被诊断并赋予严重程度分级。视神经胶质增生的存在应当促使仔细检查视网膜（尤其是神经节细胞层和神经纤维层）以发现并存的病理变化。相关病变，如视神经变性，应当单独诊断。相关链接：Eye - Optic Nerve - Degeneration
参考切片图（2 张）
查看英文原文
Comment
Glial cell proliferation and/or activation (gliosis) in the optic nerve usually occurs as a reactive change associated with optic nerve degeneration. It has various causes, such as trauma or increased intraocular pressure, and is characterized by focal to diffuse increases in the numbers of glial cells ( Figure 1 , Figure 2 , and Figure 3 ). The increased glial cell populations can consist of astrocytes, oligodendrocytes, and/or microglia. Proliferating astrocytes can exhibit a reactive phenotype, with increased cytoplasmic volume, thicker cell processes, and larger, more vesicular nuclei. They also become more metabolically active. Reactive oligodendrocytes and microglia also undergo morphologic and metabolic changes. Focal accumulations of reactive astrocytes, connective tissues elements, and other glial cells are sometimes referred to as "glial scars."
Recommendation
Optic nerve gliosis should be diagnosed and assigned a severity grade. The presence of optic nerve gliosis should prompt careful examination of the retina (especially the ganglion cell and nerve fiber layers) for concurrent pathology. Associated lesions, such as optic nerve degeneration, should be diagnosed separately. Related Links: Eye - Optic Nerve - Degeneration
视网膜出血Retina Hemorrhage 眼出血
描述（中文）
出血（Hemorrhage）（Figure 1、Figure 2、Figure 3）定义为血液细胞外渗（即位于血管之外）。在视网膜中，出血通常继发于创伤、脱离或炎症，但也可能由代谢性疾病或毒素导致的视网膜血管病变所引起。
诊断建议
当视网膜出血为原发性发现时，应当对其进行诊断并赋予严重程度分级。继发于其他病变（如脱离或炎症）的视网膜出血不应单独诊断（除非因严重程度而有必要），但应在病理学叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage ( Figure 1 , Figure 2 , and Figure 3 ) is defined as extravasated blood cells (i.e., outside the blood vessels). In the retina, it is usually secondary to trauma, detachment, or inflammation. but can also result from pathology of the retinal vasculature due to metabolic disease or toxins.
Recommendation
Retinal hemorrhage should be diagnosed and assigned a severity grade when it is a primary finding. Retinal hemorrhage secondary to other lesions, such as detachment or inflammation, should not be diagnosed separately (unless warranted by severity) but should be described in the pathology narrative.
视网膜发育不良Retina Dysplasia 眼其他
描述（中文）
视网膜发育不良（retinal dysplasia）（Figure 1、Figure 2）是一种偶见的发育异常，偶尔见于大鼠和小鼠。其表现为视网膜各层不同程度的 局灶性（focal） 内褶或菊形团样结构，有时伴有结构发育不良或排列紊乱。通常几乎没有并发的变性或坏死。轻微病例无临床意义。视网膜发育不良在某些小鼠中作为一种遗传性基因缺陷发生，类似的改变也可通过胎儿期某些营养素缺乏或围产期给予毒素在大鼠幼仔中诱导产生。然而，大鼠和小鼠中大多数病例的确切病因尚不清楚。
诊断建议
视网膜发育不良应诊断为存在（不指定严重程度分级）。然而，如果严重程度分级有助于阐明处理效应（尤其是在围产期暴露研究中），则可进行分级。
参考切片图（2 张）
查看英文原文
Comment
Retinal dysplasia ( Figure 1 and Figure 2 ) is an incidental developmental anomaly occasionally noted in rats and mice. It consists of variably extensive focal infoldings or rosette-like formations of the retinal layers, sometimes with poorly developed or disorganized architecture. There is usually little if any concurrent degeneration or necrosis. Minor cases are of no clinical significance. Retinal dysplasia occurs as a heritable genetic defect in some mice, and similar changes have been induced in rat pups by deficiencies of certain nutrients during the fetal period or by perinatal administration of toxins. However, the exact cause of most cases in rats and mice is unknown.
Recommendation
Retinal dysplasia should be diagnosed as present (no severity grade assigned). However, severity grades could be assigned if they would help clarify a treatment effect (especially in perinatal exposure studies).
视网膜变性Retina Degeneration 眼变性
描述（中文）
大鼠和小鼠的视网膜变性可作为衰老性改变发生，也可继发于多种损伤，如物理性创伤、视网膜脱离、炎症、感染性病原体（例如病毒）、血管紊乱（例如梗死）、眼内压升高和营养缺乏。在许多实验室小鼠和大鼠品系中也已记录到多种遗传性视网膜变性。当大鼠和小鼠（尤其是白化品系）暴露于过强的环境光照时，可发生所谓的光诱导性视网膜变性。视网膜变性也可为全身或局部给予化学物的直接毒性效应。在实验室大鼠和小鼠中也有病因不明的自发性视网膜变性报道。在许多类型的视网膜变性中，最常受累的视网膜神经元是视杆和视锥光感受器及/或神经节细胞。根据病因不同，退行性改变可局限于（或更广泛地分布于）特定的视网膜拓扑区域（即上方与下方、中央与周边）。轻度视网膜变性（Figure 2，与Figure 1比较）通常由视杆和视锥光感受器突丢失、外核层光感受器细胞凋亡、内、外核层细胞减少和结构紊乱，以及丛状层变窄或消失组成。更明显的视网膜变性（Figure 3，与Figure 1比较）通常以整体变薄、结构破坏和细胞成分丢失，以及视杆和视锥光感受器及丛状层完全消失为特征。变性视网膜还可表现出其他形态学特征，如视网膜胶质细胞（例如Müller细胞和星形胶质细胞）的弥漫性（diffuse）或nodular增生、固定皱褶和菊形团样结构、视网膜内腔隙或囊肿（“微囊样”形成和视网膜劈裂），以及相邻视网膜色素上皮的伴发性增生和/或视网膜内迁移。大鼠和小鼠还可表现出一种称为周边视网膜变性的偶然性衰老改变（与比较），其特征为由于细胞减少或视网膜各层缺失所致的周边视网膜显著（marked）变薄。尽管未附图说明，囊性腔隙（“微囊样”改变）也是这种周边年龄相关变性的常见特征。
诊断建议
视网膜变性只要存在即应诊断并分级。应在病理学描述中描述病变在视网膜内的位置（周边或中央）和范围，以及受累的视网膜各层。病理学家关于该病变是周边性、年龄相关性、背景性病变（或其加重）还是原发性治疗相关病变的意见应纳入病理学描述。视网膜变性的各种形态学特征（特定层的细胞减少、视杆和视锥光感受器突丢失等）不应单独诊断，而应在描述中加以描述。视网膜变性的存在应促使仔细检查视神经以发现伴发性病变。
参考切片图（2 张）
查看英文原文
Comment
Retinal degeneration in rats and mice can occur as an aging change or secondary to various insults, such as physical trauma, retinal detachment, inflammation, infectious agents (e.g., viruses), vascular derangements (e.g., infarction), increased intraocular pressure, and nutritional deficiencies. Numerous heritable retinal degenerations have also been documented in various strains of laboratory mice and rats. So-called light-induced retinal degeneration can occur when rats and mice (especially albino strains) are exposed to overly intense ambient light. Retinal degeneration can also be a direct toxic effect of systemically or topically administered chemical agents. Spontaneously occurring retinal degeneration of uncertain etiology has also been reported in laboratory rats and mice. In many types of retinal degeneration, the most commonly affected retinal neurons are the rod and cone photoreceptors and/or the ganglion cells. Depending on the cause, degenerative changes may be localized (or more extensive) in particular retinal topographic regions (i.e., superior vs. inferior, central vs. peripheral). Mild retinal degeneration ( Figure 2 , compare to Figure 1 ) typically consists of loss of the rod and cone photoreceptor processes, apoptosis of outer nuclear layer photoreceptor cells, hypocellularity and disorganization of the inner and outer nuclear layers, and narrowing or absence of the plexiform layers. More pronounced retinal degeneration ( Figure 3 , compare to Figure 1 ) is typically characterized by overall thinning, architectural disruption, and loss of cellular elements, as well as complete absence of the rod and cone photoreceptors and the plexiform layers. Degenerate retinas may also exhibit other morphologic features, such as diffuse or nodular proliferation of retinal glial cells (e.g., Müller cells and astrocytes), fixed fold and rosette-like formations, and intraretinal cavitations or cysts ("microcystoid" formation and retinoschisis), as well as concurrent proliferation and/or intraretinal migration of the adjacent retinal pigment epithelium. Rats and mice can also exhibit an incidental aging change known as peripheral retinal degeneration ( and , compare to ), which is characterized by marked thinning of the peripheral retina due to hypocellularity or absence of retinal layers. Although not illustrated, cystic cavitations ("microcystoid" change) are also common features of this peripheral age-related degeneration.
Recommendation
Retinal degeneration should be diagnosed and graded whenever present. The location (peripheral or central) and extent of the lesion within the retina, as well as the retinal layers affected, should be described in the pathology narrative. The pathologist's opinion as to whether it is the peripheral, age related, background form of the lesion (or an exacerbation thereof) or a primary treatment-related lesion should be included in the pathology narrative. The various morphologic features of retinal degeneration (hypocellularity of specific layers, rod and cone photoreceptor process loss, etc.) should not be diagnosed separately but should be described in the narrative. The presence of retinal degeneration should prompt careful examination of the optic nerve for concurrent lesions.
视网膜胶质增生Retina Gliosis 眼其他
描述（中文）
视网膜胶质增生（retinal gliosis，图2，与图1中的正常表现相比较），即星形胶质细胞（astrocytes）、Müller细胞和/或小胶质细胞（microglia）的增生，可发生于视网膜各层，呈局灶性（focal）至弥漫性（diffuse）分布。其特征为视网膜内胶质细胞数量增多。视网膜胶质增生可作为原发性改变（通常病因不明）发生，也可作为其他视网膜病变（如变性）的一种特征出现。
诊断建议
当作为原发性改变发生时，视网膜胶质增生应当被诊断并赋予严重程度分级。当视网膜胶质增生作为另一病理过程（如视网膜变性）的形态学特征或反应性继发结果发生时，不应单独诊断（除非因严重程度而有必要），但应在病理学描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Retinal gliosis ( Figure 2 , compare to normal in Figure 1 ), the proliferation of astrocytes, Müller cells, and/or microglia, can occur in various retinal layers with focal to diffuse distribution. It is characterized by increased numbers of glial cells in the retina. Retinal gliosis can occur as a primary change (generally of uncertain etiology) or as a feature to other retinal lesions (e.g., degeneration).
Recommendation
When occurring as a primary change, retinal gliosis should be diagnosed and assigned a severity grade. When retinal gliosis occurs as a morphologic feature or reactive sequela of another pathologic process (e.g., retinal degeneration), it should not be diagnosed separately (unless warranted by severity), but should be described in the pathology narrative.
视网膜脱离Retina Detachment 眼其他
描述（中文）
视网膜脱离（retinal detachment）指视网膜下间隙的病理性扩张，视网膜部分至完全脱离其与视网膜色素上皮（retinal pigment epithelium，RPE）的正常联系。视网膜脱离有多种原因，包括外伤性视网膜撕裂或裂孔（孔源性脱离）；异常玻璃体纤维膜的牵拉；以及视网膜下间隙的占位性物质，如浆液性或炎性渗出物、血液或肿瘤细胞。视网膜脱离也可由任何其他破坏RPE与视杆和视锥光感受器突起之间正常紧密联系的因素引起，如获得性或遗传性视网膜细胞或RPE变性；代谢性疾病；和/或视网膜或脉络膜血管系统功能障碍。病因不明的自发性脱离也可散发性发生于大鼠和小鼠。真正的脱离必须与人为分离（这是常见的死后现象）相鉴别。真正脱离的特征可包括视网膜下间隙内的液体、出血和/或炎性或肿瘤细胞，以及脱离视网膜的继发性变性（尤其是视杆和视锥光感受器）和反应性RPE肥大和/或增生。完全性视网膜脱离可形成典型的锥形或漏斗形，在显微镜横切面上呈Y形或V形构型（Figure 1、Figure 2）。大量视网膜下液体可使脱离并变性的视网膜移位，远离后极部眼底。脱离的视网膜可能发生变性，RPE可能表现为肥大和增生（Figure 2）。
诊断建议
视网膜脱离应作出诊断并赋予严重程度分级。相关病变，如RPE的肥大和增生、出血或视网膜下液体积聚，除非因严重程度需要，否则不应单独诊断，但应在病理学叙述中描述。相关病变，如炎症，应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Retinal detachment denotes pathologic expansion of the subretinal space, with partial to complete displacement of the retina from its normal association with the retinal pigment epithelium (RPE). Retinal detachment has many causes, including traumatic retinal tears or holes (rhegmatogenous detachment); traction by abnormal vitreal fibrous membranes; and space-occupying materials in the subretinal space, such as serous or inflammatory exudates, blood, or neoplastic cells. Retinal detachments can also result from any other factor that disrupts the normal intimate association of the RPE and the rod and cone photoreceptor processes, such as acquired or heritable retinal cell or RPE degenerations; metabolic diseases; and/or dysfunction of retinal or choroidal vasculature. Spontaneous detachments of uncertain etiology can also occur sporadically in rats and mice. True detachments must be distinguished from artifactual separation (which is a common postmortem occurrence). Features of true detachments can include fluid, hemorrhage, and/or inflammatory or neoplastic cells in the subretinal space, as well as secondary degeneration of the detached retina (especially the rod and cone photoreceptors) and reactive RPE hypertrophy and/or hyperplasia. Complete retinal detachment can result in a classic cone or funnel shape that in microscopic cross section has a Y- or V-like configuration ( Figure 1 and Figure 2 ). Large amounts of subretinal fluid may displace the detached and degenerate retina from the posterior fundus. The detached retina may be degenerate, and the RPE may exhibit hypertrophy and hyperplasia ( Figure 2 ).
Recommendation
Retinal detachment should be diagnosed and assigned a severity grade. Associated lesions, such as hypertrophy and hyperplasia of the RPE, hemorrhage, or subretinal fluid accumulation, should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative. Associated lesions, such as inflammation, should be diagnosed separately.
角膜囊肿Cornea Cyst 眼囊肿
描述（中文）
角膜上皮包涵囊肿（Corneal epithelial inclusion cysts）（Figure 1、Figure 2）由基质内空腔构成，空腔衬覆单层扁平细胞，腔内充满漩涡状角蛋白样物质。囊肿周围邻近基质内可继发肉芽肿性炎症。角膜包涵囊肿可起源于胎儿期，也可在出生后因物理性创伤或溃疡导致角膜上皮细胞移位并陷入基质内而发生。
诊断建议
角膜上皮包涵囊肿应诊断为“眼，角膜 - 囊肿”。该病变应诊断为存在，但不进行严重程度分级。任何继发性炎症不应单独诊断（除非其严重程度足以需要单独诊断），但应在病理学描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Corneal epithelial inclusion cysts ( Figure 1 and Figure 2 ) consist of a stromal cavitation lined by a single layer of flattened cells and filled with whorls of keratin-like material. There may be secondary granulomatous inflammation in the adjacent stroma surrounding the cyst. Corneal inclusion cysts may arise during the fetal period or may arise postnatally when corneal epithelial cells become displaced and entrapped in the stroma because of physical trauma or ulceration.
Recommendation
Corneal epithelial inclusion cysts should be diagnosed as "eye, cornea - cyst." This finding should be diagnosed as present without assignment of a severity grade. Any secondary inflammation should not be diagnosed separately (unless warranted by severity), though it should be described in the pathology narrative.
角膜坏死Cornea Necrosis 眼坏死
描述（中文）
角膜上皮细胞坏死（necrosis of corneal epithelial cells）的特征是皱缩、嗜酸性增多的坏死细胞（提示为单细胞坏死）散布于上皮层中（Figure 1、Figure 2）。这些细胞还可能表现为与相邻细胞失去附着。上皮坏死可进展为糜烂和溃疡。其他角膜细胞类型（例如角膜内皮细胞和基质角膜细胞）也可发生坏死。角膜上皮坏死可能伴有上皮增生或炎症。
诊断建议
角膜坏死一经出现即应诊断，并赋予严重程度分级。角膜坏死的亚部位（上皮、内皮、基质）可在病理学描述中说明。相关病变（例如炎症）应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Necrosis of corneal epithelial cells is characterized by shrunken, hypereosinophilic necrotic cells (suggestive of single-cell necrosis) are scattered through the epithelium ( Figure 1 and Figure 2 ). The cells may also appear to have lost their attachments to adjacent cells. Epithelial necrosis can progress to erosion and ulceration. Other corneal cell types (e.g., corneal endothelial cells and stromal keratocytes) can also undergo necrosis. Corneal epithelial necrosis may be accompanied by epithelial hyperplasia or inflammation.
Recommendation
Corneal necrosis should be diagnosed whenever present and assigned a severity grade. The subtopography of corneal necrosis (epithelium, endothelium, stroma) can be described in the pathology narrative. Associated lesions (e.g., inflammation) should be diagnosed separately.
角膜新生血管形成Cornea Neovascularization 眼其他
描述（中文）
角膜基质（corneal stroma）正常情况下无血管，但各种原因造成的损伤可导致新生血管形成。角膜新生血管化（corneal neovascularization）（Figure 1、Figure 2）的特征是角膜基质内多支小血管增生。常并发基质炎症和上皮增生。在大多数新生血管化病例中，原发损伤是各种原因引起的炎症。然而，饲喂缺乏某些营养素饲料的实验室啮齿类动物角膜也可发生新生血管化。
诊断建议
当新生血管化发生而不伴发炎症时，应作出诊断并赋予严重程度分级。当新生血管化被认为是炎症的一个特征时，不应单独诊断，除非严重程度确有必要，但应在病理学叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
The corneal stroma is normally avascular, but damage from various causes may result in neovascularization. Corneal neovascularization ( Figure 1 and Figure 2 ) is characterized by the proliferation of multiple small blood vessels in the corneal stroma. There is often concurrent stromal inflammation and epithelial hyperplasia. In most cases of neovascularization, the primary insult is inflammation resulting from various causes. However, neovascularization can also develop in the cornea of laboratory rodents fed diets deficient in certain nutrients.
Recommendation
When neovascularization occurs without concurrent inflammation, it should be diagnosed and assigned a severity grade. When neovascularization is considered a feature of inflammation, it should not be diagnosed separately, unless warranted by severity, but should be described in the pathology narrative.
角膜杯状细胞化生Cornea Metaplasia Goblet Cell 眼化生
描述（中文）
杯状细胞（goblet cell）通常存在于结膜上皮中，但当其出现在角膜上皮时，即被视为一种化生性改变（Figure 1、Figure 2）。这种所谓的角膜上皮结膜化被认为是继发性反应性改变，常与各种原因所致的角膜新生血管形成和/或炎症相关。
诊断建议
角膜杯状细胞化生一经出现即应诊断并赋予严重程度分级。该病变通常为反应性，继发于其他病理过程，但其不寻常的性质决定了必须对其进行诊断。当存在炎症时，应另行诊断。
参考切片图（2 张）
查看英文原文
Comment
Goblet cells are normally present in the conjunctival epithelium, but when they appear in the corneal epithelium, it is recognized as a metaplasitic change ( Figure 1 and Figure 2 ). Such so-called conjunctivalization of the corneal epithelium is considered a secondary reactive change, often associated with corneal neovascularization and/or inflammation from various causes.
Recommendation
Corneal goblet cell metaplasia should be diagnosed and assigned a severity grade whenever present. It is generally reactive and secondary to other pathologic processes, but it’s unusual nature necessitates its diagnosis. When present, inflammation should be diagnosed separately.
角膜水肿Cornea Edema 眼水肿
描述（中文）
角膜的透明度在一定程度上归因于其相对脱水的正常状态（与其他组织相比）以及有序的基质层板结构。基质液体的增加（水肿）会增加角膜的水合作用并破坏层板排列，从而导致透明度丧失（临床上常描述为角膜“雾状混浊”或“混浊”）。角膜水肿常与炎症（各种病因所致）相关，但也可能由角膜内皮功能障碍引起的渗透性紊乱、角膜缘血管通透性增加以及眼内压变化所致。角膜基质水肿有时难以与人为裂隙和稀疏化相区分。角膜基质水肿（嗜酸性蛋白性液体的积聚）导致角膜整体增厚（Figure 1，与Figure 2中的正常角膜相比较）。水肿的角膜还可能表现为基质胶原层板的排列紊乱和分离、基质新生血管形成以及Descemet膜折叠（Figure 1）。
诊断建议
角膜水肿应当被诊断并赋予严重程度分级。当角膜水肿被认为是炎症的一个特征时，不应单独诊断，除非严重程度足以支持单独诊断，但应在描述中予以叙述。
参考切片图（2 张）
查看英文原文
Comment
The transparency of the cornea is to some degree due to its relatively dehydrated normal state (compared with other tissues) and to the orderly stromal lamellar architecture. Increased stromal fluid (edema) increases corneal hydration and disrupts the lamellar arrays, thus resulting in loss of transparency (often described clinically as corneal "haze" or "opacity"). Corneal edema is often associated with inflammation (of various etiologies) but can also result from osmotic derangements due to corneal endothelial malfunction; increased permeability of limbal vessels; and changes in intraocular pressure. Corneal stromal edema can sometimes be difficult to distinguish from artifactual clefts and rarefaction. Corneal stromal edema (accumulation of eosinophilic proteinaceous fluid) results in overall thickening of the cornea ( Figure 1 , compare to normal cornea in Figure 2 ). The edematous cornea may also exhibit disorganization and separation of the stromal collagen lamellae, stromal neovascularization, and Descemet’s membrane folding ( Figure 1 ).
Recommendation
Corneal edema should be diagnosed and assigned a severity grade. When corneal edema is considered a feature of inflammation, it should not be diagnosed separately, unless warranted by severity, though it should be described in the narrative.
角膜溃疡Cornea Ulcer 眼溃疡
描述（中文）
角膜上皮（衬覆于角膜前表面）可发生糜烂和溃疡。其特征为角膜上皮全层局灶性剥脱，包括基底板（Figure 1、Figure 2）。溃疡通常引发炎症反应，其程度随病变的慢性程度而异。细菌可定植于溃疡区域，通常引发化脓性炎症反应（Figure 3）。角膜上皮溃疡和糜烂可由多种原因引起，包括物理性创伤、经直接局部给药接触刺激性化学物质、接触由泪腺分泌至角膜前泪膜中的全身性毒物、暴露于电离辐射或过量环境光，以及因长时间麻醉或眼睑神经支配缺陷导致的瞬目反射减弱或眼睑闭合不全。角膜上皮溃疡和糜烂也可为角膜炎症的继发病变，或为泪腺疾病所致角膜前泪膜成分改变的后遗症。尽管较上皮性改变少见，单层角膜内皮（衬覆于角膜后表面）的溃疡亦可发生。角膜上皮糜烂为部分上皮剥脱而基底板保持完整，属相似的病变，但通常范围较小。
诊断建议
角膜溃疡和/或糜烂应作出诊断并赋予严重程度分级。诊断中应包含适当的亚部位修饰词（如epithelium、endothelium）。若同一动物同时存在溃疡和糜烂，应诊断最严重的病变（溃疡）。若同一研究中同时诊断了溃疡和糜烂，应在叙述中讨论二者属于同一病理过程这一事实。相关病变如炎症和坏死不应单独诊断，除非严重程度足以支持，但应在病理学叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Erosion and ulceration can occur in the corneal epithelium (lining the anterior surface of the cornea). They are characterized by focal denudation of all layers of the corneal epithelium, including the basal lamina ( Figure 1 and Figure 2 ). Ulcers typically incite an inflammatory reaction, which varies with the chronicity of the lesion. Bacteria may colonize the ulcerated region, which usually incites a suppurative inflammatory reaction ( Figure 3 ). Corneal epithelial ulceration and erosion can result from many causes, including physical trauma, contact with irritating chemicals via direct topical administration, contact with systemic toxicants secreted by the lacrimal glands into the precorneal tear film, exposure to ionizing radiation or excess ambient light, and reduced blinking reflex or eyelid closure due to prolonged anesthesia or deficits of eyelid innervation. Corneal epithelial ulcers and erosions can also be sequelae of corneal inflammation or alterations in the precorneal tear film composition due to lacrimal gland disease. Although less common than epithelial changes, ulceration of the single-layered corneal endothelium (lining the posterior surface of the cornea) can also occur. Corneal epithelial erosions, in which there is partial epithelial denudation with retention of an intact basal lamina, are similar lesions, though typically less extensive.
Recommendation
Corneal ulcers and/or erosions should be diagnosed and assigned a severity grade. An appropriate subtopography modifier (e.g., epithelium, endothelium) should be includedd in the diagnosis. If both ulcers and erosions are present in the same animal, the most severe lesion (ulcer) should be diagnosed. If both ulcers and erosions are diagnosed in the same study, the fact that they are part of the same pathologic process should be discussed in the narrative. Associated lesions such as inflammation and necrosis should not be diagnosed separately, unless warranted by severity, but should be described in the pathology narrative.
角膜矿化Cornea Mineralization 眼矿化
描述（中文）
大鼠和小鼠的角膜矿化（corneal mineralization）可为创伤或炎症的后遗症，也可由接触局部刺激物或全身性毒素引起，或作为一种自发性变化发生。在大鼠和小鼠中自发性发生的一种矿化形式，临床上称为角膜营养不良（corneal dystrophy）、带状角膜病变（band keratopathy）或钙化性角膜病变（calcific keratopathy）。临床上，首先在中央（轴性）角膜相当于睑裂间区域的部位观察到白色、点状至线状角膜混浊。显微镜下，在中央角膜上皮基底膜内或紧邻其下可见线状至不规则的矿化聚集物（Figure 1）。覆盖其上的角膜上皮呈弥漫性变薄，角膜上皮基底细胞肿胀。矿化也可发生于角膜基质更深处（Figure 2）。矿化也可发生于角膜缘（Figure 3）。矿化可伴有角膜上皮增生或继发性肉芽肿性炎症。
诊断建议
当矿化被视为原发性变化时，应予以诊断并赋予严重程度分级。矿物沉积的部位（例如上皮下）应在病理学描述中予以描述。当矿化继发于炎症时，不应单独诊断，除非严重程度确有必要，但应在描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Corneal mineralization in rats and mice can be a sequela to trauma or inflammation, can result from exposure to topical irritants or systemic toxins, or can occur as a spontaneous change. One form of mineralization that occurs spontaneously in rats and mice is known clinically as corneal dystrophy, band keratopathy, or calcific keratopathy. Clinically, white, punctuate to linear corneal opacities are first noted in the central (axial) cornea in the zone corresponding to the interpalpebral fissure. Microscopically, linear to irregular aggregates of mineralization are present within or just under the central corneal epithelial basement membrane ( Figure 1 ). There is diffuse thinning of the overlying corneal epithelium and swelling of the corneal epithelial basal cells. Mineralization can also occur deeper in the corneal stroma ( Figure 2 ). Mineralization may also occur at the corneal limbus ( Figure 3 ). Mineralization may be accompanied by corneal epithelial hyperplasia or secondary granulomatous inflammation.
Recommendation
When mineralization is considered a primary change, it should be diagnosed and assigned a severity grade. The location of the mineral deposits (e.g., subepithelial) should be described in the pathology narrative. When mineralization is secondary to inflammation, it should not be diagnosed separately, unless warranted by severity, though it should be described in the narrative.
角膜纤维化Cornea Fibrosis 眼纤维化
描述（中文）
角膜基质纤维化（corneal stromal fibrosis）（Figure 1）的特征是正常的规则胶原板层结构被粗糙、不规则的胶原纤维束（瘢痕组织）所取代。这些变化导致角膜透明度丧失。新替代的胶原由常驻的基质角膜细胞（stromal keratocytes）产生，这些细胞对损伤作出反应，发生表型转变成为成纤维细胞（fibroblasts）和肌成纤维细胞（myofibroblasts），同时也由骨髓来源的细胞产生，这些细胞响应损伤迁移至角膜。角膜纤维化是一种反应性改变，由多种原因引起，通常与新生血管形成和/或炎症同时发生（Figure 1）。
诊断建议
不伴有炎症或仅伴有极轻微（minimal）炎症的纤维化，应当诊断并赋予严重程度分级。当角膜纤维化被认为是继发于炎症时，不应单独诊断，除非其严重程度足以支持单独诊断，但应在病理学叙述中予以描述。
参考切片图（1 张）
查看英文原文
Comment
Fibrosis of the corneal stroma ( Figure 1 ) is characterized by replacement of the normal orderly collagen lamellar architecture by coarse, irregular bundles of collagenous fibers (scar tissue). These changes result in loss of corneal transparency. The new replacement collagen is produced by the resident stromal keratocytes, which respond to injury by undergoing phenotypic transition into fibroblasts and myofibroblasts, as well as by bone-marrow-derived cells that migrate to the cornea in response to injury. Corneal fibrosis is a reactive change resulting from various causes that generally occur in conjunction with neovascularization and/or inflammation ( Figure 1 ).
Recommendation
Fibrosis that occurs without, or with only minimal, concurrent inflammation, it should be diagnosed and assigned a severity grade. When corneal fibrosis is considered secondary to inflammation, it should not be diagnosed separately unless warranted by its severity, though it should be described in the pathology narrative.
角膜细胞质空泡化Cornea Vacuolation Cytoplasmic 眼空泡化
描述（中文）
角膜上皮空泡（Figure 1、Figure 2、Figure 3）的特征为离散、大小不一、通常清亮、单个至多个、圆形至卵形的细胞质空腔。这些空泡可发生于角膜上皮细胞、内皮细胞或基质细胞（角膜细胞）。上皮空泡可发生于特定的细胞层（例如 basal、suprabasal）。空泡可增大并融合，形成上皮内囊泡或基质腔隙。角膜细胞中的空泡可由多种原因引起，包括全身性或局部应用的毒物；可作为遗传性贮积病（如黏多糖贮积症）的特征出现；或可继发于角膜干燥或炎症。真性空泡必须与角膜细胞中常出现的伪影性清亮区（常为核周）相鉴别。空泡化可伴有下方基质（Figure 1、Figure 2、Figure 3）或前房（Figure 1）中的炎症细胞，以及角膜上皮增生和角化过度（Figure 3）。
诊断建议
如果作为原发性毒性或遗传性效应发生，角膜细胞质空泡化应予以诊断并赋予严重程度分级。诊断中应包含适当的部位修饰词（例如 epithelium、endothelium、stroma），以指示受累细胞的位置。当作为另一病理过程（例如炎症）的特征或后遗症发生时，角膜细胞质空泡化不应单独诊断，除非严重程度足以支持，但应在病理学叙述中描述。相关链接：Eye - Cornea - Edema
参考切片图（2 张）
查看英文原文
Comment
Corneal epithelial vacuoles ( Figure 1 , Figure 2 , and Figure 3 ) are characterized as discrete, variably sized, generally clear, single to multiple, round to oval cytoplasmic spaces. These can occur in the corneal epithelial, endothelial, or stromal cells (keratocytes). Epithelial vacuoles can occur in specific cell layers (e.g., basal, suprabasal). Vacuoles may enlarge and coalesce to form intraepithelial vesicles or stromal lacunae. Vacuoles in corneal cells can result from various causes, including systemic or topically applied toxins; can appear as features of inherited storage diseases, such as mucopolysaccharidoses; or can be secondary to corneal desiccation or inflammation. True vacuoles must be distinguished from the artifactual clear zones (often perinuclear) that often occur in corneal cells. The vacuolation may be accompanied by inflammatory cells in the underlying stroma ( Figure 1 , Figure 2 , and Figure 3 ) or the anterior chamber ( Figure 1 ), and corneal epithelial hyperplasia and hyperkeratosis ( Figure 3 ).
Recommendation
If occurring as a primary toxic or heritable effect, corneal cytoplasmic vacuolation should be diagnosed and assigned a severity grade. An appropriate site modifier (e.g., epithelium, endothelium, stroma) should be included in the diagnosis to indicate the location of the affected cells. When occurring as a feature or sequela to another pathologic process (e.g., inflammation), corneal cytoplasmic vacuolation should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative. Related Links: Eye - Cornea - Edema
角膜鳞状上皮增生Cornea Hyperplasia Squamous 眼增生
描述（中文）
角膜复层鳞状上皮（被覆于角膜前表面）以及内皮（被覆于角膜后表面）均可发生增生，但上皮增生更为常见。角膜上皮鳞状增生（Figure 1、Figure 2、Figure 3、Figure 4）是一种局灶性（focal）至弥漫性（diffuse）的改变，以细胞层数增多为特征，常伴有上皮过度角化（Figure 1、Figure 2）。如 Figure 3、Figure 4 所示，范围更广泛的角膜上皮鳞状增生表现为细胞层数进一步增多，并呈外生性和/或内生性（网嵴样）生长方式。角膜上皮增生可由多种原因引起，包括局部应用的化学性和物理性刺激物；全身给药的毒物；泪液分泌减少；细菌、病毒或真菌感染；营养缺乏；遗传性缺陷；以及由占位性眶内肿物所致的眼球突出。角膜基质炎症、新生血管形成和/或纤维化常同时存在。
诊断建议
角膜上皮鳞状增生应当诊断并赋予严重程度分级。相关病变如炎症或水肿应当单独诊断。角膜内皮增生应当单独诊断并赋予严重程度分级。应使用部位修饰词“epithelium”和“endothelium”以指示角膜上皮增生与内皮增生（例如，Eye, Cornea, Endothelium - Hyperplasia）。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia can occur in the stratified squamous corneal epithelium (lining the anterior surface of the cornea), as well as in the endothelium (lining the posterior surface of the cornea), though epithelial hyperplasia is more common. Corneal epithelial squamous hyperplasia ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is a focal to diffuse change characterized by increased cell layers and is often associated with epithelial hyperkeratosis ( Figure 1 and Figure 2 ). As illustrated in Figure 3 and Figure 4 , more extensive corneal epithelial squamous hyperplasia is characterized by even greater numbers of cell layers with exophytic and/or endophytic (rete-peg-like) growth patterns. Corneal epithelial hyperplasia can result from many causes, including topically applied chemical and physical irritants; systemically administered toxins; reduced tear production; bacterial, viral, or fungal infections; nutritional deficiencies; heritable defects; and exophthalmos due to space-occupying orbital masses. Corneal stromal inflammation, neovascularization, and/or fibrosis is often concurrently present.
Recommendation
Squamous hyperplasia of the corneal epithelium should be diagnosed and assigned a severity grade. Associated lesions such as inflammation or edema should be diagnosed separately. Hyperplasia of the corneal endothelium should be diagnosed separately and assigned a severity grade. The site modifiers "epithelium" and "endothelium" should be used to indicate corneal epithelial versus endothelial hyperplasia (e.g., Eye, Cornea, Endothelium - Hyperplasia).
上皮增生Epithelium Hyperplasia 耳增生
描述（中文）
耳部各区域被覆上皮的增生通常由局部应用的刺激物引起，或继发于同时存在的炎症。形态学上，病变表现多样，从外耳道鳞状上皮因细胞层数增加并伴有一定程度的网嵴形成而呈弥漫性（diffuse）增厚（Figure 1），到局灶性（focal）但更为显著的上皮增生并伴有外生性乳头状形成（Figure 2、Figure 3、Figure 4）。还可能出现明显的鳞状上皮继发性角化过度，其特征为厚层角蛋白板层脱落进入耳道腔（Figure 3、Figure 4）。
诊断建议
当作为原发性、治疗相关效应发生时，耳部上皮增生应当被诊断并分级。诊断中应包含适当的部位修饰词（外耳道等）和类型修饰词（鳞状等）。继发于同时存在的炎症的鳞状增生不应单独诊断，除非其严重程度足以支持单独诊断，但应在病理描述中予以描述。角化过度几乎总是继发于同时存在的鳞状上皮增生，因此不应单独诊断（除非其严重程度足以支持单独诊断），但应在病理描述中作为增生的一个特征予以描述。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of the lining epithelium of various ear regions is usually due to topically applied irritants or secondary to concurrent inflammation. Morphologically, the lesions vary from diffuse thickening of the external ear canal squamous epithelium due to increased cell layers with some rete peg formation ( Figure 1 ) to focal but more pronounced epithelial hyperplasia with exophytic papillary formation ( Figure 2 , Figure 3 , and Figure 4 ). There may also be prominent secondary hyperkeratosis of the squamous epithelium, characterized by thick layers of keratin lamellae sloughing into the canal lumen ( Figure 3 and Figure 4 ).
Recommendation
When occurring as a primary, treatment-related effect, epithelial hyperplasia of the ear should be diagnosed and graded. An appropriate site modifier (external ear canal, etc.) and type modifier (squamous, etc.) should be included in the diagnosis. Squamous hyperplasia secondary to concurrent inflammation should not be diagnosed separately unless warranted by severity, though it should be described in the pathology narrative. Hyperkeratosis is almost always secondary to concurrent squamous epithelial hyperplasia, and thus should not be diagnosed separately (unless warranted by severity), though it should be described as a feature of the hyperplasia in the pathology narrative.
溃疡Ulcer 耳溃疡
描述（中文）
溃疡（ulcer）的特征是上皮衬里呈节段性或更广泛的缺失，包括上皮基底膜缺失并暴露出其下的固有层（Figure 1、Figure 2、Figure 3）。糜烂（erosion）也表现为部分或全部上皮细胞层呈局灶性（focal）至广泛的缺失。然而，与溃疡不同的是，糜烂以基底膜保持完整为特征。这些病变通常伴有炎症，且常被渗出性痂皮覆盖（Figure 1）。
诊断建议
耳部糜烂和溃疡应结合适当的部位修饰词（外耳、中耳等）进行诊断，并赋予严重程度分级。被视为糜烂和溃疡继发的所见（充血、出血、水肿、炎症等）不应单独诊断，除非其严重程度足以支持单独诊断。然而，继发病变应在病理学描述中予以描述。如果同一动物同时存在糜烂和溃疡，则仅应诊断溃疡（即更严重的病变）。
参考切片图（2 张）
查看英文原文
Comment
Ulcers are characterized by segmental or more extensive loss of the lining epithelium, including loss of the epithelial basement membrane with exposure of the underlying lamina propria ( Figure 1 , Figure 2 , and Figure 3 ). Erosions also exhibit focal to extensive loss of some or all epithelial cell layers. However, in contrast to ulcers, erosions are distinguished by retention of an intact basement membrane. These lesions are typically accompanied by inflammation and are often covered by an exudative crust ( Figure 1 ).
Recommendation
Erosions and ulcers in the ear should be diagnosed with an appropriate topography modifier (external ear, middle ear, etc.) and assigned a severity grade. Findings considered secondary to erosions and ulcers (congestion, hemorrhage, edema, inflammation, etc.) should not be diagnosed separately unless warranted by severity. The secondary lesions should, however, be described in the pathology narrative. If both erosions and ulcers are present in the same animal, then only ulcer (the more severe lesion) should be diagnosed.
炎症Inflammation 耳炎症
描述（中文）
耳部各区域的炎症可由多种原因引起，包括感染性病原体、异物、局部应用的刺激物和全身性毒物。耳部慢性炎症伴耳道内液体、耵聍和细胞碎片蓄积，可导致耳道囊性扩张（见耳-耳道-扩张）。在NTP研究中，炎症有五个标准类别：急性、化脓性、慢性、慢性活动性和肉芽肿性。在急性炎症中，主要浸润细胞是中性粒细胞，尽管也可能存在较少的巨噬细胞和淋巴细胞。也可能有水肿或充血的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，然而，在化脓性炎症中，中性粒细胞聚集，其中许多发生变性（化脓性渗出物）。渗出物中还可能存在细胞碎片（来自驻留细胞群和浸润的白细胞）、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染性病原体。肉眼观，这些病变以脓液存在为特征。在渗出物周围组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但在慢性活动性炎症中，还有显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大型、活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
耳部炎症应当诊断并分级。炎症类型（例如，急性或慢性活动性）应作为限定词在诊断中指明。同样，耳内病变的位置应使用适当的部位修饰词（外耳或中耳）指明。被认为继发性的所见（囊肿、上皮增生等）不应单独诊断，除非严重程度 warrant。未单独诊断的继发性病变应在病理学叙述中描述。相关链接：耳-耳道-扩张
参考切片图（2 张）
查看英文原文
Comment
Inflammation of various ear regions can result from many causes, including infectious agents; foreign bodies; topically applied irritants, and systemic toxins. Chronic inflammation of the ear with accumulation of fluid, cerumen, and cellular debris in the ear canal can result in cystic dilation of the ear canal (see Ear - Canal - Dilation ). In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation, the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation, however, in suppurative inflammation, the neutrophils are aggregated and many of them are degenerate (suppurative exudate). Cell debris, both from the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation. Lymphocytes also predominate in chronic-active inflammation, but in chronic-active inflammation, there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
Inflammation of the ear should be diagnosed and graded. The type of inflammation (e.g., acute or chronic active) should be indicated in the diagnosis as a qualifier. Similarly, the location of the lesion within the ear should be indicated with an appropriate site modifier (external ear or middle ear). Findings considered secondary (cyst, epithelial hyperplasia, etc.) should not be diagnosed separately unless warranted by severity. Secondary lesions not diagnosed separately should be described in the pathology narrative. Related Links: Ear - Canal - Dilation
管道扩张Canal Dilation 耳扩张
描述（中文）
外耳道扩张（Figure 1、Figure 2、Figure 3）通常继发于耳道被脱落的角化板层、耵聍和坏死碎屑形成的栓状物阻塞，这些栓状物使耳道膨胀。衬覆上皮可能增生。这些所见通常发生于老龄动物。
诊断建议
耳道扩张应结合适当的部位修饰词（外耳道等）进行诊断。扩张应诊断为存在（不进行严重程度分级）。相关病变如炎症或上皮增生除非严重程度足以支持，否则不应单独诊断，但可在病理学描述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Dilation of the external ear canal ( Figure 1 , Figure 2 , and Figure 3 ) is usually secondary occlusion of the ear canal by plugs of sloughed keratin lamellae, cerumen, and necrotic debris that distends the canal. The lining epithelium may be hyperplastic. These findings usually occur in aged animals.
Recommendation
Dilation of the ear canal should be diagnosed with an appropriate topography modifier (external ear canal, etc.). Dilation should be diagnosed as present (without assignment of a severity grade). Associated lesions such as inflammation or epithelial hyperplasia should not be diagnosed separately unless warranted by severity, though they can be described in the pathology narrative.
蛋白性液体Proteinaceous Fluid 耳其他
描述（中文）
蛋白性液体可因轻度至中度血管损伤而蓄积于内耳道、中耳道或外耳道。耳道内的蛋白性液体以嗜酸性（eosinophilic）、均质、含少量至无炎性细胞的物质为特征（Figure 1）。
诊断建议
蛋白性液体应作出诊断并赋予严重程度分级。诊断中应使用适当的部位修饰词（例如中耳或外耳）以标明液体的位置。若该液体为炎症过程所致（即周围组织存在其他炎症证据），则应诊断炎症，并在病理学描述中记述蛋白性液体。
参考切片图（1 张）
查看英文原文
Comment
Proteinaceous fluid may accumulate in the inner, middle, or external ear canals as the result of mild to moderate vascular damage. Proteinaceous fluid in the ear canals is characterized by eosinophilic, homogeneous material with few to no inflammatory cells ( Figure 1 ).
Recommendation
Proteinaceous fluid should be diagnosed and assigned a severity grade. An appropriate site modifier (e.g., middle ear or external ear) should be used in the diagnosis to indicate the location of the fluid. If the fluid is the result of an inflammatory process (i.e., there is other evidence of inflammation in the surrounding tissues), inflammation should be diagnosed and the proteinaceous fluid described in the pathology narrative.
增生Hyperplasia 齐姆巴尔腺增生
描述（中文）
耵聍腺（Zymbal's gland）增生（Figure 1、Figure 2、Figure 3、Figure 4）通常为 局灶性（focal） 改变。增生可发生于致密耵聍腺（Figure 1、Figure 2），也可发生于外耳道固有层内弥漫的耵聍腺型皮脂腺组织（Figure 3、Figure 4）。耵聍腺内增生区域的特征为皮脂腺腺泡数量 局灶性 增多且常伴体积增大，常伴有小叶结构的轻度扭曲及邻近组织的轻度受压。增生区域由大小不一的腺泡组成，腺泡衬覆分化相对良好的上皮细胞，细胞核增大，胞质较正常细胞更嗜碱性且泡沫状程度减轻。腺泡细胞的正常成熟过程可能变得模糊或消失。增生缺乏肿瘤性病变所具备的显著细胞异型性、明显结构扭曲及邻近组织浸润。增生可能是继发于炎症或变性的反应性改变。在无并发变性或炎症的情况下发生的增生被视为癌前病变，是形态学上从增生向癌演变连续过程中的早期改变。
诊断建议
若判定为原发性改变，耵聍腺增生应当予以诊断并赋予严重程度分级。当继发于炎症或变性时，耵聍腺增生不应单独诊断（除非严重程度确有必要），但应在病理学描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Zymbal's gland hyperplasia ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is generally a focal change. Hyperplasia can occur in the compact Zymbal’s gland ( Figure 1 and Figure 2 ) or in the diffuse Zymbal's gland-type sebaceous tissue in the lamina propria of the external ear canal ( Figure 3 and Figure 4 ). Hyperplastic areas in the Zymbal's gland are characterized by a focal increase in the number and often the size of the sebaceous acini, often with slight distortion of the lobular architecture and slight compression of the adjacent tissue. They are composed of variably sized acini lined by relatively well-differentiated epithelial cells with enlarged nuclei and cytoplasm that is more basophilic and less foamy than in normal cells. The normal maturation sequence of the acinar cells may be obscured or absent. Hyperplasia lacks the pronounced cellular atypia, marked architectural distortion, and invasion of adjacent tissue, which are features of neoplastic lesions. Hyperplasia may be a reactive change secondary to inflammation or degeneration. Hyperplasia occurring in the absence of concurrent degeneration or inflammation is considered a preneoplastic lesion and an early-stage change in the morphologic continuum from hyperplasia to carcinoma.
Recommendation
If considered a primary change, Zymbal's gland hyperplasia should be diagnosed and assigned a severity grade. When secondary to inflammation or degeneration, Zymbal's gland hyperplasia should not be diagnosed separately (unless warranted by severity), but should be described in the pathology narrative.
导管囊肿Duct Cyst 齐姆巴尔腺囊肿
描述（中文）
Zymbal腺管囊肿（Figure 1、Figure 2、Figure 3、Figure 4）主要是Zymbal腺管的扩张，其内衬为变薄的鳞状或腺上皮，或为扁平的复层鳞状上皮。前者通常充满皮脂，而后者通常含有脱落的角蛋白板层。Zymbal腺囊肿不常见，但这可能反映了一个事实，即该组织在常规毒性研究中通常不被采样。
诊断建议
Zymbal腺管囊肿只要存在就应诊断，但不应进行分级。
参考切片图（2 张）
查看英文原文
Comment
Zymbal's gland duct cysts ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) are prominently distensions of the Zymbal's gland duct that are lined by either attenuated squamous or glandular epithelium or by flattened stratified squamous epithelium. The former are typically filled with sebum, while the latter typically contain sloughed keratin lamellae. Zymbal's gland cysts are uncommon, but this may reflect the fact that this tissue is not usually sampled in routine toxicity studies.
Recommendation
Zymbal's gland duct cysts should be diagnosed whenever present but should not be graded.
炎症Inflammation 齐姆巴尔腺炎症
描述（中文）
慢性耵聍腺炎（Zymbal's gland inflammation）（Figure 1、Figure 2）的特征是间质内单核细胞、巨噬细胞及少量中性粒细胞浸润。更广泛的化脓性耵聍腺炎（Figure 3）的特征是大片、有时为包裹性的坏死碎屑区域，其中混有和/或边缘环绕着积聚的退变炎症细胞（尤其是中性粒细胞）。在NTP研究中，炎症分为五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））。急性炎症中，主要浸润细胞为中性粒细胞，但也可能存在少量巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。化脓性炎症中，主要浸润细胞类型同样为中性粒细胞，但在化脓性炎症中，中性粒细胞聚集成团，其中许多已退变（化脓性渗出物）。渗出物中还可能存在来自 resident 细胞群和浸润白细胞的细胞碎屑、含纤维蛋白的蛋白性液体、少量巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子。肉眼观察，这些病变以脓液存在为特征。渗出物周围组织中可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。慢性炎症以淋巴细胞为主。慢性活动性炎症同样以淋巴细胞为主，但慢性活动性炎症中还存在大量中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。炎症与细胞浸润的鉴别在于是否存在其他改变，如水肿、出血、变性、坏死或其他组织损伤的证据。
诊断建议
耵聍腺炎应当诊断并赋予严重程度分级。诊断中应包含适当的类型修饰词，以表明所存在的炎症类型（急性、慢性等）。当继发于其他所见（如耵聍腺囊肿、增生或肿瘤）时，炎症不应单独诊断，除非其严重程度足以支持独立诊断，但可在病理学描述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Chronic Zymbal's gland inflammation ( Figure 1 and Figure 2 ) is characterized by interstitial infiltrates of mononuclear cells, macrophages, and few neutrophils. More extensive suppurative Zymbal's gland inflammation ( Figure 3 ) is characterized by extensive, sometimes encapsulated areas of necrotic debris admixed and/or bordered by accumulations of degenerate inflammatory cells (especially neutrophils). In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation, the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation, however, in suppurative inflammation, the neutrophils are aggregated and many of them are degenerate (suppurative exudate). Cell debris, both from the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation. Lymphocytes also predominate in chronic-active inflammation, but in chronic-active inflammation, there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammation is differentiated from cellular infiltrates by the presence of other changes, such as edema, hemorrhage, degeneration, necrosis, or other evidence of tissue damage.
Recommendation
Zymbal's gland inflammation should be diagnosed and assigned a severity grade. An appropriate type modifier should be included in the diagnosis to indicate the type of inflammation present (acute, chronic, etc.). When secondary to other findings (e.g., Zymbal's gland cyst, hyperplasia, or neoplasia), inflammation should not be diagnosed separately unless warranted by severity, but can be described in the pathology narrative.
肥大Hypertrophy 齐姆巴尔腺肥大
描述（中文）
Zymbal腺肥大（Figure 1、Figure 2、Figure 3）的特征是成簇增大的上皮细胞，其数量可能增多也可能不增多，但因淡嗜酸性、泡沫状或网状的细胞质增多而体积增大。
诊断建议
当Zymbal腺肥大作为与处理相关的效应出现时，应作出诊断并赋予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Zymbal's gland hypertrophy ( Figure 1 , Figure 2 , and Figure 3 ) is characterized by clusters of enlarged epithelial cells that may or may not be increased in number but that are enlarged by increased amounts of pale eosinophilic, foamy or lacy cytoplasm.
Recommendation
Zymbal's gland hypertrophy should be diagnosed and assigned a severity grade when present as a treatment-related effect.
体外寄生虫Ectoparasites 皮肤其他
描述（中文）
在现行动物饲养标准下，外寄生虫病（ectoparasitism）（Figure 1、Figure 2）在小鼠和大鼠中罕见。小鼠最常见的毛螨为鼠肌螨（Myocoptes musculinus）、鼠鼠螨（Myobia musculi）和亲近鼠螨（Radfordia affinis）。小鼠毛囊螨（Psorergates simplex）罕见。大鼠可见长鼠螨（Radfordia ensifera）和巴氏禽刺螨（Ornithonyssus bacoti）。啮齿动物螨病常累及头部、肩部和背部。螨所致典型病变包括表皮增生伴角化过度及极轻微（minimal）慢性或慢性活动性真皮炎（Figure 1）。严重病例可出现溃疡（通常由自我损伤所致）伴继发性细菌定植，并可导致小鼠发生全身性淀粉样变性。
诊断建议
外寄生虫病一旦存在，应记录为“皮肤 – 外寄生虫”，但无需分级。螨病可伴有炎症、表皮增生、角化过度、溃疡、淀粉样变性和细菌定植，这些应在病理学描述中予以描述，但不应作为独立诊断记录。
参考切片图（2 张）
查看英文原文
Comment
With current animal care standards, ectoparasitism ( Figure 1 and Figure 2 ) is rare in mice and rats. Myocoptes musculinus , Myobia musculi , and Radfordia affinis are the most common fur mites in mice. Psorergates simplex , the mouse follicular mite, is rarely seen. Radfordia ensifera and Ornithonyssus bacoti occur in rats. Rodent acariasis often involves the head, shoulders, and back. Typical lesions caused by mites consist of epidermal hyperplasia with hyperkeratosis and minimal chronic or chronic active dermal inflammation ( Figure 1 ). In severe cases, ulceration (usually due to self-induced trauma) with secondary bacterial colonization may be present, which can result in systemic amyloidosis in mice.
Recommendation
Whenever present, ectoparasitism should be recorded as “Skin – Ectoparasites” but need not be graded. Acariasis may be accompanied by inflammation, epidermal hyperplasia, hyperkeratosis, ulceration, amyloidosis, and bacterial colonization, which should be described in the pathology narrative but not documented as separate diagnoses.
出血Hemorrhage 皮肤出血
描述（中文）
皮肤出血的特征是血管外红细胞聚集（Figure 1）。在毒性和致癌性研究中，大多数自发性皮肤出血是由打斗（动物同笼饲养时）或接触设备粗糙边缘所致的创伤引起的血管损伤所造成。出血也可作为受试物相关皮肤刺激或损伤的组成部分出现，常伴随炎症、坏死和溃疡等其他病变。出血还可能与增生性血管病变相关，如血管扩张（angiectasis）或肿瘤形成。
诊断建议
当出血与增生性血管病变相关时，不应记录。如果出血与其他病变（如炎症或溃疡）相关，除非出血的严重程度过度或与相关病变的严重程度不相称，否则无需记录。但应在病理学描述中予以描述。无论何时记录，出血均应赋予严重程度分级。
参考切片图（1 张）
查看英文原文
Comment
Hemorrhage in the skin is characterized by clusters of extravascular erythrocytes ( Figure 1 ). In toxicity and carcinogenicity studies, most spontaneously occurring hemorrhage in the skin is caused by vascular damage due to trauma secondary to fighting (when animals are housed together) or contact with rough edges of equipment. Hemorrhage also occurs as a component of test-article–related skin irritation or damage, often accompanying other lesions such as inflammation, necrosis, and ulceration. Hemorrhage may also be associated with proliferative vascular lesions, such as angiectasis or neoplasia.
Recommendation
In cases where hemorrhage is associated with a proliferative vascular lesion, it should not be recorded. If the hemorrhage is associated with another lesion, such as inflammation or ulceration, it need not be recorded unless the severity of the hemorrhage is excessive or is not commensurate with the severity of the associated lesions. However, it should be described in the pathology narrative. Whenever it is recorded, hemorrhage should be assigned a severity grade.
坏死Necrosis 皮肤坏死
描述（中文）
在皮肤毒性研究中，对毒性物质的初始反应通常涉及一定程度的上皮细胞损伤或破坏，如变性或坏死。在NTP研究中，作为原发性病变的上皮坏死（Figure 1、Figure 2）较溃疡形成报道少见。在严重病例中，上皮坏死可延伸至毛囊（Figure 3、Figure 4）。上皮坏死和毛囊坏死的特征为角质形成细胞皱缩或肿胀，胞质呈强嗜酸性至玻璃样变，细胞核浓缩，伴有不同程度的核固缩、核溶解和核碎裂。皮肤坏死（Figure 5、Figure 6）的特征为透壁性坏死，累及表皮、真皮，并可能累及皮下组织。作为原发性病变诊断者少见。坏死最常继发于表皮损伤，并常延伸至真皮和皮下组织。延伸至皮下组织的坏死不应与脂肪坏死混淆，后者局限于皮下组织，作为背景性病变散发性发生于小鼠和大鼠腹部皮下组织。营养不良性矿化常作为皮肤坏死的组成部分出现。转移性矿化与坏死或炎症无关，而是由钙磷失衡所致。
诊断建议
观察到上皮坏死时，应作出诊断并赋予严重程度分级。在较严重病例中，毛囊上皮也可发生坏死；这应反映在赋予上皮坏死的严重程度分级中，并在病理学描述中予以描述。若毛囊坏死发生而无表皮受累，应使用术语“皮肤，毛囊 – 坏死”。相关病变，如炎症和溃疡形成，应单独诊断。皮肤坏死出现时，应记录其发生率并赋予严重程度分级。营养不良性矿化无需单独诊断，但应在病理学描述中予以描述。转移性矿化出现时应作出诊断，赋予严重程度分级，并在病理学描述中予以描述。脂肪坏死（即局限于皮下组织）应作为散发性背景性发现作出诊断、分级，并在描述中描述为“皮肤，皮下组织 – 坏死”。
参考切片图（2 张）
查看英文原文
Comment
The initial response to a toxic agent in dermal toxicity studies usually involves some degree of epithelial cell damage or destruction, such as degeneration or necrosis. Epithelial necrosis ( Figure 1 and Figure 2 ) as a primary lesion is less frequently reported than ulceration in NTP studies. In severe cases, necrosis of the epithelium may extend into the hair follicles ( Figure 3 and Figure 4 ). Epithelial necrosis and follicular necrosis are characterized by shrunken or swollen keratinocytes with hypereosinophilic to hyalinized cytoplasm and condensed nuclei with varying degrees of pyknosis, karyolysis, and karyorrhexis. Skin necrosis ( Figure 5 and Figure 6 ) is characterized by transmural necrosis affecting the epidermis, dermis, and possibly the subcutis. It is infrequently diagnosed as a primary lesion. Necrosis most commonly occurs secondary to damage of the epidermis and frequently extends into the dermis and subcutis. Necrosis extending into the subcutis is not to be confused with fat necrosis, which is limited to the subcutis and occurs sporadically as a background lesion in the subcutaneous tissue of the abdomen in mice and rats. Dystrophic mineralization is commonly seen as a component of skin necrosis. Metastatic mineralization is not associated with necrosis or inflammation but due to calcium:phosphorus imbalance.
Recommendation
When observed, epithelial necrosis should be diagnosed and assigned a severity grade. In more severe cases, the follicular epithelium may also be necrotic; this should be reflected in the severity grade assigned to epithelial necrosis and described in the pathology narrative. If follicular necrosis occurs without epidermal involvement, the term “Skin, Hair follicle – Necrosis” should be used. Associated lesions, such as inflammation and ulceration, should be diagnosed separately. Whenever present, the incidence of skin necrosis should be documented and assigned a severity grade. Dystrophic mineralization need not be diagnosed separately but should be described in the pathology narrative. Metastatic mineralization should be diagnosed whenever present, assigned a severity grade, and described in the pathology narrative. Fat necrosis (i.e., limited to the subcutis) should be diagnosed, graded, and described as a sporadic background finding in the narrative as “Skin, Subcutis – Necrosis.”
增生Hyperplasia 皮肤增生
描述（中文）
上皮增生（epithelial hyperplasia）是NTP研究中在B6C3F1小鼠皮肤观察到的最常见的自发性非肿瘤性病变。表皮及附属器上皮的增生也是皮肤局部涂抹化学物质后的常见反应。在较严重的病例中，尤其是伴有炎症时，常发生毛囊上皮、毛囊单位及皮脂腺的增生。其特征为：与对照动物的相同部位（Figure 1）相比，表皮非角化层因上皮细胞数量（层数）增加而增厚（Figure 2）。毛囊上皮也可受累。这种增厚可累及全部三个非角化层（基底层、棘层和颗粒层），但可能在棘细胞层最为明显。在较严重的病例中，毛囊上皮也可发生增生。该病变可继发于多种损伤和状况，包括自发性和实验诱发的炎症过程、暴露于刺激物或毒性物质、浅表角化层的反复磨损以及长期暴露于紫外线。皮脂腺增生的特征为皮脂腺增大，细胞数量增加，在中央导管周围形成众多小叶（Figure 3、Figure 4）。在为期2年的研究期间，皮脂腺增生有可能进展为良性和恶性皮脂腺细胞肿瘤。毛囊增生的特征为真皮和皮下组织内毛囊单位数量增加（Figure 5）。毛囊上皮增生的特征为毛囊内毛囊上皮细胞数量增加；它通常是表皮上皮增生的延伸，但也可见于无表皮增生的情况下。
诊断建议
首选“上皮增生（epithelial hyperplasia）”而非“棘层肥厚（acanthosis）”一词。只要存在，上皮增生即应作出诊断并赋予严重程度分级。当毛囊上皮也发生增生时，这一点应反映在赋予上皮增生的严重程度分级中，并在病理学描述中加以描述。如果毛囊上皮增生发生而无表皮受累，则应使用“皮肤，毛囊，上皮——增生（Skin, Hair follicle, Epithelium – Hyperplasia）”一词。相关病变，如炎症，应单独诊断。当作为再生性反应、继发于邻近溃疡而存在时，增生不应作出诊断，但应在描述中加以描述。当存在时，皮脂腺增生或毛囊增生应作出诊断并赋予严重程度分级。皮脂腺细胞的增生常伴有肥大。在此类情况下，肥大无需诊断。
参考切片图（2 张）
查看英文原文
Comment
Epithelial hyperplasia is the most common spontaneous, non-neoplastic lesion of the skin observed in B6C3F1 mice in NTP studies. Hyperplasia of the epithelium of the epidermis and adnexa is also a common response to dermal application of chemicals. In more severe cases, especially when accompanied by inflammation, hyperplasia of follicular epithelium, follicular units, and sebaceous glands often occurs. It is characterized by increased thickness of the nonkeratinized layers of the epidermis due to an increased number (layers) of epithelial cells ( Figure 2 ) compared with the same site in a control animal ( Figure 1 ). The epithelium of the hair follicles may also be affected. This increased thickness may involve all three nonkeratinized layers (basal, spinous, and granular) but may be most apparent in the spinous cell layer. In more severe cases, the follicular epithelium may also be hyperplastic ( Figure 2 ). This lesion can result after a wide variety of injuries and conditions, including spontaneous and experimentally induced inflammatory processes, exposure to irritants or toxic materials, repeated abrasion of the superficial keratin layer, and prolonged exposure to ultraviolet light. Sebaceous gland hyperplasia is characterized by large sebaceous glands with increased numbers of cells forming numerous lobules around central ducts ( Figure 3 and Figure 4 ). Over the period of a 2-year study, sebaceous hyperplasia has the potential to progress to benign and malignant sebaceous cell neoplasms. Follicular hyperplasia is characterized by increased numbers of follicular units within the dermis and subcutis ( Figure 5 ). Follicular epithelial hyperplasia is characterized by increased numbers of follicular epithelial cells within the hair follicles; it is typically an extension of epithelial hyperplasia of the epidermis but may be seen in the absence of epidermal hyperplasia.
Recommendation
“Epithelial hyperplasia” is preferred over the term “acanthosis.” Whenever present, epithelial hyperplasia should be diagnosed and assigned a severity grade. When follicular epithelium is also hyperplastic, this should be reflected in the severity grade assigned to epithelial hyperplasia and described in the pathology narrative. If follicular epithelial hyperplasia occurs without epidermal involvement, the term “Skin, Hair follicle, Epithelium – Hyperplasia” should be used. Associated lesions, such as inflammation, should be diagnosed separately. When present as a regenerative response, secondary to an adjacent ulcer, hyperplasia should not be diagnosed but should be described in the narrative. When present, sebaceous hyperplasia or follicular hyperplasia should be diagnosed and assigned a severity grade. Hyperplasia of the sebaceous cells is often accompanied by hypertrophy. In such cases, hypertrophy need not be diagnosed.
毛囊扩张和囊肿Hair Follicle Dilatationand Cyst 皮肤囊肿
描述（中文）
毛囊扩张（Figure 1、Figure 2）可能作为治疗相关病变被观察到。扩张的毛囊内常含有少量腔内角蛋白。衬覆的毛囊上皮细胞可能变扁平。毛囊扩张倾向于呈多灶性（multifocal）至弥漫性（diffuse）分布，而上皮囊肿最常表现为局灶性（focal）、孤立性病变。上皮囊肿（Figure 3、Figure 4）在大鼠和小鼠中常为自发性所见。曾与上皮囊肿同义使用的术语包括表皮包涵囊肿（epidermal inclusion cyst）、表皮样囊肿（epidermoid cyst）和毛囊囊肿（follicular cyst）。组织学上，上皮囊肿的特征为扁平的鳞状上皮围绕数量不等的浓缩角蛋白核心。推测其起源于受损的毛皮脂腺单位成分，其中产生角蛋白的鳞状上皮细胞被包裹。随着角蛋白积聚形成囊肿，衬覆的上皮细胞发生压迫性萎缩。偶尔囊肿衬覆破裂、角蛋白逸出，导致继发性炎症（Figure 4）。
诊断建议
当存在毛囊扩张时，应记录并根据大小和数量赋予严重程度分级。“Dilatation”是首选术语，而非“ectasia”。无论何时存在囊肿，均应作出诊断并记录为存在，但不应进行分级。皮肤中的囊肿应诊断为“Skin – Cyst”；无需修饰词。继发于大囊肿或破裂囊肿的所见，如炎症或纤维化，无需诊断，但应在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Dilatation of hair follicles ( Figure 1 and Figure 2 ) may be observed as treatment-related lesions. Dilated hair follicles often contain small amounts of intraluminal keratin. The lining follicular epithelial cells may be flattened. Hair follicle dilatation tends to be multifocal to diffuse, whereas epithelial cysts most often occur as focal, solitary lesions. Epithelial cysts ( Figure 3 and Figure 4 ) are often spontaneous findings in rats and mice. Terms that have been used synonymously with epithelial cyst include epidermal inclusion cyst, epidermoid cyst, and follicular cyst. Histologically, epithelial cysts are characterized by a flattened squamous epithelium surrounding a core of variable amounts of inspissated keratin. They are proposed to arise from components of injured pilosebaceous units in which squamous epithelial cells producing keratin are trapped. As keratin accumulates to form the cyst, the lining epithelial cells undergo pressure atrophy. Occasionally, the cyst lining ruptures and keratin escapes, resulting in secondary inflammation ( Figure 4 ).
Recommendation
When present, follicular dilatation should be recorded and assigned a severity grade based on the size and number. “Dilatation” is the preferred term, as opposed to “ectasia.” Whenever present, cysts should be diagnosed and documented as present but should not be graded. Cysts in the skin should be diagnosed as “Skin – Cyst”; no modifier is necessary. Findings that are secondary to a large or ruptured cyst, such as inflammation or fibrosis, need not be diagnosed but should be described in the pathology narrative.
水疱Vesicle 皮肤其他
描述（中文）
水疱（vesicle）是小的、界限清楚的、角膜下（表皮内）或表皮下的囊样腔隙，内含浆液性液体（Figure 1）。它们代表受损上皮的脱离，由此形成的腔隙被液体填充。水疱可能在接触腐蚀性物质后形成。它们也可能作为皮肤过敏反应的一部分而形成，此时最初可见水肿和充血，最终形成水疱。水疱通常出现在皮肤损伤后急性炎症的初期阶段，但在研究结束时往往不存在。因此，它们是相对罕见的所见。
诊断建议
由于水疱可以提供关于对受试物反应严重程度的信息，或者可能提示过敏型反应，因此只要存在水疱就应记录并分级。分级应基于大小和数量。皮肤中其他相关病变，如炎症或坏死，应单独诊断。
参考切片图（1 张）
查看英文原文
Comment
Vesicles are small, circumscribed, subcorneal (intraepidermal) or subepidermal cystlike spaces that contain serous fluid ( Figure 1 ). They represent detachment of damaged epithelium with the resulting space being filled by fluid. Vesicles may form after exposure to caustic agents. They may also form as part of an allergic response in the skin in which edema and congestion are seen initially, followed eventually by vesicle formation. Vesicles typically occur in the initial stages of acute inflammation after skin injury but are not often present at the end of a study. Consequently, they are a relatively rare finding.
Recommendation
Because they can provide information regarding the severity of a response to a test agent, or they may suggest an allergic type of response, vesicles should be recorded and graded whenever present. Grading should be based on size and number. Other associated lesions in the skin, such as inflammation or necrosis, should be diagnosed separately.
淀粉样物质Amyloid 皮肤其他
描述（中文）
淀粉样物质沉积（amyloid deposition）（Figure 1、Figure 2）是细胞无法清除不可溶性、错误折叠蛋白的结果。它可与慢性炎症中急性期蛋白的过度产生相关，并且通常与系统性淀粉样变性相关。淀粉样物质沉积在大鼠中罕见，但在某些小鼠品系（如Swiss小鼠（CD-1））中作为常见的年龄相关变化出现，推测具有遗传易感性。皮肤中的淀粉样物质沉积几乎总是见于真皮，典型表现为大小不等的无定形、嗜酸性、细胞外物质蓄积，通常位于血管周围。组织化学染色（如刚果红（Congo red））和免疫组织化学染色有助于明确诊断。
诊断建议
淀粉样物质沉积只要存在就应诊断并赋予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Amyloid deposition ( Figure 1 and Figure 2 ) occurs as a result of cells not being able to eliminate insoluble, misfolded protein. It can be associated with overproduction of acute-phase protein in chronic inflammation and is usually associated with systemic amyloidosis. Amyloid deposition is rare in rats but occurs as a common age-related change in some mouse strains, such as Swiss mice (CD-1), and presumably has a genetic predisposition. Amyloid deposition in the skin is almost always seen in the dermis and typically appears as variably sized accumulations of amorphous, eosinophilic, extracellular material that is usually perivascular. Histochemical (e.g., Congo red) and immunohistochemical stains are useful for definitive diagnosis.
Recommendation
Amyloid deposition should be diagnosed and assigned a severity grade whenever present.
溃疡和糜烂Ulcerand Erosion 皮肤溃疡
描述（中文）
表皮溃疡（Figure 1、Figure 2）是小鼠和大鼠中最常见的自发病变之一，但也可能与受试物的皮肤给药相关。溃疡的特征为表皮（包括基底膜）节段性或更广泛的缺失，并暴露出其下的真皮。糜烂的特征为上皮部分缺失，基底膜保持完整。糜烂可为细微、浅表的病变，仅累及上层细胞缺失，可能难以识别。除非为超急性病变，这些病变通常伴有浅表真皮炎症，并可能伴有表皮增生，尤其是在溃疡边缘。严重溃疡时，炎症可延伸至深部真皮或皮下组织。慢性化时，作为愈合反应的一部分，可能出现新生血管形成和纤维化。
诊断建议
表皮溃疡和糜烂只要存在，就应记录并赋予严重程度分级。相关所见，如炎症、表皮增生、角化过度、水肿或真皮纤维化，应在病理学描述中描述，不应单独诊断，除非病理学家判断有必要单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Epidermal ulcers ( Figure 1 and Figure 2 ) are among the most common spontaneous findings in mice and rats but may also be associated with dermal application of test agents. Ulcers are characterized by segmental or more extensive loss of the epidermis, including the basement membrane, with exposure of the underlying dermis. Erosion is characterized by the partial loss of the epithelium, with the basement membrane left intact. Erosions can be subtle, shallow lesions with loss of only the upper layers of cells and may be difficult to identify. Unless they are peracute, these lesions are typically accompanied by inflammation in the superficial dermis and may be accompanied by epidermal hyperplasia, particularly at the edges of ulcers. With severe ulcers, the inflammation may extend into the deep dermis or subcutis. With chronicity, there may be neovascularization and fibrosis as part of the healing response.
Recommendation
Whenever present, epidermal ulcerations and erosions should be documented and assigned a severity grade. Associated findings, such as inflammation, epidermal hyperplasia, hyperkeratosis, edema, or dermal fibrosis, should be described in the pathology narrative and not diagnosed separately unless, in the pathologist's judgment, a separate diagnosis is warranted.
炎症Inflammation 皮肤炎症
描述（中文）
在皮肤给药毒性/致癌性研究中，炎症是对化学物质最常见的反应之一。炎症可能是非特异性的，也可能与自我损伤（抓挠）造成的创伤、接触设备边缘、节肢动物寄生或打斗造成的伤口有关。继发性炎症还可与皮肤肿瘤相关。皮肤急性炎症（Figure 1、Figure 2、Figure 3）的特征是中性粒细胞浸润，可伴有嗜酸性粒细胞和巨噬细胞，以及偶见的肥大细胞、淋巴细胞和浆细胞。化脓性炎症的特征是离散的退化中性粒细胞和细胞碎片聚集灶（Figure 4、Figure 5）。这些聚集灶周围还可见慢性化的证据，如纤维化和淋巴浆细胞浸润。慢性炎症（Figure 6、Figure 7）的特征是存在单核细胞（淋巴细胞、巨噬细胞和浆细胞），并可伴有纤维化或真皮细胞内黑色素蓄积。慢性活动性炎症（Figure 8、Figure 9）的特征是慢性炎症成分（淋巴细胞、巨噬细胞和纤维化）与叠加的急性炎症（中性粒细胞性和/或嗜酸性粒细胞性）并存。肉芽肿性炎症（Figure 10、Figure 11、Figure 12）的特征是巨噬细胞和多核巨细胞聚集，伴有数量不等的淋巴细胞、浆细胞或中性粒细胞。肉芽肿的一种典型形式是皮肤天然产物（如角蛋白、毛干、附件分泌物）通常因创伤而被引入结缔组织。这些皮肤产物作为异物，引发“异物性肉芽肿”，其特征性表现为多核巨细胞和/或上皮样巨噬细胞。所有形式的炎症均可伴有相关病变，包括水肿（尽管水肿更常与急性炎症相关）、上皮增生、角化过度、新生血管形成或出血，伴或不伴含含铁血黄素的巨噬细胞。
诊断建议
无论何时出现，均应记录炎症的具体类型并赋予严重程度分级。当炎症作为与肿瘤、脂肪坏死或上皮坏死、或上皮囊肿或其他类型囊肿相关的继发性发现而存在时，炎症无需单独诊断，但应在病理学描述中予以描述。当存在水肿、出血或骨化生等继发性发现时，无需诊断，但应在描述中予以描述。如果炎症伴有上皮增生、角化过度或过度纤维化，此类发现应独立于慢性炎症进行诊断和分级。当肉芽肿性炎症伴有异物时，两种诊断应分别记录，但异物诊断不应分级。
参考切片图（2 张）
查看英文原文
Comment
In dermal application toxicity/carcinogenicity studies, inflammation is one of the most common responses to chemicals. Inflammation may be nonspecific or related to trauma from self-mutilation (scratching), contact with edges of equipment, arthropod parasitism, or wounds from fighting. Secondary inflammation can also be associated with cutaneous neoplasms. Acute inflammation ( Figure 1 , Figure 2 , and Figure 3 ) in the skin is characterized by infiltration of neutrophils, which may be accompanied by eosinophils and macrophages as well as occasional mast cells, lymphocytes, and plasma cells. Suppurative inflammation is characterized by discrete pockets of degenerate neutrophils and cellular debris ( Figure 4 and Figure 5 ). Evidence of chronicity, such as fibrosis and lymphoplasmacytic infiltrates, may also surround these pockets. Chronic inflammation ( Figure 6 and Figure 7 ) is characterized by the presence of mononuclear cells (lymphocytes, macrophages, and plasma cells) and may be accompanied by fibrosis or the accumulation of melanin within cells in the dermis. Chronic active inflammation ( Figure 8 and Figure 9 ) is characterized by the coexistence of elements of chronic inflammation (lymphocytes, macrophages, and fibrosis) and superimposed acute inflammation (neutrophilic and/or eosinophilic). Granulomatous inflammation ( Figure 10 , Figure 11 , and Figure 12 ) is characterized by an accumulation of macrophages and multinucleated giant cells, with variable numbers of lymphocytes, plasma cells, or neutrophils. A typical form of granuloma is one in which natural products of the skin (e.g., keratin, hair shaft, adnexal secretions) are introduced into the connective tissues, usually by trauma. These skin products act as foreign bodies, inciting a “foreign body granuloma,” a characteristic feature of which are multinucleated giant cells and/or epithelioid macrophages. All forms of inflammation may be accompanied by associated lesions, including edema (though this is more commonly associated with acute inflammation), epithelial hyperplasia, hyperkeratosis, neovascularization, or hemorrhage with or without hemosiderin-containing macrophages.
Recommendation
Whenever present, the specific type of inflammation should be recorded and assigned a severity grade. When present as a secondary finding associated with neoplasia, fat necrosis or epithelial necrosis, or epithelial or other types of cysts, inflammation need not be diagnosed separately but should be described in the pathology narrative. When secondary findings such as edema, hemorrhage, or osseous metaplasia are present, they need not be diagnosed but should be described in the narrative. If the inflammation is accompanied by epithelial hyperplasia, hyperkeratosis, or excessive fibrosis, such findings should be diagnosed and graded independently of chronic inflammation. When granulomatous inflammation is accompanied by foreign material, both diagnoses should be documented separately, but the diagnosis of foreign material should not be graded.
纤维化Fibrosis 皮肤纤维化
描述（中文）
纤维化通常是因慢性化学暴露或创伤所致表皮或真皮损伤的后遗症。其特征为真皮（Figure 1）或皮下组织中纤维性结缔组织增多，并且通常伴有慢性炎症。纤维化可能表现为一种细微的病变，尤其是在后期阶段。其特征为真皮内或毛囊周围成纤维细胞和胶原纤维增生，通常与表皮平行排列。在更严重的病例中，纤维化可向真皮和皮下组织深部延伸。与无纤维化的真皮相比，纤维化区域可能呈现轻度嗜碱性外观，但这可因染色质量和纤维化病变的成熟程度而异。在早期纤维化中，成纤维细胞通常伴有炎性细胞（尤其是当与表皮溃疡相关时）；成纤维细胞往往较大且活性较高，胶原纤维较不致密且排列更紊乱。在纤维化的后期阶段，成纤维细胞往往较小且更呈梭形；胶原纤维排列更有组织且更致密，并且炎症通常较少。在严重病例中，纤维化区域可能出现毛囊缺失。
诊断建议
在大多数病例中，纤维化应当被记录并赋予严重程度分级。作为慢性或慢性活动性炎症的次要成分而存在的纤维化，或被认为是继发于表皮溃疡的纤维化，可能不必单独诊断，但应在病理学叙述中予以描述。当炎症程度与纤维化程度不相称时（如Figure 1所示），则应当对纤维化进行诊断和分级。可能与纤维化同时见到的其他相关病变，包括表皮增生，应当单独诊断。
参考切片图（1 张）
查看英文原文
Comment
Fibrosis is often a sequela of epidermal or dermal injury due to chronic chemical exposure or trauma. It is characterized by an increase of fibrous connective tissues in the dermis ( Figure 1 ) or subcutis and usually accompanies chronic inflammation. Fibrosis may occur as a subtle finding, particularly in the later stages. It is characterized by proliferation of fibroblasts and collagen fibers in the dermis or around hair follicles, typically oriented parallel to the epidermis. In more severe cases, the fibrosis can extend deeper into the dermis and subcutis. Areas of fibrosis may have a slightly basophilic appearance compared with the nonfibrotic dermis, but this can vary with staining quality and the maturity of the fibrotic lesion. In early fibrosis, the fibroblasts are usually accompanied by inflammatory cells (particularly when associated with an epidermal ulcer); the fibroblasts tend to be larger and more active, and the collagen fibers are less compact and more disorganized. In the later stages of fibrosis, the fibroblasts tend to be smaller and more spindle shaped; the collagen fibers are more organized and compact, and there is often less inflammation. In severe cases, there may be a loss of hair follicles in the fibrotic region.
Recommendation
Fibrosis should be documented and assigned a severity grade in most cases. Fibrosis that is present as a minor component of chronic or chronic active inflammation or is considered secondary to epidermal ulceration may not warrant a separate diagnosis but should be described in the pathology narrative. When the degree of inflammation is not commensurate to that of fibrosis (as in Figure 1 ), then fibrosis should be diagnosed and graded. Other associated lesions that may be seen with fibrosis, including epidermal hyperplasia, should be diagnosed separately.
纤维附件错构瘤Fibroadnexal Hamartoma 皮肤其他
描述（中文）
纤维附属器错构瘤（fibroadnexal hamartoma）是不常见的自发性病变。它们由一个或多个毛囊皮脂腺单位组成，其中毛囊通常扩张，并可能被丰富的纤维结缔组织包围（Figure 4、Figure 5、Figure 6）。毛囊上皮可能变扁平（Figure 5、Figure 6），也可能轻度增生并突入周围结缔组织（Figure 3）。多个皮脂腺常与单个毛囊相关联。覆盖其上的表皮常增生并角化过度。病变可呈外生性（Figure 1、Figure 2、Figure 3）或扁平（Figure 4、Figure 5、Figure 6）。这些病变的发病机制尚不清楚。它们是发育不良性病变，但不太可能是肿瘤前病变。目前尚不清楚它们是在创伤部位作为异常愈合反应而发展而来，还是先天性的。在 NTP 数据库中确认的 6 例错构瘤中，4 例见于大鼠，2 例见于小鼠。其中 1 例发生于雌性大鼠；其余均发生于雄性。
诊断建议
这些病变在剖检时偶尔可肉眼观察到，需要结合组织学诊断。因此，只要存在就应作出诊断，但不应赋予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Fibroadnexal hamartomas are uncommon spontaneous lesions. They consist of one or more pilosebaceous units in which the hair follicle is usually dilated and may be surrounded by abundant fibrous connective tissue ( Figure 4 , Figure 5 , and Figure 6 ). The epithelium of the hair follicle may be flattened ( Figure 5 and Figure 6 ), or it may be slightly hyperplastic with projections into the surrounding connective tissue ( Figure 3 ). Multiple sebaceous glands are often associated with a single follicle. The overlying epidermis is often hyperplastic and hyperkeratotic. The lesions may be exophytic ( Figure 1 , Figure 2 , and Figure 3 ) or flat ( Figure 4 , Figure 5 , and Figure 6 ). The pathogenesis of these lesions is unknown. They are dysplastic lesions but are not likely to be preneoplastic. It is unknown if they develop as an abnormal healing response at sites of trauma or if they are congenital. Of 6 hamartomas identified in the NTP database, 4 have been seen in rats and 2 in mice. One occurred in a female rat; all others occurred in males.
Recommendation
These lesions are occasionally observed grossly at necropsy and require a correlating histologic diagnosis. Therefore, they should be diagnosed whenever present but should not be assigned a severity grade.
脓疱Pustule 皮肤其他
描述（中文）
脓疱（pustule）（Figure 1、Figure 2）是角质层内有或没有血清的中性粒细胞的有组织积聚。与囊泡（vesicle）一样，它们可能在接触腐蚀性物质后形成。脓疱通常出现在皮肤损伤后急性炎症的初始阶段，但在研究结束时往往不存在。脓疱破裂可能导致糜烂（erosion）或溃疡（ulcer），但由于糜烂或溃疡不一定起源于脓疱，脓疱的存在将为糜烂/溃疡的发病机制提供重要信息。
诊断建议
只要存在且没有明显的 underlying 糜烂或溃疡，就应诊断脓疱并根据大小和数量赋予严重程度分级。脓疱可能伴有真皮炎症、表皮增生或角化过度，所有这些都应作为单独的诊断记录。如果脓疱与糜烂/溃疡同时出现，则应记录并分级这两种诊断。
参考切片图（2 张）
查看英文原文
Comment
Pustules ( Figure 1 and Figure 2 ) are organized accumulations of neutrophils with or without serum within the stratum corneum. As with vesicles, they may form after exposure to caustic agents. Pustules typically occur in the initial stages of acute inflammation after skin injury but often are not present at the end of a study. Rupture of pustules may result in erosions or ulcers, but since erosions or ulcers do not necessarily arise from pustules, the presence of pustules would provide important information regarding the pathogenesis of the erosions/ulcers.
Recommendation
Whenever present without apparent underlying erosion or ulceration, pustules should be diagnosed and assigned a severity grade based on size and number. Pustules may be seen with dermal inflammation, epidermal hyperplasia, or hyperkeratosis, all of which should be recorded as separate diagnoses. If pustules are seen concurrently with erosions/ulcers, then both diagnoses should be recorded and graded.
色素Pigment 皮肤色素沉着
描述（中文）
皮肤色素的诊断以真皮或皮下组织中载色素细胞（黑素细胞或巨噬细胞）的蓄积为特征（Figure 1、Figure 2）。色素几乎仅见于皮肤给药研究，是局部涂敷受试物后反应的一部分。因此，色素通常伴随其他病变，如炎症（通常为慢性或慢性活动性）或纤维化。
诊断建议
在有指征时（根据病理学家的判断），色素应当被记录并赋予严重程度分级。如果色素是炎症的次要成分，则不必单独诊断，但应在叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
The diagnosis of pigment in the skin is characterized by the accumulation of pigment-laden cells (melanocytes or macrophages) in the dermis or subcutis ( Figure 1 and Figure 2 ). Pigment occurs almost exclusively in dermal studies as part of the response to topical application of a test article. Hence, pigment is typically accompanied by other lesions, such as inflammation (usually chronic or chronic active) or fibrosis.
Recommendation
When warranted (based on the judgment of the pathologist), pigment should be documented and assigned a severity grade. If it is a minor component of inflammation, it need not be diagnosed separately but should be described in the narrative.
萎缩Atrophy 皮肤萎缩
描述（中文）
附件萎缩（Adnexal atrophy）的特征是毛囊皮脂腺单位（pilosebaceous units）体积变小、数量减少（Figure 2、Figure 3）。严重病例中，附件可能缺失（Figure 4）。该病变可能伴有真皮内炎症。毛囊萎缩（Follicular atrophy）的特征是毛囊体积变小、数量减少，皮脂腺萎缩（sebaceous gland atrophy）的特征是皮脂腺体积变小、数量减少。附件萎缩或毛囊萎缩可能对应大体观察到的脱毛（alopecia）。脱毛的大体表现可能归因于啃毛或理毛等行为、因摩擦构造不良的饲料器或饮水装置开口所致的机械性剥脱、寄生虫侵染，以及由激素（甲状腺功能减退）和营养失衡引起的全身性疾病。某些受试物可能影响毛周期的特定阶段，从而导致脱毛。例如，许多化疗药物干扰生长期（anagen phase）毛囊的快速有丝分裂活动。已知其他化合物影响休止期（telogen phase）的毛囊，如铊（thallium）、三苯乙醇（triparanol）和香豆素（coumarin）。某些化合物，如苯基缩水甘油醚（phenyl glycidyl ether）和二噁拉嗪（dixyrazine），对生长期和休止期均有影响。受影响于特定阶段的毛囊很可能表现为萎缩。伴有毛囊萎缩或完全缺失的脱毛也可能发生于皮下或真皮肿瘤上方的皮肤。
诊断建议
如果毛囊和皮脂腺均出现萎缩，应使用术语“Skin, adnexa – Atrophy”。如果毛囊萎缩发生而不累及其他附件结构，应使用术语“Skin, Follicle – Atrophy”。如果皮脂腺萎缩发生而不累及其他附件结构，应使用术语“Skin, Sebaceous gland – Atrophy”。无论何时出现，附件萎缩、毛囊萎缩或皮脂腺萎缩均应作出诊断并赋予严重程度分级。如果这些病变作为肿瘤、慢性炎症或纤维化的继发性病变存在，则无需诊断，但应在病理学叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Adnexal atrophy is characterized by smaller and reduced numbers of pilosebaceous units ( Figure 2 and Figure 3 ). In severe cases, the adnexa may be absent ( Figure 4 ). This lesion may be accompanied by inflammation in the dermis. Follicular atrophy is characterized by smaller and reduced numbers hair follicles, and sebaceous gland atrophy is characterized by smaller and reduced numbers of sebaceous glands. Adnexal or follicular atrophy may correspond to the gross observation of alopecia. The gross appearance of alopecia may be attributed to behaviors such as hair chewing or barbering, mechanical denuding due to rubbing against poorly constructed openings for feeders or water devices, parasitic infestations, and systemic diseases from hormonal (hypothyroidism) and nutritional imbalances. Some agents may affect a specific phase of the hair cycle, resulting in alopecia. For example, many chemotherapeutic agents interfere with the rapid mitotic activity of hair follicles in the anagen phase. Other compounds are known to affect hair follicles in the telogen phase, such as thallium, triparanol, and coumarin. Some compounds, such as phenyl glycidyl ether and dixyrazine, have effects on both the anagen and telogen phases. Follicles affected in a particular phase are likely to appear atrophied. Alopecia with atrophy or complete loss of hair follicles may also occur in skin over a subcutaneous or dermal neoplasm.
Recommendation
If atrophy of both hair follicles and sebaceous glands is present, the term “Skin, adnexa – Atrophy” should be used. If follicular atrophy occurs without involvement of other adnexal structures, the term “Skin, Follicle – Atrophy” should be used. If sebaceous gland atrophy occurs without involvement of other adnexal structures, the term “Skin, Sebaceous gland – Atrophy” should be used. Whenever present, adnexal atrophy, follicular atrophy, or sebaceous gland atrophy should be diagnosed and assigned a severity grade. If these are present as a secondary lesion to neoplasia, chronic inflammation, or fibrosis, it need not be diagnosed but should be described in the pathology narrative.
角化过度Hyperkeratosis 皮肤其他
描述（中文）
角化过度最常见于皮肤给药研究，并且常伴随上皮增生或继发于上皮增生。其特征为角质层增厚（Figure 1、Figure 2）。角化过度最常见的是正角化性（角质层增厚但无残留细胞核；Figure 2）。角化不全性角化过度的特征为角质层内存在细胞核，罕见发生，并且通常与上皮增生同时存在（Figure 1）。
诊断建议
只要存在角化过度，就应记录并赋予严重程度分级。由于角化不全是角化过度的一种形式，NTP研究中只应使用“角化过度（hyperkeratosis）”这一术语。但是，应在病理学描述中说明角化过度是正角化性还是角化不全性。相关病变，如上皮增生和炎症，应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Hyperkeratosis is most commonly observed in dermal application studies and is often accompanied by or secondary to epithelial hyperplasia. It is characterized by thickening of the stratum corneum ( Figure 1 and Figure 2 ). Hyperkeratosis is most commonly orthokeratotic (thickening of the cornified layer without retained nuclei; Figure 2 ). Parakeratotic hyperkeratosis, which is characterized by the presence of nuclei in the cornified layer, occurs rarely and is usually concurrent with epithelial hyperplasia ( Figure 1 ).
Recommendation
Whenever present, hyperkeratosis should be recorded and assigned a severity grade. Since parakeratosis is simply a form of hyperkeratosis, only the term “hyperkeratosis” should be used in NTP studies. However, the hyperkeratosis should be described in the pathology narrative as being orthokeratotic or parakeratotic. Associated lesions, such as epithelial hyperplasia and inflammation, should be diagnosed separately.
异位神经元Ectopic Neuron 神经其他
描述（中文）
神经发育不良（neural dysplasia）描述了多种发育异常，其中神经元位置异常（异位和错位）常常是其中的一个组成部分。尽管在一般毒性研究中，神经元异位很少被认为是与处理相关的效应，但世代研究的出现使得识别此类神经发育畸形成为必要。严重的神经元异位可能源于胚胎受到辐射暴露。Figure 1 展示了神经发育异常的一种形式，在本例中为偶然发现。注意坐骨神经（sciatic nerve）中的异位神经元（箭头）。这些神经元可能来源于神经节，错误地位于坐骨神经的神经干内。注意明显的胞质尼氏体（Nissl substance，即粗面内质网的聚集）和细胞核的偏心定位。后者常与影响细胞骨架完整性的轻微神经元损伤相关，从而影响细胞核的位置。神经元异位更常见于小脑（cerebellum），其中浦肯野细胞（Purkinje cell）可能位于颗粒细胞层（granule cell layer）或其他部位。然而，这些应与颗粒细胞层的高尔基中间神经元（Golgi interneuron）相区分，后者常被误认为移位的浦肯野细胞。在啮齿类动物中，此类神经元异位与临床神经学发现之间尚无相关性，尽管不能排除这种可能性。
诊断建议
在 NTP 研究中，神经元异位应当被诊断，并在可能时注明具体亚部位。不需要进行严重程度分级。
参考切片图（1 张）
查看英文原文
Comment
Neural dysplasia describes a wide variety of developmental abnormalities, of which abnormal positioning of neurons (heterotopia and ectopia) is frequently a component. Although neuronal ectopia is seldom recognized as a treatment-related effect in general toxicity studies, the advent of generational studies necessitates the recognition of such malformations of neural development. Substantial neuronal ectopias may result from radiation exposure to embryos. Figure 1 represents a form of abnormal neural development, an incidental finding in this case. Note the ectopic neurons (arrow) in the sciatic nerve. The neurons, probably of ganglionic origin, are misplaced in the body of the sciatic nerve. Note the prominent cytoplasmic Nissl substance (aggregations of rough endoplasmic reticulum) and eccentric positioning of the nuclei. The latter are often associated with minor neuronal insult that affects cytoskeletal integrity, thus influencing the position of the nucleus. Neuronal ectopia is more commonly found in the cerebellum, where Purkinje cells may be located in the granule cell layer or other sites. These, however, should be distinguished from Golgi interneurons of the granular cell layer, which are commonly mistaken for displaced Purkinje cells. There has been no correlation between such neuronal ectopias and clinical neurologic findings in rodents, although it is not possible to rule out that prospect.
Recommendation
Neuronal ectopia should be diagnosed and the subsite area included when possible in NTP studies. Severity grading is not required.
背根神经节神经元空泡化Dorsal Root Ganglion Neuron Vacuolation 脊髓空泡化
描述（中文）
神经元空泡化（neuronal vacuolation）虽可见于任何发生变性的神经元群体，但其在背根神经节（dorsal root ganglia）中的神经病理学意义尤受关注。Figure 1显示了大鼠背根神经节神经元的正常形态。诊断上的问题在于要认识到，这些神经节部位的组织未接触毒性化合物时，神经元空泡化偶尔也可以低发生率出现，并且在老年啮齿类动物中更为常见。重要的是，神经元空泡化可能是毒性的显著效应。空泡表现为受累神经元核周体（perikaryon）内大小不一但通常较大的透明空泡，可伴有染色质溶解（chromatolysis）（Figure 2，箭头）。空泡的衬里由单层膜构成，该膜有短突起伸入空泡内，并伴有染色质溶解。电子显微镜图像未能明确识别受累的肿胀细胞器，但滑面内质网和高尔基体是最可能的候选者。鉴于已知神经元空泡化可作为偶发性 incidental finding 出现，仔细检查对照和治疗组在相应区域是否存在该变化十分重要。相关变化的存在，如神经元染色质溶解或胶质细胞或卫星细胞的邻近反应，可能有助于将空泡化归因为一种病变。
诊断建议
当出现时，神经元空泡化在NTP研究中应予诊断，记录其亚部位，并进行严重程度分级。存在并发病变时，通常诊断严重程度最高的病变。其他并发病变，若严重程度足以支持，可单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Neuronal vacuolation, while it may be seen in any population of neurons undergoing degeneration, is a particular concern for its neuropathologic significance in the dorsal root ganglia. Figure 1 shows the normal appearance of rat dorsal root ganglionic neurons. At issue diagnostically is the recognition that neuronal vacuolation at these ganglionic sites may occasionally be present at a low incidence in tissue not exposed to toxic compounds and is more common in older rodents. Importantly, neuronal vacuolation may be a significant effect of toxicity. The vacuoles appear as variably sized, but generally large clear vacuoles in the perikaryon of the affected neurons may be accompanied by chromatolysis ( Figure 2 , arrow). The lining of the vacuoles is composed of a single membrane, and short protrusions of this membrane occur into the vacuoles, accompanied by chromatolysis. Electron microscopic images do not clearly identify the affected swollen organelles, but smooth endoplasmic reticulum and Golgi apparatus are the most likely candidates. In view of the known occurrence of neuronal vacuolation as an occasional incidental finding, it is important to carefully examine control and treatment groups for its presence in comparable regions. The existence of associated changes such as neuronal chromatolysis or adjacent responses by glia or satellite cells may be helpful in attributing vacuolization as a lesion.
Recommendation
When present, neuronal vacuolation is diagnosed in NTP studies, the subsite recorded, and the severity graded. In the presence of concurrent lesions, lesions with the most severity are typically diagnosed. Other concurrent lesions may be diagnosed separately, if warranted by the severity.
脱髓鞘Demyelination 脊髓其他
描述（中文）
神经系统的脱髓鞘（demyelination）是一个特定术语，描述中枢和周围神经纤维髓鞘的活动性变性和吞噬作用。Figure 1、Figure 2 分别是小鼠和大鼠脊髓中枢神经纤维（Figure 1）和坐骨神经周围神经纤维（Figure 2）髓鞘脱髓鞘的示例（箭头）。Figure 2 中的箭头head显示残留的轴突。在后一种情况下，活动性髓鞘变性和吞噬作用被归因于一种独特农用化学品的毒性。“脱髓鞘”一词必须谨慎使用，不应包括神经组织梗死所致的髓鞘丢失，后者更恰当地称为“局灶性（focal） necrosis”，由毒性或已知感染性原因引起。脱髓鞘诊断中的一个常见错误是将该术语用于描述浸入福尔马林固定神经组织中常见的神经毡空泡化人工假象，或与髓鞘内水肿（intramyelinic edema）中所见的重要真实性神经毡空泡化相混淆。脱髓鞘可以是原发性或继发性。在原发性脱髓鞘中，轴突通常完整并可能被保留，特别是当髓鞘仅受到免疫系统攻击并导致吞噬作用时（原发性脱髓鞘）。相比之下，继发性脱髓鞘是轴突损伤和丢失的常见后果，因此轴突病和脱髓鞘常因经典轴突病性化合物（如有机磷制剂和丙烯酰胺）所致的轴突损伤而共存。除人类多发性硬化所致的脱髓鞘和实验动物实验性诱导的自身免疫性脑病外，罕见的人类免疫介导性脱髓鞘性神经病可发生于免疫调节、免疫抑制或抗肿瘤药物初始或维持治疗期间。Krinke 和 Zurbriggen（1997）描述了老龄小鼠胸段脊髓中的脱髓鞘，通过对其材料中病原体的免疫组织化学鉴定，将其归因于一株泰勒鼠脑脊髓炎病毒（Theiler’s murine encephalomyelitis virus，TMEMV）。其实验中脊髓的显著双侧病变见 Figure 1（箭头）。然而，TMEMV 在屏障饲养的实验室小鼠中不常见，尤其是在北美（PB Little 与 C Clifford，Charles River Laboratories 的个人通信）。
诊断建议
在 NTP 研究中，当光镜下无法将脱髓鞘与髓鞘内水肿或轴突病区分开时，该病变应诊断为白质空泡化（white matter vacuolation）。随后应由神经病理学家进行特殊评估。当在 NTP 研究中出现时，该病变应进行分级并注明亚部位。
参考切片图（2 张）
查看英文原文
Comment
Demyelination of the nervous system is a specific term describing the active degeneration and phagocytosis of myelin wrappings of central and peripheral nerve fibers. Figure 1 and Figure 2 are examples of demyelination of myelin wrappings of central ( Figure 1 ) and peripheral ( Figure 2 ) nerve fibers of the mouse and rat spinal cord (arrows) and sciatic nerve, respectively. The arrowheads in Figure 2 show remnant axon. In this latter case the active myelin degeneration and phagocytosis were attributed to toxicity to a unique agrochemical. The term “demyelination” must be used carefully and not include the loss of myelin seen as a result of infarction of nervous tissue, more appropriately called “focal necrosis,” resulting from toxic or recognized infectious causes. A common error in diagnosis of demyelination relates to use of the term to describe artifactual neuropil vacuolation commonly seen in immersion formalin-fixed neural tissue, or confusion with the important authentic neuropil vacuolation seen in intramyelinic edema. Demyelination may be primary of secondary. In primary demyelination, the axon is usually intact and may be preserved, especially if the myelin sheath is exclusively assaulted by the immune system with resulting phagocytosis (primary demyelination). In contrast, secondary demyelination is a common sequel to axonal injury and loss, such that axonopathy and demyelination often coexist as a result of axonal injury from classic axonopathic compounds such as organophosphate agents and acrylamide. In addition to demyelination resulting from multiple sclerosis in humans and the experimentally induced autoimmune encephalopathy of laboratory animals, rarely human immune-mediated demyelinating neuropathies occur during initial or maintenance treatment with immunomodulatory, immunosuppressive, or antineoplastic agents. Krinke and Zurbriggen (1997) have described a demyelination in the thoracic spinal cord of aging mice that was attributed to a strain of Theiler’s murine encephalomyelitis virus (TMEMV) using immunohistochemical identification of the agent in their material. Prominent bilateral lesions of the spinal cord from their studies are shown in Figure 1 (arrows). However, TMEMV is uncommon in barrier-raised laboratory mice, particularly in North America (PB Little, personal communication with C Clifford, Charles River Laboratories).
Recommendation
In NTP studies where demyelination cannot be differentiated from intramyelinic edema or axonopathy under light microscopy, the lesion should be diagnosed as white matter vacuolation. This should be followed by special evaluation by a neuropathologist. When present in NTP studies, this lesion should be graded and the subsite noted.
出血Hemorrhage 脑出血
描述（中文）
在图1和图2中，毛细血管损伤表现为局灶性（focal）出血，更重要的是，毛细血管周围出现富含蛋白质的液体渗出（箭头）。该病变容易被遗漏，因为出血可能看起来类似于处理新鲜脑组织及小血管破裂所致的死后伪影。通常，生前脑出血还伴有少量血管周围多形核白细胞，其存在可能仅持续数小时。应仔细检查血管区域是否存在提示坏死的纤维素样改变，或如图1所示，是否存在由血管周围毛细血管富含蛋白质的渗出物和出血所表示的更细微的损伤证据。在后续评估中，可通过免疫组织化学检测血管外血清白蛋白或辣根过氧化物酶的穿透来发现毛细血管的早期损伤。
诊断建议
在NTP研究中出现时，应诊断出血并确定其位置和严重程度。存在并发病变时，通常诊断严重程度最高的病变。其他并发病变，若严重程度允许，可单独诊断。
参考切片图（2 张）
查看英文原文
Comment
In Figure 1 and Figure 2 , capillary injury is present as evidenced by the criteria of focal hemorrhage and, importantly, the transudation of protein-rich fluid around the capillary (arrow). This lesion can easily be missed since the hemorrhage may appear similar to postmortem artifact induced by handling of fresh brain and rupture of small vessels. Commonly, antemortem brain hemorrhage is also accompanied by a few perivascular polymorphonuclear leukocytes whose presence may persist for only several hours. The vascular compartment should be closely examined for the presence of fibrinoid changes indicative of necrosis or, as shown in Figure 1 , for more subtle evidence of injury signified by perivascular capillary protein-rich transudate and hemorrhage. Early damage to capillaries may be detected in subsequent evaluations by using immunohistochemistry for extravascular serum albumin or penetration of horseradish peroxidase.
Recommendation
When present in NTP studies, hemorrhage should be diagnosed and the location and severity identified. In the presence of concurrent lesions, lesions with the most severity are typically diagnosed. Other concurrent lesions may be diagnosed separately, if warranted by the severity.
发育不良Dysplasia 脑其他
描述（中文）
随着世代毒性研究使用的日益增多，识别神经发育不良变得越来越重要。发育不良包括神经结构各组成部分在大小、组织和位置上的发育异常。Figure 1在低倍镜下显示了不常被识别的啮齿类动物海马发育不良的偶发表现。在这个显著的例子中，请注意异常的波浪状CA1区（箭头）和畸形的齿状回（箭头指示）。CA3看起来相对正常。Figure 2为便于比较而标注，显示正常大鼠海马结构。发育不良的神经元病变通常见于皮层、海马和小脑，但大脑的任何部位都可能受累。在大多数情况下，如果有影响，临床上检测不到，但可以解释个别动物出现的异常临床神经体征，如癫痫发作。大鼠神经发育不良的模型包括用甲基氧化偶氮甲醇醋酸盐处理，随后用毛果芸香碱诱导癫痫样发作。
诊断建议
在NTP研究中，只要存在此病变，就应当诊断，并将亚部位纳入诊断中。不需要进行严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
With the increasing use of generational toxicity studies, recognizing neural dysplasia is becoming increasingly important. Dysplasias include developmental abnormalities in size, organization, and location of various elements of the neural structures. Figure 1 shows, at low magnification, the appearance of uncommonly recognized incidental rodent hippocampal dysplasia. In this dramatic example, note the abnormal undulating CA1 region (arrows) and malformed dentate gyrus (arrowhead). CA3 appears relatively normal. Figure 2 , labeled for comparison, shows normal rat hippocampal structure. Dysplastic neuronal lesions are usually encountered in the cortex, hippocampus, and cerebellum, but any part of the brain can be affected. In most cases, effects, if any, are not detected clinically but could account for abnormal clinical neurologic signs such as seizures in individual animals. Models of neural dysplasia in rats include treatment with methylazoxymethanol acetate followed by induction of epileptiform seizures by pilocarpine.
Recommendation
Whenever present in NTP studies, this lesion should be diagnosed and the subsite included in the diagnosis. Severity grading is not required.
坏死Necrosis 脑坏死
描述（中文）
本节重点讨论由不同过程引起的脑坏死形态学及反应的性质。在NTP研究中，梗死被诊断为坏死，而“软化（malacia）”一词保留用于脑的大体病变。Figure 1显示了动脉栓子（箭头）所致急性血管闭塞的梗死效应。Figure 2中放大了纤维蛋白和脂肪栓子。Figure 1中白色箭头标识海马齿状回。注意提示受累区域早期坏死的苍白区（箭头），单侧累及大部分丘脑、下丘脑、大脑脚和视束。在缺血性脑病变中，神经元坏死的典型形态学标准在苏木精和伊红染色切片中可能需要超过24小时的存活时间才能显现。在Figure 1所示的时间点，病变边缘几乎没有，如果有的话，炎症细胞浸润的证据，表明梗死时间不足24小时。海马相对免受缺血影响。在大多数情况下，脑梗死的原因是偶然的，和/或归因于侵入性采样技术，如血液或骨髓采集，其中栓子进入静脉或动脉系统。Figure 3描绘了后丘（posterior colliculus）急性坏死的双侧对称性病变。还应注意外侧丘系核（nucleus of the lateral lemniscus）的坏死。边界清晰的苍白灶伴出血，双侧累及后丘核及外侧丘系核，类似于缺血性病变。与顶叶皮层一样，后丘负责听觉反射，具有高代谢率，特别易受干扰神经元能量代谢过程的影响。同样，Figure 4描绘了顶叶皮层1区（蓝色箭头）、丘脑（箭头）和压后皮层（白色箭头）的急性双侧坏死。脑区对毒性化合物效应的选择性易损性可能模仿缺血性坏死病变，应根据化合物暴露和临床病史与该类损伤相鉴别。神经病变的双侧对称性通常是毒性而非缺血性病因的有用指标。Figure 5描绘了脊髓背侧索中一种不寻常形式的区域性完全坏死（箭头）。这种类型的脊髓坏死被称为“脊髓出血（hematomyelia）”。它通常是邻近部位坏死或创伤性/肿瘤性脊髓压迫的结果，导致炎症核心的肿胀、出血和组织破坏在脊髓内向头侧和尾侧进展。Figure 6显示了伴有胶质增生和毛细血管增生的皮层梗死（箭头）。受累皮层通过缺血组织的轻微塌陷来识别，在病变的脑膜侧最为明显。即使在此低倍放大下，轻度皮层核固缩也显而易见。Figure 7显示了皮层梗死（箭头）的更晚期阶段，伴有胶质增生和巨噬细胞浸润。病变边界由胶质细胞反应界定，早期空洞形成正在整个区域进行。Figure 8描绘了已知持续时间的梗死形态。梗死72小时后，毛细血管核肥大（箭头）、早期巨噬细胞反应以及受累组织的一些碎裂显而易见。Figure 9显示了皮层梗死的较晚期阶段，此时组织丢失和皮层结构塌陷，在脑膜表面形成凹陷。这种皮层软膜下萎缩还伴有软脑膜间隙和空洞区域（箭头）的残留巨噬细胞。虽然在此苏木精和伊红切片中星形细胞肥大不明显，但胶质纤维酸性蛋白染色会显示与损伤持续时间相符的显著反应。Figure 10描绘了已知72小时持续时间的皮层梗死中的细胞反应（PB Little，个人观察）。注意毛细血管内皮的肥大和增生状态以及显著的巨噬细胞存在（箭头）。这些巨噬细胞已从驻留的小胶质细胞或血源性单核细胞分化而来，正在受累缺血区域吞噬脑脂质。它们被称为脂质吞噬细胞，或更常见地称为“格子细胞（gitter cells）”。它们还可通过365 nm波长下的自发荧光以及过碘酸雪夫染色或各种脂质染色（如Sudan III或油红O）的阳性染色进一步识别。Figure 11是严重嗅球坏死的例子，常被称为软化。该器官大部分实质丢失，伴有中央出血和坏死碎片（箭头）。软化是脑某一区域完全坏死的过程，描述大体可触及的大片受累脑坏死区域的质地。在NTP研究中，组织学上软化被诊断为坏死。显微镜下，病变中神经组织的所有成分均坏死。此处，过程已进展至坏死成分液化，仅剩无定形碎片和一些出血。最终，这样的区域注定成为充满脑脊液的囊肿。在晚期神经坏死区域，大部分可识别的组织丢失。重要的是将过程归因于坏死而非自溶，后者可能因缺乏存活神经组织而被提示。Figure 11所示邻近组织形态正常的存在有助于形成坏死的诊断。Figure 12勾勒了海马CA1区，其中存在缺血性坏死。微管相关蛋白免疫组化技术阴性勾勒出坏死区（箭头）。同样，如果研究中预期脑梗死，使用三苯基四氮唑有助于大体界定受累区域。此类特殊染色不用于常规一线评估，但了解它们在特殊情况下是有用的。
诊断建议
在NTP研究中，多灶性梗死和软化被诊断为脑，多部位，坏死。如果坏死为局灶性（focal），诊断应包括亚部位。严重程度分级基于病变范围。当单个神经元受累时，诊断应为脑，神经元，坏死。坏死的相关特征应纳入叙述中。在晚期坏死病变中，还可见胶质增生和炎症、组织塌陷及囊肿形成时，通常诊断最严重的病变。其他并发病变，如果严重程度需要，可单独诊断。
参考切片图（2 张）
查看英文原文
Comment
This section focuses on the morphology of brain necrosis caused by differing processes and the nature of the responses. In NTP studies, infarcts are diagnosed as necrosis, and the term “malacia” is reserved for gross lesions in the brain. Figure 1 identifies the infarctive effects of acute vascular occlusion by an arterial embolus (arrowhead). The fibrin and fat embolus is enlarged in Figure 2 . The hippocampal dentate gyrus is identified by a white arrow in Figure 1 . Note the pallor signifying early necrosis of the affected region (arrows) that involves much of the thalamus, hypothalamus, cerebral peduncle, and optic tract unilaterally. In ischemic brain lesions, the typical morphologic criteria of neuronal necrosis may take more than 24 hours of survival to manifest in hematoxylin and eosin sections. At the time point shown in Figure 1 , there is little, if any, evidence of inflammatory infiltrate at the margin of the lesion, indicating that the infarction is less than 24 hours old. The hippocampus is relatively spared from the ischemia. In most cases, the cause of brain infarction is incidental and/or attributable to invasive sampling techniques such as blood or marrow collection in which emboli gain access to the venous or arterial systems. Figure 3 depicts a bilaterally symmetrical lesion of acute necrosis of the posterior colliculus. Note also the necrosis of the nucleus of the lateral lemniscus. The well-defined foci of pallor, with hemorrhage, affecting the posterior collicular nucleus bilaterally, and the nucleus of the lateral lemniscus resemble those of ischemic lesions. Like the parietal cortex, the posterior colliculus, subserving auditory reflexes, has a high metabolic rate and is particularly vulnerable to processes that interfere with neuronal energy metabolism. Similarly, Figure 4 depicts acute bilateral necrosis in the parietal cortex area 1 (blue arrow), thalamus (arrowhead), and retrosplenial cortex (white arrow). Selective vulnerability of brain regions to the effects of toxic compounds may imitate the lesions of ischemic necrosis and should be differentiated from insults of that type based on compound exposure and clinical history. Bilateral symmetry of neural lesions is generally a useful indicator of toxic, rather than ischemic, etiology. Figure 5 depicts an unusual form of total regional necrosis (arrow) of the spinal cord in the dorsal spinal funiculi. This type of spinal cord necrosis is referred to as “hematomyelia.” It is usually the result of necrosis or traumatic/neoplastic spinal compression at an adjacent site with resulting propagation of an inflammatory core of swelling, hemorrhage, and tissue disruption that progresses anteriorly and posteriorly within the spinal cord. Figure 6 shows a cortical infarct with gliosis and capillary hyperplasia (arrow). The affected cortex is identified by minimal collapse of ischemic tissue, most noticeable at the meningeal extent of the lesion. Even at this low magnification, a mild degree of cortical nuclear pyknosis is apparent. In Figure 7 , a more advanced stage of cortical infarction (arrows) is shown, with gliosis and macrophage infiltration. The borders of the lesion are defined by the glial cell response, and early cavitation is proceeding throughout. Figure 8 depicts the morphology of an infarct of known duration. At 72 hours after infarction, the capillary nuclear hypertrophy (arrow), early macrophage response, and some fragmentation of the affected tissue are evident. Depicted in Figure 9 is a later stage of cortical infarction where there is loss of tissue and collapse of the cortical structure, creating a depression at the meningeal surface. This subpial atrophy of the cortex is also accompanied by residual macrophages in the leptomeningeal spaces and cavitated areas (arrows). While astrocytic hypertrophy is not apparent in this hematoxylin and eosin section, a glial fibrillary acidic protein stain would demonstrate a significant response coinciding with the duration of the insult. Figure 10 depicts the cellular responses in cortical infarction of known 72 hour duration (PB Little, personal observation). Note the hypertrophic and hyperplastic state of the capillary endothelium and the prominent macrophage presence (arrows). These macrophages have differentiated from resident microglial cells or blood-borne monocytic cells and are in the process of phagocytosis of brain lipid in the affected ischemic region. They are referred to as lipid phagocytes or, more commonly, as “gitter cells.” They can be further identified by their autofluorescence at 365 nm wavelength and by their positive staining with periodic acid Schiff or various lipid stains such as Sudan III or oil red O. Figure 11 is an example of severe olfactory bulb necrosis that has often been referred to as malacia. There is loss of much of the substance of the organ accompanied by central hemorrhage and necrotic debris (arrows). Malacia is a process of total necrosis of a region of brain and describes the gross palpable texture of the large affected necrotic region of brain. Histologically, in NTP studies, malacia is histologically diagnosed as necrosis. Microscopically, all elements of the neural tissue in a lesion are necrotic. Here, the process has advanced to liquefaction of necrotic elements, leaving little but amorphous debris and some hemorrhage. Ultimately, such an area is destined to become a cyst filled with cerebrospinal fluid. In regions of advanced neural necrosis, much of the recognizable tissue is lost. It is important to ascribe the process to necrosis rather than autolysis, which the lack of viable neural tissue may suggest. The presence of normal morphology of adjacent tissue as shown in Figure 11 is helpful in forming a diagnosis of necrosis. Figure 12 outlines the CA1 region in the hippocampus in which there is ischemic necrosis. Microtubule-associated protein immunohistochemical technique negatively outlines the necrotic zone (arrows). Similarly, if cerebral infarction is anticipated in a study, the use of triphenyltetrazolium is valuable to grossly define the region of involvement. Such special stains are not used in routine first-tier evaluation, but it is useful to be aware of them for special circumstances.
Recommendation
In NTP studies, multifocal infarction and malacia are diagnosed as Brain, Multiple sites, Necrosis. If necrosis is focal, the diagnosis should include the subsite. Severity grading is based on the extent of the lesion. When individual neurons are affected, the diagnosis should be Brain, Neuron, Necrosis. Pertinent features of the necrosis should be included in the narrative. In advanced lesions of necrosis, where gliosis and inflammation, tissue collapse, and cyst formation are also seen, lesions with the most severity are typically diagnosed. Other concurrent lesions may be diagnosed separately, if warranted by the severity.
小胶质细胞增生Microgliosis 脑其他
描述（中文）
本节讨论脑内主要反应性细胞的细胞反应：小胶质细胞（microglia）、毛细血管内皮细胞（capillary endothelial cells）和星形胶质细胞（astrocytes）。小胶质细胞是早期反应细胞，在损伤部位及其周围12–24小时内即可显现。其向可识别巨噬细胞的演变在48小时内变得明显。作为巨噬细胞，其胞质增多，脂质降解产物可通过高碘酸-雪夫试剂（periodic acid Schiff reagent）及365 nm波长下的自发荧光检测到。此类吞噬细胞称为脂质吞噬细胞，或更常称为“泡沫细胞（gitter cells）”。Figure 1 显示炎症性单核细胞血管周围套（箭头）邻近的小胶质细胞增生。注意典型小胶质细胞众多细长、不规则的细胞核。该图像显示脑对损伤的反应，即通过激活驻留小胶质细胞实现。这些中胚层细胞在神经发育的早期胚胎阶段进入脑内，具有巨噬细胞能力。在非活跃状态下，它们分布于整个脑内，因其无特征的圆形细胞核及缺乏可见胞质而难以识别。当因脑损伤的存在而被激活时，它们变为可运动并迁移至损伤部位。在迁移过程中，细胞核变得细长且形状不规则，称为“杆状细胞（rod cells）”。通过这种细胞核形态，它们易于被检测到（如本图所示），分布于远离血管周围单核细胞浸润处。除驻留小胶质细胞外，血液和骨髓来源的单核细胞穿过内皮迁移至损伤部位，在那里它们也承担类似驻留小胶质细胞的吞噬功能。这解释了Figure 1（箭头）所示损伤脑组织邻近单核细胞一定程度血管周围套形成的原因。这些血源性单核细胞的外观和功能据知与驻留小胶质细胞无异。检测脑内这些细胞特别有用的免疫组化染色是Iba-1（离子化钙结合衔接分子1）抗体。Figure 2 显示小胶质细胞（杆状细胞）激活的细长不规则细胞核（箭头）。在高倍放大下显示，这些激活的小胶质细胞在趋化刺激下向神经损伤区域迁移。无法确定这些细胞是驻留小胶质细胞还是来源于经血流携带至神经组织的浸润性单核细胞。Figure 3 描绘了大脑皮质中小胶质细胞的Iba-1免疫组化检测。注意棕色染色的细胞及其突起广泛的放射状、横断面和纵断面（箭头）。Iba-1特异性表达于巨噬细胞和小胶质细胞，并在细胞激活过程中上调。Figure 4 显示既往损伤部位的反应性胶质增生和毛细血管增生（箭头）。毛细血管对邻近组织的损伤反应迅速，内皮细胞核肥大在24小时内即可明显。对病理学家而言，在低倍镜扫描脑组织时，这些毛细血管变化往往是某区域损伤的首个指征。本图中所见的反应性胶质增生很可能是浸润性血液单核细胞与驻留小胶质细胞的混合。尚无细胞分化为可识别的巨噬细胞。因此该病变可能不足48小时。使用层粘连蛋白（laminin）和血管性血友病因子（von Willebrand factor）进行免疫组化可增强对内皮反应的选择性研究。Figure 5 显示壳核（putamen）损伤的混合性胶质增生反应，由反应性星形胶质细胞、巨噬细胞、小胶质细胞和单核细胞组成。明显可见该区域有核细胞显著增多。在此放大倍数下，仅用苏木精-伊红（H&E）染色，无法识别构成该细胞群体的特定细胞类型。在许多研究中，仅需将反应识别为混合性胶质细胞型即可，其中包括星形胶质细胞、小胶质细胞和血源性单核细胞和/或已分化为吞噬细胞的巨噬细胞。在需要特异性识别浸润细胞类型的情况下，则需要特殊染色和免疫组化。正常星形胶质细胞，包括原浆型和纤维型，弥漫分布于神经系统中，其功能包括稳定结构、维持神经环境、神经元能量过程及血脑屏障。脑内正常星形胶质细胞群体的密度在软脑膜（pia mater）正下方的胶质界膜（glia limitans）以及血管周围增高。肥胖型星形胶质细胞增生（gemistocytic astrocytosis）是许多形式神经损伤进行性反应的组成部分，有助于发现细微脑损伤，并可大致判断现存病变的时间顺序。Figure 6 在高倍放大下显示H&E染色的愈合中神经损伤部位的反应性肥胖型星形胶质细胞增生。注意这些反应性星形胶质细胞典型的偏位核和显著的嗜酸性胞质（箭头），以及较少见的微小双核形式（箭头）。此外，正常的放射状突起变大且广泛。在此例中，其中一个反应性星形胶质细胞出现罕见的双核化形式，提示反应中不仅存在肥大，还存在增生。肥胖型星形胶质细胞的出现是判断脑病变时间的有用指标，因为在H&E切片上，损伤后12–14天之前其很少充分发育。使用针对胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）的免疫组化技术——该蛋白构成星形胶质细胞中间丝——可检测反应的最早阶段。这大约在损伤后7天开始，使任何损伤部位更易识别，即使H&E切片上几乎看不到什么。因此，GFAP是细微脑损伤及相关星形胶质细胞反应非常有用、敏感的指标。虽然GFAP免疫反应性在神经病理学中广泛用于识别和定量星形胶质细胞，但其他一些细胞类型如室管膜细胞（ependymal cells）也可能表达低水平的该中间丝。
诊断建议
当反应细胞以具有上述及图示典型小胶质细胞特征为主时，应使用“小胶质细胞增生（microgliosis）”一词。当反应细胞的性质不明显，且无识别细胞的特殊技术可用时，则适合使用术语胶质增生，NOS（未另行规定）。肥胖型星形胶质细胞增生存在时即作出诊断。在局灶性病变中，应注明神经解剖亚部位。若病变见于多个部位，应诊断为脑，小胶质细胞增生。在所有病例中，病变应进行分级。存在并发病变时，通常诊断严重程度最高的病变。其他并发病变若严重程度需要，可单独诊断。
参考切片图（2 张）
查看英文原文
Comment
This section deals with the cellular responses of prominent reactive cells in the brain: microglia, capillary endothelial cells, and astrocytes. The microglia are early-responding cells and are apparent in and around an injured site within 12–24 hours. Their evolution to recognizable macrophages is apparent within 48 hours. As macrophages, they have increased cytoplasm, and products of lipid degradation can be detected with periodic acid Schiff reagent and by autofluorescence at 365 nm wavelength. Such phagocytic cells are referred to as lipid phagocytes or, more commonly, “gitter cells.” Figure 1 depicts microgliosis adjacent to an inflammatory mononuclear perivascular cuff (arrow). Note the many elongated, irregular nuclei of typical microglial cells. This image depicts the response of brain to injury by the activation of resident microglial cells. These mesodermal cells enter the brain at an early embryological stage of neural development and have macrophage capability. In the inactive state, they are distributed throughout the brain and are difficult to identify because of their nondiscriminate round nuclear character and lack of visible cytoplasm. When they are activated by the presence of brain injury, they become motile and migrate to the site of injury. In the process of migration, nuclei become elongated and irregular in shape and are referred to as “rod cells.” By this nuclear morphology, they are easily detected (as shown in this image), distributed distant from the perivascular monocytic infiltrate. As well as resident microglia, mononuclear cells of blood and bone marrow origin cross the endothelium and migrate to the injured site, where they also take up phagocytic functions like those of resident microglia. This accounts for the presence of some degree of perivascular cuffing by monocytes adjacent to injured brain tissue, as shown in Figure 1 (arrow). The appearance and function of these blood borne monocytes are not known to be different from those of resident microglia. A particularly useful immunohistochemical stain to detect these cells in brain is the Iba-1 (ionized calcium binding adaptor molecule 1) antibody. Figure 2 shows activated elongated irregular nuclei (arrows) of microglial cells (rod cells). Shown at high magnification, these activated microglial cells are migrating under chemotactic stimuli to a region of neural injury. It is not possible to say whether these cells are resident microglia or those derived from infiltrating monocytic cells carried to the nervous tissue by the blood stream. Depicted in Figure 3 is the Iba-1 immunohistochemical detection of microglia in cerebral cortex. Note the brown-staining cells and extensive radiating, cross, and longitudinal sections of their processes (arrows). Iba-1 is specifically expressed in macrophages and microglia and is upregulated during cellular activation. Figure 4 shows reactive gliosis and capillary hyperplasia (arrow) in a site of former injury. Capillaries are quickly responsive to injury of adjacent tissue, and endothelial nuclear hypertrophy is evident within 24 hours. To the pathologist these capillary changes are often, upon low-magnification scanning of brain tissue, the first indication of damage in a region. The reactive gliosis seen in this image is likely a mixture of infiltrating blood monocytes and resident microglial cells. None have yet differentiated to recognizable macrophages. The lesion is therefore probably less than 48 hours old. Selective study of endothelial responses may be enhanced by the use of immunohistochemistry using laminin and von Willebrand factor. Figure 5 displays a mixed gliotic response to injury of the putamen, consisting of reactive astrocytes, macrophages, microglia, and mononuclear cells. It is apparent that there is a significant increase in nucleated cells in the region. At this magnification, and with hematoxylin and eosin (H&E) staining alone, it is not possible to identify the specific cell types that make up the population. In many studies, it is only relevant to identify the response as being of mixed glial type, which would include astrocytes, microglial cells, and monocytic cells of blood origin and/or macrophages if they have already differentiated to phagocytic cells. In those cases where specific identification of the types of infiltrating cells is necessary, special stains and immunohistochemistry would be required. Normal astrocytes, protoplasmic and fibrillary, are diffusely distributed in the nervous system, where they serve, among other functions, to stabilize structure and maintain the neural milieu, neuronal energy processes, and the blood brain barrier. The density of the normal astrocyte population in the brain is increased in the glia limitans just beneath the pia mater, and also around blood vessels.Gemistocytic astrocytosis is an integral part of the progressive response to many forms of neural injury and is helpful in uncovering subtle brain injury, as well as giving an approximation of the chronology of the lesions present. Figure 6 shows at high magnification reactive gemistocytic astrocytosis in a site of healing neural injury stained with H&E. Note the typical eccentric nucleus and prominent eosinophilic cytoplasm of these reactive astrocytes (arrowheads) and the less frequent micro-binucleate form (arrow). In addition, the normal radiating processes become enlarged and extensive. In this example, there is a rare form of binucleation of one of the reactive astrocytes, signaling the presence not only of hypertrophy but also of hyperplasia in the response. The appearance of gemistocytic astrocytes is a useful indicator of the age of a brain lesion since it is seldom well developed on H&E sections until 12–14 days after injury. The use of the immunohistochemical technique for glial fibrillary acidic protein (GFAP), which constitutes the astrocytic intermediate filaments, will detect the earliest stages of the response. This commences at approximately 7 days postinjury and makes any site of injury more recognizable even if there is little to see with H&E sections. In this way, GFAP is a very useful, sensitive indicator of subtle brain injury and the associated astrocytic responses. While GFAP immunoreactivity is used extensively in neuropathology to identify and quantify astrocytes, some other cell types such as ependymal cells may also express a low level of this intermediate filament.
Recommendation
The term “microgliosis” should be used when the preponderance of reactive cells have the typical microglial features mentioned and illustrated above. When the nature of the reactive cells is not clearly apparent, and special techniques to identify the cells are not available, then it is appropriate to use the term Gliosis, NOS (not otherwise specified). Gemistocytic astrocytosis is diagnosed, when present. In focal lesions, the neuroanatomic subsite should be noted. If the lesion is noted in multiple sites, it should be diagnosed as Brain, Microgliosis. In all cases, the lesion should be graded. In the presence of concurrent lesions, lesions with the most severity are typically diagnosed. Other concurrent lesions may be diagnosed separately, if warranted by the severity.
炎症Inflammation 脑炎症
描述（中文）
在实验研究中偶尔可见急性细菌性或其他感染性疾病，此类感染所产生的炎症过程需要被识别和诊断，因为它们可能反映受试物对动物免疫状态的影响。Figure 1在低倍镜下显示小脑软脑膜（leptomeninges）中急性炎症细胞（箭头）的聚集。Figure 2是Figure 1中软脑膜急性炎症细胞的放大图像。该渗出物中明显可见淋巴细胞与中性粒细胞的混合。Figure 3显示小鼠软脑膜中淋巴细胞的局灶性（focal）聚集。在本例中，该病变为偶然发现。然而，此类病变的出现可能提示对神经系统近期病毒感染的反应。偶尔，一个小的、外观上无活性的单核细胞簇，且周围无任何其他反应性改变，可被称为炎症细胞浸润（inflammatory infiltrate）。然而，中性粒细胞的存在应提醒病理学家对炎症的其他补充性征象进行仔细评估。在NTP研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要的浸润细胞是中性粒细胞，尽管也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但它们聚集在一起，其中许多已变性（化脓性渗出物）。渗出物中还可能存在来自 resident 细胞群和浸润白细胞的细胞碎片、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子。肉眼上，这些病变将以脓液的存在为特征。在渗出物周围的组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大的活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
当诊断炎症时，叙述中应包含对存在细胞类型的描述。对罕见的神经化脓性或非化脓性浸润病例的识别，应附带严重程度分级及其解剖亚部位进行诊断。若认为与受试物无关，则在最终研究评估中不予计入。若研究病理学家倾向于使用非标准炎症类别（如上所述），则叙述中应包含对存在的主要细胞类型以及炎症显著特征的描述。在存在并发病变时，通常诊断严重程度最高的病变。其他并发病变若严重程度足以支持，可单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Acute bacterial or other infectious disease is occasionally seen in experimental studies, and the inflammatory processes that such infections produce need to be recognized and diagnosed since they may reflect compound effects on the immune status of the animal. Figure 1 depicts the accumulation of acute inflammatory cells (arrows) in the leptomeninges of the cerebellum at low magnification. Figure 2 is the magnified appearance of acute inflammatory cells in the leptomeninges in Figure 1 . A mixture of lymphocytes and neutrophils is apparent in this exudate. Figure 3 shows the focal aggregation of lymphocytes in the leptomeninges of a mouse. In this case, it was an incidental finding. The occurrence of such a lesion may, however, indicate a response to a recent viral infection in the nervous system. Occasionally, a small, apparently inert cluster of mononuclear cells without any other reactive responses in the vicinity may be referred to as inflammatory infiltrate. However, the presence of neutrophils should alert the pathologist to conduct a diligent evaluation for other complementary signs of inflammation. In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris from both the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
When inflammation is diagnosed, the narrative should include a description of the cell types present. The recognition of rare examples of neural suppurative or nonsuppurative infiltrates should be diagnosed with a severity grading and their anatomic subsite location. If not considered treatment related, they are discounted in the final study assessment. If the study pathologist prefers a nonstandard category of inflammation (as described above), then the narrative should include a description of the predominant cell types present along with prominent features of the inflammation. In the presence of concurrent lesions, lesions with the most severity are typically diagnosed. Other concurrent lesions may be diagnosed separately, if warranted by the severity.
矿化Mineralization 脑矿化
描述（中文）
中枢神经系统（CNS）的矿化（mineralization）包括偶然发现的多灶性微小矿物质沉积，或坏死后发生的继发性营养不良性钙化（dystrophic calcification）。Figure 1、Figure 2 分别显示了大鼠和小鼠丘脑（thalamus）中偶然发现的多灶性微小矿物质沉积。丘脑内的分布通常为双侧性，但不一定对称。该病变在 B6C3F1 小鼠中比在大鼠中更常见。仔细观察时，矿物质颗粒常具有多层结构，在神经病理学上称为钙球（calcospherites）。它们似乎位于神经毡（neuropil）内，或常与毛细血管和小血管的内皮基底膜相关联。然而，即使血管受累且管腔狭窄，也罕见发现因其存在而导致丘脑微梗死的证据。该病变可能是钙代谢方面局灶性组织稳态异常的结果，在这些偶然性病例中，它不太可能代表继发于坏死的营养不良性矿化。近年来，老龄小鼠的丘脑病变已被认为与缺乏维生素 D 受体的小鼠相关。在所有 NTP 啮齿类研究组中均出现丘脑矿化（以钙球形式），证实了该现象的偶然性、特发性本质。当此类病变仅见于处理组，或在神经系统其他部位发现时，应考虑仔细评估是否存在营养不良性矿化、全身性高钙血症、维生素 D 过量或其他形式的钙稳态和代谢异常的证据。另一方面，继发于坏死的矿物质沉积归因于常见但复杂的营养不良性矿化过程。营养不良性矿化常表现为层状钙球，继发于多个神经部位的小簇状神经元坏死，如 Figure 3、Figure 4 所示。Figure 3 显示了小脑（cerebellum）中原颗粒细胞坏死部位矿化小体（箭头）的聚集。注意神经组织的丢失，表现为原内颗粒细胞占据的间隙，以及多个小的、深染的、圆形小体的存在。此类矿化灶的存在可能导致切片过程中组织破裂。Figure 3 所示的矿化灶不应与脑提取/修整过程中常从覆盖的颅骨碎片带入脑内的骨针人为假象或异位骨组织相混淆。Figure 4 中更高放大倍数显示的钙球呈圆形、常为同心圆、层状外观，是坏死脑组织矿化晚期的典型表现。钙球沉积于原小脑内颗粒细胞坏死区域。注意较大体部的同心层状结构（箭头），而较小体部中明显缺乏该结构。在这些病例中，以钙球形式沉积矿物质需要在坏死性损伤后数周才能形成。Figure 5 显示了毗邻梨状皮质（piriform cortex）的原坏死区域，伴有一个不常见的类骨质（osteoid）（箭头）和骨化（ossification）（箭头头）的反应性灶。一大片脑坏死区被几种类型矿化小体的进展所取代。右侧为一些较小的嗜碱性钙球，左侧为较大的坏死脑组织区域，已转化为粉红色透明物质构成的类骨质，以及更晚期的骨性化生（osseous metaplasia），其中致密嗜碱性矿物质和骨细胞明显可见。
诊断建议
除非在对照组中缺失，丘脑矿化不解释为处理效应。如果与处理或剂量相关，则根据病变范围进行诊断和分级。营养不良性矿化应简单地诊断为矿化，无论残留病变谱（如钙球、类骨质或骨性化生）有何变化。此类变化应纳入描述中。诊断应包括具体部位，除非在整个脑区呈多灶性分布。严重程度分级基于病变范围。存在并发病变时，通常诊断最严重的病变。其他并发病变如有必要可根据严重程度单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Mineralization in the CNS comprises either incidental multifocal microscopic deposits of mineral or secondary dystrophic calcification occurring after necrosis. Figure 1 and Figure 2 show incidental multifocal microscopic deposits of mineral in the thalamus of rat and mouse, respectively. The thalamic distribution is usually bilateral but not necessarily symmetrical. It is a more common finding in B6C3F1 mice than in rats. The particles of mineral are often found, on close inspection, to have a multilamellar structure and are referred to neuropathologically as calcospherites. They appear to be located in the neuropil, or commonly associated with the intimal basement membrane of capillaries and small blood vessels. However, it is unusual to find any evidence of thalamic microinfarcts as a result of their presence, even when vessels are affected and the lumen is narrowed. The lesion is probably the result of focally abnormal tissue homeostasis with respect to calcium metabolism, and in these incidental cases, it is unlikely to represent dystrophic mineralization secondary to necrosis. More recently, thalamic lesions in aging mice have been associated with mice lacking vitamin D receptor. The occurrence of thalamic mineralization as calcospherites in all NTP rodent study groups confirms the incidental idiopathic nature of this phenomenon. When such lesions are seen in treated groups only, or when noted at other sites in the nervous system, careful evaluation for evidence of dystrophic mineralization, systemic hypercalcemia, vitamin D excess, or other forms of abnormal calcium homeostasis and metabolism should be considered. On the other hand, mineral deposits, secondary to necrosis, are attributed to the commonly observed but complex process of dystrophic mineralization. Dystrophic mineralization is often seen as lamellar calcospherites found secondary to small clustered regions of neuronal necrosis at various neural sites, such as depicted in Figure 3 and Figure 4 . Figure 3 shows the aggregation of mineralized bodies (arrow) in sites of former granule cell necrosis in the cerebellum. Note the loss of neural tissue represented by spaces formerly occupied by internal granule cells, and the presence of multiple small, dark, round bodies. The presence of such mineralized foci may lead to disruption of the tissue during microtomy. The mineralized foci shown in Figure 3 should not be confused with the artifactual presence of boney spicules often carried into brain from overlying skull fragments during brain extraction/trimming or with heterotopic bone tissue. The round, often concentric, lamellar appearance of calcospherites, shown at higher magnification in Figure 4 , is typical of late stages of mineralization of necrotic brain tissue. Calcospherites are deposited in a region of former cerebellar internal granule cell necrosis. Note the concentric laminated structures (arrow) of the larger bodies that are apparently absent in smaller ones. The deposition of mineral in the form of calcospherites in these cases requires several weeks to form after the necrotizing insult. Figure 5 shows a region of prior necrosis adjacent to piriform cortex with an uncommon reactive focus of osteoid (arrow) and ossification (arrowhead). A large zone of brain necrosis is replaced by a progression of mineralized bodies of several types. To the right are some smaller basophilic calcospherites, and to the left are larger zones of necrotic brain tissue transformed into both osteoid, composed of pink hyaline material, and a more advanced stage of osseous metaplasia, where dense basophilic mineral and osteocytes are apparent.
Recommendation
Mineralization in the thalamus is not interpreted as a treatment effect unless it is absent in controls. If treatment or dose related, the lesion is diagnosed and graded based on the extent of the lesion. Dystrophic mineralization should be diagnosed simply as mineralization regardless of the variation in the spectrum of residual lesions such as calcospherites, or osteoid or osseous metaplasia. Such variations should be included in the narrative. The diagnosis should include the subsite unless the incidence is multifocal across brain regions. Severity grading is based on the extent of the lesion. In the presence of concurrent lesions, the most severe lesion is typically diagnosed. Other concurrent lesions may be diagnosed separately, if warranted by the severity.
神经元变性Neuron Degeneration 脑变性
描述（中文）
病理学家必须认识到与神经元损伤相关的各种形式的细微早期变化。这些类型的神经元变化可能在接受较低剂量受试化合物的动物中明显，或在较高剂量动物的脑内较不易受该药剂影响的核团中明显。神经组织损伤可能涉及一种或多种方式，例如血管损伤，其中液体在神经毡中积聚，造成该区域空泡化外观。直接神经元损伤可能涉及细胞膜以及离子和液体转移，在这种情况下，神经元核周体（perikaryon）中可能出现空泡。通常，损伤涉及代谢过程，特别是神经元能量产生的紊乱，在这种情况下发生细胞死亡，其特征为中央性染色质溶解（central chromatolysis）、神经元坏死，并最终溶解。Figure 1、Figure 2、Figure 3 在低倍和高倍放大下描绘了嗅球内颗粒细胞的变性。注意 Figure 1 中的变化在一个嗅球上更为严重（箭头），伴有神经元变性和丢失，以及整个嗅球结构的稀疏化。对侧嗅球通过薄骨板与受影响的对应部分隔开，嗅黏膜后部位于腹侧。对侧嗅球的结构在 Figure 1、Figure 2 中提供了良好的比较，具有正常的肾小球层、外丛状层和内颗粒细胞层。在毒理学研究中，密切观察嗅球的病变很重要，即使化合物不是通过吸入途径递送的。嗅球颗粒细胞的坏死和退行性变化在形态上与其他部位的颗粒神经元相似，例如小脑的颗粒细胞层。Figure 4、Figure 5 描绘了一种常被忽视的细微早期神经元损伤形式，称为“颗粒空泡变化（granulovacuolar change）”。核周体轻度肿胀，含有小空泡和颗粒状物质（箭头），提示膜损伤以及细胞质细胞器（如内质网和线粒体）的膨胀。在这些图像中，它伴有其他神经元损伤的辅助证据，例如中央性染色质溶解（黑色箭头）和真正的嗜碱性“慢性”神经细胞变化（白色箭头）。Cavanagh 等（1998）在一项关于真菌毒素对大鼠小脑影响的序贯研究中，提供了通过光镜和电镜记录的各种阶段的神经元和星形胶质细胞变性资料。
诊断建议
当出现时，应诊断神经元变性，注明亚部位，并进行严重程度分级。在存在并发病变的情况下，通常诊断严重程度最高的病变。其他并发病变如果严重程度需要，可以单独诊断。
参考切片图（2 张）
查看英文原文
Comment
It is important for the pathologist to be aware of the various forms of subtle early changes associated with neuronal injury. These types of neuronal changes may be evident in animals receiving lower doses of the test compound, or in nuclei of the brain less vulnerable to the agent from higher dosed animals. Injury to neural tissue may involve one or more modes, such as vascular injury in which fluid accumulates in the neuropil, creating a vacuolated appearance of the region. Direct neuronal injury may involve the membrane and ion and fluid transfer, in which case vacuoles may become evident in the neuronal perikaryon. Commonly, the injury involves metabolic processes, particularly disturbances to neuronal energy production, in which case cell death occurs characterized by central chromatolysis, neuronal necrosis, and ultimately lysis. Figure 1 , Figure 2 , and Figure 3 , at low and higher magnification, depict degeneration of internal granule cells of the olfactory bulb. Note that the change in Figure Figure 1 is worse on one olfactory bulb (arrow), with degeneration and loss of neurons, as well as rarification of the entire bulb structure. The contralateral olfactory bulb is divided from its affected counterpart by a thin osseous plate, and the posterior portion of the olfactory mucosa is present ventrally. The structure of the contralateral olfactory bulb provides a good comparison in Figure 1 and Figure 2 , having a normal glomerular layer, external plexiform layer, and internal granule cell layers. Close observation of the olfactory bulb for lesions is important in toxicologic studies, even if the compound is not delivered by the inhalation route. The necrotic and degenerative changes of granule cells of the olfactory bulb have a morphology similar to that seen in granule neurons in other sites, such as the granular cell layer of the cerebellum. Figure 4 and Figure 5 depict a commonly overlooked subtle and early form of neuronal injury known as “granulovacuolar change.” The perikaryon is slightly swollen and contains small vacuoles and granularity (arrowheads), suggesting membrane injury and distension of the cytoplasmic organelles such as the endoplasmic reticulum and mitochondria. In these images, it is accompanied by other ancillary evidence of neuronal injury, such as central chromatolysis (black arrows) and genuine basophilic “chronic” nerve cell change (white arrows). Various stages of neuronal and astrocytic degeneration as documented by light and electron microscopy are available in a sequenced study by Cavanagh et al. (1998) of the effects of a mycotoxin on the rat cerebellum.
Recommendation
When present, neuron degeneration should be diagnosed, the subsite noted, and the severity graded. In the presence of concurrent lesions, lesions with the most severity are typically diagnosed. Other concurrent lesions may be diagnosed separately, if warranted by the severity.
神经元坏死Neuron Necrosis 脑坏死
描述（中文）
这组脑坏死图像旨在使病理学家熟悉神经元细胞死亡的形态学变化，涵盖从急性坏死形态到坏死晚期形态（晚期有时以矿化为显著特征）。Figure 1 展示了早期神经元坏死最常被识别的证据。其特征包括神经元胞质皱缩和强烈的嗜酸性，同时伴有细胞核皱缩和嗜碱性（黑箭头）。神经元坏死通常由缺血或任何损害神经元能量代谢的因素引起。在这种情况下，该变化被称为急性嗜酸性坏死、“急性代谢停滞”、“急性缺血性改变”，或者更通俗地称为“红死”神经元。神经元坏死应通过筛查坏死的各个阶段和/或真正坏死神经元附近是否存在炎性细胞或其他病变，与深染神经元伪影（见 Brain - Introduction）仔细鉴别。在本例中，这些坏死神经元的外观可与相邻浦肯野细胞（红箭头）更正常的形态形成对比。此外，脑组织损伤的重要佐证表现为下方神经毡的水肿性空泡化改变，以及该区域内胶质细胞坏死浓缩（核固缩）的细胞核（箭头）。Figure 2 展示了紫外显微镜图像，显示 Fluoro-Jade B 对坏死海马锥体细胞（蓝箭头）呈阳性绿色荧光经验性染色。使用 Fluoro-Jade 系列经验性神经退行性染色剂对于快速识别即使少量的退行性神经元极具价值，即使在低倍镜下也是如此。尽管已进行了大量研究，但该染色剂对坏死神经元具有这种亲和力的实际机制仍知之甚少。受累细胞的荧光可突出显示损伤的神经元，但使用苏木精和伊红（H&E）也很重要，以识别相关的神经变化，佐证荧光发现并确定病变的时间顺序。Fluoro-Jade C 是 Fluoro-Jade 染色剂系列中最新的一种，已发现其可染色所有退行性神经元，无论具体损伤或细胞死亡机制如何。Fluoro-Jade C 表现出最大的信号背景比以及最高的分辨率，因此对退行性神经元具有最大的对比度和亲和力。该染色剂还可识别退行性远端树突、轴突和终末。该染料抗褪色，并与大多数组织学方法兼容。使用胶质纤维酸性蛋白免疫荧光、Fluoro-Jade C 和 4'',6-二脒基-2-苯基吲哚（DAPI）可分别同时标记活化的星形胶质细胞、退行性神经元和细胞核。在判读时需谨慎，因为 Fluoro-Jade 也会轻度染色伪影性嗜碱性神经元（PB Little，个人观察）。注意正常的红细胞（Figure 2，白箭头）在血管中也呈阳性染色。在 Figure 3 中，梨状皮质内可见坏死神经元（箭头）邻近更正常的神经元。注意有些神经元特别淡染，几乎不可见。该图像展示了较晚期的神经元坏死，由急性嗜酸性神经元坏死（见 Figure 1）演变而来。随着时间顺序的进行性退行性改变，胞质嗜酸性和细胞核嗜碱性出现明显褪色。褪色之后是原神经元轮廓模糊，称为“幽灵形态”，随后任何可观察到的退行性结构消失。邻近区域存在更正常的神经元有助于识别这些形式的退行性细胞，从而将这些变化与自溶区分开来。根据神经毒性作用后观察时间的不同，退行性神经元形态变化的时间顺序连续谱可能较为明显。有些变化，如急性嗜酸性坏死，很容易识别；然而，病理学家必须了解 Figure 3 所示的更细微、常被忽视的变化，即神经元淡染的“幽灵”轮廓。在 Figure 4 中，嗜碱性坏死神经元未经历 Figure 3 所示的较快溶解过程。注意神经元膜细微的点状铁化（营养不良性矿化）（箭头）。退行性神经元原位保留，其表面早期有矿物质积聚（铁化）。该图像展示了多个细小的点状矿物质聚集，其中一些可能代表树突终末扣结的矿化。Figure 5 展示了 CA2 区海马锥体细胞的神经元坏死。注意神经元的铁化（营养不良性矿化）比 Figure 4 所示更显著、更晚期（箭头）。神经元形态的某些方面仍可见，但随着营养不良性矿化过程的进展，核周体更完全地被矿物质灌注。小神经元（如嗅球和齿状回的颗粒细胞以及小脑内颗粒细胞层）的坏死，在 H&E 染色上以嗜碱性核固缩为特征。在 Figure 6 中，小脑内颗粒细胞层的颗粒细胞具有这种嗜碱性核固缩外观，是该类型神经元急性坏死的典型表现（箭头）。尽管存在区域性颗粒细胞坏死，许多浦肯野细胞仍保持正常外观。为便于比较，Figure 7 是小脑颗粒细胞坏死的高倍放大图像。注意核固缩的细胞核（箭头）和相邻的正常细胞核（箭头）。将 Figure 6、Figure 7 所示的颗粒细胞坏死与自溶中所见的形态学变化区分开来很重要。在自溶中，虽然颗粒细胞核皱缩，但组织中还有其他自溶指标，如广泛的组织淡染和神经毡空泡化。相邻正常细胞与坏死细胞之间的显著对比有助于将自溶与神经组织的真实病变区分开来。坏死组织（包括脑细胞）的矿化随时间发生。当矿物质沉积物结壳于可识别的细胞或其树突终末扣结上时，病理学家必须识别脑内退行性细胞的这一时间顺序特征，并将其与可能混淆的酵母或真菌菌丝区分开来。
诊断建议
在 NTP 研究中，所有形式的神经元坏死均诊断为神经元坏死，并记录病变、解剖亚部位位置和严重程度。严重程度基于受累神经元的数量。当凋亡与坏死同时存在时，在 NTP 研究中诊断记录为坏死。当存在其他并发病变如炎症时，通常诊断严重程度最高的病变。如果严重程度需要，其他并发病变可单独诊断。
参考切片图（2 张）
查看英文原文
Comment
This panel of brain necrosis images is intended to familiarize pathologists with the morphologic variations of neuronal cell death ranging from the morphology of acute necrosis to that of late stages of necrosis in which mineralization sometimes is prominent. Figure 1 depicts the most commonly recognized evidence of early neuronal necrosis. Features include neuronal cytoplasmic shrinkage and intense eosinophilia accompanied by shrinkage and basophilia of the nucleus (black arrow). Neuronal necrosis is commonly the result of ischemia, or any influence that impairs neuronal energy metabolism. In this case, the change has been referred to as acute eosinophilic necrosis, “acute metabolic arrest,” “acute ischemic change,” or, more colloquially, “red dead” neurons. Neuronal necrosis should be carefully differentiated from dark neuron artifact (see Brain - Introduction ) by screening for various stages of necrosis and/or the presence of inflammatory cells or other lesions in the vicinity of the truly necrotic neurons. In this case, the appearance of these necrotic neurons can be contrasted with the more normal morphology of an adjacent Purkinje cell (red arrow). Further, important substantiating evidence of brain tissue injury is represented by the edematous vacuolar change of the subjacent neuropil and the presence of necrotic condensed (pyknotic) nuclei of glial cells (arrowhead) within that region. Figure 2 depicts an ultraviolet microscopy image showing the positive green fluorescent, empiric staining by Fluoro-Jade B of necrotic hippocampal pyramidal cells (blue arrow). Use of the Fluoro-Jade family of empiric neurodegenerative stains is extremely valuable in quickly identifying even small numbers of degenerative neurons, even at low magnification. Although given much investigation, the actual mechanism whereby the stain has this affinity for necrotic neurons is still poorly understood. Fluorescence of affected cells highlights the injured neurons, but the use of hematoxylin and eosin is also important to identify associated neural changes corroborating the fluorescent findings and defining the chronology of the lesions. Fluoro-Jade C is the most recent of the Fluoro-Jade stains and has been found to stain all degenerating neurons, regardless of specific insult or mechanism of cell death. Fluoro-Jade C exhibits the greatest signal-to-background ratio, as well as the highest resolution, therefore giving maximal contrast and affinity for degenerating neurons. The stain also identifies degenerated distal dendrites, axons, and terminals. The dye is resistant to fading and is compatible with most histologic methods. Activated astrocytes, degenerating neurons, and cell nuclei can be labeled together using glial fibrillary acidic protein immunofluorescence, Fluoro-Jade C, and 4'',6-diamidino-2-phenylindole (DAPI), respectively. Some care needs to be taken in interpretation, since Fluoro-Jade also lightly stains artifactual basophilic neurons (PB Little, personal observations). Note that normal red blood cells ( Figure 2 , white arrow) also stain positive in the blood vessels. In Figure 3 , necrotic neurons (arrows) are evident adjacent to more normal neurons in the piriform cortex. Note that some are particularly faded and almost invisible. This image depicts neuronal necrosis at a later stage, evolving from that seen with acute eosinophilic neuronal necrosis (see Figure 1 ). With chronologic progressive degenerative change, there is noticeable fading of the eosinophilia of the cytoplasm and basophilia of the nucleus. The fading is followed by vague outlines of the former neurons, referred to as “ghost forms,” followed by the loss of any observable degenerate structure. The presence of more normal neurons in adjacent areas assists with the recognition of these forms of degenerate cells differentiating the changes from that of autolysis. Depending on the time of observation after neurotoxic effects, a chronologic continuum of degenerative neuronal morphologic changes may be apparent. Some, such as acute eosinophilic necrosis, are readily apparent; however, the pathologist must be aware of the more subtle, often overlooked, changes shown in Figure 3 consisting of faded “ghost” profiles of neurons. In Figure 4 , basophilic necrotic neurons have escaped the more rapid process of dissolution shown in Figure 3 . Note the subtle punctate ferrugination (dystrophic mineralization) of neuronal membrane (arrows). The degenerate neurons remain in situ and have early accumulation of mineral (ferrugination) at their surfaces. The image depicts multiple small punctate aggregations of mineral, some of which may represent mineralization of dendritic terminal boutons. Figure 5 depicts neuronal necrosis of hippocampal pyramidal cells in the CA2 region. Note that there is more prominent, advanced ferrugination (dystrophic mineralization) of neurons (arrows) than shown in Figure 4 . Some aspects of neuronal morphology are still apparent, but the perikaryon is more completely infused with mineral as the dystrophic mineralization process proceeds. Necrosis of small neurons, such as the granule cells of the olfactory bulb and dentate gyrus and the internal granule cell layer of the cerebellum, is characterized by basophilic nuclear pyknosis with hematoxylin and eosin staining. In Figure 6 , granule cells of the cerebellar internal granule cell layer have this pyknotic basophilic appearance typical of acute necrosis for this type of neuron (arrow). Many Purkinje cells retain a normal appearance in spite of the regional granule cell necrosis. For comparison, Figure 7 is a higher magnification of the cerebellar granule necrosis. Note the pyknotic nuclei (arrows) and adjacent normal nuclei (arrowheads). It is important to differentiate granule cell necrosis shown in Figure 6 and Figure 7 from the morphologic change seen in autolysis. In autolysis, while granule cell nuclei shrink, there are other indicators of autolysis in the tissue, such as widespread tissue fading and neuropil vacuolation. The marked contrast between adjacent normal and necrotic cells is helpful in differentiation of autolysis from genuine lesions of nervous tissue. Mineralization of necrotic tissue, including brain cells, occurs over time. Where mineral deposits encrust a recognizable cell or its dendritic terminal boutons, it is important for the pathologist to recognize this chronologic feature of degenerated cells in brain and to differentiate it from yeast or mycotic hyphae with which it may be confused.
Recommendation
Neuronal necrosis is diagnosed for all forms of neuronal necrosis in NTP studies, and the lesion, anatomic subsite location, and severity are also documented. Severity is based on the number of affected neurons. When apoptosis is noted in conjunction with necrosis, the diagnosis is recorded as necrosis in NTP studies. In the presence of other concurrent lesions such as inflammation, lesions with the most severity are typically diagnosed. Other concurrent lesions may be diagnosed separately, if warranted by the severity.
神经元染色质溶解Neuron Chromatolysis 脑其他
描述（中文）
本图（Figure 1）显示的是神经元损伤中通常出现较早、往往为亚致死性的改变。它通常由毒物暴露及细胞代谢受干扰所致。就脊髓神经元而言，尤其可能继发于创伤性神经根受压或周围神经断裂。当神经元核周体中称为尼氏小体（Nissl substance）的粗面内质网及相关核糖体的正常聚集，作为对损伤的反应而分散时，即发生中央性染色质溶解（central chromatolysis，箭头）。它标志着在细胞损伤情况下神经元蛋白质合成的加速。与此同时，构成神经元细胞质骨架并支撑细胞核的细胞骨架网络受到不利影响。这种核悬浮的丧失导致细胞核失去其中心位置，变为偏位，紧邻细胞膜。在神经损伤恢复期间，尼氏小体可能重新聚集，但自中心开始，因此周边部细胞质仍保持透亮。这种改变称为“周边性染色质溶解（peripheral chromatolysis）”，被认为是早期神经元恢复的显微镜下指征。需要注意的是，脑内某些特别活跃的核团，如橄榄前核和下丘脑核团，其所含神经元正常情况下即具有明显的中央性染色质溶解，但无核偏位；因此，诊断这一改变时需谨慎。这就要求，无论中央性染色质溶解发生在何处，均应结合这些特定神经解剖部位的知识进行评估，并应与对照动物的相应部位进行比较，以避免对这一重要的神经元早期损伤特征发生误诊。
诊断建议
在 NTP 研究中，当存在染色质溶解时，应记录其解剖亚部位及严重程度分级。
参考切片图（1 张）
查看英文原文
Comment
This image ( Figure 1 ) displays the usually early, often sublethal, change that occurs in neuronal injury. It is commonly the result of toxin exposure and interference with cellular metabolism. In the case of spinal neurons, particularly, it may be secondary to traumatic radicular nerve crush or severance of the peripheral nerve. Central chromatolysis (arrow) occurs when the normal aggregations of rough endoplasmic reticulum and associated ribosomes, known as Nissl substance, in the neuronal perikaryon disperse as a response to injury. It signifies the acceleration of neuronal protein synthesis in the face of cellular injury. At the same time, the cytoskeletal network, which frames the neuronal cytosol and supports the nucleus, is negatively affected. This loss of nuclear suspension leads to the nucleus losing its central position, becoming eccentric, lying adjacent to the cell membrane. During recovery from the neural insult, the Nissl substance may reaggregate, but from the center, so that there remains cytoplasmic clarity peripherally. This change is referred to as “peripheral chromatolysis,” considered a microscopic indication of early neuronal recovery. It is important to note that some particularly active nuclei in the brain, such as the anterior olivary nucleus and hypothalamic nuclei, contain neurons that normally have apparent central chromatolysis, but not nuclear eccentricity; therefore, caution in the diagnosis of this change is required. This dictates that central chromatolysis, wherever it occurs, should be assessed with the knowledge of these particular neuroanatomic sites and should also be compared with equivalent sites in controls to avoid misdiagnosis of this important early neuronal feature of injury.
Recommendation
When present, chromatolysis, its anatomic subsite location, and severity grading are noted in NTP studies.
神经元细胞丢失Neuron Cell Loss 脑其他
描述（中文）
要检测神经元细胞丢失，必须了解大脑特定区域（海马、小脑）的正常神经解剖结构。普遍认为，常规主观光镜检查只能检测出细胞数量的显著减少。对更细微的丢失进行定量，需要采用胶质纤维酸性蛋白（glial fibrillary acidic protein）或 cresyl violet 特殊染色，或采用更精细的形态计量学和体视学技术。Figure 1 是海马 CA3 区神经元细胞丢失的一个示例。注意箭头之间锥体神经元的丢失，与邻近神经元丰富的区域形成对比。这是神经元坏死的晚期阶段。请将该图像与 Figure 2、Figure 3 中描绘的对照动物海马同一区域的图像进行比较。海马该部分的萎缩会干扰正常功能，尤其是学习、记忆和空间识别过程。必须将毒性损伤所致的神经元细胞丢失与区域性神经元发育不全（neuronal hypoplasia）及神经元萎缩（neuronal abiotrophy）相鉴别。神经元发育不全通常是自发性或诱发性发育异常，不伴有反应性胶质增生改变；而神经元萎缩是出生后发生的神经元丢失，呈进行性且与遗传相关，并可能有反应性改变。
诊断建议
在 NTP 研究中，任何检测到的神经元群体减少都应主观评定其严重程度，并诊断为神经元细胞丢失（Neuron, Cell loss）。应注明受影响的脑亚部位并纳入描述。存在并发病变时，通常诊断严重程度最高的病变。其他并发病变若有充分依据，可根据其严重程度单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Knowledge of the normal neuroanatomic structure of specialized regions of the brain (hippocampus, cerebellum) is necessary to detect neuronal cell loss. It is generally accepted that routine subjective light microscopy detects only significant reductions in cell numbers. Quantitation of more subtle losses requires special staining with glial fibrillary acidic protein or cresyl violet or with more sophisticated techniques of morphometry and stereology. Figure 1 is an example of hippocampal neuronal cell loss in the CA3 region. Note the pyramidal neuronal loss between the arrows, in contrast to the adjacent neuron-rich region. This is a late stage of neuronal necrosis. Compare this image with those of Figure 2 and Figure 3 depicting the same region of hippocampus in a control animal. The atrophy of this portion of the hippocampus interferes with normal function, notably learning, memory, and spatial recognition processes. Neuronal cell loss due to toxic insult must be differentiated from regional neuronal hypoplasia and neuronal abiotrophy. Neuronal hypoplasia is usually a spontaneous or induced developmental abnormality unassociated with reactive gliotic changes while neuronal abiotrophy is postnatal neuronal loss that is progressive and genetically related and may have reactive responses.
Recommendation
In NTP studies, any detected reduction in neuronal populations should be subjectively graded in severity and diagnosed as Neuron, Cell loss. Affected subsites of the brain should be noted and included in the narrative. In the presence of concurrent lesions, lesions with the most severity are typically diagnosed. Other concurrent lesions may be diagnosed separately, if warranted by the severity.
胆固醇裂隙Cholesterol Clefts 脑其他
描述（中文）
Figure 1（箭头）展示了一个成熟的退行性病灶，由胶质增生（gliosis）、巨噬细胞和结晶状胆固醇裂隙（cholesterol clefts）组成。这一小的消退性退行性病变毗邻海马齿状回。最显著的特征是曾由胆固醇结晶占据的空的长形针状空隙，通常称为胆固醇裂隙。溶剂组织处理已去除胆固醇。与胆固醇裂隙相关的是许多混合性胶质细胞和巨噬细胞。此类过程通常由脑坏死伴髓鞘蛋白脂质复合物释放所致，或源于慢性炎症过程中对外渗血液或降解细胞的吞噬作用。溶解细胞膜产生的降解脂质导致游离胆固醇和三酰甘油及其他化合物在细胞内蓄积。当巨噬细胞负载这些后述化合物且通常防止过量游离胆固醇蓄积的细胞安全机制失效时，即发生巨噬细胞凋亡。巨噬细胞释放游离胆固醇，后者在邻近组织中沉淀为结晶。这些胆固醇结晶在组织中存留很长时间，常为终生。脑组织中胆固醇结晶的显著外观通常应被识别为对既存脑坏死、慢性炎症或出血的反应的组成部分。
诊断建议
胆固醇裂隙存在时，在NTP研究中必须作出诊断并记录亚部位。存在并发病变时，通常诊断严重程度最高的病变。其他并发病变若严重程度允许，可单独诊断。
参考切片图（1 张）
查看英文原文
Comment
A mature degenerate focus is represented in Figure 1 (arrow) consisting of gliosis, macrophages, and crystalline-shaped cholesterol clefts. This small resolving degenerative lesion is adjacent to the dentate gyrus of the hippocampus. The most striking feature is the empty elongated spicular spaces formerly occupied by cholesterol crystals, often referred to as cholesterol clefts. Tissue processing with solvent has removed the cholesterol. Associated with cholesterol clefts are many mixed glial cells and macrophages. This type of process is usually the result of brain necrosis with liberation of myelin proteolipid complexes or from phagocytosis of extravasated blood or degraded cells in chronic inflammatory processes. The degraded lipid from lysed cell membranes results in intracellular accumulation of free cholesterol and triacylglycerol, along with other compounds. Apoptosis of macrophages results when they are loaded with these latter compounds and the usual cellular safety mechanisms preventing excess free cholesterol accumulation fail. The macrophages release free cholesterol, which precipitate as crystals in the adjacent tissue. These cholesterol crystals remain in the tissue for prolonged, often lifelong, periods. The striking appearance of cholesterol crystals in brain tissue should be recognized usually as a component of the response to pre-existing brain necrosis, chronic inflammation, or hemorrhage.
Recommendation
Cholesterol clefts, when present, must be diagnosed in NTP studies and the subsite recorded. In the presence of concurrent lesions, lesions with the most severity are typically diagnosed. Other concurrent lesions may be diagnosed separately, if warranted by the severity.
脑积水Hydrocephalus 脑其他
描述（中文）
脑积水（hydrocephalus）可为交通性或非交通性；也就是说，前者没有明显的梗阻过程，而后者在脑室连接通路的某处存在梗阻性病因。最常见的是，交通性脑积水被认为由脑脊液生成的特发性增加或吸收减少所致。然而，大多数病例并未得到明确的探究。Figure 1 是一例非交通性、梗阻性脑积水，侧脑室（箭头）因垂体肿瘤（arrowhead）阻塞第三脑室腹侧而继发扩张。Figure 2 描绘了正常立方状室管膜细胞（ependymal cell）（箭头）变扁的衰减改变。这是由于与偶然发现的垂体囊肿相关的梗阻性脑积水性室室扩张所致。在此例中，脑积水时脑室内压增高对室管膜细胞的影响显而易见。正常的立方状室管膜细胞被拉伸以覆盖增加的脑室表面积。上皮与下方脑组织之间存在一定程度的水肿性分离，邻近神经毡（neuropil）有轻度空泡化。病理学家通常认为室管膜细胞对各种损伤反应能力差，只是发生变性和坏死。然而，在大鼠受控脊髓损伤的研究中，室管膜细胞及与之紧密相关的下方细胞似乎反应相当活跃，至少对创伤如此。Nestin 和 GAP-43（未成熟神经干细胞的免疫组化指标）以及胶质纤维酸性蛋白（glial fibrillary acid protein）在创伤后于被鉴定为室管膜细胞的体内细胞中被检出，提示室管膜细胞去分化为神经干细胞和胶质细胞，并可能在脊髓损伤修复中发挥作用。
诊断建议
在 NTP 研究中，应尽可能确定脑积水的病因。除非脑积水继发于肿瘤阻塞，否则应诊断为脑积水。此病变无需分级。
参考切片图（2 张）
查看英文原文
Comment
Hydrocephalus may be communicating or noncommunicating; that is, the former has no apparent obstructive process, whereas the latter has an obstructive cause somewhere in the ventricular connections. Most commonly, communicating hydrocephalus is considered to result from an idiopathic increase in cerebrospinal fluid production or deceased resorption. However, most examples are not clearly investigated. Figure 1 is an example of noncommunicating, obstructive hydrocephalus of the lateral ventricles (arrows) secondary to a pituitary neoplasm (arrowhead) obstructing the ventral aspect of the third ventricle. Figure 2 depicts the flattened attenuation of normally cuboidal ependymal cells (arrow). This is due to obstructive hydrocephalic ventricular expansion associated with incidental pituitary cysts. In this example, the effects of increased intraventricular pressure in hydrocephalus are evident on ependymal cells. The normally cuboidal ependymal cells are stretched to cover the increased ventricular surface area. There is some edematous separation of the epithelium from underlying brain and mild vacuolation of subjacent neuropil. Ependymal cells have been generally considered by pathologists to be poorly responsive to insults, simply undergoing degeneration and necrosis. However, in investigations of controlled spinal injury of rats, ependymal cells and closely associated subjacent cells appear to be quite responsive, at least to trauma. Nestin and GAP-43, immunohistochemical indicators of immature neural stem cells, and glial fibrillary acid protein were detected posttrauma in in vivo cells identified as ependymal, suggesting dedifferentiation of ependymal cells to neural stem cells and glia and their potential role in spinal injury repair.
Recommendation
In NTP studies, the cause of the hydrocephalus should be determined if possible. Hydrocephalus is diagnosed unless it is secondary to obstruction by tumor. This lesion need not be graded.
色素Pigment 脑色素沉着
描述（中文）
多种形式的色素，如金黄色蜡样脂褐素（ceroid/lipofuscin）和深棕色含铁血黄素（hemosiderin），可沉积于脑内，有时是衰老过程或代谢异常的一部分。蜡样脂褐素在365 nm波长下自发荧光，过碘酸雪夫染色（PAS）可突出显示这些沉积物。含铁血黄素的正常铁含量可通过Perls普鲁士蓝染色检测为蓝色至紫色颗粒。含铁血黄素负载巨噬细胞的存在提示既往神经损伤伴相关出血，导致巨噬细胞对外渗红细胞及其血红蛋白内容物进行吞噬降解。Figure 1（箭头）显示胼胝体内存在多个棕色色素性含铁血黄素负载巨噬细胞，提示既往出血。
诊断建议
在NTP研究中，应记录色素的存在（诊断中无需指明色素类型）、其严重程度分级及解剖亚部位位置。即使使用一系列特殊染色，在组织学切片中确定色素鉴定通常也很困难。因此，推荐诊断为色素（而非诊断色素类型，例如含铁血黄素或脂褐素）最为恰当。病理学描述应描述色素沉着的形态学特征。并非所有色素都必须诊断，因为有些色素在衰老动物中普遍存在或与其他疾病过程相关，且无毒理学意义。病理学家应运用其判断来决定色素继发性沉积是否足够显著以值得单独诊断。
参考切片图（1 张）
查看英文原文
Comment
Various forms of pigment, such as yellow-golden ceroid/lipofuscin and dark brown hemosiderin, are deposited in the brain sometimes as part of the aging process or metabolic abnormalities. Ceroid/lipofuscin autofluoresces at 365 nm wavelength, and periodic acid Schiff stain highlights the deposits. The normal iron content of hemosiderin can be detected as blue to purple particles using Perls Prussian blue stain. The presence of hemosiderin-laden macrophages indicates prior neural injury with associated hemorrhage resulting in macrophage phagocytic degradation of extravasated red blood cells and their hemoglobin content. Figure 1 (arrow) shows multiple brown-pigmented hemosiderin-laden macrophages present in the corpus callosum suggesting previous hemorrhage.
Recommendation
The presence of pigments (type of pigment need not be specified in the diagnosis), their severity grading, and anatomic subsite location should be documented in NTP studies. Definitive pigment identification is often difficult in histological sections, even with a battery of special stains. Therefore, it is recommended that a diagnosis of pigment (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should describe the morphological features of the pigmentation. Not all pigments have to be diagnosed, as some are ubiquitous in aging animals or related to some other disease process and are not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether or not secondary deposits of pigment are prominent enough to warrant a separate diagnosis.
血管扩张Angiectasis 脑扩张
描述（中文）
Figure 1、Figure 2 展示了血管扩张（angiectasis）的一个示例。识别脑内局灶性增多的、结构相对正常的血管，是自发性偶然性血管扩张的标志性特征。此处小脑脑膜内可见数条扩张的血管静脉，其中部分血管内已发生血栓形成（Figure 1，箭头）。此类相互连通的异常窦样血管内可能存在的湍流血流会激活凝血级联反应，从而导致血栓形成。Figure 2 以更高放大倍数展示了与 Figure 1 相同的标本。注意内皮外观正常。将此类血管改变与血管瘤（hemangioma）和血管肉瘤（hemangiosarcoma）相鉴别十分重要。在血管肉瘤中，肿瘤具有压迫性和浸润性，血管直径不一，多为毛细血管性质，而在最恶性的类型中，内皮细胞核异常肥大并伴有梭形间质。应尝试对血管扩张与血管瘤进行区分，尽管这种区分并不总是显而易见。血管瘤倾向于为边界清楚、无包膜的肿块，由紧密排列的扩张血管腔隙构成。每个血管腔隙均由单层外观正常的内皮细胞围成并衬覆，这些内皮细胞排列于胶原性间隔上，间隔通常较薄，但部分具有宽阔的胶原性间质。血管扩张通常不表现为边界清楚的肿块；扩张的血管通道常不规则地穿行于组织之中。
诊断建议
在 NTP 研究中，血管扩张在出现时即应作出诊断，并根据病变范围进行分级。应记录其具体部位。
参考切片图（2 张）
查看英文原文
Comment
Figure 1 and Figure 2 show an example of angiectasis. The recognition of a focal excess of relatively normally configured vessels in a brain is the hallmark of spontaneous incidental angiectasis. Here there are several large angiectatic veins in the meninges of the cerebellum, and thrombosis ( Figure 1 , arrows) has occurred in some of these vessels. The probably turbulent blood flow in such interconnected abnormal sinusoid-like vessels leads to activation of the clotting cascade resulting in thrombosis. Figure 2 shows the same specimen as Figure 1 at higher magnification. Note the normal appearance of the endothelium. Differentiation of such vascular changes from that of hemangioma and hemangiosarcoma is important. In hemangiosarcoma, the tumor is compressive and infiltrative, and the vessels are of varied diameters, are mostly of a capillary nature, and, in the most malignant forms, have abnormal hypertrophied endothelial nuclei and spindloid stroma. A distinction between angiectasis and hemangioma should be attempted, although the distinction is not always obvious. Hemangiomas tend to be well-circumscribed, unencapsulated masses composed of tightly packed, dilated vascular spaces. Each vascular space is enclosed and lined by a single layer of normal-appearing endothelial cells aligned on collagenous septa, which are usually thin, although some have broad collagenous stroma. Angiectasis does not usually present as a well-circumscribed mass; the dilated vascular channels often course irregularly through the tissue.
Recommendation
In NTP studies, the angiectasis is diagnosed when present and graded based on extent of the lesion. The subsite should be recorded.
表皮样囊肿Epidermoid Cyst 脑囊肿
描述（中文）
表皮样囊肿（epidermoid cyst）是良性错构瘤性结构，从其位置和大小来看，可能干扰正常神经功能，但通常临床上无症状，因为其体积缓慢增大，使神经系统能够对占位性病变的存在进行适应和代偿。在图1中，发育不良的表皮样囊肿位于背侧额顶中线位置的扣带皮质回。此类表皮样囊肿被认为起源于表皮组织的胚胎残余，当神经管与上覆神经板分离时，这些残余与内陷的神经管保持密切关联。囊肿形成过程中压迫皮质，具有薄层表皮衬里，通常为复层鳞状上皮，核心处有少量角蛋白碎屑。注意双侧胼胝体上回（induseum griseum），这是一个紧凑的正常神经元细胞区域，属于与海马中继相关的边缘系统的一部分。图2描绘了一个位于腰段腹侧脊髓索的蛛网膜下表皮样囊肿的更晚期发展。其外侧毗邻脊神经根，内侧毗邻腹侧脊髓灰质柱。索组织受到广泛压迫显而易见，但未在该动物中检测到临床症状。图3显示了位于软脑膜下方的偶发性皮质蛛网膜下表皮样囊肿的位置。存在对下方皮质的压迫以及邻近核团神经元的丢失。角蛋白核心中央部分存在营养不良性矿化。在图4中，这个大型偶发性表皮样囊肿位于间脑上方的中线位置，压迫邻近的海马齿状回和缰核结构。注意该囊肿细胞丰富且角化程度相对较差。在图5中，表皮样囊肿局限于脊髓神经根（radicle），其进行性增大已完全破坏神经纤维，仅留下神经外膜和神经束膜完整。
诊断建议
尽管表皮样囊肿通常被认为是背景病变，但在NTP研究中应连同亚部位一起诊断。表皮样囊肿无需分级。
参考切片图（2 张）
查看英文原文
Comment
Epidermoid cysts are benign hamartomatous structures, which, from their location and size, may interfere with normal neural functions but are usually clinically silent since the slow increase in size allows for adaptation and compensation by the nervous system to the presence of the space-occupying mass. In Figure 1 , the poorly developed epidermoid cyst is located in the cingulate cortical gyrus at the dorsal frontoparietal midline location. Such epidermoid cysts are considered to arise from embryonic rests of epidermal tissue that remain closely associated with the infolding neural tube when it separates from the overlying neural plate. The cyst, as it forms, compresses the cortex and has a thin epidermal, often stratified squamous epithelial lining and modest amount of keratin debris at the core. Note the bilateral induseum griseum, a compact normal region of neuronal cells, which is part of the limbic system associated with hippocampal relays. Figure 2 depicts a more advanced development of a sub-leptomeningeal epidermoid cyst located in the lumbar ventral spinal funiculus. Adjacent laterally are spinal nerve roots, and adjacent internally is the ventral spinal gray matter column. The extensive compression of the funicular tissue is apparent, but no clinical signs were detected in the animal. Figure 3 shows the location of an incidental cortical sub-leptomeningeal epidermoid cyst underlaid by the pia mater. There is compression of the underlying cortex and loss of neurons in the adjacent nucleus. Dystrophic mineralization of the central portion of the keratin core is present. In Figure 4 , this large incidental epidermoid cyst has a midline location above the diencephalon and compresses the adjacent hippocampal dentate gyrus and habenular nuclear structures. Note that the cyst is cellular and relatively poorly keratinized. In Figure 5 , the epidermoid cyst confines itself to a spinal radicle (nerve root), where its progressive enlargement has totally effaced the nerve fibers, leaving only the epineurium and perineurium intact.
Recommendation
Although epidermoid cysts are generally considered background lesions, they should be diagnosed in NTP studies along with the subsite. Epidermoid cysts do not need to be graded.
软脑膜脂肪瘤性错构瘤Leptomeninges Hamartoma Lipomatous 脑肿瘤性病变
描述（中文）
Figure 1 展示了一种神经发育异常。该中线脑膜脂瘤性错构瘤（leptomeningeal lipomatous hamartoma）位于扣带回（cingulate gyrus）基底部，紧邻胼胝体（corpus callosum）和隔核（septal nuclei）上方。由正常白色脂肪细胞（white adipocyte）构成，处于脂瘤性错构瘤的常见部位。错构瘤的膨胀对邻近结构几乎没有压迫效应，也未伴有明显的临床神经学体征。此类错构瘤在啮齿类动物研究中不常见。不应将其与脂肪瘤（lipoma）或脂肪肉瘤（liposarcoma）混淆。
诊断建议
在 NTP 研究中，脂瘤性错构瘤应当被诊断，并指明具体部位。
参考切片图（1 张）
查看英文原文
Comment
Figure 1 depicts a neurodevelopmental anomaly. This midline leptomeningeal lipomatous hamartoma is located at the base of the cingulate gyrus, immediately above the corpus callosum and septal nuclei. Consisting of normal white adipocytes, it is in the common location for a lipomatous hamartoma. The expansion of the hamartoma has had little compressive effect on adjacent structures and was not accompanied by noticeable clinical neurological signs. This type of hamartoma is uncommon in rodent studies. It is not to be confused with a lipoma or liposarcoma.
Recommendation
Lipomatous hamartomas should be diagnosed in NTP studies and the subsite specified.
轴索病Axonopathy 脑其他
描述（中文）
“轴索病（axonopathy）”是一个通用术语，描述发生于脑、脊髓和周围神经的多种轴索病变。在低倍镜下必须注意，确保轴索病的判定标准（轴索肿胀、断裂、丢失等）不被误认为人为空泡化而忽视。其在脑和脊髓特定区域的出现以及常呈对称性分布，是判断其为真实病变的有用线索。需要仔细检查白质和神经组织的所有区域，才能正确发现和解释此类病变。年龄相关轴索病常见于马尾、腹侧脊神经根、脊髓腹索和侧索、坐骨神经和臂神经以及低位脑干。对老龄大鼠脊髓和神经根性（神经根）轴索病的解释应谨慎，因为它可能是衰老的结果，在24月龄或以上大鼠中的发生率为75-90%。在专门的毒理学-神经病理学研究中，使用特殊轴索染色如Bielschowsky银浸染和de Olmos氨基铜银染色分别突出显示正常轴索和轴索病变，可能有助于界定这些常较细微病变的严重程度和分布。Figure 1显示低倍镜下脊髓，展示背侧本体感觉索即本例中薄束内轴索病的表现。注意在此放大倍数下，病变表现为通常由正常上行轴索占据的局灶性（focal）区域出现细微空泡化（箭头）。该区域轴索受损导致轴索及其髓鞘肿胀，从而形成扩张的空隙。此图采用甲苯胺蓝染色。Figure 2为亚慢性毒性研究中脊髓薄束轴索肿胀的甲苯胺蓝染色高倍切片。注意许多膨大的轴索（箭头），大多数仍被其髓鞘包围。有髓纤维明显减少，尤其在索的最深部，使这些区域肿胀的有髓轴索如大“空泡”般凸显。Figure 3、Figure 4、Figure 5描绘肿胀的轴索。在Figure 3中，注意扩张空隙中央偶见轻度增大的肿胀轴索（箭头），该空隙原先由正常、致密的板层状髓鞘占据。许多扩张空隙是空的，因为轴索已经发生崩解、溶解并被巨噬细胞吞噬。空隙看似空虚是因为组织处理中使用的脂肪溶剂去除了构成髓鞘的残留复合脂质。Figure 4代表更高放大倍数下的肿胀退变轴索（箭头），其周围扩张空隙的直径约为相邻外观正常轴索周围空隙的三倍。Figure 5代表脊髓索轴索病，详示一个肿胀轴索，即所谓的球状体（spheroid）（箭头）。注意空泡内一个核固缩的巨噬细胞，代表轴索变性后期阶段，特征为轴索被吞噬（箭头）。在大多数轴索变性病例中，可识别的巨噬细胞通常已坏死，推测是由于轴索变性过程中吞噬髓鞘脂质和释放细胞因子的影响。当巨噬细胞负载游离胆固醇和三酰甘油时，即发生凋亡。在此高倍苏木精-伊红染色图像中，大的肿胀轴索呈双嗜性外观。这是轴索肿胀早期、即轴索崩解之前球状体的良好示例。Figure 6显示脑切片中嗜酸性球状体和卵圆形至长条形结构（箭头），代表受损轴索，因切片平面不同而形态各异。脑内肿胀轴索的出现通常不伴有脊髓和周围神经中所见的髓鞘显著扩张。另请注意该区域混合性胶质细胞群轻度增多，为相关炎症反应的一部分。Figure 7显示轴索变性伴典型“消化腔（digestion chamber）”，内含轴索碎片（箭头）。在此坐骨神经纵切面苏木精-伊红染色图像中，称为沃勒变性（Wallerian degeneration）的轴索变性典型表现清晰可见。“沃勒变性”一词最好保留用于描述周围神经的轴索病；然而，脊髓和脑内也可见类似改变。Augustus Waller于1850年通过对实验性神经挤压伤的序贯研究，提出了周围神经轴索病的判定标准。远端神经尤其在挤压伤后，特征为进行性轴索肿胀，并在挤压后约36小时出现纤维断裂、Schwann细胞核肥大、巨噬细胞浸润以及所谓消化腔的形成。在Figure 7中，消化腔含数个退变轴索碎片，周围为含脂质分解产物和巨噬细胞的透明空隙。相邻神经组织中可见Schwann细胞增大的核。Figure 8显示坐骨神经轴索变性伴Schwann细胞反应性增生和核肥大（箭头）。这些呈线性带状增殖的Schwann细胞称为Büngner带（bands of Büngner）。它们是在轴索损伤后Schwann细胞失去其轴索联系时作为反应而形成的。残留的基底膜形成神经内膜管，对引导近端再生轴索芽生十分重要。Schwann细胞和血源性巨噬细胞在吞噬断裂轴索以清除神经内膜管、利于轴索再生方面起重要作用。Büngner带不应解释为炎性纤维化，而应视为周围轴索显著变性后神经再支配过程的一部分。
诊断建议
在NTP研究中，所有形式的轴索损伤均首选“轴索病（axonopathy）”一词。该病变应在对照和治疗动物中诊断，并注明其解剖亚部位。严重程度分级应连同判定标准一并记录，以便根据发生率和严重程度决定其与治疗的相关性。努力寻找轴索病的明确判定标准，对于在病变演变的多个阶段确认其真实性质十分重要。在NTP研究中，若研究病理学家对白质局灶性（focal）空泡性病变的发病机制不确定，或病变无法与脱髓鞘或髓鞘内水肿区分，则该病变应诊断为白质空泡化（white matter vacuolation）。描述应说明病变为局灶性、单侧还是双侧等特征。随后应由神经病理学家进行专门评估。
参考切片图（2 张）
查看英文原文
Comment
“Axonopathy” is a generic term describing a variety of lesions of the axon occurring in brain, spinal cord, and peripheral nerve. Care must be taken at low magnifications to ensure that the criteria for axonopathy (axonal swelling, fragmentation, loss, etc.) are not disregarded as artifactual vacuolation. Its presence in defined regions of brain and spinal cord and frequent symmetrical distribution are useful clues to its genuine nature. Close examination of all regions of white matter and nerve tissue is required to correctly discover and interpret this type of lesion. Age-related axonopathy occurs commonly in the cauda equina, ventral spinal nerve roots, ventral and lateral spinal funiculi, sciatic and brachial nerves, and lower brainstem. Caution should be given to interpretation of spinal and radicular (nerve root) axonopathy in aged rats since it may be a result of senescence and has an incidence of 75-90% in rats 24 or more months of age. In specialized toxicologic-neuropathologic studies, use of special axonal stains such as Bielschowsky silver impregnation and de Olmos amino cupric silver to highlight the normal axon and axonal lesions, respectively, may be helpful in delineating the severity and distribution of these often subtle lesions. Figure 1 shows spinal cord at low magnification demonstrating the appearance of axonopathy in the dorsal proprioceptive funiculi, in this case the fasciculus gracilis. Note, at this magnification, that the lesion is represented by subtle vacuolation (arrow) of a focal area ordinarily populated by normal ascending axons. Damage to the axons in this zone leads to swelling of both the axon and its myelin sheath, thus creating a dilated space. This image uses toluidine blue stain. Figure 2 is a higher-magnification toluidine blue–stained section of spinal cord showing axonal swelling in the fasciculus gracilis in a subchronic toxicity study. Note the many distended axons (arrows), most still surrounded by their myelin sheath. There is a prominent reduction in myelinated fibers, particularly in the deepest parts of the funiculi, making the swollen myelinated axons in these regions stand out in relief as large ”vacuoles.” Figure 3 , Figure 4 , and Figure 5 depict swollen axons. In Figure 3 , note the slightly enlarged occasional swollen axons (arrows) at the center of dilated spaces formerly occupied by a normal, compact lamellar myelin sheath. Many of the dilated spaces are empty because the axon has already undergone disintegration, lysis, and phagocytosis by macrophages. The space appears empty because the use of fat solvents in tissue processing has removed any remaining complex lipids, which made up the myelin sheath. Figure 4 represents swollen degenerate axons at higher magnification (arrows), where the diameter of the distended space surrounding them is approximately three times larger than the space around adjacent, apparently normal axons. Figure 5 represents spinal funicular axonopathy with detail of a swollen axon, a so-called spheroid (arrow). Note the pyknotic macrophage in a vacuole representing a later stage of axonal degeneration characterized by axonal phagocytosis (arrowhead). In most cases of axonal degeneration, identifiable macrophages are usually necrotic, presumably from the effects of myelin lipid phagocytosis and cytokine release during the axonal degenerative process. Apoptosis of macrophages results when they are loaded with free cholesterol and triacylglycerol. In this high-magnification hematoxylin and eosin–stained image, the large swollen axon has an amphophilic appearance. This is a good example of a spheroid at an early stage of axonal swelling that precedes axonal disintegration. Figure 6 shows eosinophilic spheroids and oval to elongated structures (arrows) that represent injured axons in the brain sectioned in various planes, thus affecting their appearance. The presence of swollen axons in the brain is not generally accompanied by dramatic distension of the myelin sheath such as those seen in spinal cord and peripheral nerves. Note also that there is a mild increase in a mixed population of glial cells in the region, part of the associated inflammatory response. Figure 7 shows axon degeneration with a typical “digestion chamber,” containing axonal fragments (arrow). In this hematoxylin and eosin–stained image of a longitudinal section of the sciatic nerve, the typical appearance of axonal degeneration referred to as Wallerian degeneration is evident. The term “Wallerian degeneration” is best reserved to describe axonopathy in peripheral nerve; however, similar changes can be seen in spinal cord and brain. Augustus Waller, in 1850, introduced the criteria for axonopathy in peripheral nerve from his sequential studies of experimental nerve crush injury. The distal nerve, particularly after crush, is characterized by progressive axonal swelling and, approximately 36 hours after crush, by fragmentation of the fiber, Schwann cell nuclear hypertrophy, infiltration of macrophages, and the formation of so-called digestion chambers. In Figure 7 the digestion chamber contains several fragments of degenerate axon surrounded by a clear space, containing lipid breakdown products and macrophages. The enlarged nuclei of Schwann cells can be seen in adjacent nerve tissue. Figure 8 shows sciatic nerve axon degeneration with reactive hyperplasia and hypertrophic nuclei of Schwann cells (arrows). These linear band-like proliferative Schwann cells are known as bands of Büngner. They are formed as a response to axonal injury when Schwann cells lose their axonal complement. The remaining basement membrane forms endoneurial tubes, important in the guidance of regenerating proximal axonal sprouts. Schwann cells and blood-borne macrophages are important in phagocytosis of fragmented axons to clear endoneurial tubes for axonal regeneration. The bands of Büngner should not be interpreted as inflammatory fibrosis but, rather, as a part of the reinnervation process subsequent to significant axon degeneration in peripheral axons.
Recommendation
In NTP studies, the term “axonopathy” is preferred for all forms of axonal injury. This lesion should be diagnosed in control and treated animals with its anatomic subsite location. Severity grade should be included with criteria, allowing a decision on its treatment-related significance to be based on incidence and severity. Searching diligently for tangible criteria of axonopathy is important in confirming the genuine nature of the lesions at several stages of their evolution. In NTP studies where focal vacuolar lesions in white matter are of uncertain pathogenesis to the study pathologist, or in studies where the lesion cannot be differentiated from demyelination or intramyelinic edema, the lesion should be diagnosed as white matter vacuolation. The narrative should describe features including whether the lesion is focal, unilateral, or bilateral. This should be followed by special evaluation by a neuropathologist.
髓鞘内水肿Intramyelinic Edema 脑水肿
描述（中文）
白质的“海绵状”（sponginess）（Figure 4，箭头）表现始终是神经病理学家关注的问题，因为它通常是固定不良和自溶的伪影。Figure 1、Figure 2 显示了大鼠小脑白质中髓鞘经Luxol fast blue和cresyl violet染色后的正常形态。评估组织是否存在固定不良和自溶的指标，对于判定真正的白质病变极为重要。真正的白质病变如脱髓鞘（demyelination）具有一些有用的真实性标志（见脊髓-脱髓鞘），如双侧对称性以及受累区域存在肿胀的轴突或巨噬细胞。其他白质病变如髓鞘内水肿（intramyelinic edema）表现为白质严重的海绵状改变，而无任何髓鞘破坏或细胞反应的证据。典型情况下，髓鞘内水肿由亲脂性化合物引起，导致髓鞘板层在周期内线（intraperiod line）处分离（经电子显微镜证实）。在中枢神经系统中，这是由于少突胶质细胞胞质内液体积聚所致。对此类白质病变研究较为充分的例子包括六氯酚（hexachlorophene）暴露，如Figure 3、Figure 4 所示。慢性六氯酚暴露还可产生星形细胞肥大和增生，如胶质纤维酸性蛋白免疫组化染色所示。已证明停止六氯酚暴露可使大鼠的临床和镜下海绵状效应逆转。
诊断建议
在NTP研究中，当光镜下无法将髓鞘内水肿与脱髓鞘或轴突病（axonopathy）区分时，该病变应诊断为白质空泡化（white matter vacuolation）。随后应由神经病理学家进行特殊评估。在怀疑髓鞘内水肿的情况下，通常不存在轴突病和炎症反应，仅对固定良好的材料进行电子显微镜检查可能具有确诊作用。在NTP研究中出现时，应注明亚部位并对病变严重程度进行分级。
参考切片图（2 张）
查看英文原文
Comment
The presence of “sponginess” ( Figure 4 , arrow) of the white matter is always of concern to the neuropathologist since it is commonly an artifact of poor fixation and autolysis. Figure 1 and Figure 2 show the normal appearance of myelin in rat cerebellar white matter stained with Luxol fast blue and cresyl violet. Assessment of the tissue for indicators of poor fixation and autolysis is extremely important to determine genuine white matter lesions. Valid white matter lesions such as demyelination have some useful hallmarks of authenticity (see Spinal Cord - Demyelination ), such as bilateral symmetry and the presence of swollen axons or macrophages in affected areas. Other white matter lesions such as intramyelinic edema are observed as severe spongiform change of white matter without any evidence of myelin breakdown or cellular reaction. Classically, intramyelinic edema is caused by lipophilic compounds that result in separation of myelin lamellae at the intraperiod line (confirmed by electron microscopy). In the CNS, this is due to the accumulation of fluid in the cytoplasm of oligodendroglial cells. Well-studied examples of this form of white matter lesion include exposure to hexachlorophene, as shown in Figure 3 and Figure 4 . Chronic exposure to hexachlorophene also produces astrocytic hypertrophy and proliferation, as demonstrated by glial fibrillary acid protein immunohistochemical staining. Removal of hexachlorophene exposure has been shown to lead to a reversal of the clinical and microscopic spongiform effects in rats.
Recommendation
In NTP studies where intramyelinic edema cannot be differentiated from demyelination or axonopathy under light microscopy, the lesion should be diagnosed as white matter vacuolation. This should be followed by special evaluation by a neuropathologist. In the case of suspected intramyelinic edema, where axonopathy and inflammatory responses are generally absent, examination of only well-fixed material by electron microscopy may be confirmatory. When present in NTP studies, the subsite should be noted and lesion severity graded.
卵圆细胞增生Oval Cell Hyperplasia 肝增生
描述（中文）
卵圆细胞增生（oval cell hyperplasia）（Figure 1）在对照动物中罕见。它通常始于汇管区周围区域或肝脏被膜下区域。增生的卵圆细胞呈纺锤状，初期以线性排列方式从汇管区向外延伸；它们可环绕肝小叶，严重病例中可形成增殖细胞的不规则实性巢。由于卵圆细胞增生主要发生于经肝毒性外源化学物处理的动物或感染病例中，因此通常伴有不同程度的肝细胞变性和坏死以及胆管增生。Figure 1评为2+（轻微（mild）），Figure 2、Figure 3、Figure 4评为4+（显著（marked））。
诊断建议
卵圆细胞增生只要存在即应作出诊断并给出严重程度分级，即使它是复杂肝脏病变组合的一部分。卵圆细胞增生的模式和范围应连同伴随的肝脏病变一起在病理学描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Oval cell hyperplasia ( Figure 1 ) is rarely seen in control animals. It typically begins either in periportal areas or in subcapsular regions of the liver. The proliferating oval cells are spindloid and initially extend out from portal areas in a linear array; they may encircle hepatic lobules, and in severe cases they may form irregular solid nests of proliferating cells. Since oval cell hyperplasia occurs primarily in animals treated with hepatotoxic xenobiotics or in cases of infection, it is usually associated with varying degrees of hepatocyte degeneration and necrosis and bile duct hyperplasia. Figure 1 was graded as 2+ (mild), and Figure 2 , Figure 3 , and Figure 4 as 4+ (marked).
Recommendation
Oval cell hyperplasia should be diagnosed and given a severity grade whenever present, even when part of a complex set of hepatic changes. The pattern and extent of oval cell hyperplasia should be described in the pathology narrative along with accompanying hepatic changes.
坏死Necrosis 肝坏死
描述（中文）
肝细胞坏死（hepatocellular necrosis）的范围、模式及形态学特征取决于肝毒性外源化学物（hepatotoxic xenobiotics）的代谢活化程度、宿主对毒物的反应、外源化学物暴露的剂量与持续时间，以及给药后肝样本评估的时间。经典凝固性坏死（coagulation necrosis）通常由缺血或梗死引起，由于负责蛋白水解的溶酶体酶变性失活，组织结构在一定程度上得以保持。另一种坏死形式——液化性坏死（liquefaction necrosis）——可导致细胞溶解和细胞学结构丧失。可能伴随坏死出现的变化包括出血、脂肪变（fatty change）、细胞质空泡化、细胞学退变及炎性细胞浸润。Figure 1、Figure 2 代表边界清晰的小叶中央性坏死，伴肝细胞细胞学细节丧失。Figure 3、Figure 4 代表不规则的斑片状凝固性坏死区域，伴早期炎性细胞浸润。该坏死无明显的肝小叶模式。Figure 5、Figure 6 代表以肝细胞丧失并被红细胞替代为特征的坏死示例。这是出血性坏死（hemorrhagic necrosis）的一个例子。Figure 7、Figure 8 代表与脂肪变相关的 局灶性（focal） 坏死。坏死斑片（见 Figure 8 ，底部中央）呈强嗜酸性（hypereosinophilic），脂肪变为小叶中央性并明显延伸至小叶中部区域。Figure 9、Figure 10 代表肝细胞坏死伴肝细胞退变、微泡性脂肪变（microvesicular fatty change）、核固缩（nuclear pyknosis）及炎症的诊断。“退变”（degeneration）一词常用于表示可逆的细胞或组织损伤，被认为是坏死的前驱阶段。由于炎症反应广泛存在，为更准确地反映持续进行的病变过程，附加炎症（细胞浸润）的诊断可能是适当的。
诊断建议
坏死不应根据类型进行细分，单细胞坏死（single-cell necrosis）除外。对于给定的外源化学物，剂量和动物反应的个体差异可影响肝细胞坏死为全小叶性还是小叶中央性，以及为 局灶性（focal） 还是呈广泛不规则斑片状分布。若基本过程相同，病变应简单地记录为坏死并赋予严重程度分级。肝细胞坏死的模式及其他特征应在病理学描述（pathology narrative）中描述。将诊断拆分得过细会导致发生率表格复杂化，并可能妨碍对任何诱导性毒性的恰当解释。当伴随变化如脂肪变或炎症足够广泛时，可能需要单独诊断，并进行严重程度分级及在病理学描述中讨论。由于退变被认为是坏死过程所涉及变化连续体的一部分，当与坏死同时存在时不应单独诊断。然而，无坏死的退变可发生在低于引起坏死的剂量水平的暴露下，因此可能值得单独诊断。在某些情况下，肝细胞坏死可在肝实质内形成海绵状、充满血液的腔隙。这些充满血液的腔隙不应诊断为出血，因为它们是坏死的继发改变。
参考切片图（2 张）
查看英文原文
Comment
The extent, pattern, and morphologic features of hepatocellular necrosis depend on the degree of metabolic activation of hepatotoxic xenobiotics, host response to the toxicant, dose and duration of xenobiotic exposure, and timing of liver sample evaluation after dosing. Classical coagulation necrosis is typically caused by ischemia or infarction, and tissue architecture is somewhat maintained because lysosomal enzymes responsible for proteolysis are denatured. Another form of necrosis, liquefaction necrosis, may result in cellular dissolution and loss of cytologic architecture. Changes that may accompany necrosis include hemorrhage, fatty change, cytoplasmic vacuolization, cytologic degeneration, and inflammatory cell infiltration. Figure 1 and Figure 2 represent sharply demarcated centrilobular necrosis with loss of hepatocyte cytologic detail. Figure 3 and Figure 4 represent irregular patchy areas of coagulation necrosis with early infiltration of inflammatory cells. There is no distinctive lobular pattern to this necrosis. Figure 5 and Figure 6 represent an example of necrosis characterized by loss of hepatocytes and replacement with erythrocytes. This is an example of hemorrhagic necrosis. Figure 7 and Figure 8 represent focal necrosis associated with fatty change. The patches of necrosis (see Figure 8 , bottom center) are hypereosinophilic, and the fatty change is centrilobular with extension well into midlobular areas. Figure 9 and Figure 10 represent a diagnosis of hepatocyte necrosis accompanied by hepatocyte degeneration, microvesicular fatty change, nuclear pyknosis, and inflammation. “Degeneration” is a term often used to indicate reversible cell or tissue damage and is considered to be a precursor to necrosis. Because the presence of the inflammatory response is extensive, an additional diagnosis of inflammation (cellular infiltrate) to capture the ongoing process with more fidelity may be appropriate.
Recommendation
Necrosis should not be subclassified based on type, with the exception of single-cell necrosis. For a given xenobiotic, dose and animal variability in response can influence whether hepatocellular necrosis is panlobular or centrilobular and whether it is focal or occurs in extensive irregular patches. If the fundamental process is the same, the lesion(s) should be recorded simply as necrosis and assigned a severity grade. The pattern and other features of the hepatocellular necrosis should be described in the pathology narrative. Splitting out diagnoses too finely will result in complicated incidence tables and may compromise appropriate interpretation of any induced toxicity. When accompanying changes such as fatty change or inflammation are sufficiently extensive, separate diagnoses may be warranted with severity grading and discussion in the pathology narrative. Since degeneration is considered part of the continuum of changes involved in the necrotic process, it should not be diagnosed separately when present with necrosis. However, degeneration without necrosis may occur at exposure levels below doses that cause necrosis and thus may warrant a separate diagnosis. In some cases, hepatocellular necrosis can result in cavernous, blood-filled spaces within the hepatic parenchyma. These blood-filled spaces should not be diagnosed as hemorrhage because they are secondary to necrosis.
张力性脂质沉积症Tension Lipidosis 肝其他
描述（中文）
张力性脂质沉积（tension lipidosis，Figure 1，箭头）是发生于小鼠胆囊附近及镰状韧带附着处的局灶性（focal）胞质空泡化。此病变不被视为一种病理实体，但应与其他形式的胞质空泡化相鉴别。理论上，该病变可见于任何年龄。镰状韧带是胎儿腹侧系膜的残余，从肝门附近的膈区延伸至腹侧腹壁。张力性脂质沉积通常见于中叶脏膜面正下方。
诊断建议
对该病变的观察取决于组织采样和切片平面，并非必然见于所有动物。鼓励将其记录为张力性脂质沉积，以避免与肝实质的其他局灶性（focal）改变相混淆。病理学描述应提及这是一种无病理学意义的改变。相关链接：肝脏 - 脂肪变（Liver - Fatty Change）
参考切片图（2 张）
查看英文原文
Comment
Tension lipidosis ( Figure 1 , arrows) is a focal cytoplasmic vacuolization that occurs near the gallbladder and the attachment of the falciform ligament in mice. This is not considered a pathologic entity but should be distinguished from other forms of cytoplasmic vacuolation. Theoretically, it could be seen at any age. The falciform ligament is a remnant of the ventral mesentery of the fetus that extends from the diaphragmatic area near the liver hilus to the ventral abdominal wall. Tension lipidosis is typically seen just below the parietal surface of the median lobe.
Recommendation
Observation of this lesion is dependent on tissue sampling and plane of section and will not necessarily be seen in all animals. Documentation as tension lipidosis is encouraged to avoid confusion with other focal changes in hepatic parenchyma. The pathology narrative should mention that it is a change without pathologic significance. Related Links: Liver - Fatty Change
星状细胞增生Stellate Cell Hyperplasia 肝增生
描述（中文）
肝星状细胞（hepatic stellate cell，即 Ito 细胞或肝窦周细胞）增生在小鼠中罕见，在 NTP 大鼠研究中尚未见记载。该病变由星状细胞（贮脂细胞，区别于肝细胞内的巨泡性脂肪）呈 弥漫性（diffuse） 或 多灶性（multifocal） 增生构成，不伴有对周围实质的明显压迫。星状细胞储存类视黄醇化合物，活化后可转变为梭形形态（Figure 1、Figure 2，箭头），并响应肝损伤产生细胞外基质蛋白和胶原（瘢痕组织）。与星状细胞肿瘤的鉴别在于后者更为局限并引起周围肝实质的压迫。
诊断建议
星状细胞的增生应予以记载并给出严重程度分级。如果同一研究中存在星状细胞肿瘤，应在病理学描述中提及。
参考切片图（2 张）
查看英文原文
Comment
Hepatic stellate cell (Ito cell or perisinusoidal cell) hyperplasia is rare in mice and has not been documented in NTP rat studies. It consists of a diffuse or multifocal proliferation of stellate cells (fat-storing cells, as opposed to macrovesicular fat within hepatocytes) without prominent compression of surrounding parenchyma. Stellate cells store retinoid compounds and when activated may convert to a spindloid morphology ( Figure 1 and Figure 2 , arrow) and produce extracellular matrix proteins and collagen (scar tissue) in response to hepatic injury. Distinction from stellate cell tumors is based on the latter being more discrete and causing compression of surrounding hepatic parenchyma.
Recommendation
Proliferations of stellate cells should be documented and given a severity grade. If stellate cell tumors are present in the same study, it should be mentioned in the pathology narrative.
枯否细胞增生Kupffer Cell Hyperplasia 肝增生
描述（中文）
Kupffer细胞肥大与增生通常同时发生，可见于摄取外源性物质、受试物或代谢产物之后，其中任一情况均可能使细胞质着色为色素性。Kupffer细胞增生与肥大亦可发生于炎症状态下。增大的Kupffer细胞可形成片状或小结节状。
诊断建议
该组织学改变在未处理啮齿类动物中罕见，一旦出现即应作出诊断并分级。应在病理学描述中详细说明其形态学特征及组织分布。由于肥大是这些细胞吞噬活性的结果，通常无需单独作出肥大的诊断。若色素沉着显著，可单独作出色素沉着的诊断，并附严重程度的定性分级。
参考切片图（1 张）
查看英文原文
Comment
Kupffer cell hypertrophy and hyperplasia usually occur together and can be seen following uptake of foreign material, test agent, or metabolite, any of which may impart a pigment to the cytoplasm. Kupffer hyperplasia and hypertrophy may also occur in inflammatory conditions. The enlarged Kupffer cells may form sheets or small nodules.
Recommendation
This tissue change is rare in untreated rodents and should be diagnosed and graded whenever present. A description of the morphologic features and tissue distribution should be detailed in the pathology narrative. Because hypertrophy is a consequence of the phagocytic activity of these cells, a separate diagnosis of hypertrophy is generally not necessary. If pigmentation is prominent, a separate diagnosis of pigmentation, along with a qualitative grading of severity, may be appropriate.
淀粉样物质Amyloid 肝其他
描述（中文）
淀粉样物质（amyloid）（Figure 1，箭头所示）是细胞无法清除不可溶性错误折叠蛋白的结果。它可能与慢性炎症中急性期蛋白的过度产生有关。淀粉样物质沉积在大鼠中罕见，但在某些推测具有遗传易感性的小鼠品系中是常见的年龄相关变化。肝脏中的淀粉样物质被认为是继发性淀粉样变性，可见于肝窦和血管壁内。组织化学染色（如刚果红（Congo red））和免疫组织化学染色有助于明确诊断。
诊断建议
淀粉样物质一旦出现即应作出诊断并给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Amyloid ( Figure 1 , arrows) occurs as a result of cells not being able to eliminate insoluble misfolded protein. It can be associated with overproduction of acute-phase protein in chronic inflammation. Amyloid deposition is rare in rats but is a common age-related change in some mouse strains that presumably have a genetic predisposition. Amyloid in the liver is considered secondary amyloidosis and is seen within sinusoids and blood vessel walls. Histochemical (e.g., Congo red) and immunohistochemical stains are useful for definitive diagnosis.
Recommendation
Amyloid should be diagnosed and given a severity grade whenever present.
灶Focus 肝坏死灶
描述（中文）
细胞改变灶（foci of cellular alteration）在NTP研究中简称为“灶”（foci），可在大鼠和小鼠中自发发生，但也可能由受试物诱导产生。其大小范围从小于一个肝小叶到数个肝小叶不等。灶是推定的癌前病变（presumptive preneoplastic lesions），其表现可从几乎难以察觉至细胞形态学和染色特性上界限分明的病变不等。灶通常与周围肝实质界限不清地融合，且不压迫周围肝实质，但可能发生轻微压迫。灶在慢性研究中相对常见，但在90天研究中不常见。根据苏木精-伊红（hematoxylin and eosin）染色特性和细胞质特征对其进行亚分类。嗜碱性灶（basophilic foci）主要被苏木精着色（Figure 1，箭头；Figure 2）。在大鼠中已鉴定出虎斑型变体（tigroid variant），但被视为嗜碱性灶的一个亚分类。嗜酸性灶（eosinophilic foci）的染色通常比周围肝细胞更具嗜酸性，且常由比邻近正常实质更大的肝细胞组成（Figure 3，箭头；Figure 4）。透明细胞灶（clear cell foci）在中央定位的细胞核周围的肝细胞胞质中具有空泡。这些透明空泡代表在固定和处理过程中溶解流失的糖原。透明细胞灶易于识别，因为它们在胞质嗜酸性更为均匀的周围实质背景下显得突出（Figure 5、Figure 6）。某些文献讨论了空泡细胞灶（vacuolated cell foci），但这些现在被诊断为局灶性（focal） fatty change，不再被视为灶。当不存在单一优势表型时，诊断为混合细胞灶（mixed cell focus）。Figure 7、Figure 8展示了一个由透明细胞、空泡细胞和双染性细胞（amphophilic cells）组成的混合细胞灶，其中无单一细胞类型占灶细胞的80%以上。Figure 9、Figure 10展示了一个混合灶，由外周的嗜碱性细胞环围绕内部的透明细胞核心组成，各占现存细胞类型的相等比例。
诊断建议
由于灶是推定的癌前病变，只要存在即应诊断。NTP目前的建议是记录所有灶并将其分类为亚型（嗜碱性、嗜酸性、透明细胞或混合型）。灶不需要严重程度分级，除非病理学家认为有必要突出研究组间的差异。相关链接：肝脏 - 肝细胞 - 糖原蓄积与耗竭（Liver - Hepatocyte - Glycogen Accumulation and Depletion）
参考切片图（2 张）
查看英文原文
Comment
Foci of cellular alteration, diagnosed simply as “foci” in NTP studies, can occur spontaneously in rats and mice but may also be induced by treatment. They range from less than a lobule to several lobules in size. Foci are presumptive preneoplastic lesions that can vary from barely perceptible to cytomorphologically and tinctorially discrete lesions. Foci typically blend imperceptibly with, and do not compress, surrounding hepatic parenchyma, though minimal compression may occur. Foci are relatively common in chronic studies but uncommon in 90-day studies. They are subclassified based on hematoxylin and eosin tinctorial properties and cytoplasmic features. Basophilic foci predominantly stain with hematoxylin ( Figure 1 , arrows; Figure 2 ). A tigroid variant has been identified in rats but is considered a subclassification of basophilic focus. Eosinophilic foci typically stain more eosinophilic than surrounding hepatocytes and often consist of hepatocytes that are larger than the adjacent normal parenchyma ( Figure 3 , arrows; Figure 4 ). Clear cell foci have empty spaces in hepatocyte cytoplasm surrounding centrally localized nuclei. The clear spaces represent glycogen dissolved out during fixation and processing. Clear cell foci are readily identified because they stand out against surrounding parenchyma that has a more uniformly eosinophilic cytoplasm ( Figure 5 and Figure 6 ). Some texts discuss vacuolated cell foci, but these are now diagnosed as focal fatty change and are not considered foci. Mixed cell focus is diagnosed when there is no single predominant phenotype. Figure 7 and Figure 8 represent a mixed cell focus composed of clear cells, vacuolated cells, and amphophilic cells with no single cell type constituting more than 80% of the focus cells. Figure 9 and Figure 10 present a mixed focus composed of an outer rim of basophilic cells surrounding an inner core of clear cells, each comprising an equal proportion of the cell types present.
Recommendation
Because foci are presumptive preneoplastic lesions, they should be diagnosed whenever present. The current NTP recommendation is to document all foci and to classify these into subtypes (basophilic, eosinophilic, clear cell, or mixed). A severity grade is not required for foci unless the pathologist feels it is necessary to highlight differences among the study groups. Related Links: Liver - Hepatocyte - Glycogen Accumulation and Depletion
炎症Inflammation 肝炎症
描述（中文）
炎症，局灶性（focal）是指单个或多个、局灶性、随机分布的炎症细胞聚集灶，在肝脏中作为背景性病变可见，且在老年小鼠和大鼠中比在年轻动物中更为常见。然而，这些炎症细胞灶可在亚慢性研究的啮齿类动物肝脏中自发出现（Figure 1、Figure 2）。浸润细胞以淋巴细胞为主，但可能包含较少量的中性粒细胞和/或巨噬细胞。炎症细胞聚集灶可能伴有肝细胞坏死的证据（Figure 3、Figure 4）。这些灶的大小可能不一（Figure 6、Figure 7），但通常肉眼不明显。这些病变可能在雌性动物中更为常见（Harada et al. 1996），并可能与感染性病原体有关（Hall et al. 1992）。最常见的原因是未知的。如果在标准组织学切片中仅见一或两个炎症灶，则严重程度分级为1+（极轻微（minimal））。与同期对照相比，外源性化学物暴露也可能增加这些病变的严重程度和/或数量。局灶性炎症是啮齿类动物毒性研究中肝脏最常见的炎症性病变，是慢性炎症的一种形式。在慢性炎症中，以淋巴细胞为主。慢性活动性炎症同样以淋巴细胞为主，但也包含相当数量的中性粒细胞。两种病变均可能含有巨噬细胞。然而，只有当病变在某种定性方式上与上述“炎症，局灶性”的描述不同时，才可使用“慢性炎症”或“慢性活动性炎症”这一术语。其他较少见的炎症形式包括急性、化脓性和肉芽肿性炎症。在急性炎症中，中性粒细胞是主要的浸润细胞，尽管也可能存在较少的巨噬细胞和淋巴细胞，以及水肿或充血的表现。在化脓性炎症中，中性粒细胞同样是主要的浸润细胞类型，但它们聚集在一起，且许多已变性。渗出物中还可能存在来自 resident 细胞群和浸润白细胞的细胞碎片，以及含有纤维蛋白的蛋白性液体、少量巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染性病原体。肉眼上，这些病变以脓液的存在为特征。渗出物周围组织可能含有成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。肉芽肿性炎症是另一种形式的慢性炎症，其诊断要求存在大量聚集的、大的活化巨噬细胞、上皮样巨噬细胞和/或多核巨细胞。“细胞浸润”一词曾被用于描述炎症细胞的存在而无炎症过程的其他证据（例如水肿、细胞坏死或变性，或血管损伤的证据）。此类炎症细胞浸润通常相当小，可能不值得诊断。如果足够显著而值得记录，白细胞聚集应诊断为“炎症”。偶尔，肝脏中可见非白细胞性细胞（如肥大细胞）的浸润；这些应诊断为“细胞浸润”。
诊断建议
形态学上与上述局灶性（focal）炎症描述一致的炎症性病变应记录为“炎症，局灶性”，无论是否与受试物相关。严重程度分级应反映组间任何与受试物相关的差异。对照组中一或两个小的局灶性炎症细胞聚集灶，在受试物组中无任何加重、增多或减少的情况下，被视为背景性病变。如果在特定研究中未记录，病理学叙述应说明其偶尔可见且研究各组间无任何差异。如果在研究中记录，则每次观察到时均应一致地记录和分级。由于该病变与衰老相关，其在28天或90天研究中的出现可能值得记录。如果存在的炎症性病变在某种定性方式上（形态学、分布等）与上述局灶性炎症的描述不同，则可使用上述其他诊断术语之一。然而，由于局灶性炎症是如此常见的病变，且可能与其他类型的炎症同时存在，这些病变必须在叙述中详细描述，以便能与局灶性炎症明确区分。“炎症”一词应用于指白细胞，但当肝脏中存在非白细胞性细胞（如肥大细胞）时，可使用“浸润，细胞性”。所有这些病变应根据肝脏受累范围进行分级。形态学特征如分布模式可在病理学叙述中呈现。任何相关变化，如肝细胞变性、坏死、色素沉着或血管变化，如果这些相关病变的严重程度值得，可作为独立病变诊断。相关链接：肝脏 - 胆管纤维化（cholangiofibrosis）
参考切片图（2 张）
查看英文原文
Comment
Inflammation, focal is the term used to denote single or multiple, focal, randomly distributed aggregates of inflammatory cells that are seen in the liver as a background lesion and are more frequent in aging mice and rats than in young animals. However, these foci of inflammatory cells can occur spontaneously in livers of rodents in prechronic studies ( Figure 1 and Figure 2 ). The infiltrating cells are predominantly lymphocytes but may include fewer numbers of neutrophils and/or macrophages. Inflammatory cell aggregates may be accompanied by evidence of hepatocellular necrosis ( Figure 3 and Figure 4 ). These foci may vary in size ( Figure 6 and Figure 7 ) but typically are not grossly apparent. These lesions may be more common in females (Harada et al. 1996) and may be related to infectious agents (Hall et al. 1992). Most often the cause is unknown. If only one or two foci of inflammation are seen in the standard histologic sections, the severity grade would be 1+ (minimal). Xenobiotic exposure may also increase the severity and/or number of these lesions compared with concurrent controls. Focal inflammation is the most frequently seen inflammatory lesion of the liver in rodent toxicity studies and is a form of chronic inflammation. In chronic inflammation, lymphocytes predominate. Chronic active inflammation predominately involves lymphocytes as well but also includes a significant number of neutrophils. Both lesions may contain macrophages. However, the term “chronic inflammation” or “chronic active inflammation” may be used only if the lesion differs in some qualitative way from the above description of “inflammation, focal.” Other less common forms of inflammation include acute, suppurative, and granulomatous inflammation. In acute inflammation , neutrophils are the predominant infiltrating cell, though fewer macrophages and lymphocytes may also be present, as well as evidence of edema or hyperemia. In suppurative inflammation , neutrophils are also the predominant infiltrating cell type but they are aggregated, and many are degenerate. Cell debris from both the resident cell populations and infiltrating leukocytes may also be present in the exudate, as well as proteinaceous fluid containing fibrin, a few macrophages, occasional lymphocytes or plasma cells, and possibly an infectious agent. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may contain fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Granulomatous inflammation is another form of chronic inflammation whose diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, and/or multinucleated giant cells. The term “cellular infiltrate” has been used to describe the presence of inflammatory cells without other evidence of an inflammatory process (e.g., edema, necrosis or degeneration of cells, or evidence of vascular injury). Such infiltrates of inflammatory cells are generally quite small and may not warrant diagnosis. If significant enough to warrant documentation, accumulations of leukocytes should be diagnosed as “inflammation.” Occasionally, infiltrates of nonleukocytic cells such as mast cells are seen in the liver; these should be diagnosed as “cellular infiltrate.”
Recommendation
Inflammatory lesions that are morphologically consistent with the above description of focal inflammation should be recorded as “inflammation, focal” whether or not they are related to treatment. The severity grades should reflect any treatment-related differences between groups. One or two small focal inflammatory cell aggregates in controls in the absence of any exacerbation, increase, or decrease in treated groups is considered a background lesion. If it is not documented in a specific study, the pathology narrative should indicate that it was occasionally seen without any differences among study groups. If it is documented in a study, it should be consistently recorded and graded whenever seen. Because this lesion is associated with aging, its occurrence in 28- or 90-day studies may warrant documentation. If an inflammatory lesion is present that differs in some qualitative manner (morphology, distribution, etc.) from the above description of focal inflammation, one of the other diagnostic terms described above may be used. However, because focal inflammation is such a common lesion and may be present concurrently with another type of inflammation, these lesions must be thoroughly described in the narrative so that they may be clearly differentiated from focal inflammation. The term “inflammation” should be used in reference to leukocytes, but “infiltration, cellular” may be used when nonleukocytic cells are present in the liver (e.g., mast cells). All of these lesions should be graded based on the extent of liver involvement. Morphologic features such as the distribution pattern can be presented in the pathology narrative. Any associated changes, such as hepatocyte degeneration, necrosis, pigmentation, or vascular changes, may be diagnosed as a separate lesion if warranted by the severity of these associated lesions. Related Links: Liver - Cholangiofibrosis
肝细胞内红细胞Intrahepatocellular Erythrocytes 肝其他
描述（中文）
肝细胞内红细胞（intrahepatocellular erythrocytes）不常见，在老龄小鼠中可作为自发性改变出现。然而，在一些NTP研究中，该改变似乎因受试物处理而加重。在低倍镜下，它可能与血管扩张（angiectasis）相混淆；在高倍镜下，增大的肝细胞被大量红细胞填充并扩张。关于该改变由红细胞吞噬作用（erythrophagocytosis）或伸入运动（emperipolesis）所致的推测尚未经超微结构研究证实。
诊断建议
肝细胞内红细胞只要存在就应记录，病理描述中应包含该改变范围的描述。肝实质中任何相关的退行性或其他改变，若根据这些病变的严重程度有必要，应单独诊断；否则，应在病理描述中提及。
参考切片图（2 张）
查看英文原文
Comment
Intrahepatocellular erythrocytes are uncommon and may be seen as a spontaneous change in aging mice. However, in some NTP studies, this change appears to have been exacerbated by treatment. At low magnification, it may be confused with angiectasis; at higher magnification, enlarged hepatocytes are filled and expanded by numerous erythrocytes. Speculation that this change occurs by erythrophagocytosis or emperipolesis has not been confirmed by ultrastructural studies.
Recommendation
Intrahepatocellular erythrocytes should be documented whenever present, and the pathology narrative should include a description of the extent of the change. Any associated degenerative or other changes in the hepatic parenchyma should be diagnosed separately if warranted by the severity of these lesions; otherwise, they should be mentioned in the pathology narrative.
肝细胞凋亡Hepatocyte Apoptosis 肝凋亡
描述（中文）
必须认识到，肝细胞的单细胞死亡通常以凋亡（apoptosis）方式发生。肝脏中的细胞死亡表现为一系列形态学模式，这些模式可单独出现或组合出现。然而，细胞死亡有两种主要表现形式：坏死（necrosis）和凋亡。凋亡代表一种能量依赖性细胞死亡（程序性细胞死亡）形式，通常表现为单个肝细胞的死亡。与坏死不同，凋亡是一个受调控且受基因控制的过程。单个肝细胞的凋亡可随肝细胞老化并被替换而自发发生，也可在损伤后发生，如暴露于肝毒性外源化学物或循环血液中氧张力过低。通常凋亡不伴有炎症。受累细胞与相邻正常肝细胞相比，胞质浓缩、呈深嗜酸性，并且要么无染色质，要么含有核固缩或核碎裂的物质。受累时，凋亡肝细胞可呈小、圆形，周围有透明晕。该变化在形态学上与凋亡的晚期阶段相符，这些小细胞碎片被称为凋亡小体（apoptotic bodies）（Figure 1、Figure 2，箭头）。较大、呈角状轮廓的深嗜酸性肝细胞（Figure 1、Figure 2，箭头头）代表凋亡的早期阶段，早于上述凋亡典型特征的形成。坏死通常不发生于单个细胞，尽管单细胞坏死在罕见情况下可见。坏死通常发生于成组细胞、区域性区域或带。单细胞坏死和较大面积坏死通常均伴有炎症。在某些情况下，凋亡和坏死可同时发生。
诊断建议
凋亡存在时应予以诊断，并根据凋亡细胞的数量给出严重程度分级。尽管难以与坏死区分，凋亡也可见于某些融合性凝固性坏死区域的外周边缘。在这种情况下，应诊断坏死这一主要变化。如果同一外源化学物在同一研究内于高剂量时发生坏死，而于低剂量时见凋亡，则应对每个剂量组及组内每只动物诊断最丰富的细胞死亡形式，并在病理学叙述中给出拟议的解释。
参考切片图（2 张）
查看英文原文
Comment
It is necessary to recognize that single-cell death of hepatocytes usually occurs by apoptosis. Cell death in the liver manifests as a spectrum of morphological patterns that can occur alone or in combinations. However, cell death has two primary manifestations: necrosis and apoptosis. Apoptosis represents a form of energy-dependent cell death (programmed cell death) that typically occurs as death of individual hepatocytes. In contrast to necrosis, apoptosis is a regulated and genetically controlled process. Apoptosis of individual hepatocytes may occur spontaneously as hepatocytes age and are replaced, or following injury such as exposure to hepatotoxic xenobiotics or low oxygen tension in the circulating blood. Usually no inflammation is associated with apoptosis. Affected cells have condensed, deeply eosinophilic cytoplasm in contrast to adjacent normal hepatocytes and either are devoid of chromatin or contain pyknotic or fragmented nuclear material. When affected, apoptotic hepatocytes may be small, rounded, and surrounded by a clear halo. This change is morphologically compatible with an advance stage of apoptosis, and the small cell fragments are referred to as apoptotic bodies ( Figure 1 and Figure 2 , arrows). Larger, angular profiles of hypereosinophilic hepatocytes ( Figure 1 and Figure 2 , arrowheads) represent early stages of apoptosis prior to development of the classical features of apoptosis described above. Necrosis does not typically occur in individual cells, though single-cell necrosis is seen in rare instances. Necrosis usually occurs in groups of cells, regional areas, or zones. Both single-cell necrosis and larger areas of necrosis are typically accompanied by inflammation. In some cases, apoptosis and necrosis can occur together.
Recommendation
Apoptosis should be diagnosed when present and given a severity grade based on the number of apoptotic cells. Although difficult to distinguish from necrosis, apoptosis can also be found at the peripheral edges of some regions of confluent coagulation necrosis. In this situation the predominant change of necrosis should be diagnosed. If necrosis occurs at high doses of a xenobiotic but apoptosis is seen at low doses with the same xenobiotic and within the same study, then the most abundant form of cell death should be diagnosed for each dose group and animal within a group and a proposed interpretation given in the pathology narrative.
肝细胞核分裂增多Hepatocyte - Increased Mitosis 肝其他
描述（中文）
在早期生长阶段、妊娠等生理状态下，或在对其他部位荷瘤的啮齿类动物中，可见高的核分裂频率。虽然在正常肝脏中可见偶见的核分裂，但每10个高倍视野中发现超过一或两个核分裂对成年啮齿类动物来说并不典型。在本例中，高的核分裂频率（Figure 1，箭头）是肝毒性物质处理后继发于肝细胞丢失的修复反应。
诊断建议
核分裂频率增高并不常见；无论何时出现都应记录，并给予定性严重程度分级。
参考切片图（1 张）
查看英文原文
Comment
A high mitotic frequency can be seen during phases of early growth, during physiologic conditions such as pregnancy, or in rodents bearing tumors at other sites. While occasional mitoses can be seen in a normal liver, finding more than one or two mitoses per 10 high-power fields is not typical for adult rodents. In this example, the high frequency of mitosis ( Figure 1 , arrows) is a repair response following hepatocyte loss secondary to treatment with a hepatotoxicant.
Recommendation
An increased frequency of mitosis is unusual; it should be documented whenever present and given a qualitative severity grade.
肝细胞核增大Hepatocyte Karyomegaly 肝其他
描述（中文）
尽管核增大（karyomegaly）主要是一种细胞核改变，但 Figure 1、Figure 2（箭头）显示肝细胞质和细胞核均增大。该改变遍布肝小叶，但在小叶中央区更为显著。细胞核大小的增加与多倍体化（polyploidy）一致，但在这项亚慢性研究中，其严重程度显著大于在该年龄（约4.5个月）时所预期的程度。尽管在本研究中肝脏重量增加与肝细胞增大相关，但肝细胞增大的不均匀性加上核增大可将此改变与肝细胞酶诱导区分开来。核胞体增大（karyocytomegaly）的自发性发生在衰老啮齿类动物中常见，通常不与肝脏重量增加相关。这种衰老性改变常被称为多倍体化，在小鼠中比在大鼠中更为常见。
诊断建议
虽然一定程度上的核增大在小鼠中经常可见，尤其是作为一种衰老性改变，但 Figure 1、Figure 2 中所示的核增大程度及伴随的肝细胞增大在亚慢性研究中的对照小鼠中通常不会见到。在此情况下，它是一种潜在的处理效应，应当予以诊断并给出严重程度分级。在慢性研究中通常不予记录，除非与同期对照相比存在明显的处理相关增加或减少。如果细胞质增大而细胞核不增大，则应使用术语“肥大（hypertrophy）”。
参考切片图（2 张）
查看英文原文
Comment
Though karyomegaly is predominantly a nuclear change, Figure 1 and Figure 2 (arrow) show enlargement of both hepatocyte cytoplasm and nuclei. The change is throughout the hepatic lobule but is more prominent in the centrilobular areas. The increase in nuclear size is consistent with polyploidy, but in this subchronic study, the severity is significantly greater than one would expect at this age (~4.5 months). Although a liver weight increase was associated with enlarged hepatocytes in this study, the nonuniform hepatocyte enlargement plus the karyomegaly distinguish this change from hepatocyte enzyme induction. Spontaneous occurrence of karyocytomegaly is commonly seen in aging rodents and is not typically associated with increased liver weight. This aging change, often referred to as polyploidy, is more common in mice than in rats.
Recommendation
While some degree of nuclear enlargement is frequently seen in mice, particularly as an aging change, the degree of nuclear enlargement and the accompanying enlargement of hepatocytes shown in Figure 1 and Figure 2 are not typically seen in control mice in prechronic studies. In this case it is a potential treatment effect and should be diagnosed and given a severity grade. It is typically not documented in chronic studies unless there is an obvious treatment-associated increase or decrease compared with concurrent controls. If the cytoplasm is enlarged but the nuclei are not, then the term “hypertrophy” should be used.
肝细胞糖原蓄积与耗竭Hepatocyte Glycogen Accumulationand Depletion 肝其他
描述（中文）
由于啮齿类动物通常在夜间进食，肝细胞内糖原蓄积的程度一般在清晨时段最高，并在整个白天逐渐减少。该变化通常累及每个肝小叶内的所有肝细胞（Figure 1、Figure 3）。它最初在小叶中央区肝细胞中消失（Figure 2），并在白天逐渐进展至汇管区周围肝细胞。因此，动物间的比较应考虑剖检时间。Figure 4来自一只在清晨剖检的受试小鼠（与Figure 3来自同一研究）。其肝细胞内糖原明显耗竭。也可能出现超出Figure 1、Figure 3所示程度的糖原过度蓄积。肝细胞内糖原的形态学表现具有特征性，使糖原蓄积或耗竭在多数情况下易于诊断。然而，要获得糖原沉积的明确证据，需要适当的固定和确证性特殊染色。在某些情况下，尤其是当糖原量的差异伴随其他胞质改变时，糖原蓄积或耗竭可能不易辨别。
诊断建议
在研究内不存在任何与处理相关的变化时，Figure 1、Figure 2、Figure 3所示的糖原程度被视为背景性（自发性）变化，不应作出诊断。相反，若与对照动物相比，受试动物肝细胞内糖原出现与处理相关的增加，则应在受试动物中诊断糖原蓄积并赋予严重程度分级。同样，若存在与处理相关的糖原耗竭（如Figure 4相较于Figure 3），则应在受试动物中诊断糖原耗竭并给予严重程度分级。在毒性研究的背景下，部分受试动物可能食欲下降，与同期对照相比肝脏糖原量减少。因此，对糖原耗竭的判读应考虑采食量和动物总体健康状况。肝细胞糖原量的变化常伴随其他胞质改变，如脂肪变性或胞质空泡化，且糖原含量的改变可能难以与伴随的改变相区分。在这些情况下，诊断为肝细胞胞质空泡化并附严重程度分级是恰当的，但应在病理学描述中详尽描述肝细胞胞质改变的形态学。病理学描述还应包括病理学家关于胞质空泡内容的意见。
参考切片图（2 张）
查看英文原文
Comment
Because rodents typically feed at night, the degree of glycogen accumulation within hepatocytes is typically highest in the early morning hours and wanes throughout the day. It also typically involves all hepatocytes in each lobule ( Figure 1 and Figure 3 ). It initially disappears in the centrilobular hepatocytes ( Figure 2 ), with progression to the periportal hepatocytes during the day. Consequently, comparisons among animals should take the time of necropsy into consideration. Figure 4 is from a treated mouse (from the same study as Figure 3 ) that was necropsied in the early morning. There is a notable depletion of glycogen within hepatocytes. Excess glycogen accumulation beyond that present in Figure 1 and Figure 3 may also occur. The morphologic appearance of glycogen in hepatocytes is distinctive, allowing glycogen accumulation or depletion to be readily diagnosed in most cases. However, appropriate fixation and definitive special staining are necessary for unequivocal evidence of glycogen deposition. In some cases, particularly when differences in the amount of glycogen are accompanied by other cytoplasmic changes, glycogen accumulation or depletion may not be easily discerned.
Recommendation
In the absence of any treatment-related changes within a study, the degrees of glycogen demonstrated in Figure 1 , Figure 2 , and Figure 3 are considered background (spontaneous) changes and should not be diagnosed. If, in contrast to the control animals, there is a treatment-related increase in glycogen in the hepatocytes, glycogen accumulation should be diagnosed in the treated animals and assigned a severity grade. Likewise, if there is a treatment-related glycogen depletion (as in Figure 4 vs. Figure Figure 3 ), glycogen depletion should be diagnosed in the treated animals and given a severity grade. In the context of a toxicity study, some treated animals may have a depressed appetite and will have decreased amounts of glycogen in the liver, in contrast to the concurrent controls. Consequently, interpretation of glycogen depletion should take food consumption and general animal health into consideration. Changes in the amount of hepatocellular glycogen are frequently accompanied by other cytoplasmic alterations, such as fatty change or cytoplasmic vacuolization, and alterations in glycogen content can be difficult to distinguish from the accompanying changes. In those situations, a diagnosis of hepatocyte cytoplasmic vacuolization is appropriate, along with a severity grade, but the morphology of the cytoplasmic changes in the hepatocytes should be thoroughly described in the pathology narrative. The pathology narrative should also include the pathologist’s opinions regarding the contents of the cytoplasmic vacuoles.
肝细胞结节性增生Hepatocyte - Hyperplasia Nodular 肝增生
描述（中文）
结节性增生（nodular hyperplasia）可作为慢性肝毒性的后遗症出现，也可发生于其他方面正常的肝脏。它也可能继发于大颗粒细胞淋巴瘤（单核细胞白血病）。它通常由多个肝细胞增生结节组成，结节之间被卵圆细胞带、胶原沉积和塌陷的肝小叶分隔（Figure 1、Figure 2）。还可能存在数量不等的单核白细胞。结节性增生导致肝脏大体变形，并保留明显扭曲的肝小叶结构。存在当前或既往肝毒性的证据提示再生性发病机制。
诊断建议
无论何时出现，这种慢性、增生性肝脏反应均应作出诊断并给出严重程度分级，严重程度取决于肝脏受累范围。相关病变，如炎症、纤维化或肝细胞坏死，若其严重程度足以支持，应单独作出诊断。其关联可在病理学描述中说明。当前或既往肝毒性应在病理学描述中予以评述。
参考切片图（2 张）
查看英文原文
Comment
Nodular hyperplasia can occur as a sequela to chronic hepatotoxicity or may arise in an otherwise normal liver. It may also be secondary to large granular cell lymphoma (mononuclear cell leukemia). It usually consists of multiple nodules of hepatocellular hyperplasia separated by bands of oval cells, collagen deposition, and collapsed hepatic lobules ( Figure 1 and Figure 2 ). Varying numbers of mononuclear leukocytes may also be present. Nodular hyperplasia results in gross distortion of the liver with retention of a markedly distorted hepatic lobular structure. Evidence of current or history of antecedent hepatotoxicity indicates a regenerative pathogenesis.
Recommendation
Whenever present, this chronic, proliferative, hepatic response should be diagnosed and given a severity grade, with severity dependent on the extent of liver involvement. Associated lesions, such as inflammation, fibrosis, or hepatocellular necrosis, should be diagnosed separately if warranted by the severity of these lesions. Their association can be made clear in the pathology narrative. Current or antecedent hepatotoxicity should be commented on in the pathology narrative.
肝细胞肥大Hepatocyte Hypertrophy 肝肥大
描述（中文）
肝细胞肥大（hepatocyte hypertrophy）是一种细胞学改变，其诊断依据是与同期对照肝脏相比，肝细胞体积出现可观察到的增大。当肝细胞肥大呈现常见的中央小叶（centrilobular）分布模式时，最为显而易见；当其为全小叶性（panlobular）时，与同期对照的比较可提供诊断性确认。当病变为轻度时，肝细胞肥大的检出可能较为困难，但在低倍放大下其识别会更为容易。肝细胞肥大通常与继发于某些外源性化学物（xenobiotics）暴露的微粒体酶诱导相关（Figure 1、Figure 2、Figure 3）。其最常累及中央小叶肝细胞，具体取决于外源性化学物及给药剂量，尽管肥大可扩展至肝小叶中部或变为全小叶性。也可能以门管区周围（periportal）肝细胞受累为主，但必须注意不要将门管区周围肥大与导致中央小叶肝细胞皱缩的过程（例如糖原耗竭）相混淆。Figure 4 为同一研究中正常的对照肝脏，用于与 Figure 3 进行比较。取决于所涉及的具体外源性化学物，肥大肝细胞的胞质可呈苍白、毛玻璃样外观，或呈颗粒状且嗜酸性增强，尤其是在过氧化物酶体增殖剂（peroxisome proliferators）暴露后（Figure 5）。Figure 6 为同期对照肝脏，用于与 Figure 5 进行比较。长期暴露于某些非遗传毒性肝脏毒物时，可见伴有核增大（karyomegaly）和多核肝细胞的显著肥大。Figure 7 中可见一狭窄的中央小叶区肝细胞肥大（Figure 8 为更高倍放大）。增大肝细胞中细颗粒状嗜酸性胞质与过氧化物酶体增殖时所见的相似，但在本例中，导致肝细胞肥大的细胞学改变被认为是透明变性（hyaline change）。在极端形式下，透明变性可形成明确的胞质内包涵体，有时称为Mallory小体（Mallory bodies）。Figure 9 为 Figure 5 中央静脉区的高倍放大，显示肝细胞凋亡（箭头）和胆色素潴留（箭）。由于增大的肝细胞压迫肝窦导致血流减少，可发生肝细胞变性和细胞死亡。
诊断建议
肝细胞肥大只要存在即应诊断并分级。轻微病例可能难以诊断，在许多情况下，需要与同期对照进行比较以确认诊断。如果怀疑肥大但不明确，则适宜对切片进行盲法评估，将相关剂量组与对照进行比较。当改变处于临界状态时，伴随的肝脏重量增加可为诊断提供一定的支持。在可能的情况下，肝细胞肥大的诊断应附以分布模式限定，并给予定性严重程度分级。如果肝细胞增大是由于胞质空泡或包涵体的存在所致，则不应诊断肝细胞肥大；而应记录胞质空泡化或胞质内包涵体，除非有其他确凿的肥大证据。
参考切片图（2 张）
查看英文原文
Comment
Hepatocyte hypertrophy is a form of cytologic alteration that is diagnosed based on an observable increased size of hepatocytes compared with concurrent control liver. It is most readily apparent when it has the commonly occurring centrilobular distribution pattern; when it is panlobular, comparison with concurrent controls can provide diagnostic confirmation. When mild, detection of hepatocyte hypertrophy may be difficult, but its identification is facilitated at low magnification. Hepatocyte hypertrophy is commonly associated with microsomal enzyme induction secondary to exposure to certain xenobiotics ( Figure 1 , Figure 2 , and Figure 3 ). It most frequently affects centrilobular hepatocytes, depending upon the xenobiotic and the dose administered, although the hypertrophy can extend into the middle of the hepatic lobule or become panlobular. It is also possible for periportal hepatocytes to be primarily affected, though care must be taken not to confuse periportal hypertrophy with processes that result in shrinkage of centrilobular hepatocytes (e.g., glycogen depletion). Figure 4 is a normal control liver from the same study for comparison with Figure 3 . Depending upon the specific xenobiotic responsible, hypertrophic hepatocyte cytoplasm may have a pale, ground glass appearance or be granular and intensely eosinophilic, especially following exposure to peroxisome proliferators ( Figure 5 ). Figure 6 is a concurrent control liver for comparison with Figure 5 . Marked hypertrophy with associated karyomegaly and multinucleated hepatocytes may be seen with chronic exposure to some nongenotoxic hepatic toxicants. A narrow centrilobular zone of hepatocyte hypertrophy is present in Figure 7 (higher magnification in Figure 8 ). The finely granular eosinophilic cytoplasm in the enlarged hepatocytes is similar to that seen with peroxisome proliferation, but in this case the cytologic alteration responsible for the hepatocyte hypertrophy was considered hyaline change. In extreme forms, hyaline change can form distinct cytoplasmic inclusions, sometimes referred to as Mallory bodies. Figure 9 is a high magnification of the central vein area of Figure 5 and shows apoptosis of hepatocytes (arrowhead) and retention of bile pigment (arrows). Hepatocyte degeneration and cell death can occur because of reduced blood flow secondary to sinusoidal compression by enlarged hepatocytes.
Recommendation
Hepatocyte hypertrophy should be diagnosed and graded whenever present. Subtle cases may be difficult to diagnose, and in many instances, comparison with concurrent controls is necessary to confirm the diagnosis. If hypertrophy is suspected but not clear-cut, then a blind evaluation of the slides comparing the relevant dose groups with controls is appropriate. Accompanying increases in liver weight may provide some comfort in diagnosis when the change is marginal. When possible, the diagnosis of hepatocyte hypertrophy should be qualified with a distribution pattern and given a qualitative severity grade. If the hepatocytes are enlarged due to the presence of cytoplasmic vacuoles or inclusions, hypertrophy should not be diagnosed; rather, the cytoplasmic vacuolization or cytoplasmic inclusions should be recorded, unless there is other, definitive evidence of hypertrophy.
肝细胞胞质内包涵体Hepatocyte Cytoplasmic Inclusions 肝其他
描述（中文）
在对照组以及处理过的啮齿类动物中均可发现嗜酸性或胞质内包涵体或物质（Figure 2，箭头）。这些玻璃样变包涵体也可见于肝细胞肿瘤。Figure 1、Figure 2 中的示例代表一种死后随时间推移而形成的伪影，尤其常见于剖检时未完全放血的雄性大鼠。胞质内空泡含有已进入受累肝细胞胞质（血浆内流）的血浆（Li et al. 2003）。对照组和处理过的啮齿类动物中可见类似但更为离散的嗜酸性玻璃样变包涵体，其可能代表溶酶体中存在的蛋白质，这些包涵体也可见于肝细胞肿瘤。
诊断建议
玻璃样胞质内包涵体相对少见，因此应当予以记录，并根据受累肝细胞的频率给出严重程度分级。如果有理由认为它们是剖检时放血不完全相关的随时间推移而形成的伪影，则应在病理学描述中加以讨论。当胞质内包涵体存在于肿瘤性肝细胞中时，无需记录。
参考切片图（2 张）
查看英文原文
Comment
Eosinophilic or cytoplasmic inclusions or material ( Figure 2 , arrows) can be found in control as well as treated rodents. These hyalinized inclusions are also seen in hepatocellular neoplasms. The examples in Figure 1 and Figure 2 represent a postmortem, time-dependent artifact especially common in male rats that are not completely exsanguinated at necropsy. The cytoplasmic vacuoles contain plasma that has entered the hepatocyte cytoplasm (plasma influx) of affected hepatocytes (Li et al. 2003). Similar but more discrete eosinophilic hyalinized inclusions, which may represent protein present in lysosomes, can be seen in control and treated rodents and are also seen in hepatocellular neoplasms.
Recommendation
Hyaline intracytoplasmic inclusions are relatively uncommon and thus should be documented and given a severity grade that is based on the frequency of affected hepatocytes. If there is reason to believe that they are a time-dependent artifact associated with incomplete exsanguination at necropsy, this should be discussed in the pathology narrative. Cytoplasmic inclusions need not be documented when present in neoplastic hepatocytes.
肝膈结节Hepatodiaphragmatic Nodule 肝其他
描述（中文）
肝中叶一部分突入膈肌是各年龄段大鼠的先天性病变，小鼠中偶见。该异常同时累及肝脏和膈肌。肝脏突出部分并不穿透膈肌，而是被膈肌薄层纤维腱膜覆盖。这些结节通常边界不清，具有正常的肝脏结构（Figure 1）。结节内肝细胞核可能含有线性染色质排列，类似于Anitschkow肌细胞中所见的核轮廓（Figure 2、Figure 3）。
诊断建议
尽管这是一种偶发且不受处理影响的背景病变，但它是先天性病变，只要存在就应诊断。这些病变不应进行分级。
参考切片图（2 张）
查看英文原文
Comment
Protrusion of a portion of the median lobe into the diaphragm represents a congenital lesion in rats of any age and is occasionally seen in mice. This anomaly involves both the liver and the diaphragm. The protrusion of the liver does not penetrate the diaphragm but is covered by the thin fibrous tendon of the diaphragm. These nodules typically are not well demarcated and have normal hepatic architecture ( Figure 1 ). Hepatocyte nuclei within the nodule may contain linear chromatin arrangements resembling nuclear profiles seen in Anitschkow myocytes ( Figure 2 and Figure 3 ).
Recommendation
Although this is a background lesion that occurs sporadically and is not affected by treatment, it is a congenital lesion and should be diagnosed whenever present. These lesions should not be graded.
胆管囊肿Bile Duct Cyst 肝囊肿
描述（中文）
单房和多房性胆管囊肿（biliary cysts）可在老年大鼠和小鼠中自发发生。它们可作为单个扩张的胆管结构、多个相邻的扩张胆管结构（Figure 1、Figure 2）或多房性囊肿（Figure 3）出现。胆管囊肿可伴随肝毒性，并可能与外周或基底部的胶原沉积有关（Figure 4）。它们通常由单层扁平或低立方上皮衬覆，几乎没有活跃增殖的证据。与胆管瘤（cholangiomas）不同，它们不压迫相邻的肝实质。
诊断建议
小的胆管囊肿偶尔可见于未处理的对照大鼠，但更常与处理相关。因此，只要存在就应记录并给予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Single and multiloculated biliary cysts can occur spontaneously in older rats and mice. They can occur as single dilated biliary structures, multiple adjacent dilated biliary structures ( Figure 1 and Figure 2 ), or a multiloculated cyst ( Figure 3 ). Biliary cysts may accompany hepatic toxicity and may be associated with peripheral or sub-basilar collagen deposition ( Figure 4 ). They are typically lined by a single layer of flattened or low cuboidal epithelium ( Figure 4 ), with little evidence of active proliferation. In contrast to cholangiomas, they do not compress the adjacent hepatic parenchyma.
Recommendation
Small biliary cysts may occasionally be seen in untreated rats but are more often associated with treatment. Consequently, they should be documented whenever present and given a severity grade.
胆管增生Bile Duct Hyperplasia 肝增生
描述（中文）
胆管增生（bile duct hyperplasia）在亚慢性研究（prechronic studies）中不常见，但属于常见的衰老性病变。在慢性研究中，若各研究组之间在发生率或严重程度上均无差异而偶见胆管增生，则很可能代表背景性病变。该病变在大鼠中比在小鼠中更常见。可能仅累及部分汇管区。胆管增生可伴有胆管周围纤维化（peribiliary fibrosis）。当伴有炎症细胞和/或卵圆细胞增生时，胆管增生可能是毒性损伤的结果。Figure 1、Figure 2 显示单个局灶性增生区域；在该大鼠受检的其他肝脏切片中未见类似病变。此种程度的胆管增生在90天研究的对照大鼠中不常见。
诊断建议
当胆管增生作为与受试物相关的改变而出现时，或当其程度过度时（如本示例所示），应当予以诊断并赋予严重程度分级。由于胆管增生是常见的年龄相关改变，是否予以诊断的决定将取决于动物的年龄。相关病变，如炎症、纤维化或胆管扩张，若其严重程度足以支持，应当单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Bile duct hyperplasia is not commonly seen in prechronic studies but is a common aging lesion. In chronic studies, the occasional occurrence of bile duct hyperplasia in the absence of any differences in incidence or severity among study groups likely represents a background lesion. It is more commonly seen in rats than in mice. Only some portal areas may be affected. Biliary hyperplasia may be associated with peribiliary fibrosis. When accompanied by inflammatory cells and/or oval cell proliferation, bile duct hyperplasia may be the consequence of a toxic insult. Figure 1 and Figure 2 show a single focal area of hyperplasia; similar lesions were not present in the other liver sections examined from this rat. This degree of bile duct hyperplasia is not commonly present in control rats in 90-day studies.
Recommendation
Bile duct hyperplasia should be diagnosed and assigned a severity grade whenever present as a treatment-associated change or when excessive, as in this example. Since bile duct hyperplasia is a common age-related change, the decision to diagnose it will depend upon the age of the animal. Associated lesions, such as inflammation, fibrosis, or bile duct dilation, should be diagnosed separately if warranted by the severity of these lesions
胆管纤维化Cholangiofibrosis 肝纤维化
描述（中文）
这种慢性炎症过程最初伴有卵圆细胞增生和胆管增生，增生的胆管扩张。胆管内容物包括黏液、坏死碎片和脱落的上皮细胞（Figure 3）。胆道结构常由深染的立方至柱状细胞和杯状细胞（肠上皮化生）不完全衬覆（新月形胆管；Figure 1，箭头）。随着病变进展，出现胆管周围纤维化和混合性炎症细胞浸润（Figure 1、Figure 2）。肝叶的大面积区域可能受累，病变通过硬化性结缔组织的形成而逐渐消退，同时保留部分胆道腺泡和残留的黏液池。胆管纤维化可能类似胆管癌，但可通过后者更为显著的胆管上皮改变（例如上皮细胞多层或堆积以及多形性）加以区分。然而，上皮细胞异型性和核分裂象增多可见于这两种病变，因此无助于区分胆管纤维化与胆管癌。一些文献指出，明显的胆管扩张和胆管上皮的肠上皮化生并非胆管癌的显著特征。
诊断建议
这种肝脏炎症反应应予以记录并给出严重程度分级，严重程度取决于肝脏受累范围。上述所有特征均包括在胆管纤维化的诊断中，不应单独诊断，除非它们明确代表独立的病变过程。相关链接：肝脏 - 炎症
参考切片图（2 张）
查看英文原文
Comment
This chronic inflammatory process is initially associated with oval cell proliferation and bile duct hyperplasia with dilation of proliferating bile ducts. Bile duct contents include mucus, necrotic debris, and desquamated epithelial cells ( Figure 3 ). Biliary structures are frequently incompletely lined (crescent-shaped bile ducts; Figure 1 , arrows) by hyperchromatic cuboidal to columnar cells and goblet cells (intestinal metaplasia). As the lesion progresses, there is peribiliary fibrosis and a mixed inflammatory cell infiltrate ( Figure 1 and Figure 2 ). Large areas of hepatic lobe may be affected, with progressive resolution of lesions by development of sclerotic connective tissue, with retention of some biliary glandular acini and residual pools of mucus. Cholangiofibrosis may resemble cholangiocarcinoma but may be differentiated by the latter’s more prominent biliary epithelial changes (e.g., multiple layers or piling up of epithelial cells and pleomorphism). Epithelial cell atypia and increased mitotic figures may be present in either lesion, however, and therefore are not useful in differentiating cholangiofibrosis from cholangiocarcinoma. Some references indicate that significant bile duct dilation and intestinal metaplasia of the biliary epithelium are not prominent features of cholangiocarcinoma.
Recommendation
This inflammatory hepatic response should be documented and given a severity grade, with severity dependent on the extent of liver involvement. All the features described above are included in the diagnosis of cholangiofibrosis and should not be diagnosed separately unless they clearly represent separate processes. Related Links: Liver - Inflammation
脂肪变性Fatty Change 肝其他
描述（中文）
脂肪变（fatty change）可为局灶性（focal）（Figure 1，箭头；Figure 2）或弥漫性（diffuse）（Figure 3、Figure 4、Figure 5、Figure 6），并可为大泡性（macrovesicular）（Figure 3、Figure 4）或小泡性（microvesicular）（Figure 5、Figure 6）。大泡性脂肪变常与代谢紊乱相关，且通常易于逆转，而小泡性脂肪变更可能是毒性的反映，可能涉及线粒体功能障碍。Figure 1、Figure 2代表局灶性病变，其中空泡化肝细胞的形态学特征同时符合大泡性和小泡性脂肪变。局灶性脂肪变可为自发性病变，且在某些品系中可能比其他品系更常见，而弥漫性或带状（如小叶中心性或门管区周围性）脂肪变更可能与受试物相关。Figure 3、Figure 4中的细胞质空泡化为弥漫性，由肝细胞内大小不一的单个或双个细胞质空泡组成。其形态学特征符合大泡性脂肪变，伴有受累肝细胞核受压缩并被推移至周边。相比之下，Figure 5、Figure 6代表小泡性脂肪变，在门管区周围和小叶中部区域反应更为显著。细胞质改变由充满细胞质的多个小空泡组成，无明显肝细胞核压缩或移位。肝窦可被肥大的肝细胞压迫而塌陷。Figure 7、Figure 8代表大泡性脂肪变与肝细胞内糖原蓄积的混合。可见糖原与大泡性及小泡性脂肪变的混合形式。磷脂沉积症（phospholipidosis）是肝细胞细胞质空泡化的另一种形式，与暴露于阳离子两亲性外源化学物相关，需特殊染色和/或电子显微镜检查才能确诊。
诊断建议
脂肪变的形态学表现具有足够的特征性，无需确认性特殊染色或其他程序即可作出诊断。只要存在，就应记录肝细胞脂肪变的诊断。由于未处理或溶媒对照动物中可能发生一定程度的脂肪变，推荐进行严重程度分级以记录潜在的受试物相关效应。由于局灶性（focal）脂肪变可能为自发性，当病变为局灶性时，诊断中应包含分布修饰词“局灶性”。当病变为弥漫性（diffuse）时，不应使用分布修饰词（即，当诊断中未指定分布时，假定病变为弥漫性）。脂肪变的形态学特征（如大泡性、小泡性或两者兼有）应在病理学描述中予以描述。其他特征性表现，如分布模式，也应在病理学描述中予以描述。脂肪变常伴有其他细胞质改变，如糖原蓄积或耗竭，且细胞质形态学上不同类型的改变可能难以区分。在这些情况下，适合作出肝细胞细胞质空泡化的诊断并附严重程度分级，但应在病理学描述中详尽描述肝细胞细胞质改变的形态学。病理学描述还应包括病理学家关于细胞质空泡内容的意见。相关链接：肝脏——张力性脂质沉积症（Liver - Tension Lipidosis）
参考切片图（2 张）
查看英文原文
Comment
Fatty change can be focal ( Figure 1 , arrow; Figure 2 ) or diffuse ( Figure 3 , Figure 4 , Figure 5 , and Figure 6 ) and macrovesicular ( Figure 3 and Figure 4 ) or microvesicular ( Figure 5 and Figure 6 ). Macrovesicular fatty change is often associated with metabolic disturbances and is generally readily reversible, whereas microvesicular fatty change is more likely a reflection of toxicity, possibly involving mitochondrial disturbances. Figures Figure 1 and Figure 2 represent a focal lesion in which the morphologic features of the vacuolated hepatocytes are consistent with both macrovesicular and microvesicular fatty change. Focal fatty change can be a spontaneous lesion and may be more common in some strains than others, whereas diffuse or zonal (e.g., centrilobular or periportal) fatty change is more likely to be treatment related. The cytoplasmic vacuolization in Figures Figure 3 and Figure 4 is diffuse and consists of both large and small single or double cytoplasmic vacuoles within hepatocytes. The morphologic features are consistent with macrovesicular fatty change, with compression and displacement of the nuclei to the periphery of affected hepatocytes. In contrast, Figure 5 and Figure 6 are representative of microvesicular fatty change, with a more prominent response in periportal and midlobular areas. The cytoplasmic change consists of multiple small vacuoles filling the cytoplasm without prominent compression or displacement of hepatocyte nuclei. Sinusoids may be collapsed by the hypertrophic hepatocytes. Figure 7 and Figure 8 represent a mixture of both macrovesicular fatty change and glycogen accumulation in hepatocytes. Mixtures of glycogen and both macrovesicular and microvesicular fatty change may be seen. Phospholipidosis is another form of hepatocyte cytoplasmic vacuolization that is associated with exposure to cationic amphophilic xenobiotics and requires special staining and/or electron microscopy for definitive confirmation.
Recommendation
The morphologic appearance of fatty change is distinctive enough to allow its diagnosis in the absence of confirmatory special stains or other procedures. Whenever present, diagnosis of hepatocellular fatty change should be recorded. Since some degree of fatty change may occur in untreated or vehicle controls, severity grading is recommended to document potential treatment-related effects. Because focal fatty change may be spontaneous, the distribution modifier “focal” should be included in the diagnosis when the lesion is focal. When the lesion is diffuse, no distribution modifier should be used (i.e., the lesion is assumed to be diffuse when the distribution is not specified in the diagnosis). The morphologic features of the fatty change (e.g., macrovesicular, microvesicular, or both) should be described in the pathology narrative. Other distinctive features, such as the pattern of distribution, should also be described in the pathology narrative. Fatty change is frequently accompanied by other cytoplasmic alterations, such as glycogen accumulation or depletion, and it can be difficult to distinguish the different types of alterations in cytoplasmic morphology. In those situations, a diagnosis of hepatocyte cytoplasmic vacuolization is appropriate, along with a severity grade, but the morphology of the cytoplasmic changes in the hepatocytes should be thoroughly described in the pathology narrative. The pathology narrative should also include the pathologist’s opinions regarding the contents of the cytoplasmic vacuoles. Related Links: Liver - Tension Lipidosis
色素Pigment 肝色素沉着
描述（中文）
内源性和外源性色素均可出现于肝细胞，但色素沉着更常发生于Kupffer细胞。色素在门管区可能较为显著。肝脏色素的鉴定通常需要多种特殊染色。不同色素常含有一定量的铁，因此用Prussian blue染色会呈现不同程度的阳性。Figure 1中，色素沉积于聚集的Kupffer细胞簇中，其严重程度分级为3+（中度（moderate））。Figure 2、Figure 3显示Kupffer细胞及肝细胞中均有色素沉积的证据。色素沉积主要位于小叶中央，严重程度分级为3+（中度）。Figure 4中，色素沉积主要位于肝细胞内，呈全小叶性分布。
诊断建议
即使使用一系列特殊染色，在组织学切片中确定性鉴定色素往往仍很困难。因此，诊断为“色素”最为恰当。病理学描述应说明色素沉着的形态学特征、小叶分布、受累细胞类型以及与色素沉积可能相关的任何伴随组织学改变。病理学家也可在病理学描述中对存在的色素类型作出推测。应根据色素存在的相对数量进行严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Both endogenous and exogenous pigment can occur in hepatocytes, but pigmentation occurs more often in Kupffer cells. Pigment may be prominent in portal areas. Identification of hepatic pigment typically requires multiple special stains. Different pigments frequently contain some iron and will thus have variable positivity with Prussian blue stain. In Figure 1 , pigment is deposited in clusters of aggregated Kupffer cells, which was given a severity grade of 3+ (moderate). Figure 2 and Figure 3 show evidence of pigment deposition in Kupffer cells as well as in hepatocytes. The pigment deposition is primarily centrilobular and was given a severity grade of 3+ (moderate). In Figure 4 , the pigment deposition is primarily within hepatocytes and has a panlobular distribution.
Recommendation
Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, a diagnosis of “pigment” is most appropriate. The pathology narrative should describe the morphologic features of the pigmentation, the lobular distribution, the cell type affected, and any accompanying histologic changes that might be associated with the pigment deposition. The pathologist may also speculate in the pathology narrative as to the type of pigment present. A severity grade should be assigned based on the relative amounts of pigment present.
萎缩Atrophy 肝萎缩
描述（中文）
严重热量缺乏以及动物暴露于高剂量外源性化学物质时可出现肝萎缩（hepatic atrophy）。肝细胞及其细胞核体积缩小，细胞核显得排列更为紧密。通常没有糖原蓄积的证据，Kupffer细胞和肝细胞中可能存在代表细胞分解的色素沉着（最可能是脂褐素）（Figure 2）。Figure 3、Figure 4代表正常肝脏。
诊断建议
除像本例这样显著的例子外，肝萎缩的诊断是一项困难的形态学判断，可能最好通过器官重量来评估。肝萎缩的分级同样困难。如果确有必要准确记录细微的萎缩性改变，推荐对切片进行盲法评估，将相关剂量组与对照组进行比较。
参考切片图（2 张）
查看英文原文
Comment
Hepatic atrophy is seen with severe caloric deficits as well as when animals are exposed to high doses of xenobiotics. The size of the hepatocytes and their nuclei is reduced, with nuclei appearing more closely spaced. There is typically no evidence of glycogen accumulation, and pigmentation (most likely lipofuscin) representative of cellular breakdown may be present in Kupffer cells and hepatocytes ( Figure 2 ). Figure 3 and Figure 4 represent a normal liver.
Recommendation
Except in dramatic examples, as in this case, diagnosis of hepatic atrophy is a difficult morphologic determination and may be better assessed by organ weight. Grading of hepatic atrophy is likewise difficult. If it becomes necessary to accurately document subtle atrophic changes, a blind evaluation of the slides comparing the relevant dose groups with controls is recommended.
血管扩张Angiectasis 肝扩张
描述（中文）
局灶性（focal） 和 多灶性（multifocal） 血管扩张（angiectasis）（Figure 1、Figure 2）可自发发生，且随动物年龄增长而更频繁出现，但也可由亚硝胺（nitrosamines）等化学物质引起。其由扩张的血窦腔隙构成，内衬外观正常的内皮细胞（endothelial cell）（Figure 3）。在较大的扩张腔隙中，内皮细胞可增生以衬覆扩张的腔隙。邻近血管扩张腔隙的肝细胞可正常或轻度萎缩。血管扩张与囊性变性（cystic degeneration）的鉴别在于内皮衬覆的通道内存在红细胞。显著（marked） 的血管扩张病例与血管瘤（hemangioma）之间的区分常不明确。
诊断建议
血管扩张只要作为独立事件存在，就应记录并分级，但若与另一病变（如灶性病变或肿瘤）相关，则不应诊断。扩张腔隙的数量及其扩张程度将影响分级。任何提示治疗诱导的血管扩张的迹象均应记录、分级，并在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Focal and multifocal angiectasis ( Figure 1 and Figure 2 ) occurs spontaneously, and more frequently as animals age, but it can also be caused by chemicals such as nitrosamines. It consists of dilated sinusoidal spaces that are lined by normal-appearing endothelial cells ( Figure 3 ). In larger dilated spaces, endothelial cells may multiply to line the dilated spaces. Hepatocytes adjacent to angiectatic spaces may be normal or slightly atrophic. Angiectasis is distinguished from cystic degeneration by the presence of erythrocytes in endothelial-lined channels. The distinction between marked cases of angiectasis and hemangioma is often unclear.
Recommendation
Angiectasis should be documented and graded whenever present as an independent event but should not be diagnosed if it is associated with another lesion, such as a focus or a neoplasm. The number of dilated spaces and their degree of dilation will influence grading. Any indication of treatment-induced angiectasis should be recorded, graded, and described in the pathology narrative.
髓外造血Extramedullary Hematopoiesis 肝其他
描述（中文）
髓外造血（extramedullary hematopoiesis）在成年啮齿类动物中属于非预期病变，通常与病理状态相关。其与炎性细胞浸润的鉴别在于：存在有核红细胞、未成熟粒细胞和/或未分化祖细胞，且不伴有肝细胞坏死。Figure 1、Figure 2 中可见成簇的红系细胞（箭头）。该病变最常见于经毒物处理的动物，并可能与肝细胞变性、色素沉积和/或脂肪变性相关（Figure 2）。Figure 2 中可见一个巨核细胞（箭头）。Figure 3、Figure 4 中多处血管周围细胞聚集主要由发育中的粒细胞构成。
诊断建议
无论何时出现，髓外造血均应予以诊断并分级。检查骨髓、淋巴结和脾脏切片可能显示其与肝脏髓外造血的相关性。若能识别，所涉及细胞的类型（如红系、粒系、混合型）应在病理学描述中注明。相关链接：肾上腺——髓外造血；脾脏——髓外造血
参考切片图（2 张）
查看英文原文
Comment
Extramedullary hematopoiesis is unexpected in adult rodents and is typically associated with pathologic conditions. It is distinguished from inflammatory cell infiltrates by the presence of nucleated erythrocytes, immature granulocytes, and/or undifferentiated progenitor cells in the absence of associated hepatocellular necrosis. Clusters of erythroid cells are present in Figure 1 and Figure 2 (arrows). It is most often seen in animals treated with a toxicant and may be associated with hepatocellular degeneration, pigment deposition, and/or fatty change ( Figure 2 ). A megakaryocyte is present in Figure 2 (arrowhead). Multiple perivascular cellular accumulations in Figure 3 and Figure 4 consist predominantly of developing granulocytes.
Recommendation
Whenever present, extramedullary hematopoiesis should be diagnosed and graded. Examination of bone marrow, lymph node, and spleen sections may show a correlation with extramedullary hematopoiesis in the liver. The types of cells involved (e.g., erythroid, granulocytic, mixed) should be indicated in the pathology narrative if they can be identified. Related Links: Adrenal Gland - Extramedullary Hematopoiesis Spleen - Extramedullary Hematopoiesis
上皮增生Epithelium Hyperplasia 胆囊增生
描述（中文）
Figure 1、Figure 2 来自一个部分塌陷的正常胆囊。注意肌壁的厚度。胆囊增生从乳头状皱襞上的少数细胞到累及大部分黏膜的弥漫性乳头状突起不等（Figure 3、Figure 4，箭头）。衬覆上皮中可能存在玻璃样液滴（hyaline droplets）。
诊断建议
胆囊黏膜或上皮增生在 NTP 研究中不常见，只要存在就应记录并给出严重程度分级。相关的严重病变，如炎症或玻璃样液滴蓄积，应单独诊断。病理学描述应明确所诊断病例的任何异常特征。
参考切片图（2 张）
查看英文原文
Comment
Figure 1 and Figure 2 are from a partially collapsed normal gallbladder. Note the thickness of the muscular wall. Gallbladder hyperplasia varies from a few cells on papillary folds to generalized papillary projections involving most of the mucosa ( Figure 3 and Figure 4 , arrows). Hyaline droplets may be present in the lining epithelium.
Recommendation
Mucosal or epithelial hyperplasia of the gallbladder is uncommon in NTP studies and should be recorded whenever present and given a severity grade. Severe associated lesions such as inflammation or hyaline droplet accumulation should be diagnosed separately. The pathology narrative should define any unusual features of the case(s) being diagnosed.
炎症Inflammation 胆囊炎症
描述（中文）
胆囊的炎症可能表现为管腔内的急性炎症细胞浸润（Figure 1、Figure 2），但更常见的是炎症浸润主要发生在胆囊壁，并伴有黏膜衬里的增生。Figure 3、Figure 4显示胆囊增生上皮衬里中致密的胞质玻璃样沉积物。胆囊炎症（胆囊炎，cholecystitis）可能伴有黏膜溃疡或糜烂及出血（Figure 5、Figure 6）。胆囊炎更常见于老年小鼠。
诊断建议
胆囊炎症只要存在即应诊断，并给出严重程度分级。诊断中应包含描述炎症性质的修饰词（即急性（acute）、化脓性（suppurative）、慢性（chronic）、慢性 active或肉芽肿性（granulomatous））（关于这些修饰词的描述，见Liver - Inflammation）。炎症的性质及任何其他形态学特征也应在病理学叙述中描述。伴随病变，如溃疡形成或玻璃样滴状物积聚，如果足够显著，应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Inflammation of the gallbladder may involve acute inflammatory cell infiltrates in the lumen ( Figure 1 and Figure 2 ), but more commonly inflammatory infiltration occurs primarily in the gallbladder wall and is accompanied by hyperplasia of the mucosal lining. Figure 3 and Figure 4 show dense cytoplasmic hyaline deposits in the hyperplastic epithelial lining of the gall bladder. Inflammation of the gallbladder (cholecystitis) may be associated with mucosal ulcers or erosions and hemorrhage ( Figure 5 and Figure 6 ). Cholecystitis is more commonly seen in older mice.
Recommendation
Inflammation of the gallbladder should be diagnosed whenever present and given a severity grade. A modifier describing the character of the inflammation (i.e., acute, suppurative, chronic, chronic active, or granulomatous) should be included in the diagnosis (for a description of these modifiers, see Liver - Inflammation ). The character of the inflammation and any other morphologic features should also be described in the pathology narrative. Accompanying lesions, such as ulceration or hyaline droplet accumulation, should be diagnosed separately if sufficiently prominent.
透明滴蓄积Hyaline Droplet Accumulation 胆囊其他
描述（中文）
在年龄较大的小鼠中，肝内胆管上皮细胞以及胆囊上皮细胞中可见由均质嗜酸性透明样物质构成的胞质内包涵体（Figure 1、Figure 2、Figure 3）。在显著（marked）的病例中，可见腺上皮增生，且嗜酸性包涵体物质的结晶形态可能同时存在于细胞内和细胞外。该透明样物质已被鉴定为一种功能未知的几丁质酶样蛋白。
诊断建议
透明滴积聚应当被诊断并给出严重程度分级，且应在病理学叙述中描述其显著特征。相关病变，如炎症或上皮细胞变性、坏死或增生，若足够显著，应当单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Cytoplasmic inclusions of homogeneous eosinophilic hyaline-like material may be seen in older mice in intrahepatic biliary epithelial cells, as well as epithelial cells in the gallbladder ( Figure 1 , Figure 2 , and Figure 3 ). In marked cases, there is hyperplasia of the glandular epithelium, and crystalline forms of the eosinophilic inclusion material may be present both intracellularly and extracellularly. The hyaline material has been identified as a chitinase-like protein of unknown function.
Recommendation
Hyaline droplet accumulation should be diagnosed and given a severity grade, and salient features should be described in the pathology narrative. Associated lesions, such as inflammation or epithelial cell degeneration, necrosis, or hyperplasia, should be diagnosed separately if sufficiently prominent.
坏死Necrosis 骨髓坏死
描述（中文）
骨髓坏死（bone marrow necrosis）的特征是细胞质空泡化、细胞边界不清、核固缩、核溶解和核碎裂（Figure 1、Figure 2）。将这些变化与死后自溶（postmortem autolysis）相区分很重要，后者可具有相似的外观。随着时间推移，受影响的造血组织被无定形颗粒状嗜酸性碎片（Figure 3、Figure 4、Figure 5）所取代，不应将其与纤维蛋白沉积相混淆。在急性期，坏死可能伴有急性炎症或出血，而后期或亚急性坏死病例可能与坏死区域内及周围巨噬细胞数量增多有关。病变分布可为局灶性（focal）、多灶性（multifocal）或弥漫性（diffuse），在缺血的情况下，可能取决于受累骨髓的血液供应。随着时间推移，坏死骨髓最终可能由造血细胞重新填充，在某些情况下，先前坏死的区域可能被纤维化所取代。骨髓坏死有若干已知原因。它可能是化合物给药（例如环磷酰胺）的直接结果，也可能继发于严重感染性疾病状态（例如败血症）或由血管损伤、血栓形成或血管闭塞引起的组织缺血。后者的具体原因包括肿瘤形成（例如肿瘤栓子、血管闭塞）、弥散性血管内凝血（血栓形成）以及暴露于内毒素（血管损伤）。由血液供应阻塞引起的坏死（梗死）在显微镜下通常具有界限清晰的边缘作为鉴别特征（Figure 3、Figure 4）。在一项评估饲料限制对常见毒理学参数影响的大鼠研究中，仅两周的严重饮食限制（减少75%）即导致骨髓坏死和变性。具体观察包括空泡化或呈坏死外观的基质细胞、造血细胞坏死、残留造血组织<25%同期对照、局灶性出血区域以及巨核细胞内易于观察到的中性粒细胞伸入运动（emperipolesis）。
诊断建议
坏死应始终记录并分级，分布应在病理学叙述中描述。关于坏死和炎症，必须区分原发性或继发性炎症过程：原发性过程应单独记录，而继发性过程仅在严重程度需要时记录或描述。大体形态学描述词，如“凝固性（coagulative）”和“干酪样（caseous）”，不应用于坏死病变的组织学描述。当观察到血栓或认为血栓是坏死的原因时，可在叙述中将其描述并解释为缺血性坏死/梗死，血栓（如存在）应单独记录。相关链接：骨髓-血管扩张 骨髓-炎症
参考切片图（2 张）
查看英文原文
Comment
Bone marrow necrosis is characterized by cytoplasmic vacuolization, indistinct cell borders, nuclear pyknosis, karyolysis, and karyorrhexis ( Figure 1 and Figure 2 ). It is important to distinguish these changes from postmortem autolysis, which can have a similar appearance. With time, affected hematopoietic tissue is replaced with amorphous granular eosinophilic debris ( Figure 3 , Figure 4 , and Figure 5 ) that should not be confused with fibrin deposition. In the acute stage, necrosis may be accompanied by acute inflammation or hemorrhage, while later stages or cases of subacute necrosis may be associated with increased numbers of macrophages in and around the necrotic area. Lesion distribution may be focal, multifocal, or diffuse and, in the case of ischemia, may be determined by the affected marrow blood supply. With time, necrotic marrow may eventually repopulate with hematopoietic cells, and in some cases, areas of previous necrosis may be replaced by fibrosis. There are several known causes of bone marrow necrosis. It may occur as a direct result of compound administration (e.g.,cyclophosphamide) or may be secondary to severe infectious disease states (e.g., septicemia) or tissue ischemia caused by vascular injury, thrombosis, or vascular occlusion. Specific causes of the latter include neoplasia (e.g., tumor emboli, vascular occlusion), disseminated intravascular coagulation (thrombosis), and exposure to endotoxin (vascular injury). Necrosis caused by an obstruction of the blood supply (infarct) generally has well-delineated borders microscopically as a distinguishing feature ( Figure 3 and Figure 4 ). In a rat study to evaluate the effects of feed restriction on common toxicologic parameters, severe diet restriction (75% reduction) of only two weeks resulted in bone marrow necrosis and degeneration. Specific observations included vacuolated or necrotic-appearing stromal cells, necrosis of hematopoietic cells, remaining hematopoietic tissue <25% of concurrent controls, focal areas of hemorrhage, and readily observed emperipolesis of neutrophils within the megakaryocytes.
Recommendation
Necrosis should always be recorded and graded, and the distribution should be described in the pathology narrative. Regarding necrosis and inflammation, primary or secondary inflammatory processes must be distinguished: a primary process should be recorded separately, while a secondary process need only be recorded or described if warranted by its severity. Gross morphologic descriptors, such as “coagulative” and “caseous,” should not be used for histologic description of necrotic lesions. When a thrombus is seen or is perceived to be the cause of the necrosis, it may be described and interpreted as ischemic necrosis/infarct in the narrative and the thrombus, if present, recorded separately. Related Links: Bone Marrow - Angiectasis Bone Marrow - Inflammation
炎症Inflammation 骨髓炎症
描述（中文）
肉芽肿性炎症（肉芽肿性（granulomatous） inflammation）有时可见于啮齿类动物的骨髓。此类炎症主要由空泡化或上皮样巨噬细胞（epithelioid macrophage）构成，这些细胞呈相对界限清楚至有结构的聚集灶（Figure 1、Figure 2）或形成界限分明的致密肉芽肿（Figure 3、Figure 4）。上皮样巨噬细胞具有大量嗜酸性胞质及卵圆形至长形细胞核，染色质呈分散分布，其中数个细胞可融合形成多核巨细胞。与肉芽肿性炎症相关的其他细胞类型包括淋巴细胞、浆细胞、中性粒细胞和成纤维细胞，但这些并非恒定出现的特征。细胞内可见色素（含铁血黄素）或胆固醇裂隙。偶见肉芽肿性炎症伴有脂质空泡，这些空泡通常小于骨髓脂肪细胞的空泡，可见于巨噬细胞内及细胞外。这些病变似乎类似于已在人和犬骨髓中描述的所谓脂质性肉芽肿。肉芽肿性炎症可能与受试物给药或感染因子有关，但有时为非特异性所见。化脓性炎症（化脓性（suppurative） inflammation），如细菌性脓毒症时所发生者，在毒理学研究涉及的啮齿类动物骨髓中罕见观察到。其由非退变和退变的中性粒细胞聚集构成（Figure 5、Figure 6）。聚集灶内还可见来自驻留造血细胞和浸润白细胞的细胞碎片，以及蛋白性液体、纤维蛋白和少量淋巴细胞、浆细胞及巨噬细胞。其他所见可包括窦状隙扩张、间质水肿和/或出血。在NTP研究中，另有三种标准炎症类别：急性（急性（acute））、慢性（慢性（chronic））和慢性活动性（慢性活动性（chronic-active））。简言之，急性炎症中主要浸润细胞为中性粒细胞，但也可能有少量巨噬细胞和淋巴细胞。慢性炎症中以淋巴细胞为主；慢性活动性炎症中同样以淋巴细胞为主，但还存在相当数量的中性粒细胞——两种病变均可能含有巨噬细胞。这三种其他类别的炎症在骨髓中不常见或难以辨识，因为中性粒细胞属于驻留细胞群，而淋巴细胞不易识别——其形态与红系前体细胞极为相似。
诊断建议
炎症应始终予以记录。严重程度分级应作为诊断的一部分，如有必要，应在病理描述中描述分布模式。相关病变，如血管扩张（angiectasis）或坏死，如严重程度需要，可单独诊断。不应使用“增生（hyperplasia）”、“浸润（infiltration）”或“细胞增多（hypercellularity）”这些术语来诊断这些特定病变。相关链接：骨髓 - 细胞浸润，组织细胞；骨髓 - 坏死
参考切片图（2 张）
查看英文原文
Comment
Granulomatous inflammation is sometimes observed in the bone marrow of rodents. This type of inflammation consists predominately of vacuolated or epithelioid macrophages that occur in relatively well-defined to organized aggregates ( Figure 1 and Figure 2 ) or distinct compact granulomas ( Figure 3 and Figure 4 ). Epithelioid macrophages have large amounts of eosinophilic cytoplasm and an oval to elongated nucleus with a dispersed chromatin pattern, several of which may fuse to form a multinucleated giant cell. Other cell types associated with granulomatous inflammation are lymphocytes, plasma cells, neutrophils, and fibroblasts, but they are not all constant features. Intracellularly, pigment (hemosiderin) or cholesterol clefts may be seen. Occasionally, granulomatous inflammation is associated with lipid vacuoles that are usually smaller than the vacuoles of marrow adipocytes and are seen within macrophages and extracellularly. These lesions appear to be similar to the so-called lipid granulomas that have been described in human and canine bone marrow. Granulomatous inflammation may be associated with compound administration or infectious agents but is sometimes a nonspecific finding. Suppurative inflammation , as occurs with bacterial sepsis, is rarely observed in the bone marrow of rodents involved in toxicologic studies. It consists of aggregates of nondegenerate and degenerate neutrophils ( Figure 5 and Figure 6 ). Cell debris from the resident hematopoietic cells and the infiltrating leukocytes, as well as proteinaceous fluid, fibrin, and fewer lymphocytes, plasma cells, and macrophages, may also be present within the aggregates. Additional findings may include dilated sinusoids, interstitial edema, and/or hemorrhage. In NTP studies, there are three other standard categories of inflammation: acute, chronic, and chronic-active. Briefly, in acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. Lymphocytes predominate in chronic inflammation ; lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils—both lesions may contain macrophages. These three other categories of inflammation are uncommon or are difficult to appreciate in the bone marrow because neutrophils are a resident population and lymphocytes are not easily identified—appearing very similar to erythroid precursors.
Recommendation
Inflammation should always be recorded. Severity grading should be part of the diagnosis, and if warranted, the distribution pattern should be described in the pathology narrative. Associated lesions, such as angiectasis or necrosis, may be diagnosed separately if warranted by the severity. The terms "hyperplasia," "infiltration," or "hypercellularity" should not be used to diagnose these particular lesions. Related Links: Bone Marrow - Infiltration Cellular, Histiocyte Bone Marrow - Necrosis
纤维化Fibrosis 骨髓纤维化
描述（中文）
骨髓纤维化（bone marrow fibrosis）是一种以网状纤维（reticulin fibers）或网状纤维和胶原纤维（collagen fibers）增多和/或成纤维细胞（fibroblasts）增生为特征的病变。它是一种继发性改变，与炎症、骨髓坏死、骨髓损伤以及骨髓增殖性疾病（如急性髓系白血病）和淋巴增殖性疾病（如淋巴瘤）等相关。纤维化可为局灶性（focal）、多灶性（multifocal）或弥漫性（diffuse），范围从成纤维细胞轻度增多伴散在、疏松的嗜酸性胶原/网状纤维，到致密的纤维组织（Figure 1、Figure 2、Figure 3）。网状纤维的轻度增多可能难以辨认，但可通过银浸染技术（如Gomori染色）予以确认。胶原纤维表现为嗜酸性纤维，可呈束状，并通过三色染色（如Mallory染色或Masson染色）予以确认。虽然在啮齿类动物毒性研究或临床前研究中尚不清楚是否有必要区分纤维化类型，但近年来在人类中对此已有较多认识。在人类中，网状纤维增多与许多良性和恶性疾病相关，而胶原增多则在骨髓增殖性疾病晚期或骨髓转移后较为突出。骨髓中网状纤维染色的量常与疾病严重程度无相关性，而胶原染色的增多则与更严重的疾病和更差的预后相关。此外，在去除病因或成功治疗致病性疾病后，网状纤维性纤维化比胶原性纤维化更可能逆转。尽管关于（继发性）骨髓纤维化的病理生理学仍有许多问题有待阐明，但已知来自骨髓巨噬细胞、巨核细胞和血小板的细胞因子似乎是纤维化发生所必需的。这些细胞因子包括血小板源性生长因子和转化生长因子-β。此外，给小鼠注射大量重组血小板生成素（thrombopoietin）可诱导纤维化。
诊断建议
仅在纤维化是病变的突出特征时，才应在亚慢性研究和慢性研究中诊断（继发性）纤维化并对其进行分级。严重程度基于纤维化的范围；如果认为其对研究具有重要意义或属于与处理相关的改变，则应在病理学描述中描述其模式。纤维性骨营养不良的纤维增殖性和骨硬化性病变以及纤维骨性病变是啮齿类动物骨骼中界限明确的病变，具有独特的组织学特征（见骨章节）。因此，使用“纤维化（fibrosis）”一词来诊断这些病变是不恰当的。不应使用诊断术语“骨髓纤维化（myelofibrosis）”来描述小鼠和大鼠骨髓的纤维化病变。在人类中，myelofibrosis是一个缩写术语，用于指慢性特发性骨髓纤维化或原发性骨髓纤维化。该病是一种独特的克隆性骨髓增殖性疾病，其特征为继发于肿瘤性髓系和/或巨核细胞增殖的反应性、进行性纤维化，并伴有特定的血液学和临床所见。由于在啮齿类动物中尚未记录到类似的疾病，最好避免使用“myelofibrosis”一词。
参考切片图（2 张）
查看英文原文
Comment
Bone marrow fibrosis is a lesion characterized by an increase of reticulin fibers or reticulin and collagen fibers, and/or proliferating fibroblasts. It is a secondary change associated with such disorders as inflammation, bone marrow necrosis, bone marrow injury, and disorders of myeloproliferation (e.g., acute myeloid leukemia) and lymphoproliferation (e.g., lymphoma). Fibrosis can be focal, multifocal, or diffuse and range from a mild increase in fibroblasts, with the presence of scattered, loose eosinophilic collagen/reticulin fibers, to dense fibrosis tissue ( Figure 1 , Figure 2 , and Figure 3 ). Modest increases in reticulin fibers can be difficult to appreciate but can be confirmed with a silver impregnation technique, such as Gomori stain. Collagen fibers are identified as eosinophilic fibers that may be in bundles and are confirmed with the use of a trichrome stain (e.g., Mallory’s or Masson’s). While it is not clear in rodent toxicity or preclinical studies if there is a need to distinguish among fibrosis types, much has been recently learned in humans regarding this topic. In humans, increased reticulin fibers are associated with many benign and malignant conditions, while increased collagen is prominent in late stages of myeloproliferative diseases or following metastasis to the bone marrow. The amount of reticulin staining in the bone marrow often has no correlation with disease severity, while increases in collagen staining are associated with more severe disease and a poorer prognosis. In addition, reticulin fibrosis is more likely to reverse than is collagen fibrosis after removal or successful treatment of the causative disorder. Although much about the pathophysiology of (secondary) bone marrow fibrosis remains to be elucidated, it is known that cytokines from bone marrow macrophages, megakaryocytes, and platelets appear to be necessary for fibrosis to occur. These include platelet-derived growth factor and transforming growth factor-β. Additionally, fibrosis has been induced in mice injected with high amounts of recombinant thrombopoietin.
Recommendation
Fibrosis (secondary) should be diagnosed and graded in subchronic and chronic studies only when it is a prominent feature of a lesion. Severity is based on the extent of the fibrosis, and if considered to be important to the study or a treatment-related change, the pattern should be described in the pathology narrative. The fibroproliferative and osteosclerotic lesions of fibrous osteodystrophy and fibro-osseous lesions are well-defined lesions of rodent bone with distinct histologic characteristics (see the chapter on bone). Thus, it is inappropriate to use the term “fibrosis” to diagnose these lesions. The diagnostic term “myelofibrosis” should not be used to describe fibrotic lesions of the bone marrow in mice and rats. In humans, myelofibrosis is an abbreviated term that has been used in reference to chronic idiopathic myelofibrosis or primary myelofibrosis. This disease is a distinct clonal myeloproliferative disease characterized by a reactive, progressive fibrosis occurring in response to a neoplastic myeloid and/or megakaryocytic proliferation and is accompanied by specific hematologic and clinical findings. Since a similar disorder has not been documented in rodents, it is best to avoid use of the term “myelofibrosis.”
组织细胞性细胞浸润Infiltration Cellular Histiocyte 骨髓浸润
描述（中文）
组织细胞浸润（histiocytic infiltration）定义为骨髓中巨噬细胞（macrophage）或组织细胞（histiocyte）数量增多。这些巨噬细胞可呈空泡化（vacuolated）和/或含有数量不等的细胞碎片、胆固醇裂隙（cholesterol cleft）或色素（如含铁血黄素（hemosiderin）），通常以界限不清、无组织的聚集形式存在（Figure 1、Figure 2、Figure 3、Figure 4）。"组织细胞浸润"一词仅用于巨噬细胞浸润存在而无其他炎症证据的情况。若出现（a）上皮样（epithelioid）或多核巨噬细胞，可形成有组织的聚集（肉芽肿（granuloma）），（b）该区域存在其他炎症细胞，或（c）血管改变，如水肿（edema），则需诊断为肉芽肿性炎症（肉芽肿性（granulomatous） inflammation）。组织细胞浸润通常代表一种反应性过程，其在啮齿类动物中的原因尚未明确。具有细胞毒性（cytotoxic）并引起骨髓坏死的化合物可导致巨噬细胞数量增多，以清除细胞碎片。此外，任何能够引起骨髓损伤或炎症的病症均可导致巨噬细胞增多。在其他物种（人类和犬）中，非炎症性组织细胞浸润与骨髓增生（bone marrow hyperplasia）、无效造血（ineffective hematopoiesis）或血细胞破坏增加有关。
诊断建议
组织细胞浸润应对研究中所有动物一致记录并分级。分级基于浸润程度和/或聚集数量。相关链接：骨髓 - 坏死（Bone Marrow - Necrosis）
参考切片图（2 张）
查看英文原文
Comment
Histiocytic infiltration is defined as an increase in the numbers of macrophages or histiocytes in the bone marrow. These macrophages may be vacuolated and/or contain variable amounts of cellular debris, cholesterol clefts, or pigment (e.g., hemosiderin) and are usually found in ill-defined, unorganized aggregates ( Figure 1 , Figure 2 , Figure 3 , and, Figure 4 ). Use of the term “histiocytic infiltration” is reserved for those instances when macrophage infiltration is present without other evidence of inflammation. The presence of (a) epithelioid or multinucleated macrophages, which may form organized aggregates (granulomas), (b) other inflammatory cells in the area, or (c) vascular changes, such as edema, warrants a diagnosis of granulomatous inflammation. Histiocytic infiltration usually represents a reactive process, the reasons for which are not well defined in rodents. Compounds that are cytotoxic and cause necrosis of the bone marrow may result in increased numbers of macrophages, which serve to remove the cellular debris. In addition, any condition capable of causing bone marrow injury or inflammation can result in increased macrophages. In other species (humans and dogs), noninflammatory histiocytic infiltrates have been associated with bone marrow hyperplasia, ineffective hematopoiesis, or increased breakdown of blood cells.
Recommendation
Histiocytic infiltration should be consistently recorded and graded for all animals in a study. Grading is based on the degree of infiltration and/or numbers of aggregates. Related Links: Bone Marrow - Necrosis
细胞减少Hypocellularity 骨髓其他
描述（中文）
骨髓细胞密度（bone marrow cellularity）指造血细胞相对于骨髓脂肪的数量或百分比。已有研究表明，2月龄大鼠的正常骨髓（胸骨和股骨）含80%或以上的造血细胞，其余细胞大部分由脂肪细胞（adipocyte）构成；4–16月龄大鼠的正常骨髓含约60–75%的造血细胞。已知随着啮齿类动物及其他物种衰老，正常骨髓细胞密度降低，并伴有脂肪细胞的相对增多。此外，2岁大鼠的动物间变异性大于4–16月龄大鼠。一般而言，同年龄小鼠的总体骨髓细胞密度高于大鼠。骨髓细胞密度的变化可累及所有或单个细胞系。红系（erythroid）或髓系（myeloid）细胞系的变化可使M:E比值相对于对照发生偏移。据报道，大鼠和小鼠的正常M:E比值为0.80至2.79，平均为1.5，且取决于品系和年龄，这强调了将受试动物与同期对照（concurrent control）进行比较的重要性。组织学切片可对M:E比值进行粗略估计，以辅助细胞密度的评价，而细胞学制片（cytologic preparation）则用于更精确地测定M:E比值以及评价成熟同步性（synchrony of maturation）的细微变化。当受试动物与同期对照相比造血细胞相对于脂肪细胞减少时，记录为骨髓细胞密度减低（hypocellularity）（Figure 2、Figure 4、Figure 5、Figure 6）。细胞密度减低可作为治疗相关的直接或间接效应发生，此类例子众多，但一般包括影响血红蛋白生成、改变造血速率、干扰卟啉代谢（如铅）、改变细胞因子网络或诱导直接细胞损伤（如化疗药、某些抗菌药）的外源化学物（xenobiotic），以及慢性炎症或慢性肾衰竭（即肾脏促红细胞生成素生成减少）等状况。在严重病例（如再生障碍，aplasia）中，骨髓将表现为缺乏造血细胞系，主要由脂肪组织和血管窦（vascular sinus）构成。根据外源化学物或处理（如辐射）的发病机制或作用机制，还可能观察到少量散在的淋巴细胞、巨噬细胞和浆细胞。偶尔可见相对界限清楚的局灶性（focal）细胞密度减低区（以前称为“局灶性 atrophy”）。这些区域可能含有数量不等的脂肪细胞和/或网状基质（reticular stromata）的相对增多。该所见已在年轻成年大鼠中描述，在雌性中发生率明显较高。仅这些区域似乎无临床意义。局灶性细胞密度减低区可能是骨髓细胞密度总体降低的一部分，或导致（若存在多个区域）骨髓细胞密度总体降低。此类所见应归入细胞密度减低或诊断为细胞密度减低，而不是作为“局灶性”细胞密度减低的独立 distinct 所见记录。已知饮食限制和严重食欲不振可引起所有造血细胞减少，并伴有骨髓脂肪细胞的明显增多；M:E比值似乎不受影响。具体而言，在一项研究中，足以使年轻大鼠停止体重增长的饮食限制分别引起红系、髓系和巨核细胞系（megakaryocytic）前体细胞50%、40%和20%的减少。
诊断建议
为评价骨髓细胞密度，即造血细胞相对于骨髓脂肪的百分比，必须将受试动物的骨髓与相同部位的同期对照骨髓进行比较。细胞密度的变化应记录并分级，分级方案应在文字描述（narrative）中说明。分级基于与研究病理学家（study pathologist）所定义的同期对照相比的变化程度。虽然细胞密度的变化可能由特定细胞系的变化所致，但仅凭组织学评价可能难以识别这一点。如果特定细胞系的变化不明确，则更适合仅将变化记录为细胞密度减低。不适宜诊断脂肪细胞的同期增多，因为其被认为是继发于造血细胞减少。记录骨髓细胞密度变化时，不应使用临床、解释性或诊断性术语（如“atrophy”“hypoplasia”），而应使用本文所讨论的描述性术语“hypocellularity”。当细胞密度变化需要进一步解释或与处理相关时，应在病理学文字描述中对其进行描述和解释，此时解释性术语或诊断（如再生障碍性贫血，aplastic anemia）可结合其他组织学所见、可获得的血液学数据、生前所见以及骨髓细胞学（如M:E比值）或流式细胞术所见加以使用。
参考切片图（2 张）
查看英文原文
Comment
Bone marrow cellularity refers to the amount or percentage of hematopoietic cells relative to marrow fat. It has been shown that normal bone marrow (sternum and femur) of rats 2 months of age contains 80% or more hematopoietic cells, with the majority of the remaining cells composed of adipocytes; normal bone marrow of rats 4–16 months of age contains approximately 60–75% hematopoietic cells. It is known that as rodents and other species age, normal bone marrow cellularity decreases and is accompanied by a relative increase in adipocytes. In addition, rats 2 years of age show greater interanimal variability than do 4- to 16-month-old rats. In general, mice have higher overall bone marrow cellularity than do rats of the same age. Changes in bone marrow cellularity may involve all or individual cell lines. Changes in the erythroid or myeloid cell lines may shift the M:E ratio relative to controls. Normal M:E ratios of rats and mice are reported between 0.80 and 2.79, with an average of 1.5, and are dependent on strain and age, stressing the importance of comparing treated animals with concurrent controls. Histologic sections allow for a rough estimate of the M:E ratio to aid in the evaluation of cellularity, while cytologic preparations are needed for a more precise determination of the M:E ratio and evaluation of subtle changes in synchrony of maturation. Hypocellularity of the bone marrow is recorded in treated animals when there is a decrease in hematopoietic cells relative to adipocytes compared with concurrent controls ( Figure 2 , Figure 4 , Figure 5 , and Figure 6 ). Hypocellularity may occur as a direct or indirect treatment-related effect, of which numerous examples exist but in general include xenobiotics that affect hemoglobin production, alter rates of hematopoiesis, disrupt porphyrin metabolism (e.g., lead), alter cytokine networks, or induce direct cellular injury (e.g., chemotherapeutics, certain antimicrobials), as well as such conditions as chronic inflammation or chronic renal failure (i.e., reduced renal erythropoietin production). In severe cases (e.g., aplasia), the marrow will appear devoid of hematopoietic cell lines and consist primarily of adipose tissue and vascular sinuses. Low numbers of scattered lymphocytes, macrophages, and plasma cells may also be observed, depending on the pathogenesis or mechanism of action of the xenobiotic or treatment (e.g., radiation). Occasionally, relatively well-delineated focal areas of hypocellularity (previously known as “focal atrophy”) have been seen. These areas may contain variable numbers of adipocytes and/or a relative increase in reticular stromata. This finding has been described in young adult rats, with an apparent higher rate among females. These areas alone seemingly have no clinical significance. Focal areas of hypocellularity may be part of, or result in (if numerous areas exist), an overall decrease in bone marrow cellularity. Such observations should be included with, or diagnosed as, hypocellularity rather than recorded as a separate distinct finding of “focal” hypocellularity. Diet restriction and severe inappetence are known to cause decreases in all hematopoietic cells with an apparent increase in marrow fat cells; the M:E ratio seems unaffected. Specifically, in one study, diet restriction sufficient to stop weight gain in young rats caused 50%, 40%, and 20% decreases in erythroid, myeloid, and megakaryocytic precursors, respectively.
Recommendation
To evaluate bone marrow cellularity, that is, the percentage of hematopoietic cells relative to marrow fat, bone marrow from treated animals must be compared with same-site concurrent control bone marrow. Changes in cellularity should be recorded and graded, and the grading scheme should be described in the narrative. Grading is based on the degree of change compared with concurrent controls as defined by the study pathologist. While changes in cellularity may be due to a change in a specific cell line, it can be difficult to appreciate this with histologic evaluation alone. If changes in specific cell lines are not explicitly clear, it is more appropriate to record the changes as just hypocellularity. It is not appropriate to diagnose the concurrent increase in adipocytes because it is considered secondary to the decrease in hematopoietic cells. Clinical, interpretative, or diagnostic terms (e.g., “atrophy,” “hypoplasia”) should not be used when recording changes in bone marrow cellularity but rather the descriptive term “hypocellularity” as discussed herein. When changes in cellularity warrant further explanation or are treatment related, they should be described and interpreted in the pathology narrative, where interpretive terms or diagnoses, such as aplastic anemia, can be used in context with other histologic findings, available hematologic data, in-life findings, and bone marrow cytologic (e.g., M:E ratio) or flow cytometric findings.
细胞增多Hypercellularity 骨髓其他
描述（中文）
骨髓细胞密度（bone marrow cellularity）指造血细胞相对于骨髓脂肪的数量或百分比。已有研究表明，2月龄大鼠的正常骨髓（胸骨和股骨）含80%或以上的造血细胞，其余细胞大部分由脂肪细胞组成；4–16月龄大鼠的正常骨髓含约60–75%的造血细胞。已知随着啮齿类动物及其他物种衰老，正常骨髓细胞密度降低，并伴有脂肪细胞的相对增多。此外，2岁大鼠的动物间变异大于4–16月龄大鼠。一般而言，同年龄小鼠的总体骨髓细胞密度高于大鼠。骨髓细胞密度的变化可累及所有或单个细胞系。红系或髓系细胞系的变化可能使M:E比例相对于对照组发生偏移。据报道，大鼠和小鼠的正常M:E比例为0.80至2.79，平均为1.5，且取决于品系和年龄，这强调了将受试动物与同期对照进行比较的重要性。组织学切片可对M:E比例进行粗略估计，以辅助评估细胞密度，而细胞学制片则用于更精确地测定M:E比例并评估成熟同步性的细微变化。当受试动物与同期对照相比造血细胞相对于脂肪细胞增多时，记录为骨髓细胞密度增高（hypercellularity）（Figure 2、Figure 4、Figure 5）。细胞密度增高可作为对化合物给药的非特异性或直接（例如给予细胞因子时）反应而发生，但更常见的是由于外周血细胞减少、外源物质所致骨髓损伤的恢复或炎症所引起的再生性反应。例如，细胞密度增高可继发于脓毒症，或由失血、溶血性贫血或血小板消耗/破坏所致。刺激某一细胞系产生增多可引起其他细胞系产生增加，导致骨髓细胞密度总体增高。在显著（marked）细胞密度增高时，造血细胞可充满整个骨髓腔，甚至延伸穿过滋养孔。
诊断建议
为评估骨髓细胞密度，即造血细胞相对于骨髓脂肪的百分比，必须将受试动物的骨髓与同部位同期对照骨髓进行比较。细胞密度的变化应记录并分级，分级方案应在文字描述中说明。分级基于与研究病理学家所定义的同期对照相比的变化程度。虽然细胞密度的变化可能由特定细胞系的变化所致，但仅凭组织学评估可能难以识别这一点。如果特定细胞系的变化并不明确，则仅记录为细胞密度增高更为恰当。不宜诊断同时存在的脂肪细胞减少，因为其被视为继发于造血细胞增多。记录骨髓细胞密度变化时，不应使用临床、解释性或诊断性术语（例如“增生（hyperplasia）”），而应使用本文所述的描述性术语“细胞密度增高（hypercellularity）”。当细胞密度变化需要进一步解释或与受试物相关时，应在病理学文字描述中对其进行描述和解释，此时解释性术语或诊断（如红系增生（erythroid hyperplasia））可结合其他组织学所见、可获得的血液学数据、生前所见以及骨髓细胞学（例如M:E比例）或流式细胞术所见加以使用。
参考切片图（2 张）
查看英文原文
Comment
Bone marrow cellularity refers to the amount or percentage of hematopoietic cells relative to marrow fat. It has been shown that normal bone marrow (sternum and femur) of rats 2 months of age contains 80% or more hematopoietic cells, with the majority of the remaining cells composed of adipocytes; normal bone marrow of rats 4–16 months of age contains approximately 60–75% hematopoietic cells. It is known that as rodents and other species age, normal bone marrow cellularity decreases and is accompanied by a relative increase in adipocytes. In addition, rats 2 years of age show greater interanimal variability than do 4- to 16-month-old rats. In general, mice have higher overall bone marrow cellularity than do rats of the same age. Changes in bone marrow cellularity may involve all or individual cell lines. Changes in the erythroid or myeloid cell lines may shift the M:E ratio relative to controls. Normal M:E ratios of rats and mice are reported between 0.80 and 2.79, with an average of 1.5, and are dependent on strain and age, stressing the importance of comparing treated animals with concurrent controls. Histologic sections allow for a rough estimate of the M:E ratio to aid in the evaluation of cellularity, while cytologic preparations are needed for a more precise determination of the M:E ratio and evaluation of subtle changes in synchrony of maturation. Hypercellularity of the bone marrow is recorded in treated animals when there is an increase in hematopoietic cells relative to adipocytes compared with concurrent controls ( Figure 2 , Figure 4 , and Figure 5 ). Hypercellularity may occur as a nonspecific or direct (e.g., with cytokine administration) response to compound administration but more commonly is due to a regenerative response as a consequence of decreases in peripheral blood cells, recovery from a xenobiotic-induced bone marrow injury, or inflammation. For example, hypercellularity may be secondary to sepsis or a result of blood loss, hemolytic anemia or platelet consumption/destruction. Stimulation to produce more of one cell line can cause increased production of other cell lines, causing an overall increase in bone marrow cellularity. With marked hypercellularity, hematopoietic cells may fill the entire marrow space, even extending through the nutrient foramina.
Recommendation
To evaluate bone marrow cellularity, that is, the percentage of hematopoietic cells relative to marrow fat, bone marrow from treated animals must be compared with same-site concurrent control bone marrow. Changes in cellularity should be recorded and graded, and the grading scheme should be described in the narrative. Grading is based on the degree of change compared with concurrent controls as defined by the study pathologist. While changes in cellularity may be due to a change in a specific cell line, it can be difficult to appreciate this with histologic evaluation alone. If changes in specific cell lines are not explicitly clear, it is more appropriate to record the changes as just hypercellularity. It is not appropriate to diagnose the concurrent decrease in adipocytes because it is considered secondary to the increase in hematopoietic cells. Clinical, interpretative, or diagnostic terms (e.g., “hyperplasia”) should not be used when recording changes in bone marrow cellularity but rather the descriptive term “hypercellularity” as discussed herein. When changes in cellularity warrant further explanation or are treatment related, they should be described and interpreted in the pathology narrative, where interpretive terms or diagnoses, such as erythroid hyperplasia, can be used in context with other histologic findings, available hematologic data, in-life findings, and bone marrow cytologic (e.g., M:E ratio) or flow cytometric findings.
肥大细胞性细胞浸润Infiltration Cellular Mast Cell 骨髓浸润
描述（中文）
肥大细胞浸润是一种反应性改变，定义为与同期对照相比，形态正常的肥大细胞呈疏松散在分布且数量增多。在大鼠中，肥大细胞在骨髓中数量相对较多，约占所有有核骨髓细胞的1-3%，这与犬不同，犬骨髓细胞学中极少观察到肥大细胞，而人类则占所有有核骨髓细胞不足0.1%。关于小鼠骨髓中肥大细胞总数所知较少。典型的肥大细胞呈圆形至卵圆形，核位于中央或稍偏位、呈圆形，胞质淡染颗粒状，如在苏木精-伊红（hematoxylin and eosin，H&E）染色的组织学切片上所見（Figure 1、Figure 2）。用大多数罗曼诺夫斯基型染色（如Giemsa），肥大细胞因其异染性胞质颗粒而易于识别（Figure 3、Figure 4）。啮齿类动物骨髓肥大细胞增多的原因尚未明确。在人类和犬中，肥大细胞浸润继发于炎症、寄生虫感染、尿毒症（肾衰竭）、再生障碍性贫血、骨质疏松症和血液系统疾病（如白血病前期、淋巴增殖性疾病）等状况。肥大细胞增多可能伴有淋巴细胞和浆细胞增多。
诊断建议
由于啮齿类动物骨髓中正常肥大细胞数量的变异性，当在处理组动物中观察到骨髓肥大细胞 perceived 增多时，与同期对照的比较尤为重要。肥大细胞数量增多应始终记录并给予严重程度分级。“肥大细胞增多症（mastocytosis）”一词不应替代肥大细胞浸润的诊断。在人类中，肥大细胞增多症是指一组异质性疾病（其中大多数已被证明为克隆性，并包括人类相当于肥大细胞瘤的疾病），其特征为肥大细胞在一个或多个器官系统中异常生长和积聚。当肥大细胞呈多灶性（multifocal）或弥漫性（diffuse）、密集紧凑的簇状或片状分布时，诊断为啮齿类动物骨髓肥大细胞瘤是恰当的。然而，疏松散在的肥大细胞数量增多本身即足以诊断为浸润，除非有其他标准（如非典型形态、其他部位的肥大细胞瘤）提示肿瘤性病变。
参考切片图（2 张）
查看英文原文
Comment
Mast cell infiltration is a reactive change defined as increased numbers of loosely scattered, morphologically normal mast cells compared with concurrent controls. In rats, mast cells are present in relatively high numbers in the bone marrow, comprising approximately 1-3% of all nucleated bone marrow cells, in contrast to dogs, where they are rarely observed in bone marrow cytology, and humans, where they comprise less than 0.1% of all nucleated bone marrow cells. Less is known about total mast cell numbers in the bone marrow of mice. Typical mast cells are round to oval with a central to slightly eccentric, round nucleus and a pale granular cytoplasm as seen on hematoxylin and eosin–stained histologic slides ( Figure 1 and Figure 2 ). With most Romanowsky-type stains (e.g., Giemsa), mast cells are easily identified by their metachromatic cytoplasmic granules ( Figure 3 and Figure 4 ). The causes of increased bone marrow mast cells in rodents are not well defined. In humans and dogs, mast cell infiltration is secondary to such conditions as inflammation, parasitism, uremia (renal failure), aplastic anemia, osteoporosis, and hematologic diseases (e.g., preleukemias, lymphoproliferative diseases). The increased mast cells may be accompanied by increases in lymphocytes and plasma cells.
Recommendation
Because of the variability of normal mast cell numbers in rodent bone marrow, comparison with concurrent controls is especially important when a perceived increase in marrow mast cells is observed in treated animals. Increases in numbers of mast cells should always be recorded and given a severity grade. The term “mastocytosis” should not be used in lieu of the diagnosis of mast cell infiltration. In humans, mastocytosis refers to a heterogeneous group of disorders (most of which have been shown to be clonal and includes the human equivalent of mast cell tumors) characterized by abnormal growth and accumulation of mast cells in one or more organ systems. The diagnosis of a bone marrow mast cell tumor in rodents is appropriate when mast cells are found in multifocal or diffuse, dense compact clusters or sheets. However, the presence of increased numbers of loosely scattered mast cells in and of itself warrants a diagnosis of infiltration, unless other criteria (e.g., atypical morphology, mast cell tumor in another location) are indicative of neoplasia.
色素Pigment 骨髓色素沉着
描述（中文）
铁以含铁血黄素（hemosiderin）的形式储存于骨髓的驻留巨噬细胞中。骨髓内含铁血黄素量的增加记录为色素（增加）。含铁血黄素在苏木精和伊红（H&E）染色下呈金黄色至棕褐色色素，在Wright染色下呈绿色、蓝绿色或黑色。尽管巨噬细胞中见到的金黄色至棕褐色色素最可能代表含铁血黄素，但需要特殊染色（如Prussian blue）加以确认。由于铁通常储存于骨髓中，因此需与同部位同期对照比较来评估和分级色素沉着的程度。骨髓含铁血黄素增加与陈旧性或慢性出血或溶血性贫血相关，或由经口或胃肠外给予过量铁（铁过载）所致。炎症性（或慢性）疾病所致贫血也可导致骨髓含铁血黄素增加。这是由于肝脏产生hepcidin增加所致，hepcidin是炎症性贫血的关键介质。Hepcidin通过抑制肠道上皮对膳食铁的吸收和阻止铁从巨噬细胞输出，在维持正常铁稳态中发挥作用。炎症性和肿瘤性疾病引起hepcidin产生增加，随时间推移导致骨髓内铁储存增加。这些铁储存无法用于红细胞生成，进而促进贫血的发生。
诊断建议
虽然骨髓内的金黄色至棕褐色色素被推定为含铁血黄素，但未经特殊染色无法确认。因此，“色素”被认为是最合适的诊断。亚慢性和慢性研究中的色素增加应始终记录，其分级基于与同部位同期对照相比所存在色素的相对量。当色素增加与受试物相关时，应在叙述中描述为与含铁血黄素一致。
参考切片图（2 张）
查看英文原文
Comment
Iron is stored as hemosiderin in resident macrophages of the bone marrow. An increase in the amount of hemosiderin within the bone marrow is recorded as (increased) pigment. Hemosiderin appears as a golden brown pigment with hematoxylin and eosin stain and as green, blue-green, or black with Wright’s stain. Although golden brown pigment seen in macrophages most likely represents hemosiderin, a special stain, such as Prussian blue, would be needed for confirmation. Since iron is normally stored in the marrow, the level of pigmentation is assessed and graded in comparison with same-site concurrent controls. Increased hemosiderin of the bone marrow is associated with old or chronic hemorrhage or hemolytic anemia or is due to the administration of excessive amounts of oral or parenteral iron (iron overload). Anemia of inflammatory (or chronic) disease may also result in increased bone marrow hemosiderin. This is due to increased production of hepcidin, a key mediator of anemia of inflammation, by the liver. Hepcidin plays a role in maintaining normal iron homeostasis by inhibiting absorption of dietary iron from the intestinal epithelium and preventing the export of iron from macrophages. Inflammatory and neoplastic disorders cause an increase in hepcidin production that with time results in increased iron stores within the bone marrow. These iron stores are unavailable for erythropoiesis, subsequently contributing to the development of anemia.
Recommendation
While golden brown pigment within the bone marrow is presumed to be hemosiderin, it cannot be confirmed without special stains. Thus, “pigment” is deemed the most appropriate diagnosis. Increases in pigment in subchronic and chronic studies should always be documented, with grading based on the relative amounts of pigment present in comparison with same-site concurrent controls. When an increase in pigment is treatment related, it should be described in the narrative as being consistent with hemosiderin.
血管扩张Angiectasis 骨髓扩张
描述（中文）
骨髓的血管供应最终以毛细血管开口于窦状隙丛而告终，窦状隙内衬内皮细胞，外层为不完整的外膜细胞层。骨髓血管扩张（angiectasis）定义为这些血管或窦状隙被血液扩张。在某些情况下，扩张可严重到出现大的红细胞和/或蛋白性液体（血清）湖，不应将其与出血混淆（Figure 1、Figure 2）。连续完整的内皮衬里的存在有助于将血管扩张与出血区分开来。随着血管系统更严重或慢性的充血，有时可在扩张的血管周围见到含有色素和/或胆固醇裂隙的巨噬细胞。应尝试区分血管扩张与血管瘤（hemangioma），尽管这种区分并不总是显而易见。血管瘤往往边界清楚、无包膜，由紧密排列的扩张血管腔隙构成。每个血管腔隙均由单层外观正常的内皮细胞围成并衬里，这些内皮细胞排列于胶原性间隔上，间隔通常较薄，尽管有些具有宽阔的胶原性间质。血管扩张通常不表现为边界清楚的肿块：扩张的血管通道常不规则地穿行于造血组织中。血管扩张已在造血组织严重丧失的啮齿动物中观察到。它也作为非特异性所见被观察到，或与炎症、肿瘤形成或血管/心血管疾病（例如血栓、充血性心力衰竭）相关。
诊断建议
在亚慢性研究和慢性研究中，只要存在血管扩张，就应进行诊断并分级。与处理相关的血管扩张还应在病理学叙述中描述。分级基于扩张腔隙的数量和扩张程度的综合评估。不应使用术语“ectasia”代替血管扩张。
参考切片图（2 张）
查看英文原文
Comment
The vascular supply of the bone marrow culminates with capillaries opening into a plexus of sinusoids lined with endothelial cells and an incomplete outer layer of adventitial cells. Angiectasis of the bone marrow is defined as dilatation of these vessels or sinusoids with blood. In some cases, the dilatation can be so severe as to cause the appearance of large lakes of erythrocytes and/or proteinaceous fluid (serum) that should not be confused with hemorrhage ( Figure 1 and Figure 2 ). The presence of a continuous intact endothelial lining helps distinguish angiectasis from hemorrhage. With more severe or chronic congestion of the vasculature, macrophages sometimes containing pigment and/or cholesterol clefts may be seen around the dilated vasculature. A distinction between angiectasis and hemangioma should be attempted, although the distinction is not always obvious. Hemangiomas tend to be well-circumscribed, unencapsulated masses composed of tightly packed, dilated vascular spaces. Each vascular space is enclosed and lined by a single layer of normal-appearing endothelial cells aligned on collagenous septa, which are usually thin, although some have broad collagenous stroma. Angiectasis does not usually present as a well-circumscribed mass: the dilated vascular channels often course irregularly through the hematopoietic tissue. Angiectasis has been observed in rodents with severe loss of hematopoietic tissue. It is also observed as a nonspecific finding or in association with inflammation, neoplasia, or vascular/cardiovascular disorders (e.g., thrombi, congestive heart failure).
Recommendation
Angiectasis should be diagnosed and graded in subchronic and chronic studies whenever it is present. Treatment-related angiectasis should also be described in the pathology narrative. Grading is based on a combination of the number of dilated spaces and the degree of dilatation. The term “ectasia” should not be used in place of angiectasis.
骨髓凝胶样转化Gelatinous Transformation 骨髓其他
描述（中文）
骨髓胶样转化（gelatinous transformation of bone marrow，GMT），以前称为“脂肪浆液性萎缩（serous atrophy of fat）”，是一种不常见的病变，表现为脂肪细胞（脂肪萎缩）和造血细胞丢失，代之以细胞外基质（ground substance）增多（Figure 1、Figure 2、Figure 3）。该病变最常呈局灶性（focal）或多灶性（multifocal）分布。基质为无定形、淡粉色，有时外观略呈颗粒状，通常由酸性黏多糖组成，在pH 2.5时Alcian blue染色呈阳性（人类、马）。为确保Alcian blue染色阳性，需要特定的组织制备和处理。GMT曾在衰弱啮齿类动物中有描述，通常与恶病质（如继发于肿瘤、内分泌病）和晚期严重营养不良（如消化不良）相关。然而，在当前的饲养标准下，GMT在如今的NTP研究中很少遇到。尽管GMT的发病机制仍不清楚，但其与多种疾病的关联提示，它可能源于晚期疾病状态下被激活的基本生物调节过程。有观点认为，基质可能是对疾病分解代谢状态下被消耗的脂肪细胞的替代，而造血细胞丢失可能是由于骨髓微环境不利所致，这与造血底物不足以及缺乏脂肪细胞和纤维细胞的刺激有关。
诊断建议
骨髓胶样转化应始终记录并分级。严重程度分级基于骨髓受累的范围。较旧的术语“浆液性变性（serous degeneration）”、“骨髓变性（bone marrow degeneration）”、“脂肪浆液性萎缩（serous atrophy of fat）”和“脂肪变性（fat degeneration）”不应被用于诊断该病变。
参考切片图（2 张）
查看英文原文
Comment
Gelatinous transformation of bone marrow (GMT), previously known as "serous atrophy of fat," is an uncommon condition in which there is a loss of adipocytes (fat atrophy) and hematopoietic cells, with replacement by an increased amount of extracellular ground substance ( Figure 1 , Figure 2 , and Figure 3 ). This lesion is most often focal or multifocal. The ground substance is amorphous, light pink, and sometimes slightly granular in appearance and typically consists of acid mucopolysaccharides that stain positive with Alcian blue at pH 2.5 (humans, equids). To ensure Alcian blue positivity, specific tissue preparation and processing are necessary. GMT has been described in debilitated rodents and in general is associated with cachexia (e.g., secondary to neoplasia, endocrinopathies) and advanced severe malnutrition (e.g., maldigestion). Under current husbandry standards, however, GMT is rarely encountered in NTP studies today. Although the pathogenesis of GMT remains unclear, its association with a wide range of diseases suggests it may result from basic bioregulatory processes that are activated in states of advanced illness. It has been suggested that the ground substance may be a replacement for the adipocytes that are used in catabolic states of disease, while the hematopoietic cell loss may be due to an unfavorable bone marrow microenvironment related to inadequate hematopoietic substrates and lack of stimulation by adipocytes and fibrocytes.
Recommendation
Gelatinous transformation of bone marrow should always be recorded and graded. Severity grade is based on the extent of marrow affected. The older terms "serous degeneration," "bone marrow degeneration," "serous atrophy of fat," and "fat degeneration" should not be used to diagnose this finding.
增生Hyperplasia 凝固腺增生
描述（中文）
凝固腺增生由衬覆上皮的增殖构成。细胞可堆积（箭头，Figure 1）、形成短乳头状皱褶，或向腺泡腔内突出。Figure 1所示的增生为多灶性（multifocal）但轻微（mild）；在Figure 2、Figure 3中则为focally extensive，并在腺泡腔内形成乳头状皱褶。凝固腺增生很可能是与年龄相关的改变。产前暴露于雌激素类物质（包括己烯雌酚）所致的雌性化，已在啮齿类动物中与凝固腺的增生性和化生性改变相关联。
诊断建议
增生应进行分级并记录，当双侧凝固腺均受累时应注明为双侧性。严重程度应依据受累较重的腺体判定。与其他附属性腺中可能存在的类似改变的相关性，应在病理学描述中提及。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of the coagulating gland consists of proliferation of the lining epithelium. The cells may pile up (arrows, Figure 1 ), form short papillary folds, or bulge into the acinar lumen. Hyperplasia shown in Figure 1 is multifocal but mild; in Figure 2 and Figure 3 it is focally extensive, with formation of papillary folds in the acinar lumen. Hyperplasia of the coagulating gland is likely an age-related change. Feminization from prenatal exposure to estrogenic agents, including diethylstilbestrol, has been associated with hyperplastic and metaplastic changes in the coagulating glands of rodents.
Recommendation
Hyperplasia should be graded and recorded, with qualification as bilateral when both coagulating glands are affected. Severity should be based on the more severely affected gland. Correlations with similar changes that may be present in other accessory sex gland should be mentioned in the pathology narrative.
炎症Inflammation 凝固腺炎症
描述（中文）
凝固腺（coagulating gland）的炎症可以是急性的（Figure 1、Figure 2）、形成脓肿（Figure 3），或为慢性至慢性活动性（Figure 4）。在急性炎症中，细胞浸润物存在于腺上皮、间质和分泌物中。在慢性炎症中，间质因混合细胞性渗出物、成纤维细胞和胶原而扩张。在某些病例中，鳞状化生（squamous metaplasia）可伴随炎症出现。凝固腺炎症可作为偶然发现出现，通常与外源性化学物（xenobiotics）的给予无关。NTP研究有五个标准的炎症类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞是中性粒细胞（neutrophil），尽管也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血（hyperemia）的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但它们聚集在一起，其中许多发生变性（化脓性渗出物）。来自 resident 细胞群和浸润白细胞的细胞碎片、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子，也可能存在于渗出物中。肉眼上，这些病变将以脓液的存在为特征。渗出物周围的组织可能有成纤维细胞、纤维结缔组织和混合炎性细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大的、活化的巨噬细胞、上皮样巨噬细胞（epithelioid macrophages）或多核巨细胞（multinucleated giant cells）。
诊断建议
无论何时出现，炎症均应予以诊断、分类和分级。继发性改变如鳞状化生不需要单独诊断，除非其严重程度需要如此。当两个腺体均受累时，诊断应限定为双侧性（双侧（bilateral）），严重程度应基于受累更严重的腺体。
参考切片图（2 张）
查看英文原文
Comment
Inflammation of the coagulating gland can be acute ( Figure 1 and Figure 2 ), form abscesses ( Figure 3 ), or be chronic to chronic-active ( Figure 4 ). In acute inflammation, the cellular infiltrates are present in the glandular epithelium, stroma, and secretion. In chronic inflammation, the stroma is expanded by mixed cellular exudate, fibroblasts, and collagen. Squamous metaplasia may accompany inflammation in some cases. Coagulating gland inflammation may occur as an incidental finding and is usually unrelated to administration of xenobiotics. NTP studies have five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris from both the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may have fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
Whenever present, inflammation should be diagnosed, classified, and graded. Secondary changes such as squamous metaplasia do not require a separate diagnosis unless warranted by their degree of severity. When both glands are involved, the diagnosis should be qualified as bilateral and the severity based on the more severely affected gland.
腺泡扩张Dilation Acinar 凝固腺扩张
描述（中文）
腺泡扩张（acinar dilation）的特征是腺泡因大量分泌产物而膨胀，上皮乳头状皱襞减少或消失，被覆上皮变扁平。扩张的腺泡可通过其胀满的外观、潴留分泌物染色强度增加以及腺泡体积增大来识别。这很可能是与年龄相关的变化，与受试物给药之间的因果关系尚未确立。一些病理学家不对Figure 1所示程度的扩张作出诊断，认为其属于正常变异范围。Figure 2所示的腺泡扩张程度则明确需要诊断。
诊断建议
如果对Figure 1所示程度的扩张作出腺泡扩张的诊断，则应对该变化进行分级，并在所有动物中一致地进行评估。在这种情况下，病理学描述可提供支持该诊断所用的诊断标准。Figure 2所示的扩张程度超出了预期的正常变异范围，应当作出诊断并进行分级。
参考切片图（2 张）
查看英文原文
Comment
Acinar dilation is characterized by distension of glandular acini with abundant secretory product, reduction or loss of epithelial papillary folds, and flattening of the lining epithelium. Dilated acini may be distinguished by their turgid appearance, increased staining intensity of the retained secretion, and increased acinar size. This is likely an age-related change, and a causal association with chemical administration has not been established. Some pathologists do not diagnose the degree of dilation shown in Figure 1 and consider it to be within normal variation. The degree of ascinar dilation shown in Figure 2 definitely warrants diagnosis.
Recommendation
If a diagnosis of acinar dilation is made for a degree of dilation as shown in Figure 1 , this change should be graded and consistently evaluated in all animals. In such a situation, the pathology narrative can provide diagnostic criteria used to support the diagnosis. The degree of dilation shown in Figure 2 is beyond expected normal variation and should be diagnosed and graded.
萎缩Atrophy 凝固腺萎缩
描述（中文）
凝固腺（coagulating gland）萎缩表现为腺泡及衬覆上皮体积缩小。腺泡缩小和/或塌陷导致腺泡周围纤维肌肉组织更加显著。衬覆上皮细胞变薄，管腔内分泌物可能减少或消失。萎缩性改变可能与年龄相关，也可由去势或暴露于某些具有激素活性的外源性化学物引起。
诊断建议
凝固腺萎缩应当诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Atrophy of the coagulating gland consists of reduction in size of acini and of the lining epithelium. The ascinar reduction and/or collapse causes an increased prominence of the periacinar fibromuscular tissue. The lining epithelial cells are attenuated, and there may be reduction or absence of luminal secretory product. Atrophic changes may be age related and can be caused by castration or exposure to some hormonally active xenobiotics.
Recommendation
Atrophy of the coagulating gland should be diagnosed and graded.
上皮变性Epithelium Degeneration 前列腺变性
描述（中文）
上皮变性（epithelial degeneration）的特征是增大的腺泡上皮细胞胞质呈颗粒状至泡沫状改变，这些细胞形成单层衬覆层（Figure 1、Figure 2），或脱落并阻塞腺泡腔（Figure 3）。受累细胞增大，胞质富含细颗粒状物质，可发生破裂和解体。上皮变性可为局灶性（focal）或多灶性（multifocal）。该病变可见于任何叶，但最常见于腹侧叶。上皮变性在老龄前列腺中是相当常见的观察所见。该病变可伴有炎性浸润。
诊断建议
存在时，该病变应当诊断并分级。化学物质所致的加重值得在病理学叙述中记录。如有可能，应确定受累的叶，并在组织标识中指明。若成对的叶均受累，诊断应指明该变化为双侧性，严重程度依据受累更严重的叶判定。
参考切片图（2 张）
查看英文原文
Comment
Epithelial degeneration is characterized by granular to foamy cytoplasm alteration of enlarged acinar epithelial cells that form a single lining layer ( Figure 1 and Figure 2 ) or exfoliate and occlude the lumen of acini ( Figure 3 ). Affected cells are enlarged with abundant finely granular cytoplasm and may rupture and disintegrate. Epithelial degeneration can be focal or multifocal. The lesion can be observed in any lobe, but is most commonly found in the ventral lobe. Epithelial degeneration is a fairly common observation in the aging prostate. The lesion may be accompanied by inflammatory infiltrates.
Recommendation
When present, this lesion should be diagnosed and graded. Exacerbation by chemical agents warrants documentation in the pathology narrative. The affected lobe(s) should be identified if possible and indicated in the tissue identification. If paired lobes are involved, the diagnosis should indicate that the change is bilateral, with severity based on the more severely affected lobe.
上皮增生Epithelium Hyperplasia 前列腺增生
描述（中文）
增生（hyperplasia）的特征是上皮腺泡衬覆细胞数量增多，通常突入腺泡腔。增生通常累及1至3个相邻腺泡，衬覆细胞可几乎完全充满腺泡腔，但不压迫相邻腺泡。增生的细胞呈立方状至高柱状，在大鼠通常具有颗粒状嗜酸性胞质。当存在多个孤立的分泌区域时，可呈多房外观（Figure 3、Figure 4）。随着增生细胞堆积，部分细胞发生变性、坏死或凋亡（箭头，Figure 2）。在大鼠皮下给予α-雄激素激动剂去氧肾上腺素（phenylephrine）可诱导前列腺增生，其特征为上皮细胞堆积，呈乳头状和筛状结构并出芽。已有报道，老年 brown Norway 大鼠前列腺背叶和腹叶出现与增生一致的自发性年龄依赖性细胞过度生长。前列腺增生见于老龄动物，可累及任何叶。与前列腺腺瘤的鉴别主要基于：腺瘤为膨胀性、相对离散的上皮增生充满腺泡并压迫相邻腺泡。相比之下，TRAMP 小鼠中所见的前列腺增生由深嗜碱性细胞堆积构成（箭头，Figure 5）。在 TRAMP 小鼠中，部分研究者将这些病变视为前列腺上皮内瘤变（prostatic intraepithelial neoplasia）病变。
诊断建议
应记录增生的分布以及该病变的严重程度。如有可能，应确定受累的叶并在组织识别中注明（例如，prostate, ventral lobe, epithelium hyperplasia, 轻微（mild））。如果成对的叶均受累，诊断应限定为双侧性，严重程度评分以受累更严重的叶确定。任何可能治疗相关的增生增加均应记录在病理学叙述中，并与其他生殖和内分泌组织的相关变化相联系。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia is characterized by an increased number of epithelial acinar lining cells that typically project into the acinar lumen. Hyperplasia typically affects one to three contiguous acini, and the lining cells may almost completely fill the acinar lumen but do not compress contiguous acini. The hyperplastic cells range from cuboidal to tall columnar and in the rat usually have a granular eosinophilic cytoplasm. There may be a multilocular appearance when there are multiple isolated areas of secretion ( Figure 3 and Figure 4 ). As the hyperplastic cells pile up, some undergo degeneration and necrosis or apoptosis (arrow, Figure 2 ). Subcutaneous administration of the α-androgenic agonist phenylephrine in rats induces prostatic hyperplasia characterized by piling up of epithelial cells, with papillary and cribriform patterns and budding out. Spontaneous age-dependent overgrowth of cells, consistent with hyperplasia, in the dorsal and ventral lobes of prostate in old brown Norway rats has been reported. Prostatic hyperplasia is seen in aging animals and can involve any lobe. Distinction from prostatic adenoma is based largely on compression of contiguous acini by an expanding and relatively discrete epithelial proliferation filling acini. By way of contrast, the prostatic hyperplasia seen in the TRAMP mouse consists of piling up of hyperbasophilic cells (arrows, Figure 5 ). In the TRAMP mouse these are considered prostatic intraepithelial neoplasia lesions by some investigators.
Recommendation
The distribution of hyperplasia should be recorded, along with the severity of this lesion. The affected lobe(s) should be identified if possible and indicated in the tissue identification (e.g., prostate, ventral lobe, epithelium hyperplasia, mild). If paired lobes are affected, the diagnosis should be qualified as bilateral and the severity score determined by the more severely affected lobe. Any potentially treatment-related increase in hyperplasia should be documented in the pathology narrative and correlated with related changes in other reproductive and endocrine tissues.
水肿Edema 前列腺水肿
描述（中文）
水肿（edema）在前列腺中不是常见所见，可能与血管引流受阻有关。间质因淡染的嗜酸性、纤细的丝状物质而扩张。当出现时，宜查找明显的原因。炎症细胞因子、P物质（substance P）以及细胞毒性炎症因子1型阳性大肠杆菌（E. coli）已在大鼠中与前列腺水肿相关。NTP大鼠和小鼠研究中已记录到散发性前列腺水肿病例。
诊断建议
当出现时，水肿应当被诊断并分级。由于其位于间质，一个或多个叶可能受累，可能不需要叶的限定词。
参考切片图（2 张）
查看英文原文
Comment
Edema is not a common finding in the prostate and may be related to interruption of vascular drainage. The interstitium is expanded by lightly staining eosinophilic and delicate wispy material. When present, a search for an apparent cause is appropriate. Inflammatory cytokines, substance P, and cytotoxic inflammatory factor type 1-positive E. coli have been associated with prostate edema in rats. Sporadic cases of prostate edema have been documented in NTP rat and mouse studies.
Recommendation
When present, edema should be diagnosed and graded. Because it is interstitial, one or more lobes may be affected, and a lobe qualifier may not be needed.
炎症Inflammation 前列腺炎症
描述（中文）
前列腺炎（prostatitis）是啮齿类动物在化学品安全性和慢性毒性评价中常见的显微镜下所见。前列腺炎可为急性（Figure 1）、化脓性（Figure 2）、慢性活动性伴腺泡腔中性粒细胞及间质单核细胞浸润（Figure 3），或慢性伴间质纤维化（Figure 4）。腺泡衬覆上皮可保持完整，或可见变性、坏死或鳞状化生（Figure 2、Figure 3）。中性粒细胞穿过腺泡黏膜进入腺泡腔（Figure 1，箭头）。炎症可发生在前列腺的任何叶，或累及多叶。在啮齿类动物中引起前列腺炎的化学物罕见。然而，已有报道围产期暴露于雌激素类物质的大鼠发生前列腺炎。在大鼠中，经胎盘暴露于农用化学品阿特拉津（atrazine）可导致成年子代发生前列腺炎。一般认为，雌二醇诱导的大鼠侧叶前列腺炎症至少部分由垂体释放催乳素（prolactin）所介导。通过长期给予舒必利（sulpiride，一种具有抗精神病作用的 dopamine D2 拮抗剂）诱导实验性高催乳素血症，已证实可发生前列腺炎症。NTP 研究将炎症分为五个标准类别：急性、化脓性、慢性、慢性活动性和肉芽肿性。在急性炎症（急性（acute） inflammation）中，主要浸润细胞为中性粒细胞，但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症（化脓性（suppurative） inflammation）中的主要浸润细胞类型，但它们聚集在一起，其中许多已变性（化脓性渗出物）。渗出物中还可存在来自 resident 细胞群和浸润白细胞的细胞碎片、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子。肉眼上，这些病变以脓液存在为特征。渗出物周围组织可有成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。慢性炎症（慢性（chronic） inflammation）中以淋巴细胞为主。慢性活动性炎症（慢性活动性（chronic-active） inflammation）中也以淋巴细胞为主，但还存在显著数量的中性粒细胞。两种病变均可含有巨噬细胞。肉芽肿性炎症（肉芽肿性（granulomatous） inflammation）是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大的活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
前列腺炎及其被化学物加重的情况应进行分级和分类。如有可能，应确定受累的叶，并在组织标识中注明（例如，prostate, lateral lobe - inflammation, 化脓性（suppurative）, 中度（moderate））。当配对叶受累时，诊断应注明炎症为双侧性，严重程度分级应基于受累更严重的叶。相关变化如化生或变性，除非其范围和严重程度足以支持，否则不应诊断。
参考切片图（2 张）
查看英文原文
Comment
Prostatitis is a common microscopic observation in rodents observed during the safety and chronic toxicity assessments of chemicals. Prostatitis can be acute ( Figure 1 ), suppurative ( Figure 2 ), chronic-active with neutrophils in acinar lumens and mononuclear cells in the interstitium ( Figure 3 ), or chronic with interstitial fibrosis ( Figure 4 ). The acinar lining epithelium may remain intact ( Figure 1 ) or have evidence of degeneration, necrosis, or squamous metaplasia ( Figure 2 and Figure 3 ). Neutrophils gain access to the acinar lumen by passing through the acinar mucosa ( Figure 1 , arrows). Inflammation can occur in any lobe of the prostate or involve multiple lobes. Chemical agents causing prostatitis in rodents are rare. However, prostatitis has been recorded in rats exposed to estrogenic agents perinatally. In rats, transplacental exposure of atrazine, an agrochemical, results in prostatitis in the adult offspring. It is thought that estradiol-induced inflammation in the rat lateral prostate is mediated, at least in part, by the release of prolactin from the pituitary gland. Prostatic inflammation was demonstrated by experimental hyperprolactinemia induced by chronic administration of sulpiride, a dopamine D2 antagonist with antipsychotic effect. NTP studies have five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris from both the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may have fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
Prostatitis and its exacerbation by chemical agents should be graded and classified. The affected lobe(s) should be identified if possible and indicated in the tissue identification (e.g., prostate, lateral lobe - inflammation, suppurative, moderate). When paired lobes are affected, the diagnosis should indicate the inflammation is bilateral, and the severity grade should be based on the more severely affected lobe. Associated changes such as metaplasia or degeneration should not be diagnosed unless warranted by their extent and severity.
矿化Mineralization 前列腺矿化
描述（中文）
矿化（mineralization）的特征是局灶性（focal）至弥漫性（diffuse）的嗜碱性、各向异性、不规则颗粒状物质蓄积，可累及腺泡（Figure 1、Figure 2）或血管壁。此种程度的矿化不常见。可能发生两种类型的矿化：转移性（metastatic，与血钙水平升高相关的正常组织钙化）或营养不良性（dystrophic，与血钙水平升高无关的异常或退化组织中的矿物质沉积）。
诊断建议
在前列腺的组织病理学评价中，应诊断矿化并给出严重程度分级。如有可能，应确定受累的叶，并在组织标识中注明。如果成对的叶均受累，诊断应注明为双侧性，严重程度以受累较重的叶为准。
参考切片图（2 张）
查看英文原文
Comment
Mineralization is characterized by focal to diffuse accumulation of basophilic, anisotropic, irregular granular material that may involve the glandular acini ( Figure 1 and Figure 2 ) or vessel wall. This degree of mineralization is unusual. Two types of mineralization may occur: metastatic (calcification of normal tissue associated with high blood levels of calcium) or dystrophic (mineral deposits in abnormal or degenerating tissue not associated with increased blood levels of calcium).
Recommendation
Mineralization should be diagnosed during histopathologic evaluation of prostate and given a severity grade. The affected lobe(s) should be identified if possible and indicated in the tissue identification. If paired lobes are affected, the diagnosis should be indicated as bilateral and the degree of severity based on more severely affected lobe.
腺泡分泌改变（含凝结物）Acinus Secretoryalteration(concretions) 前列腺其他
描述（中文）
随着啮齿类动物年龄增长，生殖活动减少，前列腺腺泡（prostatic acini）内的分泌物质发生改变。这种改变可以是弥漫性的，也可以局限于任一叶，但以腹叶（ventral lobe）多见。组织学表现多样，从玻璃样团块，到细颗粒或粗颗粒状分泌物，再到深嗜碱性颗粒状沉淀物（箭头，Figure 2），常呈混合性表现（Figure 1、Figure 2）。腺泡上皮衬里通常为低立方状至扁平状。发生改变的分泌物有时称为凝结物（concretions），本质上是变性的分泌蛋白和细胞碎片，有时伴有矿化。
诊断建议
分泌改变在慢性研究中常见，除非存在明显的与处理相关的影响，通常不予记录。然而，在持续时间不超过90天的亚慢性研究中，该改变并不常见，若有任何提示处理直接或间接作用的迹象，则应在这些研究中作出诊断。如有可能，应确定受累的叶，并在组织标识中注明。任何诊断均应给出严重程度分级；若成对叶均受累，诊断应限定为双侧性（双侧（bilateral）），严重程度以受累较重的一侧叶为准。
参考切片图（2 张）
查看英文原文
Comment
As rodents age, there is decreased reproductive activity and alterations of secretory material in prostatic acini. This can be generalized or localized within any lobe, but with a predilection for the ventral lobe. The histologic appearance varies from hyaline masses, to finely or coarsely granulated secretion, to deeply basophilic granular precipitates (arrows, Figure 2 ), often appearing as a mixture ( Figure 1 and Figure 2 ). The acinar epithelial lining typically is low cuboidal to flattened. The altered secretion, sometimes referred to as concretions, is essentially denatured secretory protein and cellular debris, sometimes with mineralization.
Recommendation
Secretory alteration is common in chronic studies and is typically not documented unless there is an obvious treatment-related effect. However, it is not common in prechronic studies up to 90 days in duration and should be diagnosed in those studies if there is any indication of a direct or indirect effect of treatment. The affected lobe(s) should be identified if possible and indicated in the tissue identification. Any diagnosis should be given a severity grade, and if paired lobes are affected, the diagnosis should be qualified as bilateral, with severity based on the more severely affected lobe.
腺泡囊肿（黏液性）Acinus Cyst(s)Mucinous 前列腺囊肿
描述（中文）
尽管黏液性囊肿是前列腺导管扩张的一种类型，但该病变近期在研究中被发现，值得单独诊断。黏液性囊肿（Figure 1、Figure 2）已在大黄素和蒽醌慢性研究中的少量受处理F344大鼠中记录到。黏液性囊肿衬覆上皮内可见杯状细胞（Figure 2，箭头）。
诊断建议
前列腺黏液性囊肿代表一种独立的病变实体，目前需要单独诊断以与腺泡扩张相区分。应记录其发生情况并进行分级，如存在双侧受累应予记录，严重程度依据受累更严重的叶判定。在可能的情况下，应确定受累的前列腺叶。
参考切片图（2 张）
查看英文原文
Comment
Although mucinous cysts are a type of prostate duct dilation, the condition has recently been seen in studies and warrants a separate diagnosis. Mucinous cysts ( Figure 1 and Figure 2 ) have been documented in a small number of treated F344 rats in emodin and anthraquinone chronic studies. Goblet cells are present in the lining epithelium of the mucinous cysts ( Figure 2 , arrows).
Recommendation
Prostatic mucinous cysts represent a distinct entity that presently requires a separate diagnosis to distinguish it from acinar dilation. Their occurrence should be graded, and bilateral involvement should be documented if present, with severity based on the more severely affected lobe. When possible, the affected prostate lobe should be identified.
腺泡扩张Acinus Dilation 前列腺扩张
描述（中文）
前列腺扩张（ectasia）或扩张（dilation）的特征是腺泡有时因分泌物质而膨胀，并被变薄的上皮细胞所衬覆（Figure 1、Figure 2、Figure 3、Figure 4）。可能出现明显的腺泡增大，尤其是伴有周围未受累腺泡和实质的显著受压，扩张呈囊性外观（Figure 3、Figure 4）。受累腺泡的分泌物质可表现为接近正常的染色反应（Figure 1、Figure 2），也可如 Figure 3、Figure 4 中所示的静息腺体那样染色不良。受累腺泡可见于任何叶，并可累及叶的一部分或整个叶。这很可能是与年龄相关的病变，并可能与间质炎症相关。
诊断建议
在毒性研究的前列腺组织病理学评价中，前列腺扩张应被记录并给予严重程度分级。如有可能，应确定受累的叶，并在组织标识中注明（例如，prostate, dorsolateral lobe, acinus - dilation, 中度（moderate））。如果成对的叶均受累，诊断应限定为双侧性（双侧（bilateral）），严重程度基于受累更严重的腺体。
参考切片图（2 张）
查看英文原文
Comment
Ectasia or dilation of the prostate is characterized by acini that are sometimes distended with secretory material and lined by attenuated epithelial cells ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). There may be marked acinar enlargement, particularly with significant compression of surrounding unaffected acini and parenchyma, with the dilation appearing cystic ( Figure 3 and Figure 4 ). Affected acinar secretory material can exhibit either a near normal staining reaction ( Figure 1 and Figure 2 ) or can be poorly stained as in the quiescent gland shown in Figure 3 and Figure 4 . Affected acini can be observed in any lobe and can involve either a part or the entire lobe. This is likely an age-related lesion and may be associated with interstitial inflammation.
Recommendation
Prostatic dilatation should be recorded and given a severity grade during histopathologic evaluation of prostate from toxicity studies. The affected lobe(s) should be identified if possible and indicated in the tissue identification (e.g., prostate, dorsolateral lobe, acinus - dilation, moderate). If paired lobes are both affected, the diagnosis should be qualified as bilateral, with severity based on the more severely affected gland.
腺泡萎缩Acinus Atrophy 前列腺萎缩
描述（中文）
前列腺萎缩（prostatic atrophy）表现为腺体皱缩，显微镜下特征为腺泡（acini）体积减小、被覆上皮细胞变薄、分泌物质稀少以及间质突出度增加（星号，Figure 4）。Figure 1、Figure 2 展示正常前列腺的背侧叶（dorsolateral lobe）以供比较。一般而言，萎缩累及前列腺所有叶。抑制促性腺激素类固醇和垂体激素可导致睾丸及附属生殖器官（包括前列腺）萎缩。5α-还原酶（5α-reductases）是参与前列腺内睾酮转化为其生物活性形式双氢睾酮（dihydrotestosterone）的酶，其抑制剂如非那雄胺（finasteride）和依普甾胺（epristeride）已知可诱导前列腺萎缩。同样，抗雄激素物质如羟基氟他胺（hydroxyflutamide）可引起前列腺萎缩。雌激素使腹侧前列腺和精囊的腺上皮体积减小、纤维肌性间质增加。锌指转录因子 Egr 家族（如 Egr4 和 Egr1）的缺陷，如在 Egr4-Egr1 双突变小鼠中，导致前列腺、睾丸、附睾和精囊萎缩。自发性前列腺萎缩是一种与年龄相关的病变。
诊断建议
前列腺萎缩应当诊断并分级，治疗相关的加重应在病理叙述中指明。如有可能，应确定受累的叶并在组织识别中指明（例如，prostate, dorsolateral lobe, acinus - atrophy, severe）。当已知时，应指明双侧受累，并根据受累更严重的叶确定严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Prostatic atrophy represents glandular shrinkage and is microscopically characterized by reduction in the size of acini, attenuation of lining epithelial cells, scanty secretory material, and increased stromal prominence (asterisks, Figure 4 ). Figure 1 and Figure 2 represent the dorsolateral lobe of normal prostate for comparison. In general, atrophy involves all lobes of the prostate. Inhibition of gonadal steroid and pituitary hormones results in atrophy of testes and accessory sex organs, including prostate. Inhibitors of 5α-reductases, enzymes involved in intraprostatic conversion of testosterone to its biologically active form dihydrotestosterone, such as finasteride and epristeride, are known to induce atrophy of prostate. Similarly, antiandrogenic substances such as hydroxyflutamide cause prostatic atrophy. Estrogens decrease the volume of the glandular epithelium and increase the fibromuscular stroma in both ventral prostate and seminal vesicle. Deficiency of the Egr family of zinc finger transcription factors such as Egr4 and Egr1, as in Egr4-Egr1 double-mutant mice, leads to atrophy of prostate, testis, epididymis, and seminal vesicle. Spontaneous prostatic atrophy is an age-related lesion.
Recommendation
Prostatic atrophy should be diagnosed and graded, and treatment-associated exacerbation should be indicated in the pathology narrative. The affected lobe(s) should be identified if possible and indicated in the tissue identification (e.g., prostate, dorsolateral lobe, acinus - atrophy, severe). When known, bilateral involvement should be indicated and the severity grade determined by the more severely affected lobe.
坏死Necrosis 包皮腺坏死
描述（中文）
包皮腺坏死表现为细胞细节丧失、嗜酸性粒细胞增多（hypereosinophilia），以及被细胞碎片和核碎裂碎片所取代（星号，Figure 1、Figure 2）。坏死区域通常与邻近未受累的腺体界限分明（Figure 1、Figure 2）。坏死碎片应仔细与正常情况下在导管内观察到的嗜酸性角化物质相鉴别。坏死可为局灶性（focal）或多灶性（multifocal），可能累及一个或两个腺体，并可能与炎症相关。在 Figure 1、Figure 2 中，坏死是主要反应，不伴有炎症。
诊断建议
坏死应记录并分级，若因化学物给药而加重，则应在病理学叙述中予以记录。若两个腺体均受累，诊断应限定为双侧（bilateral），严重程度基于受累更严重的腺体。当坏死作为炎症的继发反应出现时，除非异常严重，否则无需诊断，但可在病理学叙述中提及。
参考切片图（2 张）
查看英文原文
Comment
Necrosis of preputial gland consists of loss of cellular detail, hypereosinophilia, and replacement by cellular and karyorrhectic debris (asterisk, Figure 1 and Figure 2 ). The necrotic area is often distinct from the adjacent unaffected gland ( Figure 1 and Figure 2 ). The necrotic debris should be carefully differentiated from the hypereosinophilic keratinous material normally observed within ducts. Necrosis can be focal or multifocal, may involve one or both glands, and may be associated with inflammation. In Figure 1 and Figure 2 , the necrosis is the major response without associated inflammation.
Recommendation
Necrosis should be recorded and graded, and if exacerbated by chemical administration, this should be documented in the pathology narrative. If both glands are affected, the diagnosis should be qualified as bilateral and the severity based on the more severely affected gland. When necrosis is present as a secondary response to inflammation, it need not be diagnosed unless unusually severe but may be mentioned in the pathology narrative.
增生Hyperplasia 包皮腺增生
描述（中文）
腺体增生（glandular hyperplasia）的特征是腺泡（acini）数量和体积增加（Figure 1、Figure 2）。增大的（肥大的）上皮细胞使腺泡轮廓变形，这些细胞可能含有嗜酸性颗粒状物质（星号，Figure 2）。肥大区域可边缘性地压迫邻近腺体。腺体增生与年龄相关。导管增生（ductular hyperplasia）的特征是导管鳞状上皮增厚，常形成吻合的梁状模式（箭头，Figure 3）。偶见导管增生与腺泡增生见于同一腺体。导管增生在老年啮齿类动物中常见，可能是鳞状细胞癌的前驱病变。腺泡增生被认为是肿瘤前病变（preneoplastic），应与腺瘤相鉴别。在腺泡增生中，腺泡显得比正常更大，并有一定程度的拥挤。包皮腺腺瘤（preputial glandular adenomas）更为局限，并伴有邻近组织的压迫，且腺泡的细胞组织结构可能不规则。同样，导管增生应与鳞状细胞乳头状瘤相鉴别。后者可形成由结缔组织核心支持的乳头，并可能有相互连接的增殖性鳞状上皮索。
诊断建议
包皮腺的导管增生和腺体增生应记录并分级。如果两者同时发生，两者均应诊断。当两侧腺体均受累时，诊断应限定为双侧（双侧（bilateral）），严重程度分级应基于受累更严重的腺体。
参考切片图（2 张）
查看英文原文
Comment
Glandular hyperplasia is characterized by an increase in the number and size of acini ( Figure 1 and Figure 2 ). The acinar outline is distorted by enlarged (hypertrophic) epithelial cells that may contain eosinophilic granular material (asterisks, Figure 2 ). The hypertrophic area may marginally compress the adjoining glands. Glandular hyperplasia is age related. Ductular hyperplasia is characterized by increased thickness of ductal squamous epithelium that often forms an anastomosing trabecular pattern (arrows, Figure 3 ). Occasionally, ductular and acinar hyperplasias may be seen in the same gland. Ductular hyperplasia is common in aged rodents and may be a precursor to squamous cell carcinoma. Acinar hyperplasia is considered preneoplastic and should be differentiated from adenomas. In acinar hyperplasia, the acini appear larger than normal, with some crowding. Preputial glandular adenomas are more circumscribed and are associated with compression of adjacent tissue, and cellular organization with acini may be irregular. Likewise, ductular hyperplasia should be distinguished from squamous cell papillomas. The latter may form papillae supported by connective tissue cores and may have interconnecting cords of proliferative squamous epithelium.
Recommendation
Ductular and glandular hyperplasia of the preputial gland should be recorded and graded. If they occur together, both should be diagnosed. When both glands are involved, the diagnosis should be qualified as bilateral, and the severity grade should be based on the more severely affected gland.
导管扩张Duct Dilation 包皮腺扩张
描述（中文）
Figure 1、Figure 2 显示若干囊性结构；大多数衬覆扁平上皮，为扩张的导管。导管扩张（ductular dilation）的特征可能为积聚明亮的嗜酸性物质，符合角蛋白及角蛋白碎屑（Figure 3、Figure 4）。扩张导管的衬覆上皮常呈萎缩。导管扩张随年龄增长而加重。
诊断建议
囊肿（cyst）和导管扩张应记录并分级。若双侧腺体均受累，诊断应限定为双侧性（双侧（bilateral）），严重程度分级应基于受累更严重的腺体。潜在的治疗相关效应应在病理学描述中记录。
参考切片图（2 张）
查看英文原文
Comment
Figure 1 and Figure 2 show several cystic structures; most are lined by flattened epithelium and are dilated ducts. Ductular dilation may be characterized by accumulation of brightly eosinophilic material consistent with keratin and keratin debris ( Figure 3 and Figure 4 ). The lining epithelium of dilated ducts is often atrophic. Ductular dilatation increases with age.
Recommendation
Cyst and ductular dilatation should be recorded and graded. If both glands are involved, the diagnosis should be qualified as bilateral and the severity grade based on the more severely affected gland. Potential treatment-related effects should be documented in the pathology narrative.
炎症Inflammation 包皮腺炎症
描述（中文）
包皮腺炎症由腺体和导管内大量细胞性渗出物浸润构成（星号，Figure 1、Figure 2、Figure 3、Figure 4）。该炎症可为化脓性（Figure 1、Figure 2）或慢性/慢性活动性（Figure 3、Figure 4）。炎症常见，尤其是在年龄较大的动物中。该病变可为局灶性（focal）、多灶性（multifocal）或弥漫性（diffuse），并可累及一侧或双侧腺体。NTP研究将炎症分为五个标准类别：急性、化脓性、慢性、慢性活动性和肉芽肿性。在急性炎症中，主要浸润细胞为中性粒细胞，但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但它们聚集在一起，其中许多发生变性（化脓性渗出物）。渗出物中还可能存在来自 resident 细胞群和浸润白细胞的细胞碎片、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子。肉眼观察，这些病变将以脓液存在为特征。渗出物周围组织可能有成纤维细胞、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但还存在大量中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的、活化的巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
包皮腺炎症应当记录、分类并分级。如果双侧腺体均受累，诊断应当明确为双侧性，严重程度基于受累更严重的腺体。
参考切片图（2 张）
查看英文原文
Comment
Preputial gland inflammation consists of infiltration of abundant cellular exudates (asterisks, Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) in the gland and the ducts. The inflammation can be suppurative ( Figure 1 and Figure 2 ) or chronic/chronic-active ( Figure 3 and Figure 4 ). Inflammation is common, particularly in older animals. This lesion can be focal, multifocal, or diffuse and may involve one or both glands. NTP studies have five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris from both the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may have fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
Inflammation of the preputial gland should be recorded, classified, and graded. If both glands are involved, the diagnosis should be clarified as bilateral and the severity based on the more severely affected gland.
矿化Mineralization 包皮腺矿化
描述（中文）
矿化（mineralization）由不规则无定形嗜碱性物质沉积构成（箭头，Figure 1、Figure 2）。矿化可发生两种类型：转移性（metastatic，与血钙水平升高相关的正常组织钙化）或营养不良性（dystrophic，与血钙水平升高无关的异常或退化组织中的矿物质沉积）。当呈全身性时，转移性矿化可存在于多个器官。矿化可为局灶性（focal）或多灶性（multifocal）。包皮腺中的矿化不常见，很可能是与化学处理无关的偶然发现。然而，它可能与炎症相关（Figure 2）。
诊断建议
矿化应记录并给予严重程度分级。如果两侧腺体均受累，诊断应限定为双侧（bilateral），严重程度基于受累更严重的腺体。如果作为全身性反应发生于多个组织，则不必单独诊断包皮腺中的矿化。然而，其在包皮腺中的存在可在病理学叙述中提及。
参考切片图（2 张）
查看英文原文
Comment
Mineralization consists of deposition of irregular amorphous basophilic material (arrows, Figure 1 and Figure 2 ). Two types of mineralization may occur: metastatic (calcification of normal tissue associated with high blood levels of calcium) or dystrophic (mineral deposits in abnormal or degenerating tissue not associated with increased blood levels of calcium). When systemic, metastatic mineralization can be present in multiple organs. Mineralization can be focal or multifocal. Mineralization in the preputial gland is unusual and is likely an incidental finding unrelated to chemical treatment. However, it may be associated with inflammation ( Figure 2 ).
Recommendation
Mineralization should be recorded and given a severity grade. If both glands are affected, the diagnosis should be qualified as bilateral and the severity based on the more severely affected gland. If it occurs in multiple tissues as a systemic response, it is not necessary to separately diagnose mineralization in the preputial gland. However, its presence in the preputial gland may be mentioned in the pathology narrative.
萎缩Atrophy 包皮腺萎缩
描述（中文）
包皮腺萎缩（preputial gland atrophy）表现为腺泡体积缩小，以及构成萎缩腺泡的腺泡上皮细胞数量减少。明显的纤维化（fibrosis）可与腺泡萎缩相伴出现（Figure 1）。包皮腺萎缩可能是一种背景性病变。它常与慢性炎症或其他年龄相关病变有关。
诊断建议
当包皮腺萎缩是主要改变时，应当予以诊断并分级。如果认为它继发于炎症或其他病变，则不应单独诊断，除非其严重程度足以支持单独诊断。同样，相关病变如果被认为是继发于萎缩，也不应单独诊断，除非其严重程度足以支持单独诊断。如果两个腺体均存在萎缩，应注明为双侧性（双侧（bilateral））。
参考切片图（1 张）
查看英文原文
Comment
Preputial gland atrophy consists of reduction in the size of acini and reduction in the number of acinar epithelial cells comprising the atrophic acini. Prominent fibrosis may be associated with the acinar atrophy ( Figure 1 ). Preputial gland atrophy may be a background lesion. It is often associated with chronic inflammation or other age-associated lesions.
Recommendation
Preputial gland atrophy should be diagnosed and graded when it is a predominant change. If it is considered secondary to inflammation or another lesion, it should not be diagnosed separately unless warranted by severity. Likewise, associated lesions, if considered secondary to atrophy, should not be diagnosed separately unless warranted by severity. If atrophy is present in both glands, it should be qualified as bilateral.
骨性化生Metaplasia Osseous 包皮腺化生
描述（中文）
以类骨质（星号，Figure 2）形成以及矿化类骨质取代腺体实质为特征的骨化生是一种不常见的观察所见，很可能是偶然发现。
诊断建议
骨化生应当记录并分级。如果两侧腺体均受累，诊断应当限定为双侧性，严重程度依据受累更严重的腺体判定。
参考切片图（2 张）
查看英文原文
Comment
Osseous metaplasia characterized by formation of osteoid (asterisk, Figure 2 ), and mineralized osteoid that replaces the glandular parenchymal is an uncommon observation and likely an incidental finding.
Recommendation
Osseous metaplasia should be recorded and graded. If both glands are affected, the diagnosis should be qualified as bilateral and the severity based on the more severely affected gland.
淀粉样物质Amyloid 睾丸其他
描述（中文）
睾丸淀粉样变是指间质内出现细胞外积聚的均质、嗜酸性、无定形物质（箭头，Figure 1、Figure 2）。刚果红染色后，该物质在偏振光下发出绿色双折射光。淀粉样物质可呈局灶性（focal）或多灶性（multifocal）分布（Figure 1、Figure 2），也可呈弥漫性（diffuse）分布（Figure 3、Figure 4），且通常为双侧分布。淀粉样物质可疏松沉积于间质间隙内（Figure 3），也可蓄积于血管壁内（Figure 2）或管周肌样细胞层内（Figure 4）。严重病例中，实质被破坏，萎缩的肾小管残余被成团的淀粉样物质广泛分隔。淀粉样物质沉积可为局限性（仅累及一个器官），或更常见地为全身性（累及多个器官系统）。
诊断建议
凡出现淀粉样变，均应作出诊断并分级；若其发生率和/或严重程度似乎与化学物给药相关，则应在病理学叙述中加以讨论。若为双侧性，应在诊断中注明。相关病变如生殖细胞变性或生精上皮萎缩，除非其严重程度足以需要单独诊断，否则不应单独诊断，但应在叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Testicular amyloid consists of extracellular accumulation of homogeneous, eosinophilic and amorphous material in the interstitium (arrows, Figure 1 and Figure 2 ). When stained with Congo red, the material emits a green birefringence with polarized light. Amyloid can be focal or multifocal ( Figure 1 and Figure 2 ) or diffuse ( Figure 3 and Figure 4 ) and is generally bilateral in distribution. The amyloid may be deposited loosely within the interstitial space ( Figure 3 ) or accumulate within the vascular walls ( Figure 2 ) or within the peritubular myoid cell layer ( Figure 4 ). In severe cases, the parenchyma is effaced and the remnants of atrophic tubules are widely separated by clumps of amyloid. Amyloid deposition may be localized (involving only one organ) or, more commonly, systemic (involving several organ systems).
Recommendation
Whenever present, amyloid should be diagnosed and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. Bilaterality should be indicated in the diagnosis if present. Associated lesions such as germ cell degeneration or germinal epithelium atrophy should not be diagnosed separately unless warranted by their severity, but should be described in the narrative.
炎症Inflammation 睾丸炎症
描述（中文）
睾丸炎症的特征是炎症细胞浸润以应对组织损伤。睾丸中的炎症反应非常罕见，通常仅在精曲小管坏死或组织损伤足以破坏构成血-睾屏障的支持细胞紧密连接时才可见到。精曲小管变性和萎缩通常不伴有炎症反应。炎症浸润很少作为对化学物质的直接反应而出现；一个例外是对支持细胞毒物邻苯二甲酸二正戊酯的急性反应，其中出现了一过性间质中性粒细胞浸润，并与任何显著小管损伤之前白细胞介素的释放相关。在大多数情况下，炎症浸润仍局限于间质区室，但可能穿透精曲小管，并且罕见地破坏并以纤维化取代它们。细胞渗出物决定炎症类型，在Figure 1、Figure 2所示的例子中主要为中性粒细胞性，但也可能为淋巴细胞性或肉芽肿性。睾丸炎症可为单侧或双侧。NTP研究有五种标准炎症类别：急性、化脓性、慢性、慢性活动性和肉芽肿性。在急性炎症中，主要浸润细胞为中性粒细胞，尽管也可能存在较少的巨噬细胞和淋巴细胞。也可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但它们聚集，且其中许多发生变性（化脓性渗出物）。来自驻留细胞群和浸润白细胞的细胞碎片、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子也可能存在于渗出物中。大体上，这些病变将以脓液的存在为特征。渗出物周围的组织可能有成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大的、活化的巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
无论何时出现，炎症都应记录、分类、分级，并在病理学叙述中描述（若因处理而加重）。如果双侧睾丸均受累，诊断应限定为双侧，严重程度基于受累更严重的睾丸。
参考切片图（2 张）
查看英文原文
Comment
Testicular inflammation is characterized by infiltration of inflammatory cells in response to tissue damage. Inflammatory responses in the testis are very uncommon and are usually seen only in response to seminiferous tubular necrosis or tissue damage sufficient to break down the Sertoli cell tight junctions that make up the blood-testis barrier. Seminiferous tubular degeneration and atrophy are generally not accompanied by an inflammatory response. Inflammatory infiltrates are rarely seen as a direct response to chemical agents; an exception is the acute response to the Sertoli cell toxicant di-n-pentyl phthalate, where a transient, interstitial neutrophilic infiltrate occurred and was associated with the release of interleukin prior to any significant tubular damage. In most cases the inflammatory infiltrate remains in the interstitial compartment, but it may penetrate the seminiferous tubules and, rarely, destroy and replace them with fibrosis. The cellular exudate determines the type of inflammation, which is predominantly neutrophilic in the example shown in Figure 1 and Figure 2 but may also be lymphocytic or granulomatous. Testicular inflammation can be unilateral or bilateral. NTP studies have five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, thoughfewer macrophages and lymphocytes may also be present. There may also be evidence of edema orhyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris from both the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present within the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may have fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
Whenever present, inflammation should be recorded, classified, graded, and described in the pathology narrative, if exacerbated by treatment. If both testes are affected, the diagnosis should be qualified as bilateral and the severity based on the more severely affected testis.
生殖细胞脱落Germ Cell Exfoliation 睾丸其他
描述（中文）
生精上皮内的生殖细胞可发生变性和/或凋亡，也可与周围支持细胞胞质突起失去接触而脱落进入管腔（Figure 1、Figure 2）。脱落的生殖细胞通常保持相对正常的形态。这些细胞会迅速被输送至附睾，并出现在附睾管腔内。该发现不应与尸检解剖时挤压睾丸所致的生殖细胞人为脱落相混淆。在尸检创伤所致脱落的情况下，附睾中不会见到生殖细胞。生殖细胞脱落已被描述为给予邻苯二甲酸酯类以及微管抑制剂（如秋水仙碱和杀菌剂多菌灵）后的主要发现。
诊断建议
“生殖细胞脱落”一词应保留用于以生殖细胞大量脱落进入管腔为主要发现的情形。在这些情形下，应诊断生殖细胞脱落并对其进行分级，且若其发生率和/或严重程度似乎与受试物给予相关，应在病理学叙述中加以讨论。存在双侧受累时应予以诊断。若同时存在显著的生殖细胞变性，也应予以诊断并给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Germ cells may undergo degeneration and/or apoptosis within the seminiferous epithelium, or they may lose contact with the surrounding Sertoli cell cytoplasmic processes and be shed into the tubular lumen ( Figure 1 and Figure 2 ). Often the exfoliated germ cells retain relatively normal morphology. The cells will rapidly be transported into the epididymis and will be present in the ductular lumens. The finding should not be confused with artifactual sloughing of germ cells caused by squeezing of the testis during necropsy dissection. In the case of sloughing due to necropsy trauma, germ cells will not be seen in the epididymis. Germ cell exfoliation has been described as a predominant finding following administration of phthalate esters and microtubule inhibitors such as colchicine and the fungicide carbendazim.
Recommendation
The term "germ cell exfoliation" should be reserved for those situations where there is extensive shedding of germ cells into the lumen as a predominant finding. In those situations, germ cell exfoliation should be diagnosed and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. Bilateral involvement should be diagnosed when present. If there is significant concurrent germ cell degeneration, that should also be diagnosed and given a severity grade.
生精上皮变性Germinal Epithelium Degeneration 睾丸变性
描述（中文）
生精上皮变性是一个非特异性术语，通常包括多种退行性特征，如小管空泡化、生精细胞部分或节段性耗竭、退行性（多核或凋亡）生精细胞（通常不限于特定生精细胞类型或阶段），以及生精细胞层排列紊乱（Figure 1、Figure 2、Figure 3、Figure 4）。根据严重程度，可能出现睾丸肉眼体积缩小和器官重量减轻。该病变可进展为生精细胞完全丧失，仅遗留由Sertoli细胞衬覆的收缩小管（见Testis - Germinal Epithelium - Atrophy）。生精小管常呈现混合性影响，部分显示变性，另一些已进展为萎缩。化学诱导的生精上皮变性可呈多灶性（multifocal）分布，但最常见为双侧病变，不同程度地累及大多数生精小管（Figure 1）。它也可以是任何年龄大鼠和小鼠的偶然性背景发现，但发生率随年龄增长而增加。取决于毒物不同，在短期研究（约14-28天）中，生精上皮变性的最早证据之前可能先出现特定的退行性特征，如空泡化或细胞及阶段特异性的生精细胞变性/耗竭。
诊断建议
在常规毒性研究中，生精上皮变性应当被诊断和分级，并且如果它被认为是主要改变且发生率和/或严重程度似乎与化学物给药相关，则应当在病理学叙述中讨论。如果双侧睾丸均受累，诊断应当指明该病变为双侧性，严重程度应当基于受累更严重的睾丸。由于变性被认为是萎缩的前驱病变，应当诊断变性，除非大多数小管缺乏生精细胞，在这种情况下萎缩是首选诊断。伴随存在的部分生精上皮萎缩或生精细胞特异性变性/耗竭的证据可在病理学叙述中提及。如果同一项研究中使用了这两个术语，病理学家有责任在病理学叙述中描述这两种病变之间的关系。相关链接：Testis - Germinal Epithelium - Atrophy
参考切片图（2 张）
查看英文原文
Comment
Germinal epithelium degeneration is a nonspecific term that generally includes a number of degenerative features, such as tubular vacuolation, partial or segmental depletion of germ cells, degenerating (multinucleated or apoptotic) germ cells generally not restricted to a specific germ cell type or stage, and disordered arrangement of the germ cell layers ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Depending on severity, there may be a macroscopic reduction in size of the testis and a reduction in organ weight. The condition may progress to total loss of germ cells, leaving contracted tubules lined only by Sertoli cells (see Testis - Germinal Epithelium - Atrophy ). Frequently, there is a mixed effect on seminiferous tubules, with some showing degeneration and others having progressed to atrophy. Chemically induced germinal epithelium degeneration can be multifocal in distribution, but it is most often a bilateral lesion that affects most of the seminiferous tubules to varying degrees ( Figure 1 ). It can also be an incidental background finding in rats and mice of any age, but the incidence increases with age. Depending upon the toxicant, in short-duration studies (~14-28 days) the earliest evidence of germinal epithelium degeneration may be preceded by specific degenerative features, such as vacuolation or cell- and stage -specific degeneration/depletion of germ cells.
Recommendation
In routine toxicity studies, germinal epithelium degeneration should be diagnosed and graded and should be discussed in the pathology narrative if it is considered the primary change and if the incidence and/or severity appears to be related to chemical administration. If both testes are affected, the diagnosis should indicate the condition is bilateral, and severity should be based on the more severely affected testis. Since degeneration is thought to be a precursor to atrophy, degeneration should be diagnosed unless the majority of the tubules are devoid of germ cells, in which case atrophy is the preferred diagnosis. The concomitant presence of some germinal epithelium atrophy or evidence that germ cell–specific degeneration/depletion is present can be mentioned in the pathology narrative. If both terms are used in a single study, it is incumbent upon the pathologist to describe the relationship between the two lesions in the pathology narrative. Related Links: Testis - Germinal Epithelium - Atrophy
生精上皮萎缩Germinal Epithelium Atrophy 睾丸萎缩
描述（中文）
生精上皮萎缩（Germinal epithelium atrophy）（Figure 1、Figure 2、Figure 3、Figure 4）表现为生精小管完全缺乏生殖细胞，仅由支持细胞（Sertoli cell）衬覆。生精小管可出现管腔扩张（Figure 1、Figure 2）或管腔收缩（Figure 4）。若管腔扩张，萎缩很可能由长期严重的管腔扩张所致压力（即压迫性萎缩）引起（另见 Testis - Seminiferous Tubule - Dilation）。该病变可为单侧或双侧，呈 局灶性（focal）、多灶性（multifocal） 或 弥漫性（diffuse），在小鼠和大鼠各年龄段均可作为偶发性发现出现，发生率随年龄增长而升高。生精上皮萎缩是一种终末期病变，通常先有或伴有生精小管变性。依严重程度不同，受累睾丸肉眼观可松弛，体积和重量减小。严重的 弥漫性 生精上皮萎缩常不可逆。大鼠中可见散在生精小管伴生殖细胞萎缩，属衰老性改变。
诊断建议
若生精上皮萎缩被认为是主要病变，且其发生率和/或严重程度似乎与受试物给药相关，则应作出诊断、进行分级，并在病理学叙述中加以讨论。由于生精上皮萎缩被视为变性的终末期，萎缩的诊断应保留用于大多数受累小管缺乏生殖细胞的病例，否则变性是更合适的诊断（见 Testis - Germinal Epithelium - Degeneration）。若同时存在两种病变（既有萎缩的小管又有变性小管），可在病理学叙述中描述。若同一研究中同时使用这两个术语，病理学家有责任在病理学叙述中描述两种病变之间的关系。若双侧睾丸均受累，诊断应标明为双侧，严重程度分级应基于受累更严重的睾丸。相关链接：Testis - Seminiferous Tubule - Dilation；Testis - Germinal Epithelium - Degeneration
参考切片图（2 张）
查看英文原文
Comment
Germinal epithelium atrophy ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) consists of seminiferous tubules that are completely devoid of germ cells and lined only by Sertoli cells. The seminiferous tubules may have dilated lumens ( Figure 1 and Figure 2 ) or contracted lumens ( Figure 4 ). If the tubular lumens are dilated, the atrophy is likely caused by pressure (i.e. pressure atrophy) fromprolonged and severe tubular dilation (also see Testis - Seminiferous Tubule - Dilation ) The change may be unilateral or bilateral and focal, multifocal, or diffuse and occurs as an occasional incidental finding in mice and rats at all ages, with the incidence increasing with age. Germinal epithelial atrophy is an end-stage lesion and is generally preceded, or accompanied by, seminiferous tubule degeneration. Depending on severity, the affected testes may be macroscopically flaccid and reduced in size and weight. Severe, diffuse germinal epithelial atrophy is often irreversible. Scattered seminiferous tubules with germinal cell atrophy can be seen as an aging change in rats.
Recommendation
Germinal epithelial atrophy should be diagnosed, graded and should be discussed in the pathology narrative if it is considered the primary change and if the incidence and/or severity appears to be related to chemical administration. Since germinal epithelial atrophy is considered the end stage of degeneration, the diagnosis of atrophy should be reserved for cases in which the majority of the affected tubules are devoid of germ cells, otherwise, degeneration is a more appropriate diagnosis (see Testis - Germinal Epithelium - Degeneration ). If there is a mixture of effects (both atrophied and degenerative tubules), it can be described in the pathology narrative. If both terms are used in a single study, it is incumbent upon the pathologist to describe the relationship between the two lesions in the pathology narrative. If both testes are affected, the diagnosis should be indicated as bilateral and the severity grade based on the more severely affected testis. Related Links: Testis - Seminiferous Tubule - Dilation Testis - Germinal Epithelium - Degeneration
生精小管坏死Seminiferous Tubule Necrosis 睾丸坏死
描述（中文）
生精小管坏死（seminiferous tubule necrosis）（Figure 1、Figure 2）的特征是生精小管内的生殖细胞和支持细胞发生细胞死亡。Figure 1、Figure 2中的细胞死亡由以下表现构成：细胞呈强嗜酸性、排列紊乱，可见核固缩并伴有空泡化，或继发于缺血或梗死的大片淡嗜酸性蛋白凝固区（Figure 3、Figure 4）。生精小管坏死最常见的原因是缺血性损伤，可能源于睾丸的偶然性扭转，也可能与化学物质相关。此外，一些血管活性物质，如5-羟色胺、组胺和肾上腺素，也已被证明可导致生精小管坏死。这种细胞死亡形式的一个显著特征是同时累及生精上皮和支持细胞。相比之下，仅累及生精上皮的细胞死亡通常通过细胞凋亡过程发生。已有报道，给予啮齿类动物镉后可发生化学诱导的睾丸坏死，镉是啮齿类动物睾丸的内皮毒物。坏死也可由引起睾丸血管血栓形成的物质所致。有报道称，给大鼠单次给予人绒毛膜促性腺激素后，大鼠睾丸前下部出现特征性的局灶性（focal）坏死（Figure 4）。该坏死被认为是由于Leydig细胞释放前列腺素引起的局部缺血所致。睾丸坏死不可逆，原因是支持细胞和管状结构丧失，受累区域被瘢痕组织取代。睾丸的大范围坏死也可由意外将药物直接腹腔内注射入睾丸所致（这种情况可能发生，因为啮齿类动物能将睾丸回缩入腹腔）。
诊断建议
生精小管坏死应当诊断并分级，并且如果其发生率和/或严重程度似乎与给予化学物质相关，应当在病理学描述中加以讨论。如果双侧睾丸均受累，诊断应当限定为双侧（bilateral），并根据受累更严重的睾丸给出严重程度分级。如果血管血栓形成是明显的促发原因，该事实应当在病理学描述中提及。相关病变，如炎症，如果严重程度足以需要，应当单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Seminiferous tubule necrosis ( Figure 1 and Figure 2 ) is characterized by seminiferous tubules in which germ cells and Sertoli cells are undergoing cell death. The cell death in Figure 1 and Figure 2 consists of hypereosinophilic disorganized cells showing pyknosis and associated vacuolization or larger areas of pale eosinophilic regions of protein coagulation secondary to ischemia or infarction ( Figure 3 and Figure 4 ). The most common cause of seminiferous tubule necrosis is ischemic injury, which may result from incidental torsion of the testis or may be chemically related. In addition, some vasoactive agents, such as serotonin, histamine, and epinephrine, have also been shown to produce seminiferous tubule necrosis. A salient feature of this form of cell death is that it involves both germinal epithelium and Sertoli cells. In contrast, cell death involving only germinal epithelium typically occurs through the process of apoptosis. Chemically induced testicular necrosis has been described in rodents administered cadmium, which is an endothelial toxicant in the testis of rodents. Necrosis can also be caused by agents causing vascular thrombosis in the testis. A characteristically focal necrosis at the frontal lower part of the rat testis ( Figure 4 ) has been described following a single administration of human chorionic gonadotropin to rats. The necrosis was considered to be due to local ischemia caused by prostaglandin release from Leydig cells. Testicular necrosis is not reversible, due to loss of Sertoli cells and tubular structure, and the affected area is replaced by scar tissue. Extensive necrosis of the testis can also be caused by accidental intraperitoneal injection directly into the testis (which can occur because the rodent is able to retract its testes into the abdominal cavity).
Recommendation
Seminiferous tubule necrosis should be diagnosed and graded and should be discussed in the pathology narrative if the incidence and/or severity appear to be related to chemical administration. If both testes are affected, the diagnosis should be qualified as bilateral and given a severity grade based on the more severely affected testis. If vascular thrombi are evident as a precipitating cause, that fact should be mentioned in the pathology narrative. Associated lesions, such as inflammation, should be diagnosed separately if warranted by severity.
生精小管巨细胞Seminiferous Tubule Giant Cells 睾丸其他
描述（中文）
生精小管内的多核巨细胞是退变生精细胞的一种特定形式，与非特异性生精细胞退变不同（见睾丸-生精上皮-退变）。多核巨细胞的存在可为局灶性（focal）或弥漫性（diffuse），并可累及一侧或双侧睾丸。多核巨细胞偶尔可作为背景性偶然病变出现。该现象的发生是因为正常生精细胞分裂的特征是不完全胞质分裂，因此每次细胞分裂的子代细胞通过胞质桥相互连接。在某些形式的退变过程中，这些胞质桥可以开放，使相连细胞的胞质内容物融合。一定程度的生精细胞退变/萎缩可伴有多核巨细胞形成，若属此种情况，则不应将其作为一项独立所见记录。然而，如果多核巨细胞作为睾丸病变的主要特征存在，如Figure 1、Figure 2所示，则记录“多核巨细胞”这一所见可能是恰当的。
诊断建议
当多核巨细胞构成睾丸病变中生精细胞退变的主要形式时，应当诊断并分级。存在双侧累及时应当记录，因为单侧性常提示为偶然性病变。如果多核巨细胞仅作为非特异性小管退变的次要伴随现象出现，则不应将其作为一项独立所见记录，但可在病理学描述中讨论。相关链接：睾丸-生精上皮-退变
参考切片图（2 张）
查看英文原文
Comment
Multinucleated giant cells in seminiferous tubules are a specific form of degenerating germ cell, in contrast to nonspecific germ cell degeneration (see Testis - Germinal Epithelium - Degeneration ). The presence of giant cells can be focal or diffuse and may affect one or both testes. Multinucleated giant cells can occasionally be seen as an incidental background lesion. The phenomenon occurs because normal germ cell division is characterized by incomplete cytokinesis, so the progeny of each cell division are joined to each other by cytoplasmic bridges. During some forms of degeneration, these cytoplasmic bridges can open and allow fusion of the cellular contents of the conjoined cells. Some degree of multinucleated giant cell formation may accompany germinal cell degeneration/atrophy, and if this is the case, they should not be recorded as a separate finding. However, if multinucleated giant cells are present as a dominant feature of a testicular lesion, as in Figure 1 and Figure 2 , the finding of “multinucleated giant cells” may be warranted.
Recommendation
Multinucleated giant cells should be diagnosed and graded when they represent the predominant form of germ cell degeneration in a testicular lesion. Bilateral involvement should be recorded when present because unilaterality frequently provides evidence of an incidental lesion. If multinucleated giant cells occur as a minor accompaniment to nonspecific tubular degeneration, they should not be recorded as a separate finding but may be discussed in the pathology narrative. Related Links: Testis - Germinal Epithelium - Degeneration
生精小管扩张Seminiferous Tubule Dilation 睾丸扩张
描述（中文）
生精小管扩张（seminiferous tubule dilation）的特征是生精小管管腔直径增大（Figure 1、Figure 2）。这与正常睾丸生精小管中不明显的管腔空间形成对比（Figure 3、Figure 4）。受累小管的生精上皮变薄并受压，这是由管腔内生精小管液体积增加所致的压力积聚引起的。液体增加可能是由于输出小管（efferent ducts）对液体的重吸收减少、输出小管阻塞、生精小管液体排空减少，或Sertoli细胞产生生精小管液体增加。如果液体压力持续存在，小管扩张可迅速进展为严重的生精上皮萎缩，导致生精过程不可逆地停止。当小管扩张继发于输出小管阻塞时，病变可能为单侧，而阻塞的原因仍可能与受试物相关。除非对输出小管进行采样（这在啮齿类动物中较为困难），否则小管扩张的原因将不明显。ERKO小鼠在达到青春期时发生生精小管扩张，随后出现严重的生精上皮萎缩。这是输出小管未能重吸收生精小管液体的继发后果，而该重吸收是一种雌激素依赖性功能。已有报道多种化学物可引起生精小管扩张及其萎缩后遗症，包括杀菌剂多菌灵（carbendazim）、一种PDE4抑制剂、一种白三烯抑制剂和内皮素拮抗剂。
诊断建议
小管扩张应当被诊断并分级，并且如果其发生率或严重程度似乎与化学物给药相关，应当在病理学叙述中加以讨论。当存在时，应当记录双侧受累，因为单侧性通常反映对输出小管病变的继发反应。还应当注意单侧或双侧生精小管萎缩的发生率，因为这可能是小管扩张的进展性和终末期病变。还应当注意附睾起始段或附睾脂肪垫（输出小管所在位置）内任何大体或显微镜下病变的证据，这些病变可能反映精子肉芽肿、精子淤滞或扩张的管道，这将提示起始性、阻塞性病变的可能来源。
参考切片图（2 张）
查看英文原文
Comment
Seminiferous tubule dilation is characterized by increased luminal diameter of the seminiferous tubules ( Figure 1 and Figure 2 ). This contrasts with the inconspicuous luminal space in the seminiferous tubules from a normal testis ( Figure 3 and Figure 4 ). The affected tubules have thinning and compression of the seminiferous epithelium, which is caused by pressure buildup from increased volume of seminiferous tubule fluid within the lumen. The increased fluid can be due to decreased reabsorption of fluid in the efferent ducts, efferent duct blockage, decreased emptying of fluid from the seminiferous tubules, or increased production of seminiferous tubule fluid by the Sertoli cells. If the fluid pressure is maintained, the tubular dilation can rapidly progress to severe germinal epithelial atrophy, resulting in an irreversible cessation of spermatogenesis. When the tubular dilation is secondary to blockage of the efferent ducts, the lesion may be unilateral, and yet the cause of the blockage can still be test article related. Unless the efferent ducts are sampled (which is difficult in rodents), the cause of the tubular dilation will not be apparent. The ERKO mouse develops seminiferous tubular dilation followed by severe germinal epithelial atrophy as it reaches puberty. This occurs as a secondary consequence to the failure of the efferent ducts to resorb seminiferous tubule fluid, which is an estrogen-dependent function. Seminiferous tubular dilatation with its sequel of atrophy has been reported for a number of chemicals, including the fungicide carbendazim, a PDE4 inhibitor, a leukotriene inhibitor, and endothelin antagonists.
Recommendation
Tubular dilatation should be diagnosed and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. When present, bilateral involvement should be recorded because unilaterality usually reflects a secondary response to lesions in the efferent ducts. Attention should also be paid to the incidence of unilateral or bilateral seminiferous tubule atrophy since this can be a progressive and end-stage lesion of tubular dilation. Attention should also be paid to any evidence of gross or microscopic lesions within the initial segment of the epididymis or the epididymal fat pad (location of the efferent ducts) that may reflect sperm granulomas, sperm stasis, or dilated ducts, which would indicate the likely origin of the initiating, obstructive lesion.
生精小管空泡化Seminiferous Tubule Vacuolation 睾丸空泡化
描述（中文）
生精小管空泡化（seminiferous tubule vacuolation）在形态上可表现为微空泡或大空泡。微空泡化通常发生于基底部的Sertoli细胞胞质内（Figure 1，箭头），而大空泡化则表现为生精上皮深部出现一个或几个空泡（Figure 2，箭头）。在大多数病例中，空泡位于Sertoli细胞内或Sertoli细胞之间。空泡内可能含有液体或脂质，也可能代表内质网或细胞间隙的扩张。超微结构检查有助于确定其来源。Sertoli细胞空泡化是Sertoli细胞形态学损伤常见的早期特征，在为期28天或更短时间的研究中即可见到，且出现在任何生殖细胞变性之前。另外，空泡常伴随弥漫性生殖细胞变性/萎缩出现，此时空泡可能代表缺失的生殖细胞所留下的空隙。在对照睾丸中，空泡常可见于偶见小管的偶然性发现（Figure 2，箭头），并且其发生率和/或严重程度可能随时间推移而增加。
诊断建议
生精小管空泡化应当进行诊断和分级，并且如果其发生率和/或严重程度似乎与受试物给药相关，则应当在病理学叙述中加以讨论。如果双侧睾丸均出现空泡化，则应当记录为双侧性，严重程度分级应基于受累更严重的睾丸。
参考切片图（2 张）
查看英文原文
Comment
Seminiferous tubule vacuolation can be microvacuolar or macrovacuolar in appearance. Microvacuolation generally occurs in the basal Sertoli cell cytoplasm ( Figure 1 , arrows), and macrovacuolation appears as one or a few vacuoles within the depth of the seminiferous epithelium ( Figure 2 , arrows). In most cases, the vacuoles are within or between Sertoli cells. They may contain fluid or lipid, or they may represent dilation of endoplasmic reticulum or intercellular spaces. Ultrastructural studies can be helpful to determine their origin. Vacuolation of Sertoli cells is a common early feature of morphologic injury to Sertoli cells that may be seen in studies of 28 days or less duration, prior to any germ cell degeneration. Alternatively, vacuoles often accompany generalized germinal cell degeneration/atrophy, where they probably represent spaces left by the missing germ cells. Vacuoles can often be seen as an incidental finding in occasional tubules in control testes ( Figure 2 , arrows) and may increase in incidence and/or severity over time.
Recommendation
Seminiferous tubule vacuolation should be diagnosed and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. If present in both testes, the vacuolation should be recorded as bilateral and the severity grade based on the more severely affected testis.
生精小管精子细胞滞留Seminiferous Tubule Retention Spermatid 睾丸其他
描述（中文）
精子释放（spermiation，即完全成熟的精子细胞释放入管腔）在大鼠和小鼠中通常发生于生精周期的VIII期。多种毒物已被证实可干扰精子释放，导致成熟精子细胞（大鼠为第19步精子细胞，小鼠为第17步）持续存在于IX-XI期生精小管的腔面（Figure 1、Figure 2）。滞留的精子细胞随后被拉入基底部的Sertoli细胞胞质内，并在该处被吞噬。已有报道显示，暴露于多种化学物后可出现精子细胞滞留，包括硼酸（boric acid）、2,5-己二酮（2,5-hexanedione）和二溴乙酸（dibromoacetic acid）。精子释放依赖于睾酮（testosterone），因此当睾丸内睾酮水平降低时也会发生精子细胞滞留。尽管该表现较为细微，但识别并记录它很重要，因为它通常会导致附睾精子计数减少、精子异常以及对生育力的潜在影响。在IX期生精小管的管腔处或XII期生精小管基底部被吞噬处，常可见少量滞留的精子细胞，但一般数量很少，且仅限于一两个生精小管。
诊断建议
如果发生率或严重程度似乎与化学物给药相关，则应诊断精子细胞滞留并进行分级，且应在病理学叙述中加以讨论。出现双侧受累时应予以诊断。
参考切片图（2 张）
查看英文原文
Comment
Spermiation (the release of fully mature spermatids into the tubular lumen) normally occurs during stage VIII of the spermatogenic cycle in rats and mice. Numerous toxicants have been shown to disrupt spermiation, resulting in the continued presence of the mature spermatids (step 19 spermatids in the rat, step 17 in the mouse) at the luminal surface of stage IX-XI tubules ( Figure 1 and Figure 2 ). The retained spermatids are then pulled down into the basal Sertoli cell cytoplasm, where they are phagocytized. Spermatid retention has been described following exposure to a number of chemicals, including boric acid, 2,5-hexanedione, and dibromoacetic acid. Spermiation is testosterone dependant, so spermatid retention also occurs with decreased intratesticular levels of testosterone. Although subtle, this finding is important to recognize and record since it usually results in reduced epididymal sperm count, sperm abnormalities, and potential effects on fertility. A few retained spermatids can often be seen at the lumen of stage IX tubules or phagocytized at the base of stage XII tubules, but they are generally very few in number and restricted to one or two tubules.
Recommendation
Spermatid retention should be diagnosed and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. Bilateral involvement should be diagnosed when present.
睾丸网增生Rete Hyperplasia 睾丸增生
描述（中文）
睾丸网（rete testis）上皮增生以局灶性（focal）或多灶性（multifocal）病变形式发生，在大鼠中可作为偶发性病变见到，但在CD1小鼠中更为常见。增生的上皮一般向管腔内形成乳头状或结节状突起，不压迫周围组织（Figure 1、Figure 2）。该增生常伴有睾丸网管囊性扩张和精子淤滞（Figure 2）。已观察到睾丸网增殖性病变是对产前暴露于己烯雌酚（diethyl stilbestrol）的反应。该发现需与睾丸网腺瘤（rete testis adenoma）相鉴别，后者广泛的乳头状结构和支持性间质会压迫周围组织。
诊断建议
睾丸网增生只要存在就应诊断并分级。存在双侧受累时应记录。相关病变如精子淤滞和生精小管扩张除非因严重程度需要，否则不应单独诊断，但应在病理叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of the rete testis epithelium occurs as a focal or multifocal lesion and can be seen as an occasional incidental lesion in rats but more commonly in CD1 mice. The hyperplastic epithelium generally forms papillary or knob-like projections into the lumen with no compression of surrounding tissue ( Figure 1 and Figure 2 ). The hyperplasia is frequently accompanied by cystic dilation of the rete ducts and sperm stasis ( Figure 2 ). Proliferative lesions of the rete testis have been observed in response to prenatal exposure to diethyl stilbestrol. The finding needs to be distinguished from rete testis adenoma, where extensive papillary structures and supporting stroma cause compression of the surrounding tissue.
Recommendation
Rete testis hyperplasia should be diagnosed and graded whenever present. Bilateral involvement should be recorded when present. Associated lesions such as sperm stasis and seminiferous tubule dilation should not be diagnosed separately unless warranted by severity, but should be described in the pathology narrative.
睾丸网扩张Rete Dilation 睾丸扩张
描述（中文）
睾丸网扩张（Figure 1）是老年小鼠中相对常见的偶然性发现。正常的睾丸网由一系列称为直小管的管状通道组成，位于睾丸头端被膜下方。这些管道衬以低立方上皮，并通过由Sertoli细胞和偶见生殖细胞衬覆的过渡小管与生精小管相连。过渡小管和直小管可能被误认为萎缩的生精小管（关于睾丸网的正常组织学，见Testis - Seminiferous Tubule - Dilation）。睾丸液体流出部分受阻是睾丸网扩张最常见的原因，这可以是偶然性的或化学物质诱导的。该发现也可能与邻近生精小管管腔的扩张相关（见Testis - Sperm Stasis）。扩张的管道可能是空的或充满精子（见）。
诊断建议
睾丸网扩张应当被诊断并分级，并且如果其发生率和/或严重程度似乎与化学物质给药相关，则应当在病理学叙述中加以讨论。当存在双侧受累时应当诊断为双侧受累。应当注意附睾起始段或附睾脂肪垫（输出管所在位置）内任何可能反映精子肉芽肿、精子停滞或管道扩张的肉眼或显微镜下病变的证据。睾丸网扩张可能与生精小管扩张和/或生精上皮萎缩相关，因为这些可能是液体流出受阻的结果。相关链接：Testis - Seminiferous Tubule - Dilation Testis - Sperm Stasis
参考切片图（1 张）
查看英文原文
Comment
Dilation of the rete testis ( Figure 1 ) is a relatively common incidental finding in aging mice. The normal rete testis comprises a series of ductular channels called tubuli recti that lie subjacent to the capsule at the cranial pole of the testis. They are lined by a low cuboidal epithelium and are joined to the seminiferous tubules by transitional tubules that are lined by Sertoli cells and occasional germ cells. The transitional tubules and the tubuli recti can be mistaken for atrophic seminiferous tubules (see Testis - Seminiferous Tubule - Dilation for normal histology of rete testis). Partial obstruction to the outflow of fluid from the testis is the most common cause of rete testis dilation, and this can be incidental or chemically induced. The finding may also be associated with dilation of the adjacent seminiferous tubular lumens (see Testis - Sperm Stasis ). The dilated ducts may be empty or filled with sperm (see).
Recommendation
Rete testis dilation should be diagnosed and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. Bilateral involvement should be diagnosed when present. Attention should be paid to any evidence of gross or microscopic lesions within the initial segment of the epididymis or the epididymal fat pad (location of the efferent ducts) that may reflect sperm granulomas, sperm stasis, or dilated ducts. Rete testis dilation may be associated with seminiferous tubular dilation and/or germinal epithelial atrophy, since these may be a consequence of obstruction of fluid outflow. Related Links: Testis - Seminiferous Tubule - Dilation Testis - Sperm Stasis
矿化Mineralization 睾丸矿化
描述（中文）
营养不良性矿化（dystrophic mineralization）是损伤的后遗症，可累及被膜（Figure 1）、血管（Figure 3）或生精小管（Figure 2、Figure 4）。其特征为嗜碱性、细至粗颗粒状至无定形、层状物质蓄积，伴或不伴组织结构扭曲。它常是生精小管内精子淤滞的后遗症。矿化是一种年龄相关所见，可为单侧或双侧。
诊断建议
矿化应通过恰当使用部位修饰词（如血管、被膜、生精小管）就其位置进行诊断、分级和分类。若双侧睾丸均存在，应诊断为双侧。相关病变，如变性、坏死或炎症，若严重程度需要，应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Dystrophic mineralization is a sequel of injury and may involve the capsule ( Figure 1 ), blood vessels ( Figure 3 ), or seminiferous tubules ( Figure 2 and Figure 4 ). It is characterized by accumulation of basophilic, fine to coarsely granular to amorphous, laminated material, with or without distortion of the tissue architecture. It is often a sequel to sperm stasis within the seminiferous tubules. Mineralization is an age-related finding and can be seen unilaterally or bilaterally.
Recommendation
Mineralization should be diagnosed, graded, and classified with respect to location through appropriate use of site modifiers (e.g., blood vessel, capsule, seminiferous tubule). If present in both testes, it should be diagnosed as bilateral. Associated lesions, such as degeneration, necrosis, or inflammation should be diagnosed separately if warranted by severity. Pagination Figure 1 of 4 Next page › Testis - Mineralization in a male B6C3F1 mouse from a chronic study. Mineralization involving the testicular capsule. Enlarge Image All Images Enlarge All Images Testis - Mineralization in a male B6C3F1 mouse from a chronic study. Mineralization involving the testicular capsule. "> Testis - Mineralization in a male B6C3F1 mouse from a chronic study. Mineralization involving the testicular capsule. " /> Testis - Mineralization in a male B6C3F1 mouse from a chronic study. Mineralization involving the testicular capsule. Testis - Mineralization in a male B6C3F1 mouse from a subchronic study. Mineralization involving seminiferous tubules. "> Testis - Mineralization in a male B6C3F1 mouse from a subchronic study. Mineralization involving seminiferous tubules. " /> Testis - Mineralization in a male B6C3F1 mouse from a subchronic study. Mineralization involving seminiferous tubules. Testis - Mineralization in a male F344/N rat from a chronic study. Mineralization involving blood vessels. "> Testis - Mineralization in a male F344/N rat from a chronic study. Mineralization involving blood vessels. " /> Testis - Mineralization in a male F344/N rat from a chronic study. Mineralization involving blood vessels. Testis - Mineralization in a male B6C3F1 mouse from a chronic study. Mineralized seminiferous tubules. "> Testis - Mineralization in a male B6C3F1 mouse from a chronic study. Mineralized seminiferous tubules. " /> Testis - Mineralization in a male B6C3F1 mouse from a chronic study. Mineralized seminiferous tubules.
精子停滞Sperm Stasis 睾丸其他
描述（中文）
精子停滞（sperm stasis）是由于精子在生精小管或睾丸网管内嵌塞所致。通常见于萎缩的小管内，嵌塞的精子常发生矿化（Figure 2，箭头）。精子停滞与精子囊肿（spermatocele）的鉴别在于小管尺寸较小（精子停滞时小管直径小于正常小管或管道直径的两倍），与精子肉芽肿（sperm granuloma）的鉴别在于无炎症反应。受累小管常位于睾丸网附近。精子停滞是一种常见的年龄相关偶然性发现，伴随小管变性和萎缩。
诊断建议
除非精子停滞是独立于生殖细胞变性或生精上皮萎缩而发生的显著发现，否则不应记录或记载。当确需作出诊断时，应给予严重程度分级，并在存在双侧性时将其纳入诊断。
参考切片图（2 张）
查看英文原文
Comment
Sperm stasis results from impaction of spermatozoa in a seminiferous tubule or rete testis duct. It is generally seen within an atrophic tubule, and the impacted sperm often become mineralized ( Figure 2 , arrows). Sperm stasis is distinguished from a spermatocele by the smaller size of the tubule (in sperm stasis the tubule is less than twice the diameter of a normal tubule or duct) and from a sperm granuloma by the absence of an inflammatory response. Affected tubules are often located close to the rete. Sperm stasis is a common age-associated incidental finding that accompanies tubular degeneration and atrophy.
Recommendation
Sperm stasis should not be recorded or documented unless it is a prominent finding that occurs independent of germ cell degeneration or germinal epithelial atrophy. When a diagnosis is warranted, it should be given a severity grade, and bilaterality should be included in the diagnosis when present. Pagination Figure 1 of 2 Next page › Testis - Sperm stasis in a male B6C3F1 mouse from a chronic study. Sperm stasis in a testicular tubule. Enlarge Image All Images Enlarge All Images Testis - Sperm stasis in a male B6C3F1 mouse from a chronic study. Sperm stasis in a testicular tubule. "> Testis - Sperm stasis in a male B6C3F1 mouse from a chronic study. Sperm stasis in a testicular tubule. " /> Testis - Sperm stasis in a male B6C3F1 mouse from a chronic study. Sperm stasis in a testicular tubule. Testis - Sperm stasis in a male F344/N rat from a chronic study. Arrows indicate focal mineralization of sperm. "> Testis - Sperm stasis in a male F344/N rat from a chronic study. Arrows indicate focal mineralization of sperm. " /> Testis - Sperm stasis in a male F344/N rat from a chronic study. Arrows indicate focal mineralization of sperm.
精子肉芽肿Sperm Granuloma 睾丸其他
描述（中文）
精子肉芽肿（sperm granuloma）在睾丸中不常见；在附睾中则常见得多。它们最常作为曲细精管或睾丸网内精子淤滞的继发结果出现。精子肉芽肿可进展为血-睾屏障的破坏，并使受累的生精小管被肉芽肿性炎症所取代。这最常见表现为偶然发现的背景性病变。
诊断建议
精子肉芽肿只要存在就应诊断。不必对精子肉芽肿进行分级，除非病理学家认为分级有助于将该病变识别为与处理相关。相关病变，如变性，应单独诊断。分页 图1，共1张 睾丸——雄性仓鼠的精子肉芽肿。尽管该精子肉芽肿示例来自仓鼠，但其在小鼠或大鼠中的表现相同。放大图像 所有图像 放大所有图像 睾丸——雄性仓鼠的精子肉芽肿。尽管该精子肉芽肿示例来自仓鼠，但其在小鼠或大鼠中的表现相同。"> 睾丸——雄性仓鼠的精子肉芽肿。尽管该精子肉芽肿示例来自仓鼠，但其在小鼠或大鼠中的表现相同。" /> 睾丸——雄性仓鼠的精子肉芽肿。尽管该精子肉芽肿示例来自仓鼠，但其在小鼠或大鼠中的表现相同。
参考切片图（1 张）
查看英文原文
Comment
Sperm granulomas are uncommon findings in the testis; they are much more common in the epididymis. They most often occur as a sequel to sperm stasis within a tubule or within the rete testis. Sperm granulomas may progress to disruption of the blood-testis barrier and replacement of the affected seminiferous tubule with granulomatous inflammation. This is most commonly seen as an incidental background lesion.
Recommendation
Sperm granulomas should be diagnosed whenever present. It is not necessary to grade sperm granulomas, unless the pathologist feels that grading would help identify the lesion as being treatment-related. Associated lesions, such as degeneration, should be diagnosed separately. Pagination Figure 1 of 1 Testis - Sperm granuloma in a male hamster. Though this example of a sperm granuloma is from a hamster, its appearance in a mouse or rat would be the same. Enlarge Image All Images Enlarge All Images Testis - Sperm granuloma in a male hamster. Though this example of a sperm granuloma is from a hamster, its appearance in a mouse or rat would be the same. "> Testis - Sperm granuloma in a male hamster. Though this example of a sperm granuloma is from a hamster, its appearance in a mouse or rat would be the same. " /> Testis - Sperm granuloma in a male hamster. Though this example of a sperm granuloma is from a hamster, its appearance in a mouse or rat would be the same.
精液囊肿Spermatocele 睾丸其他
描述（中文）
精液囊肿（spermatocele）是指精子在生精小管或管道内囊性积聚或阻塞，导致其直径增大至正常直径的两倍以上。若直径小于此值，则应使用“精子停滞（sperm stasis）”一词（见睾丸-精子停滞）。若积聚伴有炎症反应，则应使用“精子肉芽肿（sperm granuloma）”一词（见睾丸-精子肉芽肿）。精液囊肿更常见于附睾，但有时也见于睾丸内，尤其是小鼠的包膜下睾丸网内（Figure 1，星号及Figure 2）。精液囊肿可与输出小管液体吸收减少相关，导致精子在睾丸网及邻近生精小管内阻塞和梗阻。这可能是化学物诱导的所见，但一般而言，精液囊肿是偶发性的、与年龄相关的所见。已有描述年龄相关的生殖细胞变性（germ cell degeneration）与精液囊肿形成之间的关联。
诊断建议
精液囊肿存在时应予以诊断，但无需分级。仅在认为与处理相关时，才应在病理学叙述中讨论。存在双侧受累时应予以记录。相关链接：睾丸-精子停滞 睾丸-精子肉芽肿
参考切片图（2 张）
查看英文原文
Comment
A spermatocele refers to the cystic accumulation or impaction of spermatozoa in a seminiferous tubule or duct causing it to increase to more than twice its normal diameter. If the diameter is less than this, the term “sperm stasis” should be used (see Testis - Sperm Stasis ). If the accumulation is accompanied by an inflammatory reaction, the term “sperm granuloma” should be used (see Testis - Sperm Granuloma ). Spermatoceles occur more commonly in the epididymis, but they are also sometimes seen within the testis, and particularly within the subcapsular rete testis of the mouse ( Figure 1 , asterisk and Figure 2 ). Spermatoceles can occur in association with reduced fluid absorption in the efferent ducts leading to sperm impaction and obstruction within the rete testis and adjacent seminiferous tubules. This can be a chemically induced finding, but in general spermatoceles are incidental, age-related findings. An association between age-related germ cell degeneration and spermatocele formation has been described.
Recommendation
Spermatocele should be diagnosed when present, but need not be graded. They should be discussed in the pathology narrative only if they are considered treatment related. Bilateral involvement should be recorded when present. Related Links: Testis - Sperm Stasis Testis - Sperm Granuloma
纤维化Fibrosis 睾丸纤维化
描述（中文）
虽然睾丸慢性炎症中可见少量纤维化，但Figure 1中所见的纤维化程度足以构成独立诊断。纤维化通常与坏死和炎症后成纤维细胞和胶原替代睾丸实质有关。这可以是局灶性（focal）、多灶性（multifocal）或广泛的（Figure 1，星号），并可延伸至白膜。纤维化可能伴有矿化（箭头）和炎症（Figure 2）。分布可以是单侧或双侧。大鼠中，慢性可卡因或镉给药可诱导睾丸纤维化。
诊断建议
如果纤维化代表原发病变，且其范围和严重程度足以构成诊断依据，则应予以诊断并分级；如果其发生率和/或严重程度似乎与化学物给药相关，则应在病理学叙述中加以讨论。如果双侧睾丸均存在，则应诊断为双侧性。
参考切片图（2 张）
查看英文原文
Comment
While modest amounts of fibrosis can be seen in chronic inflammation of the testis, the degree of fibrosis present in Figure 1 warrants an independent diagnosis. Fibrosis is usually associated with replacement of testicular parenchyma by fibroblasts and collagen following necrosis and inflammation. This can be focal, multifocal, or extensive (Figure 1, asterisk), with extension to the tunica albuginea. The fibrosis may be accompanied by mineralization (arrow) and inflammation ( Figure 2 ). Distribution can be unilateral or bilateral. Testicular fibrosis is induced in rats by chronic cocaine or cadmium administration.
Recommendation
Fibrosis should be diagnosed and graded if it represents a primary lesion and when warranted by extent and severity and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. If present in both testes, it should be diagnosed as bilateral.
色素Pigment 睾丸色素沉着
描述（中文）
Figure 1、Figure 2 中显示的睾丸色素代表蜡样色素（脂褐素）在胞质内的蓄积，它是一种浅棕色、细颗粒状的脂源性色素。这偶尔可见于间质细胞，作为一种偶然发现，并可能与退行性改变有关。另一种可能因出血而见到的色素是含铁血黄素。脂褐素经 Periodic acid-Schiff 染色和 Schmorl 染色呈阳性，而含铁血黄素经 Perls 染色着色。
诊断建议
色素应当被诊断并给予严重程度分级。如果双侧睾丸均存在，应标注为双侧性，严重程度依据受累更严重的睾丸确定。即使使用一系列特殊染色，在组织学切片中明确鉴定色素类型通常仍很困难。因此，推荐作出“色素”的诊断（而非诊断色素的具体类型，例如含铁血黄素或脂褐素）最为恰当。病理学描述应描述色素沉着的形态学特征。并非所有色素都必须诊断，因为有些色素在老龄动物中普遍存在，或与其他某种疾病过程相关，而不具有毒理学意义。病理学家应运用其判断来决定继发性色素沉积是否显著到足以 warrant 单独诊断。
参考切片图（2 张）
查看英文原文
Comment
The pigment in the testis shown in Figure 1 and Figure 2 represents intracytoplasmic accumulation of ceroid pigment (lipofuscin), which is a light brown, finely granular lipid-derived pigment. This can occasionally be seen as an incidental finding in the interstitial cells and may be associated with degenerative changes. Another pigment that may be seen as a consequence of hemorrhage is hemosiderin. Lipofuscin stains positively with Periodic acid-Schiff and with Schmorl’s stain, whereas hemosiderin stains with Perls’ stain.
Recommendation
Pigment should be diagnosed and given a severity grade. If present in both testes, it should be designated as bilateral with severity based on the more severely affected testis. Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, it is recommended that a diagnosis of "pigment" (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should describe the morphologic features of the pigmentation. Not all pigments have to be diagnosed, as some are ubiquitous in aging animals or related to some other disease process and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether or not secondary deposits of pigment are prominent enough to warrant a separate diagnosis.
间质细胞合体细胞Interstitial Cell Syncytial Cells 睾丸其他
描述（中文）
合胞体细胞形成并不常见，文献中尚未见描述。间质合胞体细胞可能代表 Leydig 细胞或巨噬细胞。可使用 Periodic acid-Schiff 染色加以区分，该染色可使巨噬细胞着色，但不使 Leydig 细胞着色。该病变的发病机制及意义尚不明确。
诊断建议
间质合胞体细胞存在时应作出诊断并分级；若其发生率及/或严重程度似乎与受试物给药相关，则应在病理学叙述中加以讨论。存在双侧病变时，诊断应注明双侧性。分页 图1，共2页 下一页 › 睾丸，间质细胞 - 空泡化，见于一只慢性研究中的雄性 FVB/N 转基因小鼠。可见间质合胞体细胞（箭头）。放大图像 所有图像 放大所有图像 睾丸，间质细胞 - 空泡化，见于一只慢性研究中的雄性 FVB/N 转基因小鼠。可见间质合胞体细胞（箭头）。"> 睾丸，间质细胞 - 空泡化，见于一只慢性研究中的雄性 FVB/N 转基因小鼠。可见间质合胞体细胞（箭头）。" /> 睾丸，间质细胞 - 空泡化，见于一只慢性研究中的雄性 FVB/N 转基因小鼠。可见间质合胞体细胞（箭头）。睾丸，间质细胞 - 空泡化，见于一只慢性研究中的雄性 FVB/N 转基因小鼠。可见间质合胞体细胞（箭头），并伴有 Leydig 细胞空泡化。"> 睾丸，间质细胞 - 空泡化，见于一只慢性研究中的雄性 FVB/N 转基因小鼠。可见间质合胞体细胞（箭头），并伴有 Leydig 细胞空泡化。" /> 睾丸，间质细胞 - 空泡化，见于一只慢性研究中的雄性 FVB/N 转基因小鼠。可见间质合胞体细胞（箭头），并伴有 Leydig 细胞空泡化。
参考切片图（2 张）
查看英文原文
Comment
The syncytial cell formation is unusual and has not been described in the literature. The interstitial syncytial cells may represent Leydig cells or macrophages. These can be distinguished using a Periodic acid-Schiff stain, which stains macrophages but not Leydig cells. The pathogenesis and significance of this lesion are unknown.
Recommendation
Interstitial syncytial cells should be diagnosed and graded when present and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. Diagnosis should indicate bilaterality when present. Pagination Figure 1 of 2 Next page › Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. There are interstitial syncytial cells (arrows). Enlarge Image All Images Enlarge All Images Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. There are interstitial syncytial cells (arrows). "> Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. There are interstitial syncytial cells (arrows). " /> Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. There are interstitial syncytial cells (arrows). Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. There are interstitial syncytial cells (arrows) accompanied by vacuolation of Leydig cells. "> Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. There are interstitial syncytial cells (arrows) accompanied by vacuolation of Leydig cells. " /> Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. There are interstitial syncytial cells (arrows) accompanied by vacuolation of Leydig cells.
间质细胞增生Interstitial Cell Hyperplasia 睾丸增生
描述（中文）
间质细胞（Leydig细胞）增生可呈局灶性（focal）、多灶性（multifocal）（Figure 1、Figure 2）或弥漫性（diffuse）（Figure 3、Figure 4），由间质细胞数量增多构成，对邻近生精小管无压迫性。弥漫性增生通常是激素失衡的生理性反应，而局灶性增生常构成通向间质细胞腺瘤的连续病变过程的一部分。局灶性增生与间质细胞腺瘤的区分常基于大小，增生被定义为直径等于或小于三个生精小管。该病变可与睾丸萎缩相关。间质细胞的增殖性病变是常见的年龄相关睾丸病变，在F344大鼠中尤为常见，但在Wistar大鼠和Sprague-Dawley大鼠中也有较低发生率。小鼠中也存在品系差异。在大鼠中，任何升高循环黄体生成素水平的化学物均可轻易诱导间质细胞增生和腺瘤。这包括许多不同结构类别的化学物和药物。在小鼠中，雌激素类化合物是间质细胞增殖最常见的原因。
诊断建议
间质细胞增生若因处理而加重，应作出诊断、分级并在病理学叙述中讨论。当双侧睾丸均存在时，诊断应指明该病变为双侧性，严重程度应基于受累更严重的睾丸。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of interstitial cells (Leydig cells) can be focal, multifocal ( Figure 1 and Figure 2 ), or diffuse ( Figure 3 and Figure 4 ) and consists of an increased number of interstitial cells, which are noncompressive to the adjacent seminiferous tubules. Diffuse hyperplasia is generally a physiologic response to hormonal imbalance, whereas focal hyperplasia commonly forms part of the continuum leading to interstitial cell adenoma. Distinction between focal hyperplasia and interstitial cell adenoma is frequently based on size, with hyperplasia being defined as having a diameter equal to three or fewer seminiferous tubules. The condition may be associated with testicular atrophy. Proliferative lesions of the interstitial cell are common age-related lesions of the testis, being particularly frequent in the F344 rat but also present at lower incidences in the Wistar rat and Sprague-Dawley rat. Strain differences are also present in mice. Interstitial cell hyperplasia and adenoma can be readily induced in rats by any chemical that increases circulating levels of luteinizing hormone. This includes many different structural classes of chemicals and drugs. In mice, estrogenic compounds are the most common cause of interstitial cell proliferation.
Recommendation
Interstitial cell hyperplasia should be diagnosed, graded, and discussed in the pathology narrative, if exacerbated by treatment. When present in both testes, the diagnosis should indicate the condition is bilateral, and severity should be based on the more severely affected testis.
间质细胞空泡化Interstitial Cell Vacuolation 睾丸空泡化
描述（中文）
间质细胞的细胞质空泡化可见于化学诱导的改变，最可能代表类固醇生成障碍。其一般表现为间质细胞增大、染色浅淡，细胞质呈泡沫状空泡化（Figure 1、Figure 2、Figure 3）。在这些间质细胞空泡化的小鼠睾丸间质区，还可见合胞体巨细胞形成。Figure 1、Figure 2、Figure 3 中的转基因小鼠经炔雌醇处理。睾丸巨噬细胞也可发生空泡化，且与间质细胞无关。空泡化的细胞可能为间质细胞或巨噬细胞。二者可用 Periodic acid-Schiff 染色区分，该染色可染巨噬细胞而不染间质细胞。需注意，小鼠的正常间质细胞通常比大鼠的更大，且空泡化外观更明显。
诊断建议
间质细胞空泡化应当进行诊断和分级，并且如果其发生率和/或严重程度似乎与化学物给药相关，应当在病理学叙述中加以讨论。存在双侧病变时，诊断应当注明双侧性。
参考切片图（2 张）
查看英文原文
Comment
Cytoplasmic vacuolation of interstitial cells can be seen as a chemically induced change and most likely represents a disturbance in steroidogenesis. It generally consists of enlarged, pale-staining interstitial cells with foamy vacuolation of the cytoplasm ( Figure 1 , Figure 2 , and Figure 3 ). Syncytial giant cell formation is also present in the interstitial compartment of the testes of these mice with vacuolated interstitial cells. The transgenic mice in Figure 1 , Figure 2 , and Figure 3 were treated with ethinyl estradiol. Testicular macrophages can also become vacuolated, independent of interstitial cells. The vacuolated cells may represent interstitial cells or macrophages. These can be distinguished using a Periodic acid-Schiff stain, which stains macrophages but not interstitial cells. Note that normal interstitial cells of mice are generally larger and have a more vacuolated appearance than those of rats.
Recommendation
Interstitial cell vacuolation should be diagnosed and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. Diagnosis should indicate bilaterality when present. Pagination Figure 1 of 3 Next page › Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. The interstitial cells contain variably sized vacuoles. Enlarge Image All Images Enlarge All Images Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. The interstitial cells contain variably sized vacuoles. "> Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. The interstitial cells contain variably sized vacuoles. " /> Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. The interstitial cells contain variably sized vacuoles. Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. This higher magnification of Figure 1 shows the vacuolation of interstitial cells. "> Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. This higher magnification of Figure 1 shows the vacuolation of interstitial cells. " /> Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. This higher magnification of Figure 1 shows the vacuolation of interstitial cells. Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. This higher magnification image of Figure 2 shows the vacuoles in detail, as well as some golden brown pigment. "> Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. This higher magnification image of Figure 2 shows the vacuoles in detail, as well as some golden brown pigment. " /> Testis, Interstitial cell - Vacuolation in a male FVB/N transgenic mouse from a chronic study. This higher magnification image of Figure 2 shows the vacuoles in detail, as well as some golden brown pigment.
非典型残余体Atypical Residual Bodies 睾丸异型性
描述（中文）
残余体（residual bodies）是致密嗜碱性、球状的体，由延长的精子细胞在成熟最后阶段脱落的冗余细胞器和多余细胞质组成。它们通常见于VII期和VIII期生精小管的管腔表面，与成熟精子细胞的头部混杂在一起。一旦精子释放（spermiation）发生，残余体迅速下降至IX期和X期生精小管的基底部区域，在那里被吞噬并消失。异常大的残余体有时可见于小鼠，作为偶然的背景性发现，或见于小鼠和大鼠，作为化学诱导的退行性改变。非典型残余体通常比正常者大，并具有凋亡小体（apoptotic bodies）的外观（Figure 1、Figure 2、Figure 3、Figure 4）。它们通常位于管腔表面或悬浮于生精小管管腔中，有时可见于正常残余体从不出现的生精小管期别（Figure 2）。其意义尚不清楚，但它们可能代表精子释放过程的紊乱。在大鼠中，已有描述其发生于给予磷酸三邻甲苯酯（tri-o-cresyl phosphate）和水消毒剂化学物二溴乙酸（dibromoacetic acid）之后。
诊断建议
非典型残余体应予以诊断并分级，并且如果其发生率和/或严重程度似乎与化学物给予相关，应在病理学叙述中加以讨论。出现双侧受累时应予以诊断。
参考切片图（2 张）
查看英文原文
Comment
Residual bodies are dense basophilic, globular bodies comprising redundant organelles and excess cytoplasm shed from the elongating spermatid in its final steps of maturation. They are generally seen at the luminal surface of stage VII and VIII tubules intermixed with the heads of the mature spermatids. Once spermiation has occurred, the residual bodies rapidly descend to the basal region of the stage IX and X tubule, where they are phagocytized and disappear. Abnormally large residual bodies can sometimes be seen as an incidental background finding in mice or as a chemically induced degenerative change in mice and rats. Atypical residual bodies are generally larger than normal and have the appearance of apoptotic bodies ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). They are generally at the luminal surface or appear suspended in the lumen of tubules and can sometimes be seen in tubular stages where normal residual bodies are never present ( Figure 2 ). Their significance is unclear, but they probably represent a disruption of the spermiation process. They have been described in rats in response to administration of tri-o-cresyl phosphate and the water disinfectant chemical dibromoacetic acid.
Recommendation
Atypical residual bodies should be diagnosed and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. Bilateral involvement should be diagnosed when present.
上皮增生Epithelium Hyperplasia 精囊增生
描述（中文）
精囊（seminal vesicle）增生以腺上皮细胞数量增多为特征。增生的上皮可形成具有支撑性间质并突入腺腔的乳头状结构（Figure 1、Figure 2），或形成网状/筛状结构（Figure 3、Figure 4）。在上述两种情况下，均可见细胞核拥挤、偶见核分裂象、细胞堆积以及增生上皮轻度嗜碱性。将增生与继发于腔内分泌物减少的腺体塌陷相鉴别很重要。据报道，大鼠在同时暴露于炔雌醇（ethinyl estradiol）或睾酮（testosterone）的情况下接触甲基亚硝基脲（methylnitrosourea）后可发生精囊增生。与增生不同，精囊腺瘤形成边界清楚的增生性生长物，伴有上皮细胞拥挤、正常极性丧失以及周围组织受压。
诊断建议
增生应当被诊断并分级。如果双侧精囊均受累，诊断应当限定为双侧性，并根据受累较严重的精囊给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of the seminal vesicle is characterized by an increase in the number of glandular epithelial cells. The proliferating epithelium may form papillary structures with supporting stroma and with extension into the glandular lumen ( Figure 1 and Figure 2 ) or a reticular pattern/cribriform pattern ( Figure 3 and Figure 4 ). In both situations, there is nuclear crowding, occasional mitotic figures, piling up, and slight basophilia of the hyperplastic epithelium. It is important to distinguish hyperplasia from glandular collapse secondary to reduced luminal secretion. Seminal vesicle hyperplasia in rats has been reported following exposure to methylnitrosourea in the presence of either ethinyl estradiol or testosterone. In contrast to hyperplasia, seminal vesicle adenomas form well-delineated proliferative growths with epithelial crowding, loss of normal polarity, and compression of surrounding tissue.
Recommendation
Hyperplasia should be diagnosed and graded. If both seminal vesicles are involved, the diagnosis should be qualified as bilateral and given a severity grade based on the more severely affected seminal vesicle.
扩张Dilation 精囊扩张
描述（中文）
精囊扩张（dilation of seminal vesicles）表现为腺体因分泌物质而膨胀（Figure 1、Figure 2）。上皮细胞和乳头状皱襞变扁平并减少（箭头，Figure 1、Figure 2）。扩张可能与阻塞有关，并可能导致分泌物浓缩（inspissation）。精囊扩张通常与年龄较大相关。
诊断建议
扩张应记录并分级。如果双侧精囊均受累，诊断应限定为双侧（双侧（bilateral）），严重程度分级由受累更严重的精囊确定。
参考切片图（2 张）
查看英文原文
Comment
Dilation of seminal vesicles consists of distension of the gland with secretory material ( Figure 1 and Figure 2 ). The epithelial cells and the papillary folds are flattened and reduced (arrows, Figure 1 and Figure 2 ). Dilation may be associated with obstruction and may lead to inspissation. Seminal vesicle dilation is usually associated with older age.
Recommendation
Dilation should be recorded and graded. If both seminal vesicles are involved, the diagnosis should be qualified as bilateral and the severity grade determined by the more severely affect seminal vesicle.
淀粉样物质Amyloid 精囊其他
描述（中文）
精囊淀粉样变性（amyloidosis）的特征是均质、嗜酸性至双染性无定形物质沉积，使上皮下间质扩张（箭头，Figure 1、Figure 2）。由于其为全身性疾病，淀粉样沉积物应存在于其他组织，如脾、肝、肾和肠，尤其是血管及血管周围部位。淀粉样变性是一种与年龄相关的变化，主要发生于小鼠，且不同小鼠品系的易感性存在差异。
诊断建议
淀粉样变性应予以诊断和分级，并且当治疗使其加重时，应在病理学叙述中予以描述。如果双侧精囊均受累，诊断应限定为双侧性，严重程度应基于受累更严重的精囊。
参考切片图（2 张）
查看英文原文
Comment
Amyloidosis in the seminal vesicle is characterized by deposition of homogeneous eosinophilic to amphophilic amorphous material that expands the subepithelial stroma (arrows, Figure 1 and Figure 2 ). Since it is a systemic condition, amyloid deposits should be present in other tissues, such as spleen, liver, kidney, and intestine, particularly in vascular and perivascular sites. Amyloidosis is an age-related change that occurs primarily in mice, with variable mouse strain susceptibility.
Recommendation
Amyloidosis should be diagnosed and graded and should be described in the pathology narrative when it is exacerbated by treatment. If both seminal vesicles are involved, the diagnosis should be qualified as bilateral and severity based on the more affected seminal vesicle
炎症Inflammation 精囊炎症
描述（中文）
精囊（seminal vesicle）的炎症可为急性，表现为间质及腺腔内中性粒细胞浸润（Figure 1、Figure 2）。在Figure 2中，炎症已破坏腺体结构。在Figure 3、Figure 4中，炎症与部分受累腺体的鳞状化生（squamous metaplasia）相关。炎症反应还可伴有增生（箭头，Figure 2）和上皮坏死（箭头，Figure 2）。炎症也可表现为更为慢性的、以间质为主的反应，黏膜破裂成小的腺体结构（Figure 5、Figure 6）。精囊炎症是见于老年大鼠和小鼠的散发性偶然发现。NTP研究将炎症分为五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞为中性粒细胞，但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但它们聚集在一起，其中许多已变性（化脓性渗出物）。渗出物中还可存在来自 resident 细胞群体和浸润白细胞的细胞碎片、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子。肉眼观察，这些病变以脓液存在为特征。渗出物周围组织可能有成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。慢性炎症中以淋巴细胞为主。慢性活动性炎症中也以淋巴细胞为主，但还存在大量中性粒细胞。两种病变均可含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
炎症应当诊断并给出严重程度分级。当双侧精囊均受累时，诊断应限定为双侧性，严重程度基于受累更严重的精囊。继发于炎症的增生和鳞状化生不应单独诊断，除非严重程度需要或特别显著。继发性鳞状化生和/或增生的提示可在病理学描述中叙述。
参考切片图（2 张）
查看英文原文
Comment
Inflammation of the seminal vesicle can be acute with a neutrophilic infiltrate in the interstitial as well as in the glandular lumen ( Figure 1 and Figure 2 ). In Figure 2 the inflammation has destroyed the glandular architecture. In Figure 3 and Figure 4 it is associated with squamous metaplasia of some affected glands. The inflammatory response may also be associated with hyperplasia (arrow, Figure 2 ) and epithelial necrosis (arrowhead, Figure 2 ). Inflammation can be a more chronic, primarily interstitial reaction, with breaking up of the mucosa into small glandular structures ( Figure 5 and Figure 6 ). Seminal vesicle inflammation is a sporadic incidental finding seen in older rats and mice. NTP studies have five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris from both the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may have fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
The inflammation should be diagnosed and given a severity grade. When both seminal vesicles are involved, the diagnosis should be qualified as bilateral and the severity based on the more severely affected seminal vesicle. Hyperplasia and squamous metaplasia secondary to inflammation should not be diagnosed separately unless warranted by severity or especially dominant. Indication of secondary squamous metaplasia and/or hyperplasia can be described in the pathology narrative.
矿化Mineralization 精囊矿化
描述（中文）
矿化（mineralization）由不规则无定形嗜碱性物质沉积构成（Figure 1、Figure 2、Figure 3）。它可以是 局灶性（focal） 或 多灶性（multifocal）（箭头，Figure 1、Figure 2）。矿化在精囊中不常见，很可能是与化学处理无关的偶然发现。转移性矿化（metastatic mineralization）发生于正常组织，与血钙水平升高相关。营养不良性矿物质沉积（dystrophic mineral deposits）发生于异常组织，与血钙水平升高无关。在 Figure 1、Figure 2、Figure 3 中，精囊萎缩并伴有结缔组织增多，表明该矿化很可能是营养不良性的。
诊断建议
矿化应当被诊断并给出严重程度分级。如果双侧精囊均受累，诊断应当限定为双侧性，严重程度分级应当基于受累更严重的精囊。
参考切片图（2 张）
查看英文原文
Comment
Mineralization consists of deposition of irregular amorphous basophilic material ( Figure 1 , Figure 2 , and Figure 3 ). It can be focal or multifocal (arrows, Figure 1 and Figure 2 ). Mineralization is uncommon in the seminal vesicle and is likely an incidental finding not associated with chemical treatment. Metastatic mineralization occurs in normal tissues and is associated with elevated blood calcium levels. Dystrophic mineral deposits occur in abnormal tissues and are not associated with elevated blood calcium levels. In Figure 1 , Figure 2 , and Figure 3 , the seminal vesicle is atrophic with increased connective tissue, indicating that the mineralization is probably dystrophic.
Recommendation
Mineralization should be diagnosed and given a severity grade. If both seminal vesicles are involved, the diagnosis should be qualified as bilateral, and the severity grade should be based on the more severely affect seminal vesicle.
萎缩Atrophy 精囊萎缩
描述（中文）
精囊萎缩（seminal vesicle atrophy）的特征是精囊腺体成分及衬覆上皮细胞的大小和数量减少。这与分泌耗竭及收缩的纤维肌性间质更加显著有关。萎缩可伴有腺体内小乳头状皱褶形成（Figure 1、Figure 2）。或者，可出现黏膜塌陷，形成由立方至低立方上皮衬覆的腺样结构（Figure 3、Figure 4）。当雄激素耗竭对包括精囊在内的附属性器官产生深刻萎缩效应时，精囊萎缩可作为年龄相关变化发生。雌激素减少腺上皮体积并增加精囊纤维肌性间质的显著性。抗雄激素物质处理也可导致精囊萎缩。在大鼠中给予多柔比星（doxorubicin）可诱导包括精囊在内的数个器官发生萎缩性改变。锌指转录因子Egr家族（如Egr4和Egr1）的缺陷，如Egr4-Egr1双突变小鼠，可导致精囊、前列腺、附睾和睾丸萎缩。
诊断建议
精囊萎缩应当诊断并分级。当双侧精囊均存在时，诊断应明确为双侧性，严重程度基于受累更严重的精囊。病理学叙述中的评论应说明精囊萎缩是否因处理而加重，并应识别其他雄性生殖组织中的相关变化。
参考切片图（2 张）
查看英文原文
Comment
Seminal vesicle atrophy is characterized by a reduction in the size and number of glandular components and lining epithelial cells of the seminal vesicle. This is associated with secretory depletion and an increased prominence of the contracted fibromuscular stroma. Atrophy may be accompanied by the formation of small papillary folds in the glands ( Figure 1 and Figure 2 ). Alternatively, there may be collapse of the mucosa, with formation of glandular-appearing structures lined by cuboidal to low cuboidal epithelium ( Figure 3 and Figure 4 ). Seminal vesicle atrophy may occur as an age-related change when the depletion of androgenic hormone has a profound atrophic effect on accessory sex organs, including the seminal vesicle. Estrogens decrease the volume of the glandular epithelium and increase the prominence of the fibromuscular stroma in the seminal vesicle. Treatment with anti-androgenic substances also leads to the atrophy of the seminal vesicle. Administration of doxorubicin in rats induces atrophic changes in several organs, including the seminal vesicle. Deficiency of the Egr family of zinc finger transcription factors like Egr4 and Egr1 as in Egr4-Egr1 double-mutant mice leads to atrophy of seminal vesicle, prostate, epididymis, and testis.
Recommendation
Seminal vesicle atrophy should be diagnosed and graded. When present In both seminal vesicles, the diagnosis should be clarified as bilateral and severity based on the more severely affected seminal vesicle. Comments in the pathology narrative should address whether seminal vesicle atrophy is exacerbated by treatment and should identify related changes in other male reproductive tissues.
炎症Inflammation 输精管炎症
描述（中文）
输精管（ductus deferens）的炎症不常见，可能表现为肌层及周围组织中有炎症细胞浸润（星号，Figure 1、Figure 2）。它很可能是邻近组织类似病变的延伸。在 Figure 1、Figure 2 中，病变局限于输精管的肌层及周围组织。NTP 研究将炎症分为五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞是中性粒细胞（neutrophil），但也可能存在较少的巨噬细胞（macrophage）和淋巴细胞（lymphocyte）。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，其中中性粒细胞聚集，且许多已变性（化脓性渗出物）。渗出物中还可能存在来自 resident 细胞群和浸润白细胞的细胞碎片、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子。肉眼观察，这些病变以脓液存在为特征。渗出物周围的组织可能有成纤维细胞、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。慢性炎症中以淋巴细胞为主。慢性活动性炎症中也以淋巴细胞为主，但还有显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大的活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
输精管的炎症应当被诊断、分类和分级。如果它是附属性腺及周围组织广泛性炎症的一部分，则不必为输精管单独提供诊断，但应在病理学叙述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Inflammation of ductus deferens is uncommon and may consist of infiltration of inflammatory cells in the muscular layer and in the surrounding tissue (asterisks, Figure 1 and Figure 2 ). It is likely an extension of a similar finding in adjoining tissue. In Figure 1 and Figure 2 , it is limited to the muscular layer of the ductus deferens and surrounding tissue. NTP studies have five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , where they are aggregated, and many are degenerate (suppurative exudate). Cell debris from both the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may have fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
Inflammation of the ductus deferens should be diagnosed, classified, and graded. If it is part of a generalized inflammation of accessory sex glands and surrounding tissues, it is not necessary to provide a separate diagnosis for the ductus deferens, but it should be described in the pathology narrative.
矿化Mineralization 输精管矿化
描述（中文）
矿化（mineralization）的特征是嗜碱性、细至粗颗粒状至无定形物质的蓄积（箭头），通常不伴有组织结构的变形（Figure 1、Figure 2）。输精管（ductus deferens）内的矿化不常见，很可能是与化学处理无直接关联的偶然发现。矿化可有两种类型：转移性（metastatic，与血钙水平升高相关的正常组织钙化）或营养不良性（dystrophic，与血钙水平升高无关的异常或退化组织中的矿物质沉积）。当呈全身性时，转移性矿化可存在于多个器官。
诊断建议
矿化应当被诊断并分级。如果其作为全身性反应发生于多个组织，则不必单独诊断输精管内的矿化。然而，其在输精管内的存在可在病理学叙述中提及。
参考切片图（2 张）
查看英文原文
Comment
Mineralization is characterized by accumulation of basophilic, fine to coarsely granular to amorphous material (arrows), often without distortion of the histoarchitecture ( Figure 1 and Figure 2 ). Mineralization in the ductus deferens is unusual and is likely an incidental finding not directly associated with chemical treatment. Two types of mineralization may occur: metastatic (calcification of normal tissue associated with high blood levels of calcium) or dystrophic (mineral deposits in abnormal or degenerating tissue not associated with increased blood levels of calcium). When systemic, metastatic mineralization can be present in multiple organs.
Recommendation
Mineralization should be diagnosed and graded. If it occurs in multiple tissues as a systemic response, it is not necessary to separately diagnose mineralization in the ductus deferens. However, its presence in the ductus deferens may be mentioned in the pathology narrative.
上皮增生Epithelium Hyperplasia 阴茎增生
描述（中文）
黏膜增生（hyperplasia of the mucosa）以鳞状上皮呈乳头状皱褶形式增生为特征（箭头，Figure 1）。它是一种不常见的偶然性发现，不太可能与化学物给药相关。
诊断建议
该病变应当予以诊断并给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of the mucosa is characterized by proliferation of squamous epithelium in the form of papillary folds (arrow, Figure 1 ). It is an uncommon incidental finding and is unlikely to be associated with chemical administration.
Recommendation
This lesion should be diagnosed and given a severity grade.
包皮炎症Prepuce Inflammation 阴茎炎症
描述（中文）
本病例中包皮的炎症由肿胀和炎症细胞浸润组成，可能与创伤有关。Figure 2、Figure 3 显示包皮的急性炎症（星号）伴表层坏死。NTP研究将炎症分为五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要的浸润细胞是中性粒细胞，但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但它们聚集在一起，其中许多发生退变（化脓性渗出物）。渗出物中还可能存在来自 resident 细胞群和浸润白细胞的细胞碎片、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子。肉眼观察，这些病变以脓液存在为特征。渗出物周围的组织可能有成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。慢性炎症中以淋巴细胞为主。慢性活动性炎症中也以淋巴细胞为主，但还有显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大的活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
炎症应记录、分类并分级。
参考切片图（2 张）
查看英文原文
Comment
Inflammation of the prepuce in this case consists of swelling and infiltration of inflammatory cells and is likely associated with trauma. Figure 2 and Figure 3 represent acute inflammation (asterisks) of the prepuce with superficial necrosis. NTP studies have five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris from both the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may have fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
Inflammation should be recorded, classified, and graded.
炎症Inflammation 阴茎炎症
描述（中文）
阴茎的慢性炎症（星号，Figure 1、Figure 2）以阴茎骨骼肌纤维周围单核炎症细胞浸润为特征。阴茎炎症在啮齿类动物中不常见。化学物质与阴茎炎症的关联尚不清楚。NTP研究将炎症分为五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞为中性粒细胞（neutrophil），但也可能存在少量巨噬细胞（macrophage）和淋巴细胞（lymphocyte）。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但它们聚集在一起，其中许多已变性（化脓性渗出物）。渗出物中还可能存在来自 resident 细胞群和浸润白细胞的细胞碎片、含纤维蛋白的蛋白性液体、少量巨噬细胞、偶见淋巴细胞或浆细胞，以及可能的感染因子。肉眼观察，这些病变以脓液存在为特征。渗出物周围组织可能有成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。慢性炎症中以淋巴细胞为主。慢性活动性炎症中也以淋巴细胞为主，但还存在大量中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的、活化的巨噬细胞、上皮样巨噬细胞（epithelioid macrophage）或多核巨细胞（multinucleated giant cell）。
诊断建议
阴茎炎症应予以诊断、分类和分级。
参考切片图（2 张）
查看英文原文
Comment
Chronic inflammation of the penis (asterisks, Figure 1 and Figure 2 ) is characterized by mononuclear inflammatory cells surrounding skeletal muscle fibers in the penis. Inflammation of the penis is not common in rodents. Association of chemical agents with inflammation of the penis is unknown. NTP studies have five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris from both the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in within the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may have fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
Inflammation of the penis should be diagnosed, classified, and graded.
纤维化Fibrosis 阴茎纤维化
描述（中文）
阴茎纤维化（fibrosis of the penis）的特征是成纤维细胞（fibroblast）丰富并伴有胶原沉积（collagen deposition），使阴茎尿道（penile urethra）周围组织扩张（Figure 1、Figure 2）。阴茎纤维化不常见，且尚未确立其与化学物质的因果关系。
诊断建议
该病变应予以诊断并给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Fibrosis of the penis is characterized by abundant fibroblasts with collagen deposition that expands the tissue surrounding the penile urethra ( Figure 1 and Figure 2 ). Penile fibrosis is uncommon, and causal association with chemical agents has not been established.
Recommendation
This lesion should be diagnosed and given a severity grade.
上皮凋亡Epithelium Apoptosis 附睾凋亡
描述（中文）
附睾上皮的细胞凋亡（apoptosis，或称单细胞死亡）最常见于睾酮水平下降时的反应。正常情况下，附睾中存在低水平的背景性凋亡细胞，但如果睾酮水平显著下降，凋亡细胞数量会增加，首先出现在起始段（Figure 1），随后随时间以波浪式方式向远端推进直至附睾尾。给予雌激素类化合物也已被证明可通过干扰睾酮而产生这一变化。
诊断建议
凋亡上皮细胞水平增高应当记录并分级，并且如果其发生率和/或严重程度似乎与化学物给药相关，应当在病理学叙述中加以讨论。当双侧附睾均出现时，诊断应当明确为双侧性，严重程度评分应基于受累更严重的附睾。建议与其他雄性生殖器官的紊乱进行关联分析以助解释。
参考切片图（2 张）
查看英文原文
Comment
Apoptosis (or single cell death) of the epididymal epithelium is most commonly seen as a response to decreased testosterone levels. Normally, there is a low background level of apoptotic cells in the epididymis, but if testosterone levels decrease significantly, the number of apoptotic cells increases, first in the initial segment ( Figure 1 ) and then proceeding distally in a wave-like manner over time through to the cauda. Administration of estrogenic compounds have also been shown to produce this change through interference with testosterone.
Recommendation
Increased levels of apoptotic epithelial cells should be recorded and graded should be and discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. When present in both epididymides, the diagnosis should be clarified as bilateral and the severity score based on the more severely affected epididymis. Correlation with disturbances in other male reproductive organs is recommended to aid interpretation.
上皮变性Epithelium Degeneration 附睾变性
描述（中文）
输出管或附睾上皮的变性（degeneration）和坏死（necrosis）是罕见的发现，无论是作为背景病变还是化学诱导的病变。该病变的特征是附睾管上皮衬里的变薄和脱落。该发现不应与附睾腔内出现脱落的睾丸生殖细胞相混淆（另见附睾-管-脱落生殖细胞），在后一种情况下附睾上皮保持正常和完整。如果上皮衬里出现破损，通常伴有炎症细胞浸润，这是由于血-附睾屏障破坏导致免疫细胞暴露于具有抗原异性的精子所致。已有描述上皮变性见于暴露于甲基氯（methyl chloride）吸入后。
诊断建议
上皮变性应记录并分级，如果发生率和/或严重程度似乎与化学物给药相关，则应在病理学叙述中加以讨论。如果双侧附睾均受累，诊断应明确为双侧性，严重程度评分应基于受累更严重的附睾。与任何生精障碍的相关性应在病理学叙述中注明，以助于解释。细胞质空泡化（cytoplasmic vacuolation）虽属变性的一种形式，但应单独记录（另见附睾-上皮-空泡化）。相关链接：附睾-管-脱落生殖细胞 附睾-上皮-空泡化
参考切片图（2 张）
查看英文原文
Comment
Degeneration and necrosis of the efferent duct or epididymal epithelium are unusual findings, either as a background lesion or as a chemically induced lesion. The lesion is characterized by attenuation and sloughing of the epithelial lining of the epididymal duct. The finding should not be confused with the presence of sloughed testicular germ cells in the epididymal lumen (also see Epididymis - Duct - Exfoliated Germ Cell ), where the epididymal epithelium remains normal and intact. If there is a breach of the epithelial lining, it is generally accompanied by an inflammatory infiltrate due to breakdown in the blood-epididymal barrier resulting in exposure of immune cells to the antigenically foreign sperm. Epithelial degeneration has been described in response to methyl chloride inhalation.
Recommendation
Epithelial degeneration should be recorded and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. If both epididymides are involved, the diagnosis should be clarified as bilateral and the severity score based on the more severely affected epididymis. Correlation with any spermatogenic disturbances should be noted in the pathology narrative to aid interpretation. Cytoplasmic vacuolation, although a form of degeneration, should be recorded separately (also see Epididymis - Epithelium - Vacuolation ). Related Links: Epididymis - Duct - Exfoliated Germ Cell Epididymis - Epithelium - Vacuolation
上皮核增大Epithelium Karyomegaly 附睾其他
描述（中文）
非典型增大的细胞核（核巨大症，karyomegaly）最常出现在输精管上皮，但也可见于附睾的其他部位。核巨大症的特征是上皮细胞含有大而深染嗜碱性、常呈凹陷状的细胞核。在小鼠中，它通常被视为背景性发现。没有证据表明这种细胞异型性会进展或属于癌前病变。
诊断建议
核巨大症应当记录并分级，并且如果其发生率或严重程度似乎与化学物给药相关，应当在病理学叙述中加以讨论。适当时应当注明是否为双侧性。建议与其他雄性生殖器官的异常进行关联分析，以助于解释。
参考切片图（2 张）
查看英文原文
Comment
Atypical enlarged nuclei (karyomegaly) are most often seen in the epithelium of the ductus deferens, but can also be seen in other parts of the epididymis. Karyomegaly is characterized by epithelial cells that contain large, intensely basophilic staining nuclei that are often indented. It is generally seen as a background finding in mice. There is no evidence that this cell atypia progresses or is preneoplastic.
Recommendation
Karyomegaly should be recorded and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. Indication of bilateral should be provided if appropriate. Correlation with disturbances in other male reproductive organs is recommended to aid interpretation.
上皮空泡化Epithelium Vacuolation 附睾空泡化
描述（中文）
附睾上皮可发生多种不同形式的空泡化。这些空泡化常呈节段性和区域特异性。空泡化可能是多种退行性过程的结果，包括脂质、磷脂（磷脂沉积症）、糖蛋白或液体的蓄积。空泡可以较大（大空泡化，Figure 1）或较小（小空泡化，Figure 2），并可表现为空虚或充满嗜碱性或嗜酸性物质。嗜碱性空泡化是大鼠附睾头远端特定节段常见的年龄相关背景性所见（Figure 1）。大的透明空泡常作为偶然性所见见于大鼠附睾体尾交界处。附睾空泡化也可与受试物相关，并可呈弥漫性或节段性。透明细胞是附睾上皮的正常细胞类型，参与腔内颗粒物质的胞吞作用。当附睾腔内有细胞碎片增多时，透明细胞的数量和显著程度常增加，尤其是在附睾尾（Figure 3）。应注意将这些正常透明细胞与退行性空泡性改变相区分。由于透明细胞充满溶酶体，而溶酶体经Periodic acid-Schiff染色呈强阳性，因此可作出区分。
诊断建议
上皮的空泡化应记录并分级，并且如果其发生率和/或严重程度似乎与化学物给药相关，则应在病理学叙述中加以讨论。如果空泡化的类型和位置具有特异性且值得注意，则应予以注明。诊断应指明该改变是否为双侧性。建议与其他雄性生殖器官的紊乱进行关联分析，以助于解释。
参考切片图（2 张）
查看英文原文
Comment
The epididymal epithelium develops many different forms of vacuolation. They are often segmental and region specific. The vacuolation may be the result of a number of degenerative processes, including the accumulation of lipids, phospholipids (phospholipidosis), glycoproteins, or fluids. The vacuoles may be or large (macrovacuolation, Figure 1 ) or small (microvacuolation, Figure 2 ) and may appear empty or filled with basophilic or eosinophilic material. Basophilic vacuolation is a common age-related, background finding in a specific segment of the distal caput region of the rat ( Figure 1 ). Large clear vacuoles are frequently seen as an incidental finding at the corpus cauda junction in the rat epididymis. Vacuolation of the epididymis can also be test article related and may be diffuse or segmental. Clear cells are a normal cell type of the epididymal epithelium involved in endocytosis of luminal particulate matter. They are often increased in number and prominence, particularly in the cauda, when there is increased cell debris in the epididymal lumen ( Figure 3 ). Care should be taken to distinguish these normal clear cells from degenerative vacuolar changes. The distinction can be made since clear cells are filled with lysosomes that stain strongly positive with Periodic acid-Schiff.
Recommendation
Vacuolation of the epithelium should be recorded and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. The type and location of the vacuolation should be noted if it appears specific and noteworthy. Diagnosis should indicate if the change is bilateral. Correlation with disturbances in other male reproductive organs is recommended to aid interpretation.
导管扩张Duct Dilation 附睾扩张
描述（中文）
附睾管扩张是一种不常见的病变。附睾不同部位管腔直径差异显著，评估该病变时必须考虑这一点。该病变通常局限于附睾的特定节段。它可能与受试物相关（Figure 1、Figure 2），也可作为老年大鼠偶见的囊性背景病变出现。
诊断建议
应记录并对附睾管扩张进行分级；若其发生率或严重程度似乎与化学物给药相关，则应在病理学叙述中加以讨论。若双侧附睾均受累，诊断应注明双侧性，并依据受累较重的一侧附睾确定严重程度。
参考切片图（2 张）
查看英文原文
Comment
Dilation of the epididymal ducts is an uncommon finding. The luminal diameter of the ducts varies significantly in different parts of the epididymis, and this must be taken into account when evaluating the change. The change is usually restricted to a specific segment of the epididymis. It can be test article related ( Figure 1 and Figure 2 ) or can be seen as an occasional cystic background finding in aging rats.
Recommendation
Ductal dilation should be recorded and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. If both epididymides are involved, the diagnosis should indicate bilateral and severity based on the more severely affected epididymis.
导管脱落生精细胞Duct Exfoliated Germ Cell 附睾其他
描述（中文）
管腔内出现脱落的睾丸生殖细胞或细胞碎片是与睾丸生精障碍相关的常见改变。虽然它不是原发于附睾的病变，但记录该发现很重要，因为它提供了睾丸毒性的敏感指标，并且可能比原发睾丸病变更为敏感。该改变的特征是管腔内存在完整细胞（通常可辨认为圆形精子细胞或精母细胞）和/或细胞碎片与成熟精子混合。通过检查周围管道的上皮，可将该改变与原发于附睾的病变区分开来。如果细胞碎片伴有附睾上皮的变性或坏死，则应考虑原发于附睾的病变（见附睾-上皮-变性）。正常年轻成年大鼠附睾管腔内脱落的细胞极少；小鼠通常作为背景发现而有少量更多。青春期前和围青春期动物以及老龄啮齿动物会有更多数量的脱落睾丸生殖细胞，因此确定年龄匹配对照组中的正常背景水平很重要。
诊断建议
管腔内细胞碎片应记录并分级，并且如果发生率和/或严重程度似乎与化学物给药相关，则应在病理学叙述中讨论。如果双侧附睾均受累，诊断应注明双侧。应在叙述中注明与睾丸中任何相关生精障碍的关联。应在病理学叙述中注明与任何生精障碍的关联以助于解释。相关链接：附睾-上皮-变性
参考切片图（2 张）
查看英文原文
Comment
The presence of sloughed testicular germ cells or cell debris in the ductular lumen is a common change associated with spermatogenic disruption in the testis. Although it is not a primary epididymal lesion, it is important to record the finding because it provides a sensitive indicator of testicular toxicity and may be a more sensitive end point than the originating testicular lesion. The change is characterized by the presence of intact cells (often recognizable as round spermatids or spermatocytes) and/or cell debris intermixed with mature sperm within the ductular lumen. The change can be distinguished from a primary epididymal lesion by examination of the epithelium of the surrounding ducts. If the cell debris is associated with degeneration or necrosis of the epididymal epithelium, a primary epididymal lesion should be considered (see Epididymis - Epithelium - Degeneration ). The normal young adult rat has very few sloughed cells in the epididymal lumen; the mouse generally has a few more as a background finding. Prepubertal and peripubertal animals, as well as aging rodents, will have increased numbers of sloughed testicular germ cells, so it is important to establish the normal background level in age-matched control groups.
Recommendation
Luminal cell debris should be recorded and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. If both epididymides are involved, the diagnosis should indicate bilateral. Correlation with any associated spermatogenic disturbance in the testis should be noted in the narrative. Correlation with any spermatogenic disturbances should be noted in the pathology narrative to aid interpretation. Related Links: Epididymis - Epithelium - Degeneration
导管萎缩Duct Atrophy 附睾萎缩
描述（中文）
附睾（epididymis）萎缩通常与管腔内精子含量减少相关，继发于睾丸精子发生减少。其特征为管径减小，导致上皮向管内折叠，形成扇贝样外观。间质也可增多（Figure 3、Figure 4）。萎缩可为弥漫性或节段性。当为节段性时，最常累及附睾体与附睾尾交界处。附睾是雄激素依赖性组织，萎缩可见于睾酮减少、双氢睾酮减少（如5α-还原酶抑制）或雄激素受体拮抗。附睾萎缩是一种常见的年龄相关所见，与睾丸变性/萎缩相关。
诊断建议
导管萎缩应记录并分级，并且如果其发生率和/或严重程度似乎与化学物给药相关，应在病理学叙述中讨论。如果双侧附睾均受累，诊断应标明为双侧，严重程度基于受累更严重的附睾。建议与其他雄性生殖器官的紊乱进行关联分析以助解释。
参考切片图（2 张）
查看英文原文
Comment
Atrophy of the epididymis is generally associated with decreased luminal sperm content, secondary to decreased testicular spermatogenesis. It is characterized by a decreased diameter of the ducts, resulting in intraductal folding of the epithelium to form a scalloped appearance. The interstitial stroma may also be increased ( Figure 3 and Figure 4 ). Atrophy can be diffuse or segmental. When segmental, it most commonly affects the corpus cauda junction. The epididymis is an androgen-dependent tissue, and atrophy can be seen in response to decreased testosterone, decreased dihydrotestosterone (e.g., 5α-reductase inhibition), or androgen receptor antagonism. Epididymal atrophy is a common age-related finding that is associated with testicular degeneration/atrophy.
Recommendation
Ductal atrophy should be recorded and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. If both epididymides are involved, the diagnosis should be indicated as bilateral and the severity based on the more severely affected epididymis. Correlation with disturbances in other male reproductive organs is recommended to aid interpretation.
淀粉样物质Amyloid 附睾其他
描述（中文）
淀粉样变性（amyloidosis）是一种与年龄相关的偶然性背景病变，最常见于小鼠。它通常是一种全身性病变，但附睾是常见的沉积部位。其表现为淡染、嗜酸性细胞外物质，刚果红（Congo red）染色后在偏振光下呈绿色双折射。
诊断建议
淀粉样物质应记录并分级，如果其发生率和/或严重程度似乎与化学物给药相关，则应在病理学叙述中讨论。相关或继发性病变除非其严重程度足以需要诊断，否则不必诊断。
参考切片图（2 张）
查看英文原文
Comment
Amyloidosis is an age-related, incidental background finding most commonly seen in mice. It is generally a systemic condition, but the epididymis is a common site for deposition. It appears as pale, eosinophilic extracellular material that has a green birefringence under polarized light when stained with Congo red.
Recommendation
Amyloid should be recorded and graded and should be discussed in the pathology narrative if the incidence and/or severity appear to be related to chemical administration. Associated or secondary lesions need not be diagnosed unless warranted by their severity.
炎症Inflammation 附睾炎症
描述（中文）
炎症通常发生于组织损伤和血-附睾屏障破坏时，导致炎症细胞局灶性广泛或弥漫性浸润导管腔、上皮和/或间质，并可能伴有水肿。炎症可以是以中性粒细胞成分为主的急性炎症，也可以是以淋巴样聚集为特征的慢性炎症（Figure 1、Figure 2）。如果炎症反应包括围绕精子核心的肉芽肿性反应，则“精子肉芽肿”这一术语更为恰当（另见附睾-精子肉芽肿）。炎症是一种不常见的偶然性发现，但可能作为化学诱导的附睾变性（如甲基氯）的后遗症出现。NTP研究将炎症分为五个标准类别：急性、化脓性、慢性、慢性活动性和肉芽肿性。在急性炎症中，主要浸润细胞为中性粒细胞，但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但它们聚集在一起，其中许多已变性（化脓性渗出物）。渗出物中还可能存在来自驻留细胞群和浸润白细胞的细胞碎片、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子。大体上，这些病变以脓液存在为特征。渗出物周围的组织可能有成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。慢性炎症中以淋巴细胞为主。慢性活动性炎症中也以淋巴细胞为主，但同时有大量中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的大型活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
“炎症”一词应保留用于有相关组织损伤证据的病例。炎症应记录并分级，如果发生率或严重程度似乎与化学物给药相关，应在病理学叙述中讨论。可使用修饰词来描述主要细胞类型。如果双侧附睾均受累，诊断应明确为双侧性，严重程度评分应基于受累更严重的附睾。建议与其他雄性生殖器官的异常进行关联分析以辅助解释。相关链接：附睾-精子肉芽肿
参考切片图（2 张）
查看英文原文
Comment
Inflammation generally occurs in response to tissue injury and breakdown of the bloodepididymal barrier, resulting in focally extensive or diffuse infiltration of the ductular lumen, the epithelium, and/or the interstitium with inflammatory cells and possibly edema. The inflammation may be predominantly acute, with a significant neutrophil component, or chronic, with lymphoid aggregates ( Figure 1 and Figure 2 ). If the inflammatory response comprises a granulomatous reaction surrounding a core of sperm, the term "sperm granuloma" is more appropriate (also see Epididymis - Sperm Granuloma ). Inflammation is an uncommon incidental finding but may occur as a sequel to chemically induced epididymal degeneration (e.g., methyl chloride). NTP studies have five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris from both the resident cell populations and infiltrating leukocytes, proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may have fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
The term "inflammation" should be reserved for cases where there is associated evidence of tissue injury. Inflammation should be recorded and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. A modifier may be used to characterize the predominant cell type. If both epididymides are affected, the diagnosis should be clarified as bilateral and the severity score based on the more severely affected epididymis. Correlation with disturbances in other male reproductive organs is recommended to aid interpretation. Related Links: Epididymis - Sperm Granuloma
精子停滞Sperm Stasis 附睾其他
描述（中文）
精子停滞（sperm stasis）最常见于睾丸停止产生精子后，发生于附睾尾。精子被隔离在尾部管道内，呈强嗜酸性（Figure 1、Figure 2、Figure 3）。较近端的管道通常无精子。由阻塞性病变引起的精子停滞也可发生于附睾头和输出管。在 Figure 4 中，被隔离的精子呈嗜碱性。如果上皮衬里破损，精子进入间质，精子停滞可进展为精子肉芽肿（sperm granuloma）。
诊断建议
精子停滞应记录并分级，如果其发生率和/或严重程度似乎与化学物给药相关，应在病理学叙述中讨论。当双侧附睾均受累时，应注明双侧，严重程度分级基于受累更严重的附睾。应在病理学叙述中注明与任何生精障碍的相关性，以助于解释。
参考切片图（2 张）
查看英文原文
Comment
Sperm stasis is most commonly seen in the cauda epididymis following cessation of sperm production by the testis. Sperm become sequestered in the caudal ducts and are intensely eosinophilic ( Figure 1 , Figure 2 , and Figure 3 ). The more proximal ducts are generally empty of sperm. Sperm stasis also occurs in the caput and efferent ducts as a result of obstructive lesions. In Figure 4 , the sequestered sperm are basophilic. Sperm stasis may progress to sperm granuloma if the epithelial lining is breached and sperm gain access to the interstitium.
Recommendation
Sperm stasis should be recorded and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. Bilateral should be indicated when both epididymides are involved, with severity grade based on the more severely affected epididymis. Correlation with any spermatogenic disturbances should be noted in the pathology narrative to aid interpretation. Pagination Figure 1 of 4 Next page › Epididymis - Sperm Stasis. Ducts filled with sperm in a male B6C3F1 mouse from a chronic study. Enlarge Image All Images Enlarge All Images Epididymis - Sperm Stasis. Ducts filled with sperm in a male B6C3F1 mouse from a chronic study. "> Epididymis - Sperm Stasis. Ducts filled with sperm in a male B6C3F1 mouse from a chronic study. " /> Epididymis - Sperm Stasis. Ducts filled with sperm in a male B6C3F1 mouse from a chronic study. Epididymis - Sperm Stasis. Higher magnification of Figure 1 showing ducts filled with sperm in a male B6C3F1 mouse from a chronic study. "> Epididymis - Sperm Stasis. Higher magnification of Figure 1 showing ducts filled with sperm in a male B6C3F1 mouse from a chronic study. " /> Epididymis - Sperm Stasis. Higher magnification of Figure 1 showing ducts filled with sperm in a male B6C3F1 mouse from a chronic study. Epididymis - Sperm Stasis. Sperm stasis is present on the left and ducts without sperm on the right in a male B6C3F1 mouse from a subchronic study. "> Epididymis - Sperm Stasis. Sperm stasis is present on the left and ducts without sperm on the right in a male B6C3F1 mouse from a subchronic study. " /> Epididymis - Sperm Stasis. Sperm stasis is present on the left and ducts without sperm on the right in a male B6C3F1 mouse from a subchronic study. Epididymis - Sperm Stasis. Sperm stasis is present on the left and atrophic epididymal ducts on the right in a male F344/N rat from a chronic study. "> Epididymis - Sperm Stasis. Sperm stasis is present on the left and atrophic epididymal ducts on the right in a male F344/N rat from a chronic study. " /> Epididymis - Sperm Stasis. Sperm stasis is present on the left and atrophic epididymal ducts on the right in a male F344/N rat from a chronic study.
精子减少Hypospermia 附睾其他
描述（中文）
精子含量减少通常由睾丸精子发生减少所致，但也可能源于输出管中的阻塞性病变，使外观正常的睾丸产生的精子无法到达附睾。精子通常在3-5天内到达附睾尾并在该处储存一周或更长时间。某些毒物可导致转运时间缩短，从而减少正常精子含量（而对精子发生无影响）。睾酮水平降低也会导致附睾中精子存活率下降。精子减少常伴有脱落的睾丸生精细胞和细胞碎片增多，这是由于睾丸中相关的精子发生障碍所致。精子含量减少还常与精子及液体体积减少所致的管腔缩小（导管萎缩）相关。精子可能减少（少精子症，oligospermia）或完全缺失（无精子症，aspermia）；减少的程度可用严重程度分级来表示。围青春期大鼠（8-10周）和小鼠（5-7周）可能表现为睾丸外观正常、附睾头及附睾体中精子数量正常，但附睾尾中精子数量减少，因为它们尚未建立起充足的精子储备。对于该年龄的动物，这不应被视为异常。
诊断建议
精子含量减少应记录并分级，并且如果其发生率和/或严重程度似乎与化学物给药相关，则应在病理学叙述中加以讨论。存在双侧受累时应予以记录。重要的是将任何潜在变化与年龄匹配的对照组进行比较，并与任何可获得的精子计数数据进行关联。与睾丸精子发生障碍的任何关联也应在病理学叙述中注明，以助于解释。与任何精子发生障碍的关联也应在病理学叙述中注明，以助于解释。
参考切片图（2 张）
查看英文原文
Comment
Reduced sperm content is generally caused by reduced testicular spermatogenesis but can also be due to an obstructive lesion in the efferent ducts preventing sperm from a normal-appearing testis from reaching the epididymis. Sperm normally reach the cauda in 3-5 days and remain stored there for a week or more. Some toxicants can cause a decrease in transit time, thereby reducing normal sperm content (with no effect on spermatogenesis). Reduced testosterone levels will also result in reduced survival of sperm in the epididymis. A reduction in sperm is often accompanied by an increase in sloughed testicular germ cells and cell debris, due to associated spermatogenic disturbances in the testis. A reduction in sperm content is also often associated with a reduction in the size of the ductal lumen (ductal atrophy) due to the reduced volume of sperm and fluid. There may be a reduction (oligospermia) or a total absence (aspermia) of sperm; the degree of reduction can be represented using severity grades. Peripubertal rats (8-10 weeks) and mice (5-7 weeks) may have normal-appearing testes, normal amounts of sperm in the caput and corpus, but reduced amounts of sperm in the cauda because they have not built up full sperm reserves. This should not be considered abnormal in animals of this age.
Recommendation
Reduced sperm content should be recorded and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. Bilateral involvement should be recorded when present. It is important to compare any potential changes with age-matched controls and to correlate with any available sperm count data. Any correlation with disturbances in testicular spermatogenesis should also be noted in the pathology narrative to aid interpretation. Correlation with any spermatogenic disturbances should also be noted in the pathology narrative to aid interpretation.
精子肉芽肿Sperm Granuloma 附睾其他
描述（中文）
当精子通过上皮衬里的破裂进入间质，或炎症细胞进入小管腔内与精子接触时，就会发生精子肉芽肿（sperm granuloma）。如果向间质破裂，附睾衬里可能自行修复并通过附睾管维持精子的连续性。精子肉芽肿最常见于附睾尾，但可发生于整个附睾以及输出管。如果发生于输出管并阻碍精子和液体从睾丸流出，由于上游积聚的反压，将导致相关睾丸继发性小管扩张和/或萎缩。该病变的特征是中央积聚的精子，周围环绕肉芽肿性异物炎症反应，通常含有大量多核巨细胞（箭头，Figure 1、Figure 2）（另见附睾 - 炎症）。精子肉芽肿可作为任何年龄啮齿动物的偶然背景性发现，但也可能由化学物质诱导。
诊断建议
精子肉芽肿应当被诊断并分级，如果其发生率和/或严重程度似乎与化学物给药相关，则应当在病理学叙述中讨论。存在双侧受累时应记录，适当时可使用修饰词记录其在附睾内的位置。附睾中的相关病变不应单独诊断，除非严重程度确有必要。睾丸中的相关病变可单独诊断，并在叙述中注明其与精子肉芽肿的关联。相关链接：附睾 - 炎症
参考切片图（2 张）
查看英文原文
Comment
Sperm granulomas occur when sperm is released into the interstitium through a rupture in the epithelial lining or when inflammatory cells gain access to the sperm within the ductular lumen. If there is rupture into the interstitium, the epididymal lining may repair itself and maintain sperm continuity through the epididymal duct. Sperm granulomas are most commonly seen in the cauda epididymis but can occur throughout the epididymis, as well as the efferent ducts. If they occur in the efferent ducts and obstruct the outflow of sperm and fluid from the testis, they will result in secondary tubular dilation and/or atrophy in the associated testis due to the accumulated backpressure upstream. The lesion is characterized by a central accumulation of sperm surrounded by a granulomatous foreign body inflammatory response, which generally contains numerous multinucleated giant cells (arrows, Figure 1 and Figure 2 ) (Also see Epididymis - Inflammation ). Sperm granulomas occur as an incidental background finding in any age of rodent but can also be chemically induced.
Recommendation
Sperm granulomas should be diagnosed and graded and should be discussed in the pathology narrative if the incidence and/or severity appears to be related to chemical administration. Bilateral involvement should be recorded when present, and a modifier can be used to record location within the epididymis if appropriate. Associated lesions in the epididymides should not be diagnosed separately unless warranted by severity. Associated lesions in the testes may be diagnosed separately and their association to the sperm granuloma noted in the narrative. Related Links: Epididymis - Inflammation
精液囊肿Spermatocele 附睾其他
描述（中文）
精液囊肿（spermatocele）是附睾管的囊性扩张（直径达到正常管的3倍或以上），其内衬可为肥大的或正常的上皮。它们最常见于小鼠附睾的起始段或头区（Figure 1），内含数量不等的精子。该精液囊肿内可见局灶性（focal）矿化区（箭头，Figure 1）。精液囊肿通常作为背景性、偶然性病变出现，但也有报道其与某些化学物暴露相关。其与精子肉芽肿的鉴别在于无炎症反应。
诊断建议
精液囊肿应记录为存在（present），并且如果其发生率似乎与化学物给药相关，则应在病理学叙述中加以讨论。如果双侧附睾均存在，诊断应限定为双侧性（双侧（bilateral））。不必对精液囊肿进行分级。
参考切片图（1 张）
查看英文原文
Comment
Spermatoceles are cystic dilations of the epididymal duct (three or more times the diameter of the normal duct), which may be lined by hypertrophic or normal epithelium. They are most commonly seen in the initial segment or the caput region of the mouse epididymis (Figure 1) and are filled with varying amounts of sperm. Focal areas of mineralization are present within this spermatocele (arrows, Figure 1 ). Spermatoceles generally occur as background, incidental lesions but have been reported in association with exposure to some chemicals. They are distinguished from sperm granuloma by the absence of an inflammatory response.
Recommendation
Spermatoceles should be recorded as present and discussed in the pathology narrative if the incidence appears to be related to chemical administration. If present in both epididymides, the diagnosis should be qualified as bilateral. It is not necessary to grade spermatoceles.
上皮增生Epithelium Hyperplasia 卵巢增生
描述（中文）
卵巢表面上皮增生表现为上皮表面的小息肉样突起，以及由胞质嗜碱性（basophilic）的立方上皮细胞索向下生长（Figure 1、Figure 2）。上皮细胞增生被认为起源于覆盖卵巢表面的间皮（mesothelium）。过去，这被称为生发上皮（germinal epithelium），但“生发上皮”一词具有误导性，因为覆盖卵巢表面的上皮是腹膜（peritoneum）的延续。上皮细胞增生必须与腺瘤（adenoma）、囊腺瘤（cystadenoma）和肾小管间质肿瘤（tubulostromal neoplasms）相鉴别，也必须与管状（Sertoli细胞样）增生（tubular (Sertoliform) hyperplasia）相鉴别，后者由柱状细胞衬覆的管状结构组成，细胞质边界不清，细胞核位于基底部。
诊断建议
卵巢，上皮——增生应始终予以诊断并给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Proliferation of the epithelium lining the surface of the ovary appears as small polypoid projections from the epithelial surface and as downgrowths of cords of cuboidal epithelium cells with basophilic cytoplasm ( Figure 1 and Figure 2 ). Epithelial cell hyperplasia is thought to be derived from the mesothelium lining the ovarian surface. In the past, this has been referred to as germinal epithelium but the term "germinal epithelium" is misleading, because the epithelium covering the surface of the ovary is a continuation of the peritoneum. Epithelial cell hyperplasia must be distinguished from adenoma, cystadenoma, and tubulostromal neoplasms and from tubular (Sertoliform) hyperplasia, which consists of tubules lined by columnar cells with indistinct cytoplasmic borders and basal nuclei.
Recommendation
Ovary, Epithelium - Hyperplasia should always be diagnosed and given a severity grade.
上皮性囊肿Cyst Epithelial 卵巢囊肿
描述（中文）
上皮性囊肿（Epithelial cyst）（Figure 1、Figure 2）在小鼠中偶尔可见，在大鼠中罕见。这些囊肿被认为起源于卵巢表面上皮向下生长。囊肿内衬扁平、立方、柱状或鳞状上皮；鳞状上皮可能发生角化。内衬上皮可能与表面上皮相似。
诊断建议
卵巢上皮性囊肿应当被诊断，但作为背景病变发生的囊肿无需分级。对于上皮性囊肿，诊断应包含囊肿类型作为修饰词（即，Ovary - Cyst, Epithelial）。如果认为囊肿与受试物相关，可对其进行分级以充分表征处理效应。如适用，诊断中可包含“双侧（bilateral）”和“multiple”这两个术语。
参考切片图（2 张）
查看英文原文
Comment
Epithelial cysts ( Figure 1 and Figure 2 ) are seen occasionally in mice and are rarely seen in rats. These cysts are considered to arise from downgrowth of the surface epithelium of the ovary. The cysts are lined by flattened, cuboidal, columnar, or squamous epithelium; squamous epithelium may be keratinized. The lining epithelium may resemble that of the surface epithelium.
Recommendation
Ovarian epithelial cysts should be diagnosed, but cysts occurring as background lesions need not be graded. In the case of an epithelial cyst, the diagnosis should include the type of cyst as a modifier (i.e., Ovary - Cyst, Epithelial). If the cysts are thought to be treatment related, they may be graded to fully characterize the treatment effect. If applicable, the terms "bilateral" and "multiple" may be included in the diagnosis.
中肾管残余Mesonephric Duct Remnant 卵巢其他
描述（中文）
卵巢中的中肾管残余（mesonephric duct remnant）以卵巢周围组织内的小管簇为特征（Figure 1、Figure 2）。这些小管衬覆立方至高柱状上皮，形态令人联想到附睾小管。这些管状结构被认为是中肾管的残余。
诊断建议
卵巢——中肾管残余应始终予以诊断，但无需分级。
参考切片图（2 张）
查看英文原文
Comment
Mesonephric duct remnants in the ovary are characterized by small clusters of tubules within periovarian tissue ( Figure 1 and Figure 2 ). The tubules are lined by cuboidal to tall columnar epithelium and have an appearance reminiscent of epididymal tubules. These tubules are recognized as being remnants of mesonephric ducts.
Recommendation
Ovary - Mesonephric duct remnant should always be diagnosed but need not be graded.
卵巢旁组织囊肿Paraovarian Tissue Cyst 卵巢囊肿
描述（中文）
卵巢旁囊肿（paraovarian cysts）很可能起源于中肾管（mesonephric ducts）和副中肾管（paramesonephric ducts）的退化残余。卵巢旁囊肿与卵巢不相连；它们位于卵巢邻近的卵巢系膜（mesovarium）或输卵管系膜（mesosalpinx）内（Figure 1、Figure 2、Figure 3、Figure 4）。卵巢旁囊肿由扁平、立方或柱状上皮衬覆，上皮可具有纤毛。可见囊肿与卵巢系膜内的卵巢旁结构相连。囊壁内是否存在平滑肌不定。
诊断建议
卵巢旁囊肿应予以诊断，但作为背景性病变发生的囊肿无需分级。对于卵巢旁囊肿，诊断应包含囊肿类型/部位作为修饰词（即 Ovary, Paraovarian tissue - Cyst）。如果认为囊肿与处理相关，可对其进行分级以充分描述处理效应。如适用，诊断中可包含“双侧（bilateral）”和“multiple”这两个术语。
参考切片图（2 张）
查看英文原文
Comment
Paraovarian cysts likely arise from vestigial remnants of the mesonephric and paramesonephric ducts. Paraovarian cysts are not connected to the ovary; they are adjacent to the ovary in the mesovarium or mesosalpinx ( Figure 1 , Figure 2 , Figure 3 and Figure 4 ). Paraovarian cysts are lined by flattened, cuboidal or columnar epithelium, and the epithelium may be ciliated. A connection to paraovarian structures in the mesovarium may be seen. The presence of smooth muscle in the wall of the cyst is variable.
Recommendation
Paraovarian cysts should be diagnosed, but cysts occurring as background lesions need not be graded. In the case of paraovarian cysts, the diagnosis should include the type of cyst/location as a modifier (i.e., Ovary, Paraovarian tissue - Cyst). If the cysts are thought to be treatment related, they may be graded to fully characterize the treatment effect. If applicable, the terms "bilateral" and "multiple" may be included in the diagnosis.
卵泡囊肿Follicle Cyst 卵巢囊肿
描述（中文）
卵巢卵泡囊肿（ovarian follicular cyst）是大鼠和小鼠常见的衰老性病变。它们起源于未能排卵的次级卵泡（secondary follicle）。其大小不一，但大于正常的排卵前卵泡（preovulatory follicle），可为单个或多个、单侧或双侧。其数量通常随衰老而增加。它们也可由改变卵巢周期性活动的化学物质诱导产生。它们可能与持续性发情（persistent estrus）、囊性子宫内膜增生（cystic endometrial hyperplasia）及不孕相关。组织学上，这些囊肿壁薄，充满淡嗜酸性残留物或血液；它们可能含有细胞碎片、退化的卵母细胞（oocyte），或泡沫状、空泡化或含色素的巨噬细胞（macrophage）。这些卵泡由一至四层立方状颗粒细胞（granulosa cell）衬覆，且无黄体化（luteinization）。一些较大的囊肿可能由单层扁平细胞衬覆，位于薄纤维性囊壁上。
诊断建议
卵巢卵泡囊肿应予以诊断，但作为背景病变发生的囊肿无需分级。对于卵泡囊肿，诊断应包含囊肿类型/部位作为修饰词（即 Ovary, Follicle - Cyst）。如果认为囊肿与受试物相关，可对其进行分级以充分表征受试物效应。如适用，诊断中可包含“双侧（bilateral）”和“multiple”这两个术语。
参考切片图（2 张）
查看英文原文
Comment
Ovarian follicular cysts are common aging findings in rats and mice. They arise in secondary follicles that fail to ovulate. They vary in size but are larger than a normal preovulatory follicle and may be single or multiple, unilateral or bilateral. Their numbers usually increase with aging. They have also been induced by chemicals that modify cyclical ovarian activity. They may be associated with persistent estrus, cystic endometrial hyperplasia, and infertility. Histologically these cysts are thin walled and filled with pale acidophilic residue or blood; they may contain cell debris, degenerating oocytes, or foamy, vacuolated, or pigment-laden macrophages. These follicles are lined by one to four layers of cuboidal granulosa cells, and there is no luteinization. Some larger cysts may be lined by a single layer of flattened cells resting on a thin fibrous capsule.
Recommendation
Ovarian follicular cysts should be diagnosed, but cysts occurring as background lesions need not be graded. In the case of a follicular cyst, the diagnosis should include the type of cyst/location as a modifier (i.e., Ovary, Follicle - Cyst). If the cysts are thought to be treatment related, they may be graded to fully characterize the treatment effect. If applicable, the terms "bilateral" and "multiple" may be included in the diagnosis.
囊肿Cyst 卵巢囊肿
描述（中文）
卵巢囊肿（ovarian cyst）是大鼠和小鼠中的常见所见（Figure 1、Figure 2、Figure 3、Figure 4）。卵巢囊肿可为单侧或双侧、单个或多个，并可变得相当大。理想情况下，囊肿应按起源、部位和/或形态学外观（卵泡性、黄体性、上皮性、卵巢网、囊状、卵巢旁）进行分类，这可提供关于毒性或致癌性研究中发病机制的信息。然而，起源可能难以判定，因为囊肿的大小和数量随年龄增长而增加，且囊壁变得非常薄，以致鉴别特征丧失。卵巢囊肿的发病机制常常未知；然而，在小鼠中，其中一些可能起源于中肾管（mesonephric duct）。
诊断建议
卵巢 - 囊肿应作出诊断，但不赋予严重程度分级。只要可能，囊肿类型（卵泡性、黄体性、上皮性、卵巢网、囊状、卵巢旁）应作为修饰词纳入诊断。无修饰词的卵巢 - 囊肿诊断保留用于无法确定囊肿起源的情况。
参考切片图（2 张）
查看英文原文
Comment
Ovarian cysts are a common finding in rats and mice ( Figure 1 , Figure 2 , Figure 3 and Figure 4 ). Ovarian cysts may be unilateral or bilateral, single or multiple, and may become quite large. Ideally, cysts should be classified by origin, location, and/or morphologic appearance (follicular, luteal, epithelial, rete ovarii, bursal, paraovarian), which may provide information as to pathogenesis in toxicity or carcinogenicity studies. However, origin may be difficult to assign because the size and number of cysts increase with age, and the walls become so thin that identifying features are lost. The pathogenesis of ovarian cysts is often unknown; however, in mice some of them may be of mesonephric duct origin.
Recommendation
Ovary - Cyst should be diagnosed but not assigned a severity grade. Whenever possible, the type of cyst (follicular, luteal, epithelial, rete ovarii, bursal, paraovarian) should be included in the diagnosis as a modifier. The diagnosis of Ovary - Cyst, with no modifier, is reserved for those instances when the origin of the cyst cannot be determined.
坏死Necrosis 卵巢坏死
描述（中文）
卵巢——坏死可能表现为边界清楚、无包膜的区域，中央由无定形坏死细胞碎片构成，外周有中等数量的以单核炎症细胞为主的炎症细胞浸润（Figure 1、Figure 2、Figure 3）。卵巢中坏死的特征与其他组织相同，包括核固缩和/或核碎裂、胞质嗜酸性增强以及细胞肿胀或皱缩。
诊断建议
卵巢——当坏死为原发性病变时，应作出诊断并分级。若坏死继发于其他病变（如炎症），除非严重程度确有必要，否则不应单独诊断，但应在病理学描述中予以描述。被认为继发于坏死的病变（如炎症或出血），除非严重程度确有必要，否则不应单独诊断。闭锁卵泡或退化黄体中的凋亡细胞不应诊断为坏死。
参考切片图（2 张）
查看英文原文
Comment
Ovary - Necrosis may be present is a well-circumscribed, unencapsulated area composed of amorphous necrotic cellular debris centrally and moderate numbers of mainly mononuclear inflammatory cells peripherally ( Figure 1 , Figure 2 and Figure 3 ). The features of necrosis in the ovary, as in other tissues, include nuclear pyknosis and/or karyorrhexis, cytoplasmic eosinophilia, and cellular swelling or shrinkage.
Recommendation
Ovary - Necrosis should be diagnosed and graded when it is a primary lesion. If the necrosis is secondary to another lesion, such as inflammation, it should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative. Lesions that are considered secondary to the necrosis, such as inflammation or hemorrhage, should not be diagnosed separately unless warranted by severity. Apoptotic cells in atretic follicles or regressing corpora lutea should not be diagnosed as necrosis.
多卵卵泡Follicle Polyovular 卵巢其他
描述（中文）
单个卵泡可能彼此紧密相邻（Figure 1）。这些卵泡每一个都含有一个卵母细胞。多卵母细胞卵泡（polyovular follicle）由单个卵泡构成，内含两个卵母细胞，每个卵母细胞各有其自身的细胞核、透明带（zona pellucida）和颗粒细胞层（Figure 2）。多卵母细胞卵泡偶尔作为背景性发现可见，但在 NTP 的一项亚慢性研究中，其曾在小鼠中被记录为与处理相关的发现。
诊断建议
卵巢，卵泡 - 多卵母细胞（Ovary, Follicle - Polyovular）在出现时应予以诊断，但不必进行严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Individual follicles may be closely adjacent to each other ( Figure 1 ). Each of these follicles contains one oocyte. A polyovular follicle comprises a single follicle containing two oocytes, each with its own nucleus, zona pellucida, and layer of granulosa cells ( Figure 2 ). Polyovular follicles are occasionally seen as a background finding but have been recorded as a treatment-related finding in mice in one subchronic NTP study.
Recommendation
Ovary, Follicle - Polyovular should be diagnosed when present, but severity grading is not necessary.
支持细胞样增生Hyperplasia Sertoliform 卵巢增生
描述（中文）
卵巢支持细胞增生的关键特征是细胞在组织学上类似于睾丸的支持细胞，并且这些增生性病变常发生于卵巢门区域（Figure 1）。其特征为类似生精小管的管状结构，管壁衬覆细胞，细胞核位于基底部，胞质丰富、呈淡嗜酸性、空泡化并延伸至管腔（Figure 2）。有时可出现由支持细胞局灶性巢状聚集构成的区域，而无明显的管状结构。支持细胞增生通常为局灶性（focal）病变，大小小于或等于一个黄体；无细胞异型性，也无压迫或包膜。支持细胞增生被认为起源于萎缩卵巢中的间质细胞。该病变与衰老相关，但也可能由化学物质诱导。支持细胞增生必须与无性细胞瘤（dysgerminoma）和支持细胞瘤相鉴别。支持细胞瘤的大小大于一个黄体；存在对邻近组织的压迫，并可能出现一定程度的细胞异型性。无性细胞瘤在大鼠中未见报道，在小鼠中为罕见肿瘤；其组织学表现为大片圆形、未分化细胞。
诊断建议
卵巢——增生，支持细胞样（Hyperplasia, Sertoliform）只要存在即应作出诊断并赋予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
The key features of Sertoli cell hyperplasia in the ovary are that the cells resemble their testicular counterpart histologically and that these proliferative lesions often arise in the region of the hilus ( Figure 1 ). They are characterized by seminiferous-like tubules lined by cells with basally located nuclei and abundant, faintly eosinophilic, vacuolated cytoplasm extending into the lumen ( Figure 2 ). Sometimes there may be areas with focal nests of Sertoli cells without obvious tubular structures. Sertoli cell hyperplasia is typically a focal lesion smaller than or equal to the size of a corpus luteum; there is no cellular atypia, and neither compression nor capsules are present. Sertoli cell hyperplasia is thought to be derived from stromal cells in atrophic ovaries. This finding is associated with aging but may also be induced by chemicals. Sertoli cell hyperplasia must be differentiated from dysgerminoma and Sertoli cell tumor. Sertoli cell tumors are larger than the size of a corpus luteum; there is compression of adjacent tissue, and some cellular atypia may be present. Dysgerminomas are not reported in the rat and are a rare tumor in mice; the histologic appearance is of sheets of large, round, undifferentiated cells.
Recommendation
Ovary - Hyperplasia, Sertoliform should be diagnosed and assigned a severity grade whenever present.
淀粉样物质Amyloid 卵巢其他
描述（中文）
卵巢中的淀粉样物质（amyloid）以均质、无细胞、嗜酸性玻璃样物质的沉积为特征（Figure 1、Figure 2、Figure 3、Figure 4）。沉积物主要发生于黄体（corpora lutea）及中等大小动脉的管壁（Figure 2）。在较严重的病例中，淀粉样物质沉积几乎取代了全部实质组织（Figure 3、Figure 4）。衰老过程中的淀粉样物质沉积在若干小鼠品系中发生率增高，如 Cd-1、A、SJL 或 C57BL；然而，在 B6C3F1 小鼠和大鼠中不常见。淀粉样变性（amyloidosis）是一种由错误折叠蛋白质的组织沉积所致的复杂病变，最常见的类型为免疫球蛋白轻链蛋白。淀粉样变性的严重程度和发生率增高可能与衰老和/或慢性炎症状态（如溃疡性皮炎）相关。淀粉样物质经刚果红（Congo red）染色后，在偏振光下呈绿色双折射。
诊断建议
卵巢——淀粉样物质一旦出现即应作出诊断并分级。病理学家应在叙述中描述该病变，并评论淀粉样物质如何影响研究结果。继发于淀粉样物质沉积的病变不应单独诊断，除非其严重程度足以支持单独诊断，但应在病理学叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Amyloid in the ovary is characterized the deposition of homogeneous, acellular, eosinophilic glassy material ( Figure 1 , Figure 2 , Figure 3 and Figure 4 ). Deposits occur primarily in the corpora lutea and in the walls of medium-sized arteries ( Figure 2 ). In more severe cases, amyloid deposits replace almost all of the parenchymal tissue ( Figure 3 and Figure 4 ). Deposition of amyloid during senescence occurs at increased incidences in several strains of mice, such as Cd-1, A, SJL, or C57BL; however, it is uncommon in B6C3F1 mice and rats. Amyloidosis is a complex condition due to tissue deposition of misfolded proteins, with the most common type being immunoglobulin light-chain proteins. Increased severity and incidence of amyloidosis may occur in association with aging and/or with chronic inflammatory conditions such as ulcerative dermatitis. Amyloid shows a green birefringence under polarized light when stained with Congo red dye.
Recommendation
Ovary - Amyloid should be diagnosed and graded whenever present. The pathologist should describe this lesion in the narrative and comment on how the amyloid affects the results of the study. Lesions occurring secondary to amyloid deposition should not be diagnosed separately, unless warranted by severity, but should be described in the pathology narrative.
滑囊囊肿Bursa Cyst 卵巢囊肿
描述（中文）
腔上囊囊肿（Bursal cyst）（Figure 1、Figure 2）的特征是卵巢囊或腔上囊扩张。腔上囊囊肿在老龄小鼠和大鼠尸检时常见。这些囊肿由单层扁平上皮衬覆（Figure 3）。腔上囊囊肿应与真性卵巢囊肿或卵巢旁囊肿相鉴别。腔上囊囊肿包裹卵巢，可能造成压迫，但不存在于卵巢内。通常，膨胀的腔上囊在剖检时塌陷，显露其中完整的卵巢，而真性卵巢囊肿位于卵巢实质内，尸检时通常可完整剥离。卵巢旁囊肿存在于卵巢内和/或邻近卵巢，由扁平、立方或柱状上皮衬覆；上皮可具纤毛，并可见与卵巢系膜内卵巢旁结构的连接。腔上囊囊肿的发病机制尚未阐明。
诊断建议
卵巢腔上囊囊肿应予以诊断，但作为背景性病变发生的囊肿无需分级。对于腔上囊囊肿，诊断应包括囊肿类型/部位作为修饰词（即 Ovary, Bursa - Cyst）。如果认为囊肿与受试物相关，可对其进行分级以充分表征受试物效应。如适用，诊断中可包括“双侧（bilateral）”和“multiple”这两个术语。
参考切片图（2 张）
查看英文原文
Comment
Bursal cysts ( Figure 1 and Figure 2 ) are characterized by dilation of the ovarian capsule, or bursa. Bursal cysts are frequently found in aged mice and rats at necropsy. These cysts are lined by a simple squamous epithelium ( Figure 3 ). Bursal cysts should be distinguished from true ovarian or paraovarian cysts. Bursal cysts envelop the ovary and may cause compression but are not present within the ovary. Typically, a distended bursa collapses at dissection, disclosing an intact ovary within it, whereas a true ovarian cyst is found within the ovarian parenchyma and may generally be dissected intact at necropsy. Paraovarian cysts are present within and/or adjacent to the ovary and are lined by flattened, cuboidal or columnar epithelium; the epithelium may be ciliated, and a connection to paraovarian structures in the mesovarium may be seen. The pathogenesis of bursal cysts has not been elucidated.
Recommendation
Ovarian bursal cysts should be diagnosed, but cysts occurring as background lesions need not be graded. In the case of a bursal cyst, the diagnosis should include the type of cyst/location as a modifier (i.e., Ovary, Bursa - Cyst). If the cysts are thought to be treatment related, they may be graded to fully characterize the treatment effect. If applicable, the terms "bilateral" and "multiple" may be included in the diagnosis.
炎症Inflammation 卵巢炎症
描述（中文）
在NTP研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞是中性粒细胞（neutrophil），尽管也可能存在较少的巨噬细胞（macrophage）和淋巴细胞（lymphocyte）。还可能有水肿或充血（hyperemia）的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5），但中性粒细胞聚集，且许多已变性（化脓性渗出物，化脓性 exudate）。渗出物中还可能存在细胞碎片（来自驻留细胞群和浸润白细胞）、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞（plasma cell），以及可能的感染因子。肉眼上，这些病变以脓液存在为特征。渗出物周围组织可能含有成纤维细胞（fibroblast）、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。脓肿在组织学上应诊断为化脓性炎症。淋巴细胞在慢性炎症中占主导地位（Figure 6、Figure 7）。淋巴细胞在慢性活动性炎症中也占主导地位（Figure 8、Figure 9），但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症（Figure 10、Figure 11）是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大型、活化巨噬细胞、上皮样巨噬细胞（epithelioid macrophage）或多核巨细胞（multinucleated giant cell）。炎症与细胞浸润的鉴别在于其他改变的存在，如水肿、出血、变性、坏死或其他组织损伤证据。肉芽肿性卵巢炎症的特征是多灶性、边界清楚、大小不一且形状不规则的嗜酸性泡沫状巨噬细胞簇，周围环绕数量不等的多核巨细胞和淋巴细胞（Figure 10、Figure 11）。这种类型的炎症可见于发情前期（proestrus）对照动物的黄体（corpus luteum）中，因此该病变仅在以下情况下才应诊断：在动情周期（estrous cycle）的其他阶段见到、似乎位于黄体之外、或在处理动物中比对照动物更严重。导致炎症的卵巢感染通常为上行性，经由阴道和子宫腔。原因可能与动物饲养设施的环境因素和清洁度有关。卵巢感染可见于由多种细菌引起的全身性感染。然而，自身免疫性卵巢炎症已在胸腺切除小鼠中得到证实，可能涉及T淋巴细胞介导的机制。
诊断建议
卵巢 - 炎症：存在时应诊断并分级。诊断中应通过使用限定词指明炎症类型。继发于炎症的病变，如坏死、出血和水肿，除非严重程度 warrant，否则不应单独诊断，但应在病理叙述中描述。如果炎症继发于另一病变（例如坏死或肿瘤形成），除非严重程度 warrant，否则不应单独诊断，但应在叙述中描述为原发病变成分。相关链接：卵巢 - 细胞浸润
参考切片图（2 张）
查看英文原文
Comment
In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation ( Figure 1 , Figure 2 , Figure 3 , Figure 4 and Figure 5 ), but the neutrophils are aggregated, and many are degenerate (suppurative exudate). Cell debris, both from the resident cell populations and from infiltrating leukocytes, and proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present within the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may contain fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Abscesses should be diagnosed histologically as suppurative inflammation. Lymphocytes predominate in chronic inflammation ( Figure 6 and Figure 7 ). Lymphocytes also predominate in chronic active inflammation ( Figure 8 and Figure 9 ), but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation ( Figure 10 and Figure 11 ) is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammation is differentiated from cellular infiltrates by the presence of other changes, such as edema, hemorrhage, degeneration, necrosis, or other evidence of tissue damage. Granulomatous ovarian inflammation is characterized by multifocal, well-circumscribed, variably sized and irregularly shaped eosinophilic clusters of foamy macrophages, surrounded by variable numbers of multinucleated giant cells and lymphocytes ( Figure 10 and Figure 11 ). This type of inflammation can be seen in corpora lutea in control animals during proestrus, so this lesion should be diagnosed only if it is seen during other phases of the estrous cycle, if it appears to be outside of corpora lutea, or if it is more severe in the treated animals than in controls. Ovarian infections resulting in inflammation are generally ascending, through the vagina and uterine cavity. The cause may be related to environmental factors and cleanliness in the animal housing facility. Ovarian infections may be seen with systemic infections caused by a variety of bacteria. However, autoimmune ovarian inflammation has been demonstrated in thymectomized mice, possibly involving a T-lymphocyte-mediated mechanism.
Recommendation
Ovary - Inflammation should be diagnosed and graded whenever present. The type of inflammation should be indicated in the diagnosis by use of a qualifier. Lesions secondary to inflammation, such as necrosis, hemorrhage, and edema, should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative. If the inflammation is secondary to another lesions (e.g., necrosis or neoplasia), it should not be diagnosed separately unless warranted by severity but should be described in the narrative as a component of the primary lesion. Related Links: Ovary - Infiltration Cellular
矿物质Mineral 卵巢其他
描述（中文）
卵巢矿化（Figure 1、Figure 2）通常继发于细胞损伤或坏死（即营养不良性矿化）。卵巢营养不良性矿化在大鼠和小鼠中已有报道。卵巢矿化可见于黄体，作为正常闭锁过程的一部分；然而，也有报道其与化学物质诱导的卵巢卵泡或黄体闭锁相关。转移性矿化在小鼠和大鼠卵巢中不常见。
诊断建议
卵巢——当没有坏死或炎症证据时，应对矿物质进行诊断和分级。如果矿化继发于坏死或炎症，且异常严重，若病理学家认为有必要，可将其与坏死或炎症同时诊断。如果矿物质与处理相关，研究病理学家应尝试确定病变的根本原因。如果矿化发生在血栓中，则不应诊断。
参考切片图（2 张）
查看英文原文
Comment
Ovarian mineralization ( Figure 1 and Figure 2 ) is usually secondary to cell damage or necrosis (i.e., dystrophic mineralization). Dystrophic mineralization of the ovary has been reported in rats and mice. Ovarian mineralization can be seen in corpora lutea as part of normal atresia; however, it has also been reported in association with chemically induced ovarian follicular or corpora lutea atresia. Metastatic mineralization is uncommon in the ovaries of mice and rats.
Recommendation
Ovary - Mineral should be diagnosed and graded when there is no evidence of necrosis or inflammation. If it is secondary to necrosis or inflammation, and is unusually severe, it may be diagnosed concurrently with the necrosis or inflammation if the pathologist feels it is warranted. The study pathologist should attempt to identify the underlying cause of the lesion if mineral is treatment related. Mineralization should not be diagnosed if it occurs in a thrombus.
细胞浸润Infiltration Cellular 卵巢浸润
描述（中文）
卵巢－细胞浸润（Ovary - Infiltration cellular）的特征是存在浸润细胞，而无炎症证据（例如细胞或组织损伤、出血、充血、水肿）（Figure 1、Figure 2）。非肿瘤性炎症细胞或免疫细胞浸润可能是组织对任何损伤甚至正常生理过程变化的反应。许多免疫学因素和细胞信号通路调控细胞浸润过程，读者可参阅普通病理学教科书。如果浸润细胞伴有其他炎症征象，则应诊断为炎症（见卵巢－炎症（Ovary - Inflammation））。
诊断建议
卵巢－细胞浸润（Ovary - Infiltration cellular）应进行诊断并分级。应在诊断中通过限定词指明浸润细胞的类型（嗜酸性粒细胞（eosinophil）、淋巴细胞（lymphocyte）、巨噬细胞（macrophage）、肥大细胞（mast cell）、巨核细胞（megakaryocyte）、黑素细胞（melanocyte）、浆细胞（plasma cell）、中性粒细胞（neutrophil）或混合细胞（mixed cell））。修饰词基于主要细胞类型；如果没有一种细胞占50%或以上，则使用术语“混合细胞”。相关链接：卵巢－炎症（Ovary - Inflammation）
参考切片图（2 张）
查看英文原文
Comment
Ovary - Infiltration cellular is characterized by the presence of infiltrating cells with no evidence of inflammation (e.g., cell or tissue damage, hemorrhage, congestion, edema) ( Figure 1 and Figure 2 ). Nonneoplastic inflammatory or immune cell infiltration may be a tissue response to any insult or even a change in normal physiologic processes. Many immunologic factors and cell signaling pathways regulate the cellular infiltration process, for which the reader is referred to textbooks of general pathology. If the infiltrating cells are accompanied by other signs of inflammation, inflammation should be diagnosed (see Ovary - Inflammation ).
Recommendation
Ovary - Infiltration cellular should be diagnosed and graded. The type of infiltrating cell should be indicated in the diagnosis by use of a qualifier (eosinophil, lymphocyte, macrophage, mast cell, megakaryocyte, melanocyte, plasma cell, neutrophil, or mixed cell). The modifier is based on the predominant cell type; if no cell comprises 50% or more, then the term "mixed cell" is used. Related Links: Ovary - Inflammation
脂肪变性Fatty Change 卵巢其他
描述（中文）
卵巢——脂肪变化（fatty change）的特征是一簇边界清楚、部分有包膜、轻度压迫周围组织的细胞，其形态为典型的脂肪细胞（adipocyte）（Figure 1、Figure 2）。多边形细胞的胞质内存在大小不一的大的透明空泡，将扁平的细胞核挤向细胞边缘。间质细胞（interstitial cell）、膜细胞（thecal cell）和颗粒细胞（granulosa cell）含有大量脂滴。脂肪变化可由抑制类固醇激素合成的药物诱发，导致脂质在卵巢间质中蓄积。用咪唑类抗真菌药处理的大鼠卵巢间质细胞中脂质增加，同时还伴有脂褐素（lipofuscin）沉积。
诊断建议
卵巢——脂肪变化只要存在就应诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Ovary - Fatty change is characterized by a well-circumscribed, partially encapsulated, slightly compressing cluster of cells with the appearance typical of adipocytes ( Figure 1 and Figure 2 ). Large, variably sized, clear vacuoles are present in the cytoplasm of polygonal cells, displacing the flattened nucleus to the periphery of the cell. Interstitial, thecal, and granulosa cells contain numerous lipid droplets. Fatty change may be induced by drugs inhibiting steroid hormone synthesis, resulting in lipid accumulation in the ovarian stroma. Rats treated with an imidazole antifungal drug had increased lipid in the interstitial cells of the ovary, which was also associated with deposition of lipofuscin.
Recommendation
Ovary - Fatty change should be diagnosed and graded whenever present.
色素Pigment 卵巢色素沉着
描述（中文）
卵巢中可见的各种色素（Figure 1、Figure 2、Figure 3、Figure 4）包括蜡样质（ceroid）、含铁血黄素（hemosiderin）、血棕素（hematoidin）和黑色素（melanin）。在 NTP 项目中，已在 Fischer 344 大鼠和 B6C3F1 小鼠中观察到黄褐色、periodic-acid-Schiff 阳性且抗酸性蜡样质色素，但在小鼠中更为常见。黄色至褐色色素常被视为小鼠和大鼠卵巢的衰老性改变。蜡样质是最常见的色素，主要蓄积于间质细胞的细胞质中。给予干扰类固醇合成的化合物可能导致脂褐素（lipofuscin）蓄积。含铁血黄素和血棕素的蓄积可能与导致出血进入卵泡或黄体的血管病变有关。已有报道在有色素沉着的 B6C3F1 小鼠卵巢中发生黑色素蓄积，但所涉及的机制尚未阐明。
诊断建议
卵巢 - 色素：当认为色素与研究相关（或不清楚是否与研究相关）时，或当色素异常显著时，应作出诊断。并非所有色素都必须诊断，因为有些色素在衰老动物中普遍存在，或是另一疾病过程（例如出血）的继发改变，不具有毒理学意义。病理学家应运用其判断来决定是否应诊断色素。即使使用一系列特殊染色，在组织学切片中确定色素的种类通常也很困难。因此，最恰当的诊断是“色素”（而非诊断色素的类型，例如含铁血黄素或脂褐素）。病理学描述应描述色素沉着的形态学特征。当诊断色素时，应给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Various pigments ( Figure 1 , Figure 2 , Figure 3 and Figure 4 ) seen in ovaries include ceroid, hemosiderin, hematoidin, and melanin. In the NTP program, yellow-brown, periodic-acid-Schiff-positive and acid-fast ceroid pigment has been observed in Fischer 344 rats and B6C3F1 mice but is more common in mice. Yellow to brown pigment is often seen as an aging change in mouse and rat ovaries. Ceroid is the pigment most frequently seen, and this accumulates mainly in the cytoplasm of interstitial cells. Administration of compounds that interfere with steroid synthesis may result in accumulation of lipofuscin. Accumulation of hemosiderin and hematoidin may be associated with vascular lesions resulting in hemorrhage into follicles or corpora lutea. Accumulation of melanin has been reported in the ovaries of pigmented B6C3F1 mice, but the mechanism involved has not been clarified.
Recommendation
Ovary - Pigment should be diagnosed when it is considered to be relevant to the study (or if it is unclear whether it is relevant to the study) or if it is unusually prominent. Not all pigments have to be diagnosed, as some are ubiquitous in aging animals or are secondary to another disease process (e.g., hemorrhage) and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether pigment should be diagnosed. Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, a diagnosis of "pigment" (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should describe the morphologic features of the pigmentation. When pigment is diagnosed, it should be given a severity grade.
萎缩Atrophy 卵巢萎缩
描述（中文）
卵巢萎缩（Ovarian atrophy）随年龄增长（衰老）发生，也可能由给予药物或暴露于阻断或抑制卵巢营养性调控的化学物质引起。卵巢萎缩定义为卵巢大小和重量减小，以及卵母细胞、发育中的卵泡和黄体数量减少（Figure 1、Figure 2、Figure 3）。萎缩的卵巢体积小，卵泡和黄体明显缺失，间质增多，间质中常见明显的色素沉着（Figure 4、Figure 5、Figure 6）。在NTP致癌性研究中，B6C3F1小鼠卵巢萎缩的发生率高于F344大鼠。与卵巢萎缩相关的其他所见，如果认为相关，可单独诊断，并可能为毒性或致癌性研究中萎缩的发病机制提供信息。这些所见可能包括间质细胞增生、滤泡上皮坏死、囊性卵泡数量增多、色素或脂质蓄积、胆固醇裂隙、黄体玻璃样变性、纤维化和矿化。
诊断建议
卵巢－萎缩（Ovary - Atrophy）仅在与处理相关时记录并分级。区分处理相关萎缩与衰老所致萎缩很重要，与衰老相关的萎缩性病变不应诊断。当萎缩与处理相关时，在病理学描述中描述卵巢中存在的改变很重要。病理学家还应检查子宫和阴道的继发性萎缩以及乳腺组织中的相关改变。卵巢－萎缩是短期研究的合适诊断。如果诊断了处理相关的卵巢萎缩，应通知NTP可能需要更详细的研究（例如，原始卵泡、初级卵泡和窦卵泡及黄体的计数）。
参考切片图（2 张）
查看英文原文
Comment
Ovarian atrophy occurs with age (senescence) or may result from administration of drugs or exposure to chemicals that block or suppress trophic control of the ovary. Ovarian atrophy is defined as decreased ovarian size and weight and decreased numbers of oocytes, developing follicles, and corpora lutea ( Figure 1 , Figure 2 and Figure 3 ). Atrophic ovaries are small, with a conspicuous absence of follicles and corpora lutea and the presence of increased stroma, with frequent prominent pigment in the interstitium ( Figure 4 , Figure 5 and Figure 6 ). Atrophy occurs more frequently in B6C3F1 mice than in F344 rats in NTP carcinogenicity studies. Additional findings associated with ovarian atrophy may be diagnosed separately if deemed relevant and may provide information as to pathogenesis of atrophy in toxicity or carcinogenicity studies. These findings may include interstitial cell hyperplasia, necrosis of follicular epithelium, increased numbers of cystic follicles, accumulation of pigment or lipid, cholesterol clefts, hyaline degeneration of corpora lutea, fibrosis, and mineralization.
Recommendation
Ovary - Atrophy should be recorded and graded only when treatment related. It is important to distinguish treatment-related atrophy from senescence, and atrophic lesions associated with senescence should not be diagnosed. When atrophy is treatment related, it is important to describe the changes present in the ovary in the pathology narrative. The pathologist should also check for secondary atrophy of uterus and vagina and associated changes in mammary tissue. Ovary - Atrophy is a suitable diagnosis for a short-term study. If treatment-related ovarian atrophy is diagnosed, notify NTP that more detailed studies (e.g., counts of primordial, primary, and antral follicles and corpora lutea) may be warranted.
血栓形成Thrombosis 卵巢血栓
描述（中文）
卵巢血栓（Figure 1、Figure 2）可能较大，并由嗜酸性层状物质取代卵巢实质而形成边界清楚的区域。明显的层状结构（Zahn线）由血小板与染色较深的纤维蛋白交替层构成，其间被主要含红细胞的较深层次分隔。在血栓附着于血管壁的周边部位，可见浸润的成纤维细胞和少量炎症细胞。邻近实质受压。存在时间较长的血栓其特征为Zahn线不明显，且常含有符合矿化的无定形嗜碱性物质团块。三个因素易致血栓形成：内皮损伤、正常血流改变以及血液高凝性改变。内皮损伤可能由创伤、感染、辐射、免疫介导性损伤以及细菌毒素或内毒素引起。血流改变可能发生于因炎症、动脉粥样硬化、中膜矿化或中膜肥厚等过程而狭窄的血管中，这些过程促成淤滞或湍流，使血小板与内皮接触，和/或减慢凝血因子抑制物的流入。血液凝固性改变（即高凝状态）并非血栓形成的常见原因。然而，它们可能由凝血蛋白的遗传缺陷所致，或继发于全身性疾病（例如淋巴瘤、炎症、肾脏疾病）。
诊断建议
卵巢 - 血栓形成应予以诊断，但无需分级。继发于血栓形成的坏死应单独诊断并分级。其他被认为继发于血栓形成的病变（例如矿化）不应单独诊断，除非其严重程度足以支持这样做。
参考切片图（2 张）
查看英文原文
Comment
Ovarian thrombi ( Figure 1 and Figure 2 ) may be large and comprise well-circumscribed areas of ovarian parenchyma that have been replaced by eosinophilic laminated material. The apparent laminations (lines of Zahn) are produced by alternating layers of platelets admixed with darker-staining fibrin, separated by darker layers containing mainly erythrocytes. Peripherally, at the attachment of the thrombus to the vessel wall, there are infiltrating fibroblasts and small numbers of inflammatory cells. There is compression of the adjacent parenchyma. Thrombi of longer duration are characterized by having less prominent lines of Zahn and often have clumps of amorphous basophilic material consistent with mineralization. Three factors predispose to thrombosis: injury to endothelium, alterations in normal blood flow, and alterations in blood hypercoagulability. Endothelial injury may be due to trauma, infections, radiation, immune-mediated injuries, and bacterial toxins or endotoxins. Alterations in blood flow may occur in vessels narrowed by processes such as inflammation, atherosclerosis, medial mineralization, or medial hypertrophy that contribute to stasis or turbulence, which brings platelets into contact with the endothelium, and/or slow the inflow of clotting factor inhibitors. Alterations in blood coagulability (i.e., hypercoagulability) are not a common cause of thrombosis. However, they can be due to genetic defects in a coagulation protein or could be secondary to systemic disease (e.g., lymphoma, inflammation, renal disease).
Recommendation
Ovary - Thrombosis should be diagnosed but need not be graded. Necrosis secondary to thrombosis should be diagnosed and graded separately. Other lesions considered to be secondary to thrombosis (e.g., mineralization) should not be diagnosed separately unless warranted by severity.
血管扩张Angiectasis 卵巢扩张
描述（中文）
血管扩张（angiectasis）的特征是大小和形状不一的管道随机分布于卵巢实质中（Figure 1、Figure 2）。这些管道由单层扁平的梭形细胞衬覆，通常含有数量不等的血细胞。该病变在卵巢中的发生率小鼠高于大鼠。原有的卵巢血管扩张并充满血细胞，伴有卵巢实质受压。这是一种常见的年龄相关变化；然而，其机制尚未明确阐明。血管扩张必须与卵巢血管瘤样增生（angiomatous hyperplasia）、血管瘤（hemangioma）和血管肉瘤（hemangiosarcoma）相鉴别。在卵巢血管扩张中，血管数量不增加，衬覆扩张血管管道的内皮细胞在大小、形状和数量上均表现正常。在血管瘤样增生中，血管数量增加，但内皮细胞基本上正常。在血管瘤中，血管管道数量增加，伴有内皮细胞肥大。血管肉瘤的特征是边界不清的肿块，导致卵巢实质移位或破坏，由不规则、形成不良、具有潜在侵袭性的血管管道组成，这些管道由数量过多的多形性细胞衬覆，这些细胞通常胞质稀少，核增大、呈卵圆形、深染或呈空泡状。
诊断建议
卵巢 - 血管扩张：只要存在即应诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Angiectasis is characterized by channels of variable size and shape randomly distributed throughout the ovarian parenchyma ( Figure 1 and Figure 2 ). These channels are lined by a single layer of flattened spindle-shaped cells and generally contain variable numbers of blood cells. This occurs in the ovaries more frequently in mice than in rats. Preexisting ovarian blood vessels become dilated and filled with blood cells, accompanied by compression of the ovarian parenchyma. This is a common age-related change; however, the mechanism has not been clearly elucidated. Angiectasis must be distinguished from ovarian angiomatous hyperplasia, hemangioma, and hemangiosarcoma. In ovarian angiectasis, the number of vessels is not increased, and the endothelial cells lining the dilated vascular channels appear normal in size, shape, and number. In angiomatous hyperplasia, there is an increase in the number of vessels, but the endothelial cells are essentially normal. In hemangioma, there is an increase in the number of vascular channels with hypertrophied endothelium. Hemangiosarcoma is characterized as a poorly delineated mass causing displacement or destruction of ovarian parenchyma, consisting of irregular, poorly formed, potentially invasive vascular channels lined by an excessive number of pleomorphic cells with generally scant cytoplasm and enlarged, oval hyperchromatic or vesicular nuclei.
Recommendation
Ovary - Angiectasis should be diagnosed and graded whenever present.
间质细胞增生Interstitial Cell Hyperplasia 卵巢增生
描述（中文）
通常，在间质细胞增生（interstitial cell hyperplasia）中，许多大小不一的淡染细胞簇散布于处于不同发育阶段的数个卵泡之间，包括大的闭锁卵泡、成熟黄体、色素沉着区域和充血血管（Figure 1）。增生的间质细胞索和巢由大的多面体细胞组成，胞质呈淡嗜酸性颗粒状，核位于中央（Figure 2）。卵巢间质细胞增生是间质腺细胞成分的非肿瘤性增殖，这些细胞成分来源于闭锁卵泡、黄体或卵巢基质细胞。这是大鼠和小鼠常见的衰老性改变。它也可能由某些化学物质处理诱导，如促性腺激素和某些有机磷化合物。
诊断建议
卵巢，间质细胞 - 增生：只要存在就应诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Typically in interstitial cell hyperplasia many variably sized clusters of pale-staining cells are interspersed among several follicles in various stages of development, including large atretic follicles, mature corpora lutea, areas of pigment deposition, and congested blood vessels ( Figure 1 ). Cords and nests of hyperplastic interstitial cells are composed of large polyhedral cells with pale eosinophilic granular cytoplasm and central nuclei ( Figure 2 ). Ovarian interstitial cell hyperplasia is a nonneoplastic proliferation of cellular components of the interstitial gland, derived from atretic follicles, corpora lutea, or ovarian stromal cells. This is a common aging change in rats and mice. It may also be induced by treatment with certain chemicals, such as gonadotropins and some organophosphate compounds.
Recommendation
Ovary, Interstitial cell - Hyperplasia should be diagnosed and graded whenever present.
骨性化生Metaplasia Osseous 卵巢化生
描述（中文）
卵巢骨性化生（osseous metaplasia）（Figure 1、Figure 2）的特征为边界清楚、无包膜的病灶，由骨小梁构成，骨小梁表面衬覆成骨细胞和破骨细胞；还可见无定形无细胞性嗜碱性物质团块，最可能是钙盐的矿化沉积物，并可见邻近卵巢实质轻度受压。卵巢化生是一种与衰老和卵巢萎缩相关的改变。骨性化生偶有报道，但其机制尚未阐明。
诊断建议
卵巢——化生，骨性（Metaplasia, Osseous）只要存在即应诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Ovarian osseous metaplasia ( Figure 1 and Figure 2 ) is characterized by a well-circumscribed, unencapsulated focus composed of bony trabeculae lined by osteoblasts and osteoclasts; there may also be clumps of amorphous acellular basophilic material, which are most likely mineralized deposits of calcium salts, and mild compression of adjacent ovarian parenchyma. Ovarian metaplasia is a change associated with aging and ovarian atrophy. Osseous metaplasia has been occasionally reported, but the mechanism has not been elucidated.
Recommendation
Ovary - Metaplasia, Osseous should be diagnosed and graded whenever present.
黄体囊肿Corpus Luteum Cyst 卵巢囊肿
描述（中文）
黄体囊肿（corpora lutea cyst）（Figure 1、Figure 2、Figure 3、Figure 4）比正常黄体大，并可能使卵巢结构变形。其囊壁完全由数层多边形细胞衬覆，胞质丰富、嗜酸性、呈细空泡状的黄体细胞。囊肿形成于真正的黄体，因此囊腔内无退化卵子的证据。囊性黄体来源于排卵卵泡。若具有功能，这些囊肿可导致持续性、非周期性的孕酮刺激。黄体囊肿必须与未正常填充但随动情周期进展的黄体相鉴别。孕酮受体抑制剂可在大鼠中诱导典型的黄体囊肿。
诊断建议
卵巢黄体囊肿应予以诊断，但作为背景病变发生的囊肿无需分级。对于黄体囊肿，诊断应包含囊肿类型/部位作为修饰词（即 Ovary, Corpus luteum - Cyst）。若认为囊肿与受试物相关，可对其进行分级以充分表征受试物效应。如适用，诊断中可包含“双侧（bilateral）”和“multiple”术语。
参考切片图（2 张）
查看英文原文
Comment
Cysts of the corpora lutea ( Figure 1 , Figure 2 , Figure 3 and Figure 4 are larger than a normal corpus luteum and may distort the ovarian architecture. They are lined completely by several layers of polygonal cells, with abundant eosinophilic, finely vacuolated luteal cells. Cyst formation occurs in a true corpus luteum, so there is no evidence of degenerate ova within the cystic cavity. Cystic corpora lutea are derived from ovulatory follicles. If functional, these cysts may result in prolonged, noncyclic progesterone stimulation. Luteal cysts must be differentiated from corpora lutea that did not fill in normally but that progress through the estrous cycle. Progesterone receptor inhibitors induce typical luteal cysts in rats.
Recommendation
Ovarian luteal cysts should be diagnosed, but cysts occurring as background lesions need not be graded. In the case of a luteal cyst, the diagnosis should include the type of cyst/location as a modifier (i.e., Ovary, Corpus luteum - Cyst). If the cysts are thought to be treatment related, they may be graded to fully characterize the treatment effect. If applicable, the terms "bilateral" and "multiple" may be included in the diagnosis.
中肾管残余Mesonephric Duct Remnant 子宫其他
描述（中文）
中肾管残余（mesonephric duct remnant）（Figure 1）表现为由假复层柱状上皮和平滑肌衬覆的盘曲或分支状小管，令人联想到附睾管和输精管中所见的结构。通常这些结构见于子宫角或子宫体的侧方附着处，可为单侧或双侧。它们通常位于子宫阔韧带附着部位。这些胚胎残余必须与肿瘤相鉴别，肿瘤会表现出其肿瘤类型所特有的生长方式。
诊断建议
子宫——中肾管残余应当诊断，但无需分级，除非分级有助于表征处理效应。
参考切片图（1 张）
查看英文原文
Comment
Remnants of the mesonephric duct ( Figure 1 ) appear as coiled or branching tubules lined by pseudostratified columnar epithelium and smooth muscle and are reminiscent of that seen in the ductus epididymides and vas deferens. Typically these structures are seen laterally attached to the uterine horns or body, and they may be unilateral or bilateral. They are typically present at the site of attachment of the broad ligament of the uterus. These embryonic remnants must be differentiated from neoplasms, which display growth patterns characteristic of the tumor type.
Recommendation
Uterus - Mesonephric duct remnant should be diagnosed but need not be graded unless grading would help characterize a treatment effect.
出血Hemorrhage 子宫出血
描述（中文）
子宫出血（Uterine hemorrhage）（Figure 1、Figure 2）偶见于大鼠和小鼠。它常与F344大鼠的单核细胞白血病（mononuclear cell leukemia）相关。当发生慢性出血时，可见含铁血黄素负载的巨噬细胞（hemosiderin-laden macrophages）、胆固醇裂隙（cholesterol clefts）、营养不良性钙化或矿化（dystrophic calcification or mineralization）以及纤维化（fibrosis）。这些变化可发生于子宫腔、子宫内膜和/或子宫肌层。必须仔细检查子宫出血，以寻找内皮增生的证据，提示存在 underlying process，如内皮增生（endothelial hyperplasia）、血管瘤（hemangioma）或血管肉瘤（hemangiosarcoma）。
诊断建议
子宫－出血（Uterus - Hemorrhage）应诊断并分级。如果它是继发于其他过程（例如炎症、肿瘤），除非严重程度 warrant，否则不应诊断，但应在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Uterine hemorrhage ( Figure 1 and Figure 2 ) is seen occasionally in rats and mice. It is often associated with mononuclear cell leukemia in F344 rats. When chronic hemorrhage occurs, hemosiderin-laden macrophages, cholesterol clefts, dystrophic calcification or mineralization, and fibrosis may be evident. This may occur in the lumen, endometrium, and/or myometrium. Uterine hemorrhage must be carefully examined for evidence of endothelial proliferation that would indicate the presence of an underlying process, such as endothelial hyperplasia, hemangioma, or hemangiosarcoma.
Recommendation
Uterus - Hemorrhage should be diagnosed and graded. If it is secondary to another process (e.g., inflammation, neoplasia), it should not be diagnosed unless warranted by severity but should be described in the pathology narrative.
坏死Necrosis 子宫坏死
描述（中文）
子宫坏死（uterine necrosis）较为罕见，但其组织学表现与其他部位的坏死相似，初期表现为组织中的细胞死亡，特征为核固缩（nuclear pyknosis）和/或核碎裂（karyorrhexis）、胞质嗜酸性（cytoplasmic eosinophilia）以及细胞肿胀或皱缩。坏死的后果是肉芽组织（granulation tissue）和矿化（mineralization）（Figure 1、Figure 2）。子宫坏死可能由相关的动脉炎（arteritis）或血栓形成（thrombosis）及随后的组织梗死（infarction）引起（Figure 1、Figure 2）。
诊断建议
子宫-坏死（Uterus - Necrosis）应予以诊断并分级。如果坏死继发于其他病变，如炎症（inflammation），则不应单独诊断，除非其严重程度足以支持单独诊断。继发于坏死的病变，如炎症或出血（hemorrhage），不应单独诊断，除非其严重程度足以支持单独诊断。如果病理学家认为该坏死代表梗死（infarct），应在病理学描述（pathology narrative）中注明。
参考切片图（2 张）
查看英文原文
Comment
Uterine necrosis is rarely encountered, but the histology of the lesion is like necrosis elsewhere, with cell death in the tissue characterized by nuclear pyknosis and/or karyorrhexis, cytoplasmic eosinophilia, and cellular swelling or shrinkage initially. The consequence of necrosis is granulation tissue and mineralization ( Figure 1 and Figure 2 ). Uterine necrosis may occur due to associated arteritis or thrombosis and subsequent infarction of the tissue ( Figure 1 and Figure 2 ).
Recommendation
Uterus - Necrosis should be diagnosed and graded. If the necrosis is secondary to another lesion, such as inflammation, it should not be diagnosed separately unless warranted by severity. Lesions secondary to necrosis, such as inflammation or hemorrhage, should not be diagnosed separately unless warranted by severity. The pathologist should note in the pathology narrative if the necrosis is thought to represent an infarct.
基质增生Hyperplasia Stromal 子宫增生
描述（中文）
间质增生（stromal hyperplasia）的特征是间质组织、平滑肌和结缔组织普遍增多，导致子宫肌层厚度增加（Figure 1、Figure 2）。这可能导致子宫大体增大。
诊断建议
子宫——间质增生（Hyperplasia, Stromal）只要存在即应诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Stromal hyperplasia is characterized as a general increase in stromal tissue, smooth muscle, and connective tissue resulting in an increase in myometrial thickness ( Figure 1 and Figure 2 ). This may result in gross enlargement of the uterus.
Recommendation
Uterus - Hyperplasia, Stromal should be diagnosed and assigned a grade whenever present.
子宫内膜囊性增生Endometrium Hyperplasia Cystic 子宫增生
描述（中文）
伴有囊性成分的子宫内膜增生（囊性子宫内膜增生，或CEH）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6）在小鼠中比在大鼠中更常见，并且尤其与年龄增长相关。该病变涵盖从子宫内膜腺体轻微增生到以大型囊性腺体和残留子宫内膜极少为特征的子宫的一系列病变谱。CEH可能作为与卵巢卵泡囊肿及外源性给予雌激素类化合物相关的长期雌激素刺激的结果而发生。扩张腺体的数量增加，其衬覆染色致密的立方或柱状细胞，其间质正常。CEH不是局限性病变，尽管在显微镜下检查的少数子宫切面中它可能看起来是局限性的。受影响最严重的子宫体积增大，并衬覆变薄的 epithelium。
诊断建议
子宫，子宫内膜——增生，囊性：只要存在即应作出诊断并分级。如果两侧子宫角之间CEH的分级严重程度存在差异，应诊断较严重的级别。
参考切片图（2 张）
查看英文原文
Comment
Endometrial hyperplasia with a cystic component (cystic endometrial hyperplasia, or CEH) ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ) occurs more commonly in mice than in rats and is particularly associated with increasing age. The change encompasses a spectrum of lesions from a minimal proliferation of the endometrial glands to a uterus characterized by large cystic glands and little remaining endometrium. CEH may occur as the result of prolonged estrogen stimulation associated with ovarian follicular cysts and exogenous administration of estrogenic compounds. There is an increase in the number of dilated glands with densely staining cuboidal or columnar cells with normal intervening stroma. CEH is not a localized lesion, although it may appear localized in the few sections of uterus examined microscopically. The most severely affected uteri are large and lined by attenuated epithelium.
Recommendation
Uterus, Endometrium - Hyperplasia, Cystic should be diagnosed and graded whenever present. If there is a difference in the severity of grade of CEH between the two uterine horns, the more severe grade should be diagnosed.
子宫内膜鳞状化生Endometrium Metaplasia Squamous 子宫化生
描述（中文）
子宫内膜上皮的鳞状化生（squamous metaplasia）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6）可自发发生，也可由给予具有雌激素活性的化合物（如 genistein、diethylstilbestrol 和 dioxins）后激素变化所致。维生素 A 缺乏亦可引起鳞状化生。该病变的特征为正常柱状子宫内膜上皮被鳞状上皮取代。部分病例中，子宫内膜腺体亦可受累（Figure 7、Figure 8）。鳞状上皮细胞及管腔内其他细胞碎片发生角化并不少见。鳞状化生常伴发炎症和子宫内膜囊性增生。
诊断建议
子宫、子宫内膜 - 化生，鳞状：只要存在即应诊断并给出严重程度分级。诊断中应包含修饰词“squamous”，以明确界定病变并消除潜在混淆。共存的变化如炎症和角化过度不应单独诊断，除非其严重程度足以支持单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Squamous metaplasia of the endometrial epithelium ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , and Figure 6 ) can develop spontaneously and also occurs as a result of hormonal changes following administration of compounds with estrogenic activity, such as genistein, diethylstilbestrol, and dioxins. Vitamin A deficiency also causes squamous metaplasia. The lesion is characterized by the replacement of the normally columnar endometrial epithelium by squamous epithelium. In some cases, the endometrial glands can also be affected ( Figure 7 and Figure 8 ). Keratinization is not uncommon with squames and other cellular debris in the lumen. Inflammation and cystic hyperplasia of the endometrium are frequently seen with squamous metaplasia.
Recommendation
Uterus, Endometrium - Metaplasia, Squamous should be diagnosed and given a severity grade whenever present. The modifier "squamous" should be included in the diagnosis to clearly define the lesion and eliminate potential confusion. Coexisting changes such as inflammation and hyperkeratosis should not be diagnosed separately unless warranted by severity.
子宫腺肌症Adenomyosis 子宫其他
描述（中文）
子宫腺肌症（adenomyosis，Figure 1、Figure 2、Figure 3、Figure 4）是指正常或增生的子宫内膜腺体和间质延伸至子宫肌层内。偶见上皮细胞可延伸至子宫浆膜表面。激素失衡是关键因素。该病变在某些品系小鼠（B6C3F1）中比在大鼠中更常见，且在老年小鼠中更常见。将子宫腺肌症与肿瘤性病变相鉴别很重要。子宫腺肌症的上皮细胞无异型性，这是一项有用的鉴别特征。通过检查上皮细胞以及正常子宫间质的存在，可将子宫腺肌症与腺癌相鉴别。腺癌的恶性上皮细胞表现出细胞多形性，且常呈多层排列。子宫腺肌症不应被描述为子宫内膜异位症（endometriosis），后者仅在灵长类动物中诊断（在子宫内膜异位症中，腺体扩散至腹腔）。
诊断建议
子宫——子宫腺肌症只要存在即应诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Adenomyosis ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is the presence of normal or hyperplastic endometrial glands and stroma that extend into the myometrium. Occasionally epithelial cells can extend onto the serosal surface of the uterus. Hormonal imbalance is a key factor. It is more common in some strains of mice (B6C3F1) than in rats and is more common in aged mice. It is important to differentiate adenomyosis from neoplasms. Adenomyosis has no atypia of the epithelial cells, which is a useful distinguishing feature. Adenomyosis may be differentiated from adenocarcinoma by examining the epithelial cells and by the presence of normal uterine stroma. Malignant epithelial cells of adenocarcinomas exhibit cellular pleomorphism and often are multilayered. Adenomyosis should not be described as endometriosis, which is diagnosed only in primates (in endometriosis, the glands spread to the peritoneal cavity).
Recommendation
Uterus - Adenomyosis should be diagnosed and graded whenever present.
宫颈鳞状囊肿Cervix Cyst Squamous 子宫囊肿
描述（中文）
鳞状上皮囊肿（Squamous epithelial cyst）（Figure 1、Figure 2）偶见于大鼠的子宫颈，较少见于阴道。它们类似于皮肤中所见的表皮囊肿，囊壁由复层鳞状上皮构成，中央腔内可含有角化物质及数量不等的炎性细胞。这些囊肿有时为双侧性。这些囊肿必须与局灶性（focal）坏死或脓肿相鉴别，后两者均无上皮衬覆。它们可能起源于遗迹结构。鳞状囊肿必须与子宫的鳞状化生相鉴别，后者见于远离子宫颈的子宫体部或子宫角内。
诊断建议
发生于子宫颈的鳞状囊肿应诊断为Uterus, Cervix - Cyst, Squamous（在NTP研究中，子宫颈被归类为子宫的一个亚部位）。囊肿无需分级，除非分级有助于表征处理效应。继发于囊肿的炎性改变不应单独诊断，除非其严重程度足以支持单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Squamous epithelial cysts ( Figure 1 and Figure 2 ) are occasionally seen in the cervix and less frequently in the vagina of rats. They resemble epidermal cysts seen in the skin and have a wall of stratified squamous epithelium, and they may have a central lumen of keratin and variable numbers of inflammatory cells. These cysts are sometimes bilateral. These cysts must be distinguished from focal necrosis or abscess, neither of which would be lined by epithelium. They may arise from vestigial structures. Squamous cysts must be differentiated from squamous metaplasia of the uterus, which is observed within the body away from the cervix or in the horns of the uterus.
Recommendation
Squamous cysts occurring in the cervix should be diagnosed as Uterus, Cervix - Cyst, Squamous (in NTP studies, the cervix is classified as a subsite of the uterus). Cysts need not be graded unless grading would help characterize a treatment effect. Inflammatory changes secondary to the cyst should not be diagnosed separately unless warranted by severity.
扩张Dilation 子宫扩张
描述（中文）
子宫角扩张（Figure 1、Figure 2、Figure 3、Figure 4）在剖检时常见，且这些子宫内常在腔内蓄积过量液体。子宫扩张在 rat 和 mouse 中均相对常见，并可能呈节段性。腔性扩张可能与间质息肉（stromal polyp）相关，或继发于卵巢囊肿所致激素失衡，或继发于老年啮齿类动物发情周期停止后的持续发情状态。在 rat 中给予孕激素（progestin）、雌激素（estrogen）和他莫昔芬（tamoxifen）与子宫扩张相关。在周期性发情的啮齿类动物中，腔性扩张通常在发情前期（proestrus）和发情期（estrus）可见，不应作出诊断。浆液性液体产生增加是发情周期发情前期的一部分，依据阴道上皮判断（其显示早期角化，表面覆盖一层黏液化细胞），不应作出诊断。子宫扩张时，子宫内膜衬里通常变薄或萎缩，且由于压力增加，子宫壁变薄，但在较轻病例中子宫内膜可正常（Figure 2）。继发于炎症过程（如子宫积脓，pyometra）的扩张子宫腔不应单独诊断。子宫扩张可能需要与 显著（marked） 囊性子宫内膜增生（cystic endometrial hyperplasia）相鉴别，尤其是仅检查子宫横切面时。在囊性子宫内膜增生中，活跃增殖的腺体数量增加，其腔可能扩张。在子宫扩张中，子宫腔扩张，可能与单个扩张的腺腔混淆。因此，必须仔细检查切片，以确定扩张结构是单个子宫腺还是子宫腔。这两种病变的鉴别在子宫纵切面中更为明显。
诊断建议
Uterus - Dilation 当不属于正常发情周期性变化时，应记录并分级。
参考切片图（2 张）
查看英文原文
Comment
Dilation of uterine horns ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) is commonly observed at necropsy, and frequently these uteri have accumulations of excessive amounts of fluid within the lumen. Uterine dilation is relatively commonly seen in both rats and mice and may be segmental. Luminal dilation may be associated with stromal polyps or occur secondarily to hormonal imbalances from ovarian cysts or to a prolonged estrus state after cessation of the estrus cycle in aged rodents. Administration of progestins, estrogens, and tamoxifen in rats has been associated with uterine dilation. Luminal dilation is normally observed at proestrus and estrus in cycling rodents and should not be diagnosed. Increased serous fluid production is part of the proestrus phase of the cycle judged by the vaginal epithelium (which shows early keratinization covered by a layer of mucified cells) and should not be diagnosed. With uterine dilation, the endometrial lining is usually attenuated or atrophic and the wall of the uterus thinned due to the increasing pressure, but in less severe cases the endometrium can be normal ( Figure 2 ). Dilated uterine lumen that is secondary to an inflammatory process such as pyometra should not be diagnosed separately. Uterine dilation may need to be differentiated from marked cystic endometrial hyperplasia, particularly when only cross-sections of the uterus are examined. In cystic endometrial hyperplasia, there is an increased number of active proliferating glands that may have dilated lumens. In uterine dilation, the uterine lumen is dilated, which could be confused with a single dilated glandular lumen. Therefore, the section must be carefully examined to determine whether the dilated structure is a single uterine gland or is the uterine lumen. The differentiation of these two lesions is more obvious in longitudinal sections of uterus.
Recommendation
Uterus - Dilation should be recorded and graded when not part of normal estrous cyclicity.
水肿Edema 子宫水肿
描述（中文）
子宫内膜上皮邻近的子宫基质水肿可见于动情前期的正常情况，尤其是该阶段末期和动情期初期。子宫水肿可能是炎症的一部分，也可能由血管损伤或血管通透性改变引起。水肿的组织学表现为细胞与组织成分之间清晰间隙增大（Figure 1、Figure 2、Figure 3、Figure 4）。
诊断建议
子宫——仅当水肿为受试物效应时才应诊断。诊断时应进行分级。继发于炎症或其他原发过程的水肿不应单独诊断。被视为正常周期性变化（即动情前期期间）的水肿不应诊断。
参考切片图（2 张）
查看英文原文
Comment
Edema of the uterine stroma adjacent to the endometrial epithelium can be seen normally in proestrus, particularly toward the end of the phase and in the beginning of estrus. Uterine edema may be part of inflammation or result from vascular compromise or changes in vascular permeability. Edema has the histologic appearance of increased clear space between cells and tissue components ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ).
Recommendation
Uterus - Edema should be diagnosed only when it is an effect of treatment. When diagnosed, it should be graded. Edema that is secondary to an inflammatory or other primary process should not be diagnosed separately. Edema that is considered a normal cyclical change (i.e., during proestrus) should not be diagnosed.
淀粉样物质Amyloid 子宫其他
描述（中文）
淀粉样物质（amyloid）是一种无定形、嗜酸性、淡染的物质，在小鼠子宫内膜和子宫肌层的间质中偶见（Figure 1、Figure 2）。严重病例中，它会导致子宫增厚和硬度增加。子宫内淀粉样物质的存在可能反映动物体内其他部位的淀粉样物质沉积，主要位于中等大小动脉的外膜。淀粉样物质沉积必须与其他纤维蛋白样变化相鉴别：纤维化、水肿和纤维蛋白。
诊断建议
子宫——淀粉样物质一旦出现即应诊断并分级。继发性病变，如驻留细胞的变性或坏死，除非严重程度确有必要，否则不应单独诊断。如果淀粉样物质沉积可能影响研究的解释，则应在病理学叙述中加以讨论。
参考切片图（2 张）
查看英文原文
Comment
Amyloid, an amorphous, eosinophilic, pale-staining material, is infrequently seen in mice in the stroma of the endometrium and myometrium ( Figure 1 and Figure 2 ). In severe cases, it causes thickening and increased firmness of the uterus. The presence of amyloid in the uterus may reflect amyloid deposition elsewhere in the animal, principally in the adventitia of medium-size arteries. Amyloid deposition must be differentiated from other fibrinoid changes: fibrosis, edema, and fibrin.
Recommendation
Uterus - Amyloid should be diagnosed and graded whenever present. Secondary lesions such as degeneration or necrosis of resident cells should not be diagnosed separately unless warranted by severity. If the amyloid deposition may affect the interpretation of the study, it should be discussed in the pathology narrative.
炎症Inflammation 子宫炎症
描述（中文）
在NTP研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞是中性粒细胞（neutrophil），尽管也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血（hyperemia）的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型（Figure 1、Figure 2、Figure 3、Figure 4），但它们聚集在一起，其中许多发生变性（化脓性渗出物，化脓性 exudate）。渗出物中还可能存在细胞碎片（来自 resident 细胞群和浸润白细胞）、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，以及可能的感染因子。肉眼上，这些病变以脓液存在为特征。渗出物周围组织可能含有成纤维细胞、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。脓肿在组织学上应诊断为化脓性炎症。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位（Figure 5、Figure 6），但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症（Figure 7、Figure 8）是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大型、活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。炎症与细胞浸润的鉴别在于其他改变的存在，如水肿、出血、变性、坏死或其他组织损伤证据。严重的弥漫性化脓性炎症（子宫积脓，pyometra）罕见。慢性子宫炎症可诱导表面上皮和腺上皮的鳞状化生（squamous metaplasia），必须与雌激素优势所致的鳞状化生相鉴别。子宫炎症可能伴随其他子宫改变——子宫内膜增生、腺肌症、肿瘤形成等。子宫炎症必须与动情周期特定阶段子宫内膜中正常存在的炎症细胞相鉴别，尤其是移行性中性粒细胞/嗜酸性粒细胞/子宫内膜淋巴细胞（呈分叶状）。子宫炎症必须与组织细胞肉瘤（histiocytic sarcoma）和淋巴瘤相鉴别。炎症改变通常具有混合性细胞群体，与肿瘤不同，并且通常有其他炎症体征，如出血、水肿和组织破坏。淋巴瘤和组织细胞肉瘤通常为多中心性，由单一形态细胞群体组成。子宫内膜炎症的诊断应保留给存在显著上皮和间质炎症改变的病变。
诊断建议
子宫——炎症应诊断并分级。继发性病变如坏死、上皮增生、溃疡和纤维化不应单独诊断，除非严重程度需要，但应在病理叙述中描述。如果炎症继发于另一病变，如溃疡或坏死，则不应单独诊断，除非严重程度需要，但应在叙述中描述为原发病变成分。子宫积脓应诊断为子宫——炎症，化脓性。
参考切片图（2 张）
查看英文原文
Comment
In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ), but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris, both from the resident cell populations and from infiltrating leukocytes, and proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in within the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may contain fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Abscesses should be diagnosed histologically as suppurative inflammation. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation ( Figure 5 and Figure 6 ), but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation ( Figure 7 and Figure 8 ) is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammation is differentiated from cellular infiltrates by the presence of other changes, such as edema, hemorrhage, degeneration, necrosis, or other evidence of tissue damage. Severe diffuse suppurative inflammation (pyometra) is rarely seen. Chronic uterine inflammation can induce squamous metaplasia of superficial and glandular epithelia, which must be differentiated from squamous metaplasia that occurs due to estrogen dominance. Uterine inflammation may accompany other uterine changes – uterus endometrium hyperplasia, adenomyosis, neoplasia, and so forth. Uterus inflammation must be distinguished from the normal presence of inflammatory cells, especially transmigratory neutrophils/eosinophils/endometrial lymphocytes (which are lobulated) in the endometrium at certain stages of the estrous cycle. Uterus inflammation must be distinguished from histiocytic sarcoma and lymphoma. Inflammatory changes generally have a mixed population of cells, in contrast to neoplasms, and there are usually other signs of inflammation, such as hemorrhage, edema, and tissue destruction. Lymphoma and histiocytic sarcoma are usually multicentric and composed of monomorphic cell populations. The diagnosis of inflammation of the endometrium should be reserved for lesions where significant epithelial and stromal inflammatory changes are present.
Recommendation
Uterus - Inflammation should be diagnosed and graded. Secondary lesions such as necrosis, epithelial hyperplasia, ulcer, and fibrosis should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative. If the inflammation is secondary to another lesion, such as ulcer or necrosis, it should not be diagnosed separately unless warranted by severity but should be described in the narrative as a component of the primary lesion. Pyometra should be diagnosed as Uterus - Inflammation, Suppurative.
纤维化Fibrosis 子宫纤维化
描述（中文）
纤维化（fibrosis）是指间质被成熟的胶原、纤维状、嗜酸性物质所取代，其中散布少量细胞（Figure 1、Figure 2、Figure 3、Figure 4）。纤维化（通常为 极轻微（minimal） 至 轻微（mild））在老年小鼠的子宫肌层中可自发出现。在大鼠中，间质纤维化和子宫内膜萎缩也是与年龄相关的改变。子宫内膜和子宫肌层中纤维结缔组织进行性增多，导致细胞密度降低，进而发生透明变性（hyalinization）。在小鼠中，纤维化可由暴露于玉米赤霉烯酮（zearalenone）而诱发。纤维化也可能是慢性炎性病变（例如子宫炎或子宫积脓）的一个组成部分。
诊断建议
子宫——纤维化：凡在其他病变不存在时出现，均应诊断并分级。作为炎性病变组成部分存在的纤维化，仅当其为该病变的显著组成部分，或纤维化的严重程度与炎症的严重程度不相称时（即纤维化的严重程度超出根据炎症严重程度所预期的程度），才应诊断。如果未单独诊断纤维化，则应在病理学描述中予以描述。作出诊断时，严重程度分级应基于病变的范围。
参考切片图（2 张）
查看英文原文
Comment
Fibrosis is the replacement of the stroma with mature collagen, fibrillar, eosinophilic material with few, interspersed cells ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Fibrosis (often minimal to mild) has been encountered spontaneously in the myometrium of older mice. In rats, stromal fibrosis and endometrial atrophy are also age-related changes. There is a progressive increase in fibrous connective tissue in the endometrium and the myometrium, resulting in a reduction in cellularity, which results in a hyalinization. Fibrosis has been induced in mice by exposure to zearalenone. Fibrosis may also be a component of a chronic inflammatory lesion (e.g., metritis or pyometra).
Recommendation
Uterus - Fibrosis should be diagnosed and graded whenever it occurs in the absence of other lesions. Fibrosis that is present as a component of an inflammatory lesion should be diagnosed only if it is a prominent component of that lesion or if the severity of the fibrosis is not commensurate with that of the inflammation (i.e., the fibrosis is more severe than would be expected given the severity of the inflammation). If fibrosis is not diagnosed separately, it should be described in the pathology narrative. When diagnosed, the severity grade should be based on the extent of the lesion..
色素Pigment 子宫色素沉着
描述（中文）
子宫内有时可见金黄色至深棕色色素（Figure 1、Figure 2）。含铁血黄素（hemosiderin）可能继发于出血，尤其是在多产雌性动物的胎盘形成部位。根据病程长短，可能可见外渗的红细胞或巨噬细胞内的红细胞。也可能见到其他类型的色素，如脂褐素（lipofuscin）或蜡样质（ceroid）。
诊断建议
子宫——色素：当认为色素与研究相关（或不清楚是否与研究相关）时，或当色素异常显著时，应作出诊断。并非所有色素都必须诊断，因为有些色素在老龄动物中普遍存在，或继发于其他疾病过程（如出血），不具有毒理学意义。病理学家应运用其判断力决定是否应诊断该色素。即使使用一系列特殊染色，在组织学切片中明确鉴定色素通常也很困难。因此，诊断为“色素”（而非诊断色素的类型，如含铁血黄素或脂褐素）是最恰当的。病理学描述应描述色素沉着的形态学特征。当诊断色素时，应给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Golden brown to darker brown pigment is sometimes seen in the uterus ( Figure 1 and Figure 2 ). Hemosiderin may be seen secondary to hemorrhage, especially in multiparous females at sites of placentation. Depending on the chronicity, there may be extravasated erythrocytes or erythrocytes within macrophages. Other types of pigment may also be seen, such as lipofuscin or ceroid.
Recommendation
Uterus - Pigment should be diagnosed when it is considered to be relevant to the study (or if it is unclear whether it is relevant to the study) or if it is unusually prominent. Not all pigments have to be diagnosed, as some are ubiquitous in aging animals or are secondary to another disease process (e.g., hemorrhage) and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether or not the pigment should be diagnosed. Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, a diagnosis of "pigment" (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should describe the morphologic features of the pigmentation. When pigment is diagnosed, it should be given a severity grade.
萎缩Atrophy 子宫萎缩
描述（中文）
萎缩是一种常见的年龄相关变化，也可由引起卵巢损伤或改变卵巢类固醇生成的药物诱导。萎缩可影响子宫内膜和/或子宫肌层，并导致子宫整体大小或横截面积减小。子宫内膜腺体数量少于正常，间质可能塌陷或玻璃样变（尤其在老年啮齿类动物中），子宫肌层变薄。萎缩也见于极度营养不良的动物。萎缩可仅影响子宫的某一部分，如子宫内膜或子宫肌层。子宫萎缩必须与发育不全（hypoplasia）相鉴别。发育不全是指发育失败，极少自发出现，例外情况为生殖和致畸研究。子宫萎缩必须与未成熟相鉴别，后者可模仿萎缩；其他生殖器官也将处于未成熟状态。治疗诱导的萎缩通常发生于多只动物，并可直接与对照组比较（Figure 1）。
诊断建议
当子宫萎缩与治疗相关或发生于短期研究时，应作出诊断并进行分级。如果仅子宫的特定组成部分受累，应通过使用部位修饰词在诊断中指明所累及的具体结构（例如，epithelium、endometrium、myometrium）。
参考切片图（1 张）
查看英文原文
Comment
Atrophy is a common age-related change and can also be induced by agents that cause ovarian damage or alter steroid production from the ovary. Atrophy can affect the endometrium and/or myometrium and results in a reduction in the overall size or cross sectional area of the uterus. Endometrial glands are fewer than normal, the stroma may be collapsed or hyalinized (especially in aged rodents), and the myometrium is thin. Atrophy is also encountered in extremely malnourished animals. Atrophy can affect just one portion of the uterus, such as the endometrium or myometrium. Uterine atrophy must be differentiated from hypoplasia. Hypoplasia is a failure to develop and should very seldom be encountered spontaneously, the exceptions being reproductive and teratology studies. Uterine atrophy must be differentiated from immaturity, which can mimic atrophy; the other reproductive organs will also be immature. Treatment-induced atrophy usually occurs in several animals, and they can be compared directly with controls ( Figure 1 ).
Recommendation
Uterine atrophy should be diagnosed and graded when it is treatment related or occurs in a short-term study. If only specific components of the uterus are affected, the specific structure(s) involved should be indicated in the diagnosis through the use of a site modifier (e.g., epithelium, endometrium, myometrium).
蜕膜反应Decidual Reaction 子宫其他
描述（中文）
蜕膜反应（decidual reaction）（Figure 1、Figure 2、Figure 3、Figure 4）是子宫内膜的局灶性（focal）、非肿瘤性、增殖性改变。它们表现为由肥大间质细胞构成的局限性结节，这些细胞具有上皮样转化，有时可见类似成熟胎盘中滋养层细胞的奇异核。结节无包膜，周围界限不清。蜕膜反应的特征为大的圆形间质细胞，胞质丰富嗜酸性，核大而圆，核仁明显，偶见多核细胞。该病变曾被称为蜕膜瘤（deciduoma）或蜕膜改变。病理学家需认识到蜕膜反应的独特性，以免将其与肿瘤混淆。这种增殖性反应模拟正常着床部位，可发生于年轻和年老、未孕或假孕大鼠，偶尔见于90天研究和老年处女小鼠。蜕膜反应表现为子宫角内离散的圆形结节。可为单个或多个、单侧或双侧，蜕膜改变的局灶性病变可发生于息肉或肿瘤内。在大鼠中，生长激素及多种因素可诱导其发生，如宫内滴注芝麻油、前列腺素E2或孕激素。蜕膜反应也可由机械刺激或刺激、子宫内膜创伤以及宫内注射多种物质（平衡盐溶液、油性液体和空气）诱导。
诊断建议
子宫——蜕膜反应应予以诊断，但无需分级。肿瘤内的蜕膜反应不应单独诊断。应停止使用“蜕膜瘤（deciduoma）”一词。
参考切片图（2 张）
查看英文原文
Comment
Decidual reactions ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ) are focal, nonneoplastic, proliferative changes in the endometrium. They are observed as localized nodules consisting of hypertrophied stromal cells with epithelioid transformation and, sometimes, bizarre nuclei resembling the trophoblasts observed in mature placentae. There is no encapsulation, and clear boundaries around the nodules are not apparent. Decidual reactions are characterized by large rounded stromal cells with abundant eosinophilic cytoplasm, large round nuclei, and prominent nucleoli and occasional multinucleated cells. This lesion has been referred to as a deciduoma of decidual alteration. The pathologist needs to be aware of the uniqueness of decidual reactions so they will not be confused with neoplasia. This proliferative response mimics normal implantation sites and may occur in young and old, nonpregnant or pseudopregnant rats and is occasionally found in 90-day studies and in aged virgin mice. Decidual reactions appear as discrete round nodules in the uterine horn. They may be single or multiple, unilateral or bilateral, and a focal lesion of decidual alteration may occur in a polyp or neoplasms. They can be induced in rats by growth hormone and by a number of agents, such as intrauterine instillation of sesame oil, prostaglandin E2, or progestins. Decidual reactions can also be induced by mechanical stimulation or irritation, endometrial traumatization, and intrauterine injection of a variety of substances (balanced salt, oily fluids, and air).
Recommendation
Uterus - Decidual reaction should be diagnosed but need not be graded. Decidual reaction within a neoplasm should not be diagnosed separately. The use of the term "deciduoma" should be discontinued.
血栓Thrombus 子宫血栓
描述（中文）
大或小的血栓可能阻塞小鼠子宫血管（Figure 1、Figure 2）。由于坏死或碎屑遮蔽，可能观察不到清晰的内皮衬里。这可能伴有周围血管的突出和扩张（angiectasis）。血栓必须与血管瘤和血管肉瘤相鉴别。血管扩张的特征是血管衬以单纯的非肥厚性内皮衬里，且常与血栓形成同时出现。血管瘤和血管肉瘤具有丰满的衬里内皮细胞。血管肉瘤的内皮细胞表现出间变和核分裂率增加。
诊断建议
子宫——血栓形成（thrombosis）应被诊断，但无需分级。继发于另一过程（肿瘤）的血栓不应被诊断。由血栓引起的坏死应单独诊断和分级。
参考切片图（2 张）
查看英文原文
Comment
Large or small thrombi may occlude uterine blood vessels in mice ( Figure 1 and Figure 2 ). A distinct endothelial lining may not be observed due to necrosis or obscuring by detritus. This may be associated with prominence and dilation of the surrounding blood vessels (angiectasis). Thrombi must be differentiated from hemangioma and hemangiosarcoma. Angiectasis is characterized by blood vessels lined by a simple nonhypertrophic endothelial lining and is frequently seen with thrombosis. Hemangioma and hemangiosarcoma have plump lining endothelial cells. The endothelial cells of hemangiosarcoma exhibit anaplasia and an increased rate of mitoses.
Recommendation
Uterus - Thrombosis should be diagnosed but need not be graded. Thrombi that are secondary to another process (a neoplasm) should not be diagnosed. Necrosis that is caused by a thrombus should be diagnosed and graded separately.
非典型增生Hyperplasia Atypical 子宫增生
描述（中文）
在NTP研究中，子宫内膜的非典型性增生（非典型性（atypical） hyperplasia）更常见于子宫的纵切面，因为其最常发生的位置是靠近子宫体分叉处的近端子宫角。该病变可累及腺上皮（Figure 1、Figure 2、Figure 5）和子宫表面上皮（Figure 3、Figure 4、Figure 5）。该病变的典型特征为增大的腺体成簇分布，腺体间仅隔以少量间质，但单个腺体也可受累。受累腺体衬覆排列紊乱的上皮，厚度可达六层细胞（Figure 1、Figure 2、Figure 5）。非典型性增生的上皮细胞常表现为核极性丧失、核增大（karyomegaly）、核分裂和细胞多形性（Figure 4）。增厚的上皮常突入腺腔，形成多个增厚的内褶和突起（Figure 1、Figure 2、Figure 5）。乳头型非典型性增生累及表面上皮（Figure 3、Figure 4），由众多伸入子宫腔的小分支状上皮突起构成，偶尔位于小的纤维血管性蒂上。在某些病例中，腺体和表面上皮可同时受累（Figure 5）。非典型性增生与腺瘤的鉴别在于其无压迫性且这些病变不形成明显的肿块。
诊断建议
子宫——增生，非典型性（Uterus - Hyperplasia, 非典型性（atypical））只要存在即应作出诊断并分级。病变的位置，即位于腺体还是位于衬覆子宫腔的上皮，应在病理学描述中予以说明。
参考切片图（2 张）
查看英文原文
Comment
Atypical hyperplasia of the endometrium is more commonly seen in longitudinal sections of uteri in NTP studies because its most frequent location is in the proximal uterine horns near the bifurcation of the uterine body. This lesion can affect both glandular ( Figure 1 , Figure 2 , and Figure 5 ) and uterine surface epithelium ( Figure 3 , Figure 4 , and Figure 5 ). This lesion is typically characterized by clusters of enlarged glands separated by minimal amounts of stroma, though single glands can be affected. The affected glands are lined by a disorganized epithelium that may be up to six cell layers in thickness ( Figure 1 , Figure 2 , and Figure 5 ). The epithelial cells of atypical hyperplasia often display loss of nuclear polarization, karyomegaly, mitosis, and cellular pleomorphism ( Figure 4 ). The thickened epithelium frequently projects into the glandular lumen, forming multiple thickened infoldings and projections ( Figure 1 , Figure 2 , and Figure 5 ). The papillary type of atypical hyperplasia affects the surface epithelium ( Figure 3 and Figure 4 ) and consists of numerous small branching projections of epithelium extending into the uterine lumen, occasionally on small fibrovascular stalks. In some cases, both the glands and the surface epithelium can be affected concurrently ( Figure 5 ). Atypical hyperplasia is differentiated from adenomas by the absence of compression and the fact that these lesions do not form a distinct mass.
Recommendation
Uterus - Hyperplasia, Atypical should be diagnosed and graded whenever present. The location of the lesion, in glands or in the epithelium lining the uterine lumen, should be described in the pathology narrative.
中肾管残余Mesonephric Duct Remnant 输卵管其他
描述（中文）
这些中肾管残余可为单侧或双侧。它们呈管状或囊状结构，衬有上皮，并具有一层平滑肌（Figure 1、Figure 2）。必须将其与卵巢区域的囊肿（如滑囊囊肿）相鉴别。充盈的滑囊在剖检时塌陷，显露其中完整的卵巢。发生于卵巢的囊肿位于卵巢实质内，通常可完整剥离。卵巢旁组织的囊肿特征为子宫系膜内有一个大的充满液体的囊。这些囊肿衬以立方至柱状上皮，周围环绕平滑肌，充满淡染的嗜酸性絮状物。
诊断建议
输卵管 - 中肾管残余只要存在即应诊断，但无需分级。
参考切片图（2 张）
查看英文原文
Comment
These remnants of the mesonephric duct may be unilateral or bilateral. They are tubular or cystic structures with an epithelial lining and have a layer of smooth muscle ( Figure 1 and Figure 2 ). These must be distinguished from cysts in the region of the ovary, such as bursa cysts. A distended bursa collapses at dissection, disclosing an intact ovary within it. Cysts occurring in the ovary are found within the ovarian parenchyma and can generally be dissected intact. Cysts of the paraovarian tissue are characterized by a large fluid-filled sac in the mesovarium. These cysts are lined by cuboidal to columnar epithelium, surrounded by smooth muscle, and filled with pale-staining eosinophilic flocculent material.
Recommendation
Oviduct - Mesonephric duct remnant should be diagnosed whenever present but need not be graded.
坏死Necrosis 输卵管坏死
描述（中文）
输卵管坏死（Oviduct necrosis）在啮齿类动物研究中罕见。它可能是邻近卵巢或子宫相关炎症性改变的结果。输卵管坏死的特征为上皮细胞嗜酸性增强、离散、碎裂和脱落（Figure 1、Figure 2）。细胞核固缩和核碎裂。通常伴有炎症细胞浸润。
诊断建议
输卵管-坏死（Oviduct - Necrosis）一旦出现即应诊断并分级。继发性病变如炎症或出血，除非严重程度足以需要诊断，否则不应诊断。如果坏死继发于其他病变，如炎症，除非严重程度足以需要诊断，否则不应诊断。
参考切片图（2 张）
查看英文原文
Comment
Oviduct necrosis is rarely seen in rodent studies. It may be a result of an associated inflammatory change in the adjacent ovary or uterus. Oviduct necrosis is characterized by hypereosinophilic, dissociated, fragmented, and sloughed epithelial cells ( Figure 1 and Figure 2 ). Nuclei are pyknotic and karyorrhectic. It is usually accompanied by an inflammatory infiltrate.
Recommendation
Oviduct - Necrosis should be diagnosed and graded whenever present. Secondary lesions such as inflammation or hemorrhage should not be diagnosed unless warranted by severity. If the necrosis is secondary to another lesion, such as inflammation, it should not be diagnosed unless warranted by severity.
炎症Inflammation 输卵管炎症
描述（中文）
在NTP研究中，炎症有五种标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症（Figure 1、Figure 2、Figure 3）中，主要浸润细胞是中性粒细胞（neutrophil），但也可能存在较少的巨噬细胞（macrophage）和淋巴细胞（lymphocyte）。还可能有水肿或充血（hyperemia）的证据。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但它们聚集在一起，其中许多已变性（化脓性渗出物，化脓性 exudate）。渗出物中还可能存在细胞碎片（来自 resident 细胞群体和浸润的白细胞）、含纤维蛋白（fibrin）的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞（plasma cell），以及可能的感染因子。肉眼上，这些病变以脓液（pus）的存在为特征。渗出物周围的组织可能含有成纤维细胞（fibroblast）、纤维结缔组织（fibrous connective tissue）和混合性炎症细胞，取决于病变的慢性程度。脓肿（abscess）在组织学上诊断为化脓性炎症。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在显著数量的中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在显著数量的聚集性、大型、活化巨噬细胞、上皮样巨噬细胞（epithelioid macrophage）或多核巨细胞（multinucleated giant cell）。炎症与细胞浸润的鉴别在于其他改变的存在，如水肿、出血、变性、坏死或其他组织损伤的证据。输卵管（oviduct）的炎性疾病通常代表来自子宫的上行性感染。多种细菌微生物可能引起这些感染，但啮齿动物的感染性疾病现已罕见。输卵管与子宫一样，在妊娠期或动情周期的黄体期可能更易发生感染。Mycoplasma pulmonis 与慢性生殖道疾病相关，化脓性卵巢炎（purulent oophoritis）和输卵管炎（salpingitis）是生殖道的主要病变。
诊断建议
输卵管——炎症只要存在就应诊断并分级。应在诊断中通过使用限定词指明炎症类型。继发于炎症的病变，如坏死、出血和水肿，除非严重程度需要，不应单独诊断，但应在病理学叙述中描述。如果炎症继发于其他病变（例如坏死或肿瘤），除非严重程度需要，不应单独诊断，但应在叙述中描述为原发病变成分。
参考切片图（2 张）
查看英文原文
Comment
In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic active, and granulomatous. In acute inflammation ( Figure 1 , Figure 2 and Figure 3 ), the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris, both from the resident cell populations and from infiltrating leukocytes, and proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present in within the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may contain fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Abscesses are diagnosed histologically as suppurative inflammation. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammation is differentiated from cellular infiltrates by the presence of other changes, such as edema, hemorrhage, degeneration, necrosis, or other evidence of tissue damage. Inflammatory diseases of the oviducts usually represent an ascending infection from the uterus. A variety of bacterial organisms may cause these infections, but infectious diseases of rodents are now rare. The oviducts, like the uterus, are probably more susceptible to infections in pregnancy or the luteal phase of the estrus cycle. Mycoplasma pulmonis is associated with chronic genital disease, and a purulent oophoritis and salpingitis are the major lesions in the reproductive tract.
Recommendation
Oviduct - Inflammation should be diagnosed and graded whenever present. The type of inflammation should be indicated in the diagnosis by use of a qualifier. Lesions secondary to inflammation, such as necrosis, hemorrhage, and edema, should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative. If the inflammation is secondary to another lesions (e.g., necrosis or neoplasia), it should not be diagnosed separately unless warranted by severity, but it should be described in the narrative as a component of the primary lesion.
萎缩Atrophy 输卵管萎缩
描述（中文）
输卵管萎缩（Oviduct atrophy）是一种不常见的病变，预期会与卵巢和子宫萎缩或炎症相伴发生。输卵管萎缩的特征包括输卵管横截面直径减小、平滑肌壁厚度变薄、上皮高度降低以及伞部和/或黏膜皱襞变扁平（Figure 1、Figure 2）。该病变必须与发育不全（hypoplasia）相鉴别。
诊断建议
输卵管-萎缩（Oviduct - Atrophy）只要存在就应诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Oviduct atrophy is an uncommon lesion and would be expected to occur in association with atrophy of the ovary and uterus or with inflammation. Features of oviduct atrophy include a decrease in the cross-sectional diameter of the oviduct, decreased thickness of the smooth muscle wall, decreased epithelial height, and flattened fimbria and/or mucosal folds ( Figure 1 and Figure 2 ). This lesion must be differentiated from hypoplasia.
Recommendation
Oviduct - Atrophy should be diagnosed and graded whenever present.
增生Hyperplasia 阴蒂腺增生
描述（中文）
阴蒂腺增生（clitoral gland hyperplasia）通常为局灶性（focal）病变，更常见于腺体组织，但也可能发生于导管。该病变可为单侧或双侧。腺体增生的特征为腺泡细胞数量增多，并可伴有基底细胞数量增多。与邻近腺体组织相比，腺泡增大且显得拥挤；然而，细胞形态和排列方向正常。后述这些特征可将增生与腺瘤区分开来，腺瘤中腺泡结构扭曲，常伴有腺泡融合和肿瘤细胞的实性团簇。阴蒂腺增生为自发性病变，常继发于炎症，尤其是在老年动物中。在这些老年动物中，增生不被视为癌前改变，而是一种反应性增生，且无进展的证据（注意Figure 1、Figure 2中的炎症）。雄激素类药物可诱导阴蒂腺上皮增生。
诊断建议
阴蒂腺 - 增生：只要存在即应诊断，并给出严重程度分级。发生于增生灶内的炎症等继发性病变不应单独诊断，除非其严重程度足以支持单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Clitoral gland hyperplasia is typically a focal lesion and more commonly occurs in the glandular tissue but may also occur in the ducts. The lesion may be unilateral or bilateral. Glandular hyperplasia is characterized by an increased number of acinar cells and may be accompanied by an increased number of basal cells. The acini are enlarged and appear crowded compared with the adjacent glandular tissue; however, there is normal cellular morphology and orientation. These latter features differentiate hyperplasia from adenomas, in which acinar structure is distorted, with frequent acinar fusion and solid clusters of neoplastic cells. Clitoral gland hyperplasia occurs as a spontaneous lesion and is often secondary to inflammation, especially in older animals. Hyperplasia is not considered a preneoplastic change in these older animals but, rather, a reactive hyperplasia, and there is no evidence of progression (note inflammation in Figure 1 and Figure 2 ). Androgenic drugs can induce epithelial hyperplasia of the clitoral gland.
Recommendation
Clitoral gland - Hyperplasia should be diagnosed whenever present and given a severity grade. Secondary lesions such as inflammation occurring within a focus of hyperplasia should not be diagnosed separately unless warranted by severity.
导管扩张Duct Dilation 阴蒂腺扩张
描述（中文）
阴蒂腺导管扩张（Clitoral gland duct dilation）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6、Figure 7、Figure 8、Figure 9、Figure 10、Figure 11）是老龄啮齿类动物中常见的偶然性发现。给予雄激素类固醇也可诱导其发生。阴蒂腺导管扩张常伴有腺组织萎缩。较小导管的上皮衬里可为立方上皮、扁平上皮或角化鳞状上皮。当该病变严重时，扩张的导管可占据阴蒂腺的大部分，扩张导管之间可见腺泡组织残存，且腺体可因导管扩张而明显增大。在小鼠中诊断该病变时须谨慎，因为小鼠通常具有非常 cavernous 的导管而腺组织很少。
诊断建议
阴蒂腺 - 导管，扩张：当其被视为原发性改变时，应始终予以诊断并给出严重程度分级。由导管扩张引起的阴蒂腺萎缩无需单独诊断，但可在描述中叙述。
参考切片图（2 张）
查看英文原文
Comment
Clitoral gland duct dilation ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 , Figure 7 , Figure 8 , Figure 9 , Figure 10 and Figure 11 ) is a common incidental finding in aging rodents. It has also been induced with administration of androgenic steroids. Dilation of the ducts of the clitoral glands is frequently accompanied by atrophy of the glandular tissue. The epithelial lining of smaller ducts may be cuboidal, flattened, or keratinized squamous epithelium. When this condition is severe, the dilated ducts may occupy the majority of the clitoral gland, with remnants of the acinar tissue evident between the dilated ducts, and the glands may be grossly enlarged due to duct dilation. Care must be taken in diagnosing this lesion in mice because mice typically have very cavernous ducts with little glandular tissue.
Recommendation
Clitoral gland - Duct, Dilation should always be diagnosed and given a severity grade when it is considered a primary change. Clitoral gland atrophy caused by duct dilation does not need to be diagnosed separately but can be described in the narrative.
炎症Inflammation 阴蒂腺炎症
描述（中文）
阴蒂腺的炎症通常被视为背景性病变。然而，它也可能与受试物相关（Figure 1、Figure 2、Figure 3、Figure 4）。肉芽肿性炎症在大鼠中常见，与含有角蛋白样物质的扩张导管破裂有关。诊断中应指明炎症的类型。在 NTP 研究中，炎症有五种标准分类：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞是中性粒细胞，但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但它们聚集在一起，其中许多已变性（化脓性渗出物）。渗出物中还可能存在来自驻留细胞群和浸润白细胞的细胞碎片，以及含有纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，并可能存在感染因子。肉眼观察，这些病变的特征是存在脓液。渗出物周围的组织可能含有成纤维细胞、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。慢性炎症中以淋巴细胞为主。慢性活动性炎症中也以淋巴细胞为主，但还存在大量中性粒细胞。这两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
如果炎症作为原发性病变发生，则应予以诊断并给出严重程度分级。诊断中应指明炎症的类型（例如急性、慢性）。如果炎症继发于其他病变（例如肿瘤形成、坏死），则不应予以诊断，而应在病理学描述中加以描述。继发性病变，如出血、坏死或增生，除非严重程度确有必要，否则不应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Inflammation in the clitoral gland is commonly seen as a background lesion. It can, however, be associated with treatment ( Figure 1 , Figure 2 , Figure 3 and Figure 4 ). Granulomatous inflammation is commonly seen in rats, associated with rupture of dilated ducts containing keratin-like material. The type of inflammation should be indicated in the diagnosis. In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris, both from the resident cell populations and from infiltrating leukocytes, and proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present within the exudate. Grossly, these lesions would be characterized by the presence of pus. The tissue surrounding the exudate may contain fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation , but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
If the inflammation occurs as a primary lesion, then it should be diagnosed and given a severity grade. The type of inflammation (e.g., acute, chronic) should be indicated in the diagnosis. If the inflammation is secondary to another lesion (e.g., neoplasia, necrosis), then it should not be diagnosed but should be described in the pathology narrative. Secondary lesions, such as hemorrhage, necrosis, or hyperplasia, should not be diagnosed separately unless warranted by severity.
矿化Mineralization 阴蒂腺矿化
描述（中文）
阴蒂腺矿化可继发于坏死或炎症（即营养不良性矿化），或发生于出血区域。矿化的组织学表现为阴蒂腺导管或腺泡内可见的嗜碱性颗粒状至结晶状紫色物质聚集（Figure 1、Figure 2）。原发性或转移性矿化在阴蒂腺中不常见。
诊断建议
阴蒂腺——当矿化出现在无坏死、炎症或出血的情况下（即原发性或转移性矿化）时，应予以诊断并分级。继发于坏死、炎症或出血的矿化（即营养不良性矿化）不应诊断，除非其严重程度足以支持诊断。
参考切片图（2 张）
查看英文原文
Comment
Clitoral gland mineralization can be secondary to necrosis or inflammation (i.e., dystrophic mineralization) or in an area of hemorrhage. The histologic appearance of mineralization is basophilic granular to crystalline aggregates of purple material evident in the ducts or acini of the clitoral gland ( Figure 1 and Figure 2 ). Primary or metastatic mineralization is uncommon in the clitoral gland.
Recommendation
Clitoral gland - Mineral should be diagnosed and graded when present in the absence of necrosis, inflammation, or hemorrhage (i.e., when it is primary or metastatic). Mineralization that is secondary to necrosis, inflammation, or hemorrhage (i.e., dystrophic mineralization) should not be diagnosed unless warranted by severity.
纤维化Fibrosis 阴蒂腺纤维化
描述（中文）
阴蒂腺的间质纤维化（Figure 1）常伴随常见的自发性退行性病变（例如萎缩、导管扩张）。它也可能与慢性或慢性活动性炎症相关。早期纤维化比慢性纤维化的成熟胶原呈现更高的细胞密度外观。
诊断建议
当阴蒂腺纤维化在其他病变不存在的情况下发生时，应当诊断并赋予严重程度分级。作为炎症病变组成部分存在的纤维化，仅当炎症程度与纤维化程度不相称时（即纤维化比根据炎症严重程度所预期的更为严重）才应诊断。如果纤维化未单独诊断，则应在病理学叙述中予以描述。无论何时诊断纤维化，都应赋予严重程度分级。
参考切片图（1 张）
查看英文原文
Comment
Stromal fibrosis of the clitoral gland ( Figure 1 ) often accompanies common spontaneous degenerative lesions (e.g., atrophy, duct dilatation). It may also be associated with chronic or chronic active inflammation. Early fibrosis presents a more densely cellular appearance than the mature collagen of chronic fibrosis.
Recommendation
Clitoral gland fibrosis should be diagnosed and assigned a severity grade whenever it occurs in the absence of other lesions. Fibrosis that is present as a component of an inflammatory lesion should be diagnosed only when the degree of inflammation is not commensurate to that of fibrosis (i.e., the fibrosis is more severe than would be expected given the severity of the inflammation). If fibrosis is not diagnosed separately, it should be described in the pathology narrative. Whenever it is diagnosed, fibrosis should be assigned a severity grade.
细胞浸润Infiltration Cellular 阴蒂腺浸润
描述（中文）
阴蒂腺——细胞浸润（Infiltration, cellular）在大鼠和小鼠中可能是自发性的年龄相关变化，但也可能是受试物相关效应。其特征为组织内出现浸润细胞（例如单核细胞、中性粒细胞、肥大细胞），但无其他炎症证据，如组织损伤、坏死、病原体、出血、充血或水肿（Figure 1、Figure 2、Figure 3、Figure 4）。细胞浸润必须与炎症相鉴别，后者存在上述其他炎症证据。
诊断建议
阴蒂腺——细胞浸润应作出诊断并赋予严重程度分级。浸润细胞的类型应作为诊断中的修饰词予以注明。
参考切片图（2 张）
查看英文原文
Comment
Clitoral gland - Infiltration, cellular may be a spontaneous age-related change in rats and mice but can also be a test-article-related effect. It is characterized by the presence of infiltrating cells (e.g., mononuclear cells, neutrophils, mast cells) within the tissue but with no other evidence of inflammation, such as tissue damage, necrosis, etiologic agents, hemorrhage, congestion, or edema ( Figure 1 , Figure 2 , Figure 3 and Figure 4 ). Infiltration cellular must be differentiated from inflammation, in which there is other evidence of inflammation as listed above.
Recommendation
Clitoral gland - Infiltration cellular should be diagnosed and assigned a severity grade. The type of infiltrating cell should be specified as a modifier in the diagnosis.
色素Pigment 阴蒂腺色素沉着
描述（中文）
阴蒂腺色素沉着（Figure 1、Figure 2）可能是与年龄相关的退行性改变，但也可能是细胞损伤（蜡样质或脂褐素）或出血（含铁血黄素）的后遗症。它常伴随阴蒂腺萎缩。据报道，脂褐素可见于单个腺泡细胞的细胞质中。
诊断建议
当认为色素沉着与研究相关（或不清楚是否与研究相关）时，或当其异常显著时，应予以诊断。并非所有色素都必须诊断，因为有些色素在衰老动物中普遍存在，或是另一种疾病过程（如出血）的继发表现，且无毒理学意义。病理学家应运用其判断力决定是否应诊断该色素沉着。当色素沉着与萎缩同时出现时，不应单独诊断色素沉着，但可在病理学叙述中描述。即使使用一系列特殊染色，在组织学切片中明确鉴定色素通常也很困难。因此，最恰当的诊断是“色素沉着”（而非诊断色素类型，如含铁血黄素或脂褐素）。病理学叙述应描述色素沉着的形态学特征。当诊断色素沉着时，应给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Clitoral gland pigmentation ( Figure 1 and Figure 2 ) may be an age-associated degenerative change but may also be seen as a sequela of cell damage (ceroid or lipofuscin) or hemorrhage (hemosiderin). It often accompanies clitoral gland atrophy. Lipofuscin has been reported in the cytoplasm of individual acinar cells.
Recommendation
Pigment should be diagnosed when it is considered to be relevant to the study (or if it is unclear whether it is relevant to the study) or if it is unusually prominent. Not all pigments have to be diagnosed, as some are ubiquitous in aging animals or are secondary to another disease process (e.g., hemorrhage) and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether or not the pigment should be diagnosed. When pigment is seen concurrently with atrophy, the pigment should not be diagnosed separately but may be described in the pathology narrative. Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, a diagnosis of “pigment” (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should describe the morphologic features of the pigmentation. When pigment is diagnosed, it should be given a severity grade.
萎缩Atrophy 阴蒂腺萎缩
描述（中文）
阴蒂腺（clitoral gland）实质萎缩是小鼠和大鼠中一种自发性的衰老性改变。萎缩常伴随导管扩张（Figure 1）。轻度炎症细胞浸润也可能与腺体组织减少有关。萎缩的标志性特征是阴蒂腺腺泡组织数量减少；单个腺泡由少量皮脂腺细胞构成，这些细胞含有数量不等的深嗜酸性分泌颗粒。常见侧导管因分泌物蓄积而扩张、显著（Figure 2、Figure 3）。间质纤维组织常增多（Figure 2、Figure 3、Figure 4、Figure 5）。
诊断建议
阴蒂腺萎缩一旦出现即应作出诊断并给出严重程度分级。伴随阴蒂腺萎缩的炎症不应单独诊断，除非其严重程度足以支持单独诊断。若萎缩继发于导管扩张，则萎缩无需单独诊断，但若与受试物相关，则应在叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Atrophy of clitoral gland parenchyma is a spontaneous aging change in mice and rats. Atrophy also accompanies duct dilatation ( Figure 1 ). Mild inflammatory cell infiltrate may also be associated with the reduction in glandular tissue. The hallmark of atrophy is a reduction in the amount of acinar tissue of the clitoral gland; individual acini are composed of small numbers of sebaceous cells containing variable amounts of dark eosinophilic secretory granules. Frequently the lateral ducts, distended by accumulated secretion, are prominent ( Figure 2 and Figure 3 ). There is often an increase in the interstitial fibrous tissue ( Figure 2 , Figure 3 , Figure 4 , and Figure 5 ).
Recommendation
Clitoral gland atrophy should be diagnosed and given a severity grade whenever it is present. Inflammation accompanying clitoral gland atrophy should not be diagnosed separately unless warranted by severity. If atrophy is secondary to duct dilation, then atrophy does not need to be diagnosed separately but should be described in the narrative if treatment related.
血管扩张Angiectasis 阴蒂腺扩张
描述（中文）
在血管扩张（angiectasis）中，原有的阴蒂腺血管扩张并充满血细胞，伴有阴蒂腺实质的受压（Figure 1、Figure 2）。应尝试区分血管扩张与血管瘤（hemangioma），尽管这种区分并不总是显而易见。血管瘤往往为边界清楚、无包膜的肿块，由紧密排列的扩张血管腔隙构成。每个血管腔隙均由单层形态正常的内皮细胞围成并衬覆，这些内皮细胞排列于胶原性间隔上，间隔通常较薄，但部分具有宽阔的胶原性间质。血管扩张通常不表现为边界清楚的肿块：扩张的血管通道常不规则地穿行于组织中。血管扩张和血管瘤均可发生邻近实质的受压。
诊断建议
阴蒂腺——血管扩张：只要存在即应作出诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
In angiectasis, preexisting clitoral gland blood vessels become dilated and filled with blood cells, accompanied by compression of the clitoral gland parenchyma ( Figure 1 and Figure 2 ). A distinction between angiectasis and hemangioma should be attempted, although the distinction is not always obvious. Hemangiomas tend to be well-circumscribed, unencapsulated masses composed of tightly packed, dilated vascular spaces. Each vascular space is enclosed and lined by a single layer of normal-appearing endothelial cells aligned on collagenous septa, which are usually thin, although some have broad collagenous stroma. Angiectasis does not usually present as a well-circumscribed mass: the dilated vascular channels often course irregularly through the tissue. Compression of adjacent parenchyma may occur in both angiectasis and hemangioma.
Recommendation
Clitoral gland - Angiectasis should be diagnosed and graded whenever present.
上皮增生Epithelium Hyperplasia 阴道增生
描述（中文）
啮齿类阴道上皮增生（Figure 1、Figure 2、Figure 3、Figure 4）常伴有过角化（hyperkeratosis），且通常为弥漫性。细胞分化良好，无异型性，也无侵袭下方间质的表现。增生的细胞可向下方间质形成向下突起（网嵴，rete pegs）（Figure 3、Figure 4）。增生可发生于多种情形，包括生殖衰老期处于持续动情期的对照大鼠，以及继发于内源性雌二醇生成增加或给予具有激素活性的外源化学物。阴道上皮的局灶性（focal）增生不常见，但已有观察到。增生应与动情周期中阴道外观的正常变异相鉴别（周期性变化的描述见引言）。增生是阴道上皮厚度的增加（与正常 cycling 动物的正常动情期相比）。局灶性增生的鉴别诊断包括乳头状瘤（papilloma）和息肉（polyp）。增生细胞明显位于上皮基底膜之上，不形成离散的上皮细胞增殖性团块。增生局限于正常黏膜表面，不突入管腔。息肉主要由被覆正常或轻度角化上皮的纤维肌性核心构成。
诊断建议
阴道，上皮——增生：当与处理相关时，应作出诊断并分级。如果上皮增厚是与正常动情周期相关的正常变化，则不应诊断为增生。与增生相关的过角化除非严重程度确有必要，否则不应单独诊断，但应在病理学描述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Hyperplasia of the rodent vaginal epithelium ( Figure 1 , Figure 2 , Figure 3 and Figure 4 ) is often associated with hyperkeratosis and is usually diffuse. Cells are well differentiated with no atypia or invasion of the underlying stroma. Hyperplastic cells may form downward projections into the underlying stroma (rete pegs) ( Figure 3 and Figure 4 ). Hyperplasia occurs in a variety of settings, including control rats in persistent estrus during reproductive senescence, and secondary to increases in endogenous estradiol production or administration of hormonally active xenobiotics. Focal hyperplasia of vaginal epithelium is uncommon but has been observed. Hyperplasia should be differentiated from normal variation in the appearance of the vagina during the estrus cycle (see Introduction for description of cyclical changes). Hyperplasia is increased thickness of the vaginal epithelium (compared with normal estrus in a normally cycling animal). The differential diagnoses for focal hyperplasia are papilloma and polyp. Hyperplastic cells are evident above the basement membrane of the epithelium and do not form a discrete proliferative mass of epithelial cells. Hyperplasia is restricted to the normal mucosal surface and does not protrude into the lumen. A polyp is composed predominantly of a fibromuscular core covered by normal or slightly hyperkeratinized epithelium.
Recommendation
Vagina, Epithelium - Hyperplasia should be diagnosed and graded when it is treatment related. If the epithelial thickening is a normal change associated with the normal estrous cycle, it should not be diagnosed as hyperplasia. Hyperkeratosis associated with the hyperplasia should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative.
囊肿Cyst 阴道囊肿
描述（中文）
在大鼠阴道壁中罕见发现囊肿（Figure 1、Figure 2、Figure 3）。这些囊肿通常由复层鳞状上皮（stratified squamous epithelium）衬覆，内含角蛋白和细胞物质，其中可能含有炎性碎片。这些囊肿是扩张的、充满液体的结构，具有上皮衬覆。它们可能具有平滑肌壁（中肾管残余，mesonephric duct remnant），也可能伴有鳞状化生（squamous metaplasia）和/或角化。囊肿不得与脓肿相混淆，脓肿主要充满处于不同降解阶段的中性粒细胞，且不具有上皮衬覆。
诊断建议
阴道 - 囊肿应予以诊断，但无需分级。如果囊肿似乎与处理相关，且分级有助于表征处理效应，病理学家可自行决定对其进行分级。相关的炎性改变不应单独诊断，除非其严重程度足以支持单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Cysts are rarely found in the walls of rat vaginas ( Figure 1 , Figure 2 and Figure 3 ). These are usually lined by stratified squamous epithelium and filled with keratin and cellular material, which may have inflammatory debris. These cysts are dilated, fluid-filled structures with an epithelial lining. They may have a smooth muscle wall (mesonephric duct remnant) and also may have squamous metaplasia and/or keratinization. Cysts must not be confused with abscesses, which are predominantly filled with neutrophils in various stages of degradation and do not have an epithelial lining.
Recommendation
Vagina - Cyst should be diagnosed but need not be graded. If the cysts appear to be treatment related, they may be graded at the pathologist’s discretion if grading would help characterize the treatment effect. Associated inflammatory changes should not be diagnosed separately unless warranted by severity.
坏死Necrosis 阴道坏死
描述（中文）
阴道上皮坏死（Figure 1、Figure 2）罕见观察到。最典型的是继发于阴道内给予外源化学物、刺激性赋形剂和/或阴道内装置。阴道坏死的特征包括核固缩和/或核碎裂、胞质嗜酸性、细胞肿胀或皱缩、脱落细胞和/或管腔内细胞碎片。阴道坏死常伴有急性炎症，并可能导致糜烂/溃疡。
诊断建议
阴道上皮和肌层坏死应诊断并分级。如果坏死继发于其他病变，如炎症或肿瘤，则不应单独诊断。继发于坏死的病变，如炎症、出血或水肿，除非严重程度需要，否则不应单独诊断，而应在病理学描述中作为坏死的组成部分进行描述。
参考切片图（2 张）
查看英文原文
Comment
Necrosis of the vaginal epithelium ( Figure 1 and Figure 2 ) is rarely observed. It is most typically observed secondary to intravaginal administration of xenobiotics, irritating vehicles, and/or intravaginal devices. The features of vaginal necrosis include nuclear pyknosis and/or karyorrhexis, cytoplasmic eosinophilia, cellular swelling or shrinkage, exfoliated cells, and/or intraluminal cellular debris. Vaginal necrosis is often associated with acute inflammation and may result in erosion/ulcer.
Recommendation
Necrosis of the vaginal epithelium and muscularis should be diagnosed and graded. If the necrosis is secondary to another lesion, such as inflammation or neoplasia, it should not be diagnosed separately. Lesions that are secondary to necrosis, such as inflammation, hemorrhage, or edema, should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative as a component of the necrosis.
基质肥大Hypertrophy Stromal 阴道肥大
描述（中文）
阴道间质肥大（stromal hypertrophy）的特征是阴道壁纤维肌性间质（fibromuscular stroma）因细胞体积增大而非细胞数量增多而增厚（Figure 1、Figure 2）。间质肥大必须与肿瘤性病变相鉴别，后者与细胞数量增多有关，形成离散的、局灶性（focal）的、压迫性或浸润性肿块。其他鉴别诊断包括阴道息肉（vaginal polyp），这是一种外生性病变，主要由被覆正常或轻度角化过度上皮的纤维肌性核心构成；以及子宫内膜间质息肉（endometrial stromal polyp），这是另一种外生性病变，常经宫颈突出并出现于阴道。
诊断建议
阴道——间质肥大（Hypertrophy, Stromal）只要存在即应诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Stromal hypertrophy of the vagina is characterized by thickening of the fibromuscular stroma of the vaginal wall due to an increase in the size of cells, not the number of cells ( Figure 1 and Figure 2 ). Stromal hypertrophy must be differentiated from neoplastic lesions, which are associated with an increased number of cells forming a discrete, focal, compressive or invasive mass. Other differential diagnoses include vaginal polyp, which is an exophytic lesion composed predominantly of a fibromuscular core covered by normal or slightly hyperkeratinized epithelium, and endometrial stromal polyp, another exophytic lesion that commonly projects through the cervix and appears in the vagina.
Recommendation
Vagina - Hypertrophy, Stromal should be diagnosed and graded whenever present.
扩张Dilation 阴道扩张
描述（中文）
阴道扩张（Figure 1、Figure 2）通常继发于阴道闭锁。在幼犬中，内胚层膜正常情况下封闭阴道，该膜通常在青春期消失，阴道随之通畅。若此过程未发生，其后果即为阴道囊性扩张。这种扩张也可能与子宫积黏液、炎症及上皮增生相关。
诊断建议
阴道——当切片上扩张原因不明显时，应诊断并分级为扩张。然而，若阴道闭锁且在切片上明显可见，则应作出阴道闭锁的诊断。继发性病变，如炎症，除非严重程度足以支持，否则不应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Dilation of the vagina ( Figure 1 and Figure 2 ) usually occurs secondary to an imperforate vagina. An endodermal membrane normally occludes the vagina in the pup, and this typically disappears at puberty and the vagina becomes patent. When this does not happen, the consequence is cystic dilation of the vagina. This dilation may also be associated with mucometra, inflammation, and hyperplasia of the epithelium.
Recommendation
Vagina - Dilatation should be diagnosed and graded when the cause of the dilation is not apparent on the slide. However, if the vagina is imperforate, and this is apparent on the slide, then the diagnosis of imperforate vagina should be made. Secondary lesions, such as inflammation, should not be diagnosed separately unless warranted by severity.
溃疡Ulcer 阴道溃疡
描述（中文）
阴道溃疡（ulcer）是指上皮的局灶性（focal）缺失，并伴有下方基底膜的破损（Figure 1、Figure 2）。通常伴有相关的炎症细胞反应。最常见的原因是局部阴道内给予子宫托、外源性化学物质等物质。
诊断建议
阴道——溃疡应予以诊断并分级。相关的炎症不应单独诊断，除非其严重程度足以支持单独诊断，但应在病理描述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
An ulcer of the vagina is a focal loss of the epithelium with a breach of the underlying basement membrane ( Figure 1 and Figure 2 ). There is typically an associated inflammatory cell reaction. It is most commonly seen as a consequence of local, intravaginal administration of materials such as pessaries and xenobiotics.
Recommendation
Vagina - Ulcer should be diagnosed and graded. The associated inflammation should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative.
炎症Inflammation 阴道炎症
描述（中文）
在NTP研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性 active）和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症（Figure 1、Figure 2）中，主要的浸润细胞是中性粒细胞（neutrophil），但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症（Figure 3、Figure 4）中的主要浸润细胞类型，但它们聚集在一起，且其中许多已发生退变（化脓性渗出物）。渗出物中还可能存在来自常驻细胞群和浸润白细胞的细胞碎片，以及含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞或浆细胞，并可能存在感染因子。肉眼观察，这些病变以脓液存在为特征。在渗出物周围的组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞，具体取决于病变的慢性程度。脓肿在组织学上应诊断为化脓性炎症。慢性炎症中以淋巴细胞为主。慢性活动性炎症（Figure 5、Figure 6）中也以淋巴细胞为主，但同时还存在大量中性粒细胞。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的、活化的巨噬细胞、上皮样巨噬细胞或多核巨细胞。炎症与细胞浸润的鉴别在于是否存在其他改变，如水肿、出血、变性、坏死或其他组织损伤的证据。明显的化脓性炎症（子宫积脓，pyometra）偶尔见于阴道，且常与邻近器官（宫颈和子宫）的炎症相关。轻度炎症常见，但必须与发情周期特定阶段炎症细胞的正常存在相鉴别。在发情周期中，跨上皮移行的中性粒细胞往往较多，而管腔内积聚的中性粒细胞即使有也仅为少数。
诊断建议
阴道——只要炎症被认为是处理效应，就应进行诊断并分级。作为发情周期正常成分存在的炎症细胞不应诊断。继发于炎症的病变，如坏死，除非严重程度足以支持，否则不应单独诊断。如果炎症继发于其他病变，如坏死或肿瘤，除非严重程度足以支持，否则不应单独诊断。诊断时，应通过使用修饰词在诊断中指明炎症的类型。
参考切片图（2 张）
查看英文原文
Comment
In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic active, and granulomatous. In acute inflammation ( Figure 1 and Figure 2 ), the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation ( Figure 3 and Figure 4 ), but they are aggregated, and many of them are degenerate (suppurative exudate). Cell debris, from both the resident cell populations and infiltrating leukocytes, and proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes or plasma cells, and, possibly, an infectious agent may also be present within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Abscesses should be diagnosed histologically as suppurative inflammation. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic active inflammation ( Figure 5 and Figure 6 ), but there are also a significant number of neutrophils. Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. Inflammation is differentiated from cellular infiltrates by the presence of other changes, such as edema, hemorrhage, degeneration, necrosis, or other evidence of tissue damage. Frank suppurative inflammation (pyometra) is occasionally encountered in the vagina and is often associated with inflammation in the contiguous organs, cervix, and uterus. Mild inflammation is commonly observed, but this must be differentiated from the normal presence of inflammatory cells at certain stages in the estrous cycle. In the estrus cycle there tend to be more transepithelial migratory neutrophils, with only a few, if any, luminal accumulations of neutrophils.
Recommendation
Vagina - Inflammation should be diagnosed and graded whenever it is considered a treatment effect. Inflammatory cells present as a normal component of the estrous cycle should not be diagnosed. Lesions that are secondary to the inflammation, such as necrosis, should not be diagnosed separately unless warranted by severity. If the inflammation is secondary to another lesion, such as necrosis or neoplasia, it should not be diagnosed separately unless warranted by severity. When diagnosed, the type of inflammation should be indicated in the diagnosis through the use of a modifier.
纤维化Fibrosis 阴道纤维化
描述（中文）
阴道纤维化（Vaginal fibrosis）（Figure 1、Figure 2），即纤维结缔组织或胶原沉积并伴有少量散在细胞，已在老年大鼠中观察到，且常伴有一些慢性炎症。纤维化需与肿瘤性病变（纤维瘤或纤维肉瘤）相鉴别，后者为占位性改变；相反，纤维化通常为收缩性病变。
诊断建议
阴道——纤维化只要在其他病变不存在时出现，就应诊断。伴有慢性或慢性活动性炎症的纤维化，仅当炎症程度与纤维化程度不相称时（即纤维化比根据炎症严重程度所预期的更为严重）才应诊断。如果纤维化未单独诊断，则应在病理学叙述中描述。无论何时诊断，纤维化都应赋予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Vaginal fibrosis ( Figure 1 and Figure 2 ), deposition of fibrous connective tissue or collagen with a few interspersed cells, has been observed in older rats and is often accompanied by some chronic inflammation. Fibrosis needs to be differentiated from neoplasia (fibroma or fibrosarcoma), which is a space-occupying change; in contrast, fibrosis is generally a contracting lesion.
Recommendation
Vagina - Fibrosis should be diagnosed whenever it occurs in the absence of other lesions. Fibrosis present accompanying chronic or chronic active inflammation should be diagnosed only when the degree of inflammation is not commensurate to that of fibrosis (i.e., the fibrosis is more severe than would be expected given the severity of the inflammation). If fibrosis is not diagnosed separately, it should be described in the pathology narrative. Whenever it is diagnosed, fibrosis should be assigned a severity grade.
色素Pigment 阴道色素沉着
描述（中文）
阴道内有时可见金黄色至深棕色色素（Figure 1、Figure 2）。继发于局部出血的含铁血黄素（hemosiderin）是最常见的类型，但也可见其他类型。
诊断建议
阴道——色素：当认为色素与研究相关（或不清楚是否与研究相关）时，或当色素异常显著时，应当诊断为色素。并非所有色素都必须诊断，因为有些色素在老龄动物中普遍存在，或继发于其他疾病过程（例如出血），不具有毒理学意义。病理学家应运用其判断力决定是否应当诊断该色素。即使使用一系列特殊染色，在组织学切片中明确鉴定色素类型通常也很困难。因此，最恰当的诊断是“色素”（而非诊断色素类型，例如含铁血黄素或脂褐素）。病理学描述应描述色素沉着的形态学特征。当诊断为色素时，应当给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Golden brown to darker brown pigment is sometimes seen in the vagina ( Figure 1 and Figure 2 ). Hemosiderin secondary to local hemorrhage is the most common type, but other types may be seen.
Recommendation
Vagina - Pigment should be diagnosed when it is considered to be relevant to the study (or if it is unclear whether it is relevant to the study) or if it is unusually prominent. Not all pigments have to be diagnosed, as some are ubiquitous in aging animals or are secondary to another disease process (e.g., hemorrhage) and not toxicologically meaningful. The pathologist should use his or her judgment in deciding whether or not the pigment should be diagnosed. Definitive pigment identification is often difficult in histologic sections, even with a battery of special stains. Therefore, a diagnosis of "pigment" (as opposed to diagnosing the type of pigment, e.g., hemosiderin or lipofuscin) is most appropriate. The pathology narrative should describe the morphologic features of the pigmentation. When pigment is diagnosed, it should be given a severity grade.
血管扩张Angiectasis 阴道扩张
描述（中文）
大鼠阴道内的扩张血管罕见观察到。当作为血管扩张（angiectasis）存在时，通常是一组显著的扩张血管，内衬单层内皮细胞，细胞核扁平（Figure 1、Figure 2）。应尝试区分血管扩张与血管瘤（hemangioma），尽管这种区分并不总是显而易见。血管瘤往往边界清楚、无包膜，由紧密排列的扩张血管腔隙构成。每个血管腔隙均由单层外观正常的内皮细胞围成并衬覆，这些内皮细胞排列于胶原性间隔上，间隔通常较薄，尽管部分具有宽阔的胶原性间质。相比之下，血管扩张通常不表现为边界清楚的肿块：扩张的血管通道不规则地穿行于组织中。
诊断建议
阴道 - 血管扩张：只要存在即应诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
Dilated vessels in the rat vagina are rarely observed. When present as angiectasis, they are usually a collection of prominent dilated blood vessels lined by a single layer of endothelium with flattened nuclei ( Figure 1 and Figure 2 ). A distinction between angiectasis and hemangioma should be attempted, although the distinction is not always obvious. Hemangiomas tend to be well-circumscribed, unencapsulated masses composed of tightly packed, dilated vascular spaces. Each vascular space is enclosed and lined by a single layer of normal-appearing endothelial cells aligned on collagenous septa, which are usually thin, although some have broad collagenous stroma. In contrast, angiectasis does not usually present a well-circumscribed mass: the dilated vascular channels course irregularly through the tissue.
Recommendation
Vagina - Angiectasis should be diagnosed and graded whenever present.
黏液化Mucification 阴道其他
描述（中文）
一般而言，阴道黏膜化（vaginal mucification）（Figure 1、Figure 2）由孕酮过多诱导。因此，它正常发生于动情前期、妊娠和假妊娠期间。它也见于高催乳素血症，例如由分泌催乳素的垂体肿瘤所引起者。其组织学特征为阴道黏膜表面上皮细胞发生变化，变为立方状或圆柱状并伴有明显的空泡化。空泡化的细胞含有PAS和/或Alcian blue阳性物质（黏蛋白）。在某些情况下，阴道黏膜化可能是受试物效应。空泡化的程度、上皮的厚度以及上皮与黏膜化层之间缺乏角化带，均提示该黏膜化并非正常周期性变化的一部分。
诊断建议
阴道 - 黏膜化：当其不被认为是正常动情周期、妊娠或假妊娠的组成部分，或病理学家认为其过度时，应当诊断并分级。
参考切片图（2 张）
查看英文原文
Comment
In general, vaginal mucification ( Figure 1 and Figure 2 ) is induced by progesterone excess. Therefore, it occurs normally during proestrus, pregnancy, and pseudopregnancy. It is also seen with hyperprolactinemia, such as that caused by a prolactin-secreting pituitary neoplasm. It is characterized histologically by changes in the superficial epithelial cells of the vaginal mucosa, which become cuboidal or cylindrical with prominent vacuolation. The vacuolated cells contain PAS- and/or Alcian blue-positive material (mucin). In some cases, the mucification of the vagina may be a treatment effect. The degree of vacuolation, the thickness of the epithelium, and the lack of a band of keratinization between the epithelium and the mucified layer are indicative that the mucification is not part of a normal cyclical change.
Recommendation
Vagina - Mucification should be diagnosed and graded when it is not considered a component of normal estrous cyclicity, pregnancy, or pseudopregnancy, or if it is considered excessive in the opinion of the pathologist.
关节变性Joint Degeneration 骨变性
描述（中文）
关节退行性变（骨关节炎、关节病、骨关节病、退行性关节病）是一种非炎症性、进行性软骨疾病，其特征为关节软骨丢失、软骨下骨增厚（Figure 1）及囊肿形成，并在受累关节间隙内形成骨赘。骨关节炎的早期病变包括软骨染色性质改变，表现为软骨基质嗜碱性丧失及纤维状质地（由黏多糖丢失所致）、裂隙形成以及软骨肥大和增生，后者表现为排列不规则的增大软骨细胞簇。严重病变可伴有软骨裂隙（Figure 2），导致软骨侵蚀和丢失、关节囊和滑膜增厚（Figure 3），以及骨赘形成和软骨下骨囊肿形成。滑膜组织可变厚，伴绒毛状突起自滑膜发出并突入关节间隙。随着病程慢性化，滑膜可发生软骨性或骨性化生。严重病例可发生关节强直（融合）。超微结构上，退行性变的特征为高尔基体异常、细胞内微丝增多、蛋白聚糖颗粒数量减少以及软骨基质内胶原破坏。退行性关节病作为衰老过程的一个组成部分，几乎发生于所有品系的大鼠和小鼠。在B6C3F1 mouse中，该病在雄性中的发生率高于雌性，膝关节的发病率雄性高达2%、雌性高达4%。已知该病在小鼠中优先累及膝关节和肘关节，但也发生于胸椎远端椎骨和胸骨关节。在F344 rat中，已有报道自13月龄起即出现自发病变。尽管这是一种正常的年龄相关变化，但该病为多因素所致，除暴露于各种可导致软骨基质改变的毒物外，还受饮食、品系、性激素和体重的影响。大鼠关节软骨或生长板的软骨黏液样/囊性变性（无菌性坏死）不应与退行性关节病混淆。这是老年大鼠常见的自发病变，可导致骺板和骨骺骨小梁自发性骨折，但不引起关节软骨的退行性病变。
诊断建议
退行性关节病/骨关节炎应诊断为“骨，关节－退行性变”并给出严重程度分级。不必记录所有各个组成部分，但若该病似乎与化学物暴露相关，则应在叙述中予以描述。在叙述中，如适当，可使用“退行性关节病”或“骨关节炎”这些术语来指代与形态学相关的该病。相关链接：骨－关节－炎症
参考切片图（2 张）
查看英文原文
Comment
Degeneration of the joint (osteoarthritis arthrosis, osteoarthrosis, osteoarthropathy, degenerative joint disease) is a noninflammatory, progressive disease of cartilage characterized by loss of articular cartilage, subchondral bone thickening ( Figure 1 ) and cyst formation, and formation of osteophytes within the affected joint space. Early lesions of osteoarthritis consist of tinctorial alterations of the cartilage characterized by loss of basophilia and fibrillar consistency (resulting from loss of mucopolysaccharides) of the cartilaginous matrix, fissure formation, and hypertrophy and hyperplasia of cartilage, evidenced by irregularly arranged clusters of enlarged chondrocytes. Severe lesions may be associated with cartilaginous clefts ( Figure 2 ), leading to erosion and loss, thickening of the joint capsule and synovium ( Figure 3 ), and osteophytosis and subchondral bone cyst formation. Synovial tissue may become thickened, with villous projections emanating from the synovium and protruding into the joint space. With chronicity, the synovium may undergo cartilaginous or bony metaplasia. In severe cases, ankylosis (fusion) of the joint may occur. Ultrastructurally, degenerative changes are characterized by abnormal Golgi, increased intracellular microfilaments, decreased numbers of proteoglycan granules, and disruption of collagen within the cartilaginous matrix. Degenerative joint disease occurs in nearly all strains of rats and mice as a component of the aging process. In the B6C3F1 mouse, the disease occurs more commonly in males than females and has an incidence in the stifle joint of up to 2% for males and 4% for females. The disease is known to preferentially affect the stifle and elbow joints in the mouse but also occurs in the distal thoracic vertebrae and joints of the sternum. In the F344 rat, spontaneous lesions have been reported as early as 13 months. Although a normal age-related change, the disease is multifactorial and influenced by diet, strain, sex hormones, and weight, in addition to exposure to various toxicants, which can cause alterations in the cartilaginous matrix. Chondromucinous/cystic degeneration (aseptic necrosis) of articular cartilage or growth plates in the rat should not be confused with degenerative joint disease. This is a common spontaneous lesion in aged rats that may lead to spontaneous fractures of bony trabeculae of the physis and epiphysis but does not cause degenerative lesions of the articular cartilage.
Recommendation
Degenerative joint disease/osteoarthritis should be diagnosed as "Bone, Joint – Degeneration" and given a severity grade. It is not necessary to record all of the individual components, but they should be described in the narrative if the disease appears correlated with chemical exposure. In the narrative, the terms "degenerative joint disease" or "osteoarthritis" may be used to connote the disease associated with the morphology, if appropriate. Related Links: Bone - Joint - Inflammation
关节炎症Joint Inflammation 骨炎症
描述（中文）
大多数关节炎症（关节炎）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6、Figure 7、Figure 8）累及腿和足的远端关节（跗骨、腕骨、跖骨、掌骨）。其特征为炎性细胞浸润；关节腔及相关结缔组织内蛋白性物质和纤维蛋白；滑膜增生、水肿和纤维化；以及反应性新骨形成。炎症可导致增厚的滑膜覆盖关节面（血管翳），或通过侵蚀软骨下骨破坏关节软骨。当炎症呈慢性且严重时，可导致骨赘形成和关节强直（融合）。与骨关节炎（退行性关节病；见Bone - Joint - Degeneration）不同，微生物感染所致的关节炎伴有大量液体和关节腔内纤维蛋白性渗出物。当单个关节受累时，穿透性创伤是最可能的原因，尽管微生物也可通过从邻近组织蔓延或经血流进入关节。感染性关节炎症的原因在B6C3F1小鼠和F344大鼠中不常见。然而，穿透性创伤、打斗或其他创伤可导致累及关节或关节周围组织的局限性微生物感染。在NTP研究中，受试物暴露与关节炎症发生率增加无关。免疫抑制性化合物处理可能影响动物抵抗小的局限性感染的能力，当关节腔受累时可导致关节炎症，或引起全身播散导致多器官受累，包括多关节炎。然而，尽管与关节炎相关的病原体在啮齿类动物中已被普遍认识，但在常规毒性和致癌性研究中通常未观察到其作为关节炎症的原因。在NTP研究中，炎症有五种标准分类：急性、化脓性、慢性、慢性活动性和肉芽肿性。在急性炎症中，主要浸润细胞为中性粒细胞，但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但中性粒细胞聚集，其中许多发生退变（化脓性渗出物）。渗出物中还可能存在细胞碎片（来自 resident 细胞群和浸润白细胞）、含纤维蛋白的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞和/或浆细胞，以及可能的感染因子。大体上，这些病变以脓液存在为特征。在渗出物周围组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎性细胞，取决于病变的慢性程度。慢性和慢性活动性炎症由成纤维细胞或纤维化的存在来确定。在慢性炎症中，主要炎性细胞通常为淋巴细胞，而在慢性活动性炎症中为淋巴细胞和中性粒细胞的混合物。两种病变也可能含有巨噬细胞。然而，正是成纤维细胞或纤维化的存在决定了病变的慢性性质。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断需要存在大量聚集的、大的、活化的巨噬细胞、上皮样巨噬细胞或多核巨细胞。
诊断建议
当存在时，该病变应被诊断并给予严重程度分级。此外，炎症类型（急性、化脓性、慢性、慢性活动性或肉芽肿性）应作为修饰词纳入诊断。病变的任何可能发病机制应在病理学叙述中讨论。如果关节炎症作为关节周围软组织或覆盖真皮炎症过程的蔓延而发生（Figure 3、Figure 4），则不应单独诊断，但病变范围可在叙述中描述。病变的各个组成部分（例如，滑膜增生、出血、软骨变性、坏死）除非严重程度需要，否则不应单独诊断，但应在叙述中描述。相关链接：Bone - Joint - Degeneration Bone - Joint - Degeneration
参考切片图（2 张）
查看英文原文
Comment
Most incidences of inflammation of the joints (arthritis) ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 , Figure 7 , and Figure 8 ) involve the distal joints of the legs and feet (tarsus, carpus, metatarsus, metacarpus). They are characterized by infiltration of inflammatory cells; proteinaceous material and fibrin within the joint space and associated connective tissues; hyperplasia, edema, and fibrosis of the synovial membranes; and reactive new bone formation. Inflammation may induce thickened synovial membranes that cover the articular surfaces of the joint (pannus) or may undermine the articular cartilage by eroding subchondral bone. When chronic and severe, inflammation of the joint may lead to osteophytosis and ankylosis (fusion) of the joint. In contrast to osteoarthritis (degenerative joint disease; see Bone - Joint - Degeneration ), arthritis due to microbial infection is associated with copius fluid and fibrinous exudate within the joint space. When a single joint is affected, a penetrating wound is the most likely cause, although microbial agents may also gain access to the joint via extension from adjacent tissues or through the bloodstream. Infectious causes of joint inflammation are uncommon in the B6C3F1 mouse and F344 rat. However, penetrating wounds, fighting, or other trauma may lead to localized microbial infections involving the joint or periarticular tissues. Test article exposures have not been associated with increased incidences of joint inflammation in NTP studies. It is possible that treatment with immunosuppressive compounds may affect an animal’s ability to combat small, localized infections, which may lead to joint inflammation when the joint space is involved, or result in systemic spread leading to multiorgan involvement, including polyarthritis. However, while pathogens associated with arthritis have been recognized in rodents in general, they are not typically observed as a cause of joint inflammation in routine toxicity and carcinogenicity studies. In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate). Cell debris, both from the resident cell populations and from infiltrating leukocytes; proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes, and/or plasma cells; and possibly an infectious agent may also be present within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Chronic and chronic-active inflammation is determined by the presence of fibroblasts or fibrosis. With chronic inflammation , the predominant inflammatory cell is usually the lymphocyte, whereas in chronic-active inflammation it is a mixture of lymphocytes and neutrophils. Both lesions may also contain macrophages. However, it is the presence of fibroblasts or fibrosis that determines the chronic nature of the lesion. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells.
Recommendation
When present, this lesion should be diagnosed and given a severity grade. In addition, the type of inflammation (acute, suppurative, chronic, chronic-active, or granulomatous) should be included in the diagnosis as a modifier. Any potential pathogeneses of the lesion should be discussed in the pathology narrative. If joint inflammation occurs as an extension of an inflammatory process from the periarticular soft tissues or overlying dermis ( Figure 3 and Figure 4 ), it should not be diagnosed separately, but the extent of the lesion can be described in the narrative. The individual components of the lesion (e.g., synovial hyperplasia, hemorrhage, degeneration of cartilage, necrosis) should not be diagnosed separately unless warranted by severity but should be described in the narrative. Related Links: Bone - Joint - Degeneration Bone - Joint - Degeneration
囊肿Cyst 骨囊肿
描述（中文）
皮质骨囊肿（动脉瘤）的特征是皮质和/或骨髓腔被由薄层皮质骨壁构成的膨胀性囊性空间所扩张（Figure 1）。这些病变的膨胀性质可能引起周围骨的压迫性萎缩，伴有骨小梁或皮质骨的丢失并被结缔组织取代（Figure 2）。骨囊肿可为单房性（Figure 3）或多房性，并可含有数量不等的红细胞、纤维蛋白或蛋白性物质（Figure 4）。孤立性骨囊肿在F344大鼠中罕见观察到，其意义和发病机制尚不清楚。这些病变可发生于骨干的任何部位；然而，在大鼠中，囊肿可作为关节退变或骨软骨病的组成部分发生于软骨下骨内。
诊断建议
观察到孤立性骨囊肿时应作出诊断。然而，当囊肿作为骨软骨病（在Sprague-Dawley大鼠中表现为发育缺陷）的原发性病变或关节退变的组成部分发生时，不应作出诊断。这些病变代表B6C3F1小鼠和F344大鼠中的散发性背景性过程；骨囊肿的增加尚未与化学物暴露相关联。继发性病变，如萎缩，除非严重程度足以支持，否则不应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Cortical bone cysts (aneurysms) are characterized by expansion of the cortex and/or marrow cavity by an expansile cystic space composed of a thin wall of cortical bone ( Figure 1 ). The expansile nature of these lesions may induce pressure atrophy of the surrounding bone, with loss of bony trabeculae or cortical bone and replacement by connective tissue ( Figure 2 ). Bone cysts may be unilocular ( Figure 3 ) or multilocular and may contain variable amounts of erythrocytes, fibrin, or proteinic material ( Figure 4 ). Solitary bone cysts are rarely observed in the F344 rat, and their significance and pathogenesis are not known. These lesions may occur anywhere along the diaphysis; however, cysts may occur within the subchondral bone as a component of joint degeneration or osteochondrosis in the rat.
Recommendation
Solitary bone cysts should be diagnosed when observed. However, when a cyst occurs as a component of a primary lesion of osteochondrosis (seen as a developmental defect in Sprague-Dawley rats) or degeneration of the joint, it should not be diagnosed. These lesions represent sporadic background processes in the B6C3F1 mouse and F344 rat; increases in bone cysts have not been associated with chemical exposures. Secondary lesions, such as atrophy, should not be diagnosed separately unless warranted by severity.
坏死Necrosis 骨坏死
描述（中文）
骨坏死（Necrosis of bone）（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5）可表现为正常结构破坏、髓腔内骨小梁碎裂、骨表面成骨细胞丢失或骨陷窝内骨细胞丢失。常伴有骨髓坏死和出血。局灶性（focal） 坏死可孤立存在于死骨片（sequestra）中，或被纤维结缔组织取代。坏死可由多种病因引起，包括血管受损、炎症、创伤或肿瘤。小鼠偶可发生特发性骨坏死，尤其多见于股骨远端和胫骨近端的骨骺或干骺端；其中部分病例疑与血管受损有关。
诊断建议
骨坏死应当诊断并给出严重程度分级。如能辨别坏死的原因，应在叙述中讨论。当坏死作为另一病变过程的继发成分发生时，不应诊断，而应在叙述中描述。继发于坏死的病变，如炎症或出血，除非严重程度足以支持，否则不应单独诊断，但应在病理叙述中注明。
参考切片图（2 张）
查看英文原文
Comment
Necrosis of bone ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , and Figure 5 ) can be characterized by disruption of normal architecture and fragmentation of bony trabeculae in the medullary cavity, loss of osteoblasts from bone surfaces, or loss of osteocytes from lacunae. There is often marrow necrosis and hemorrhage. Focal necrosis may be isolated in sequestra or replaced by fibrous connective tissue. Necrosis may result from a variety of etiologies, including vascular compromise, inflammation, trauma, or neoplasia. Idiopathic necrosis of bone occasionally occurs in mice, particularly at the epiphysis or metaphysis of the distal femur and proximal tibia; vascular compromise has been suspected in some of these cases.
Recommendation
Necrosis of the bone should be diagnosed and given a severity grade. If the cause of the necrosis can be discerned, it should be discussed in the narrative. When necrosis occurs as a secondary component of another process, it should not be diagnosed but should be described in the narrative. Lesions that are secondary to necrosis, such as inflammation or hemorrhage, should not be diagnosed separately unless warranted by severity but should be noted in the pathology narrative.
椎间盘变性Intervertebral Disc Degeneration 骨变性
描述（中文）
椎间盘的功能是传递由体重和运动产生的机械负荷。椎间盘由外层的纤维结缔组织环（纤维环）和凝胶状核心（髓核）组成，后者由嵌入软骨黏液样基质中的胶原和弹性蛋白纤维构成，基质中水和蛋白聚糖含量高。椎间盘疾病以髓核的软骨黏液样变性为特征。一般而言，这是一种与年龄相关的病变，由髓核中水和蛋白聚糖的丢失所致。髓核发生不同程度的纤维软骨化生，变得易碎、碎裂或出现裂隙。纤维环不规则并变薄，最终向背侧突出进入椎管（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5）。椎间盘疾病在啮齿类动物中通常是一种与年龄相关的变化，并可能伴有与骨重塑、软骨终板改变或关节疾病（脊椎关节强硬、关节病）相关的各种变化，具体取决于严重程度和慢性程度。
诊断建议
“骨，椎间盘 - 变性”在观察到时应当诊断并给出严重程度分级。骨或软骨中的相关变化无需单独诊断，除非其严重程度确有必要；这些变化可在叙述中描述。脊髓的变性如果严重程度确有必要，应当单独诊断。
参考切片图（2 张）
查看英文原文
Comment
The intervertebral disc functions to transmit mechanical loads arising from body weight and movement. The disc is composed of an outer ring of fibrous connective tissue (annulus) and a gelatinous core (nucleus pulposus) composed of collagen and elastin fibers embedded in a chondromucinous matrix with a high water and proteoglycan content. Intervertebral disc disease is characterized by chondromucinous degeneration of the nucleus pulposus. In general, this is an age-related lesion that occurs as the result of loss of water and proteoglycans in the nucleus pulposus. The nucleus pulposa undergoes variable degrees of fibrocartilaginous metaplasia and becomes friable, fragmented, or clefted. There is irregularity and thinning of the annulus and eventual dorsal herniation into the vertebral canal ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , and Figure 5 ). Intervertebral disc disease is typically an age-related change in rodents and may be accompanied by variable changes related to bony remodeling, alterations to the cartilaginous endplates, or joint disease (spondylosis, arthrosis), depending on severity and chronicity.
Recommendation
"Bone, Intervertebral disc - Degeneration" should be diagnosed and given a severity grade whenever observed. Associated changes in the bone or cartilage do not need to be diagnosed separately unless warranted by their severity; they can be described in the narrative. Degeneration of the spinal cord should be diagnosed separately if warranted by the severity.
炎症Inflammation 骨炎症
描述（中文）
在B6C3F1/N小鼠和F344/N大鼠中，骨炎症（骨髓炎、骨炎）不常见。在啮齿类动物中，骨炎症通常由创伤（如穿透性伤口或骨折）、中耳炎或鼻窦炎导致的细菌感染引起。骨膜及邻近骨的炎症（骨膜炎）可发生于皮肤溃疡下方的区域，且常与反应性骨增生和肉芽组织相关。在许多病例中，骨炎症（尤其与葡萄球菌感染相关）与明显的局部骨吸收（Figure 1、Figure 2）相关，这是由细菌因素和破骨细胞活性增加所致，同时病变边缘出现区域性反应性骨反应和骨质增生性骨反应，以试图局限化炎症过程。将反应性骨增生和重塑过程与 underlying neoplasm 相区分通常可能较为困难。与肿瘤性骨不同，反应性骨排列有序，骨小梁垂直于邻近成熟皮质骨排列并彼此平行（Figure 3）。在反应性骨中，成骨细胞规律地散布于骨小梁表面。骨炎症的类型可能取决于病因和慢性程度。在NTP研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））。在急性炎症中，主要浸润细胞为中性粒细胞，但也可能存在较少的巨噬细胞和淋巴细胞。还可能有水肿或充血的表现。中性粒细胞也是化脓性炎症中的主要浸润细胞类型，但中性粒细胞聚集，其中许多发生退变（化脓性渗出物）。渗出物中还可能存在驻留细胞群体和浸润白细胞的细胞碎片；含纤维蛋白、巨噬细胞、淋巴细胞和/或浆细胞的蛋白性液体；以及可能的感染因子。肉眼观察，这些病变以脓液存在为特征。在渗出物周围组织中，可能存在成纤维细胞、纤维结缔组织和混合性炎症细胞群体，取决于病变的慢性程度。慢性和慢性活动性炎症由成纤维细胞或纤维化的存在来确定。在慢性炎症中，主要炎症细胞通常为淋巴细胞，而慢性活动性炎症则具有淋巴细胞和中性粒细胞的混合。两种病变也可能含有巨噬细胞。然而，正是成纤维细胞或纤维化的存在决定了病变的慢性性质。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断要求存在大量聚集的、大的活化巨噬细胞、上皮样巨噬细胞或多核巨细胞。在细菌感染在骨中确立的病例中，化脓性炎症和坏死细胞碎片常被局限化为脓肿或死骨片，以试图将炎症/感染过程包裹隔离（Figure 2）。在良好实验室规范条件下的常规毒性和致癌性生物测定中，骨炎症通常不被观察为对毒理学暴露的反应。然而，如果观察到骨髓炎发生率增加，这可能表明动物饲养管理存在问题。此外，任何引起严重免疫抑制的化合物都可能影响动物对共生病原体作出反应的能力，从而增加感染的易感性。
诊断建议
骨炎症应被诊断并给予严重程度分级。炎症的性质（化脓性、肉芽肿性等）应作为诊断的一部分。如果骨炎症与原发性创伤性损伤（如骨折、穿透性伤口）或原发性骨肿瘤同时观察到，则不应诊断，而应在叙述中描述为原发性病变的组成部分。然而，在慢性炎症已导致明显骨吸收和骨量减少并继发骨折的病例中，炎症应记录为原发性诊断，并在叙述中描述明显骨吸收的继发效应。当与其他全身性炎症病变、尤其是化脓性病变（脓肿）一致地被识别时，应记录病变谱作为全身性状况并在叙述中描述。如果骨炎症与处理相关，则应在病理学叙述中确定受影响的骨。
参考切片图（2 张）
查看英文原文
Comment
Inflammation of the bone (osteomyelitis, osteitis) is uncommon in the B6C3F1/N mouse and F344/N rat. In rodents, inflammation of the bone is typically due to bacterial infection as a result of trauma, such as penetrating wounds or fracture, otitis media, or sinusitis. Inflammation of the periosteum (periostitis) and adjacent bone may occur in regions subjacent to ulceration of the skin and is often associated with reactive bone proliferation and granulation tissue. In many cases, inflammation of the bone (especially associated with staphylococcal infection) is associated with marked localized bone resorption ( Figure 1 and Figure 2 ) due to bacterial factors and increased osteoclastic activity, as well as regional reactive and hyperostotic bone response at the lesion margin as an attempt to localize the inflammatory process. Distinguishing hyperplasia of reactive bone and remodeling processes from an underlying neoplasm often may be difficult. In contrast to neoplastic bone, reactive bone is arranged in an orderly pattern, with bony trabeculae arranged perpendicular to the adjacent mature cortical bone and parallel to each other ( Figure 3 ). In reactive bone, osteoblasts are regularly interspersed along the surface of trabeculae. The type of inflammation in bone may depend on the cause and chronicity. In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous. In acute inflammation , the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation , but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate). Cell debris from the resident cell populations and infiltrating leukocytes; proteinic fluid containing fibrin, macrophages, lymphocytes, and/or plasma cells; and possibly an infectious agent may also be present within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and a mixed population of inflammatory cells, depending on the chronicity of the lesion. Chronic and chronic-active inflammation is determined by the presence of fibroblasts or fibrosis. With chronic inflammation , the predominant inflammatory cell is usually the lymphocyte, whereas chronic-active inflammation has a mixture of lymphocytes and neutrophils. Both lesions may also contain macrophages. However, it is the presence of fibroblasts or fibrosis that determines the chronic nature of the lesion. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells. In cases in which a bacterial infection becomes established in the bone, suppurative inflammation and necrotic cellular debris are often localized as an abscess or sequestrum in an attempt to wall off the inflammatory/infectious process ( Figure 2 ). Inflammation of the bone is not typically observed as a response to toxicologic exposures in routine toxicity and carcinogenicity bioassays under Good Laboratory Practice conditions. However, if increased incidences of osteomyelitis are observed, this may indicate issues with animal husbandry. In addition, any compound causing profound immunosuppression may impact an animal’s ability to respond to commensal pathogens, thus increasing susceptibility to infection.
Recommendation
Inflammation of bone should be diagnosed and given a severity grade. The character of inflammation (suppurative, granulomatous, etc.) should be part of the diagnosis. If inflammation of the bone is observed in conjunction with a primary traumatic injury (e.g., fracture, penetrating wound) or primary bone tumor, it should not be diagnosed but should be described in the narrative as a component of the primary lesion. However, in cases in which chronic inflammation has led to marked bony resorption and osteopenia with secondary fracture, inflammation should be recorded as the primary diagnosis, with a description of the secondary effects of marked bone resorption provided in the narrative. When recognized in concordance with other systemic inflammatory lesions, especially suppurative lesions (abscesses), the spectrum of lesions as a systemic condition should be recorded and described in the narrative. If inflammation of the bone is associated with treatment, the bones affected should be identified in the pathology narrative.
类骨质增多Increased Osteoid 骨其他
描述（中文）
类骨质增多（既往称为骨软化症）的特征是类骨质（osteoid）蓄积导致骨表面积增加（Figure 1、Figure 2）。沿现有骨表面可能出现增宽的类骨质缝。矿化缺陷导致均质、未矿化的类骨质蓄积。在大鼠中，多种抑制类骨质矿化的化合物已诱导出类骨质增多，包括双膦酸盐（bisphosphonates）、铝、镉、磷缺乏和维生素 D 毒性。它也可能在新生骨快速形成时被观察到；继发于快速新生骨形成的类骨质增多应与矿化原发性缺陷或破骨细胞性骨吸收抑制相鉴别。“骨软化症（osteomalacia）”一词历史上用于描述新形成类骨质矿化失败。然而，在描述上述病变时，首选“类骨质增多（increased osteoid）”而非“骨软化症”，因为后者表示骨的肉眼形态学改变（软化）。当生长板处发生骺板或骨骺软骨矿化延迟或不足时，不应将类骨质增多用作诊断。这更恰当地记录为骺板发育不良（佝偻病），其与类骨质增多的区别在于存在增厚的软骨性生长板和干骺端内滞留的软骨核心（见 Bone - Physeal Dysplasia），而非类骨质过多。
诊断建议
当存在时，类骨质增多应予以诊断并给出严重程度分级。当类骨质增多继发于骨增多时，不应诊断类骨质增多，但可在病理学描述中将其描述为骨增多的一个组成部分。相关链接：Bone - Physeal Dysplasia
参考切片图（2 张）
查看英文原文
Comment
An increase in the osteoid (previously called osteomalacia) is characterized by an increase in the surface area of bone by the accumulation of osteoid ( Figure 1 and Figure 2 ). There may be widened seams along existing surfaces of bone. Defective mineralization results in an accumulation of homogeneous, unmineralized osteoid. Increased osteoid has been induced in rats by various compounds that inhibit mineralization of osteoid, including bisphosphonates, aluminum, cadmium, phosphorus deficiency, and vitamin D toxicity. It may also be observed as new bone is rapidly being formed; increased osteoid secondary to rapid new bone formation should be differentiated from a primary defect in mineralization or inhibition of osteoclastic bone resorption. The term "osteomalacia" has historically been used to describe failure of newly formed osteoid to mineralize. However, when describing the above lesion, the term "increased osteoid" is preferred over "osteomalacia," since the latter denotes a gross morphologic change of bone (softening). Increased osteoid should not be used as a diagnosis for delayed or inadequate mineralization of physeal or epiphyseal cartilage when occurring at the growth plates. This is more appropriately recorded as physeal dysplasia (rickets) and differs from increased osteoid by the presence of thickened cartilaginous growth plates and retained cartilage cores within the metaphysis (see Bone - Physeal Dysplasia ) rather than excess osteoid.
Recommendation
When present, increased osteoid should be diagnosed and given a severity grade. Increased osteoid should not be diagnosed when it is secondary to increased bone, but it can be described in the pathology narrative as a component of increased bone. Related Links: Bone - Physeal Dysplasia
纤维性骨病变Fibro osseous Lesion 骨其他
描述（中文）
纤维骨性病变（fibro-osseous lesions，FOLs）常见于多种小鼠品系的胸骨节、椎骨、胫骨、股骨及其他骨骼。FOL 在 B6C3F1 小鼠中的发生率高于其他品系，并且是 B6C3F1 小鼠中最常见的原发性骨病变。该病变尚未在大鼠中报道。这些病变的特征是骨小梁和骨髓腔被纤维血管性间质部分或完全取代，该间质含有嵌入嗜酸性基质中的成纤维细胞、破骨细胞和成骨细胞（Figure 1、Figure 2）。其组织病理学特征与纤维性骨营养不良相似；然而，FOL 发生于无甲状旁腺或肾脏改变的情况下，通常以 局灶性（focal） 病变形式出现在干骺端或骨内膜区域（Figure 3），并可能进展累及更大范围的骨组织（Figure 4）。FOL 的发生率随年龄增长而增加，且最常发生于雌性小鼠（B6C3F1 雌性中发生率为 40–100%，雄性中 <1%），提示雌激素参与其中。这些病变常伴有与雌激素过多症相符的子宫或卵巢改变（子宫内膜囊性增生、阴道上皮细胞增生及角化过度、卵泡发育/闭锁及囊肿）。然而，这些病变也发生于卵巢切除的雌性小鼠和去势的雄性小鼠中。历史上，FOL 曾被冠以多种名称，包括纤维骨性发育不良、纤维性发育不良、局灶性 骨营养不良、骨发育不良、骨纤维化及骨营养不良，但这些病变的首选术语是“纤维骨性病变（fibro-osseous lesion）”。
诊断建议
尽管这是 B6C3F1 小鼠中相当常见的年龄相关背景病变，但 FOL 的发生率和严重程度可能受到具有雌激素效应的化合物处理的影响。因此，只要存在该病变，就应当作出诊断、给出严重程度分级，并在叙述中予以描述。小鼠中晚期 FOL 在组织学上与纤维性骨营养不良无法区分。因此，当在小鼠中观察到该病变处于晚期状态且无甲状旁腺或肾脏病变时，应当作出 FOL 的诊断。如果该病变与慢性肾脏疾病或增生性甲状旁腺病变同时发生，则应当作出纤维性骨营养不良的诊断（见 Bone - Fibrous Osteodystrophy）。相关链接：Bone - Fibrous Osteodystrophy
参考切片图（2 张）
查看英文原文
Comment
Fibro-osseous lesions (FOLs) arise commonly within the sternebrae, vertebrae, tibias, femurs, and other bones in a variety of mouse strains. The incidence of FOL is higher in B6C3F1 mice than in other strains, and it is the most common primary bone lesion in B6C3F1 mice. This lesion has not been reported in the rat. These lesions are characterized by partial or complete replacement of bony trabeculae and marrow cavity by fibrovascular stroma containing fibroblasts, osteoclasts, and osteoblasts embedded in eosinophilic matrix ( Figure 1 and Figure 2 ). The histopathologic features are similar to fibrous osteodystrophy; however, FOLs occur in the absence of parathyroid or renal alterations, typically arise as focal lesions within the metaphyseal or endocortical regions ( Figure 3 ), and may progress to involve larger areas of the bone ( Figure 4 ). FOL increases in incidence with age and arises most often in female mice (40–100% incidence in B6C3F1 females, <1% in males), suggesting involvement of estrogens. These lesions are often accompanied by alterations in the uterus or ovary consistent with hyperestrogenism (endometrial cystic hyperplasia, vaginal epithelial cell hyperplasia and hyperkeratosis, ovarian follicular development/atresia and cysts). However, these lesions also arise in ovariectomized female mice and castrated males. Historically, FOL has been referred to by a variety of names, including fibro-osseous dysplasia, fibrous dysplasia, focal osteodystrophy, osteodysplasia, osteofibrosis, and osteodystrophy, but the preferred term for these lesions is "fibro-osseous lesion."
Recommendation
Although this is a fairly common age-related background lesion in the B6C3F1 mouse, the incidence and severity of FOL may be influenced by treatment with compounds that possess estrogenic effects. Therefore, this lesion should be diagnosed, given a severity grade, and described in the narrative whenever present. Advanced FOL in mice is indistinguishable histologically from fibrous osteodystrophy. Therefore, when this lesion is observed in mice in an advanced state and in the absence of parathyroid or renal lesions, the diagnosis of FOL should be made. If the lesion occurs concurrently with chronic renal disease or proliferative parathyroid lesions, the diagnosis of fibrous osteodystrophy should be made (see Bone - Fibrous Osteodystrophy ). Related Links: Bone - Fibrous Osteodystrophy
纤维性骨营养不良Fibrous Osteodystrophy 骨其他
描述（中文）
纤维性骨营养不良（fibrous osteodystrophy，FOD）（Figure 1、Figure 2、Figure 3）（以前称为骨发育不良、纤维性结构不良和骨纤维化）的特征是松质骨或皮质骨的破骨细胞性吸收，并被疏松至成熟的纤维结缔组织所取代。该病变是一种代谢性骨病的结果，与甲状旁腺功能亢进同时发生，无论是由功能性甲状旁腺肿瘤（原发性）还是慢性肾脏疾病（继发性）所致。原发性主细胞瘤在啮齿类动物中非常罕见且通常无功能，最常见的是，FOD 作为继发性甲状旁腺功能亢进伴随慢性进行性肾病的后果而发生。慢性进行性肾病可因各种化学物的处理而加重，导致继发性甲状旁腺功能亢进、FOD 以及包括心脏、主动脉和其他软组织在内的多种器官的转移性钙化。早期 FOD 病变的特征是受累骨呈虫蚀状外观，破骨细胞数量增加以及成熟骨的“扇贝样”改变（Figure 3），最终进展为被纤维结缔组织和未成熟类骨质所取代（Figure 1、Figure 2）。FOD 在 B6C3F1 小鼠中的发生率较低（雌性 1%，雄性 0%），这是由于该品系慢性肾衰竭的发生率较低。
诊断建议
已显示若干 NTP 化合物可因大鼠的慢性进行性肾病而诱导甲状旁腺增生，因此，FOD 可能是化合物诱导的病变。因此，尽管它可以是患有慢性进行性肾病的老年大鼠的背景病变，但在发生率或严重程度呈剂量相关增加的研究中，FOD 应被报告并给予严重程度分级。该病变应诊断为 FOD，而不是分别诊断该病变的各个组成部分（例如，骨减少、纤维化）。相关链接：骨 - 纤维骨性病变
参考切片图（2 张）
查看英文原文
Comment
Fibrous osteodystrophy (FOD) ( Figure 1 , Figure 2 , and Figure 3 ) (previously referred to as osteodysplasia, fibrous dysplasia, and osteofibrosis) is characterized by osteoclastic resorption of cancellous or cortical bone, with replacement by loose to mature fibrous connective tissue. This lesion is the result of a metabolic bone disease that occurs in conjunction with hyperparathyroidism, whether due to a functional parathyroid tumor (primary) or chronic renal disease (secondary). Primary chief cell tumors are very uncommon and usually nonfunctional in rodents, and most often, FOD occurs as a result of secondary hyperparathyroidism in conjunction with chronic progressive nephropathy. Exacerbation of chronic progressive nephropathy may result from treatment by various chemicals, leading to secondary hyperparathyroidism, FOD, and metastatic calcification of various organs, including the heart, aorta, and other soft tissues. Early FOD lesions are characterized by a moth-eaten appearance of the affected bone, with increased osteoclast numbers and "scalloping" of mature bone ( Figure 3 ), eventually progressing to replacement by fibrous connective tissue and immature osteoid ( Figure 1 and Figure 2 ). The incidence of FOD is low in B6C3F1 mice (1% in females, 0% in males) due to the low incidence of chronic renal failure in this strain.
Recommendation
Several NTP compounds have been shown to induce parathyroid hyperplasia as a result of chronic progressive nephropathy in rats, and as such, FOD may be a compound-induced lesion. Therefore, although it can be a background lesion in aged rats with chronic progressive nephropathy, FOD should be reported and given a severity grade in studies in which there is a dose-related increase in incidence or severity. This lesion should be diagnosed as FOD rather than diagnosing the components of the lesion separately (e.g., decreased bone, fibrosis). Related Links: Bone - Fibro-osseous Lesion
骨减少Decreased Bone 骨其他
描述（中文）
骨量减少可由骨形成减少或原有骨吸收增加所致。该病变的特征为骨小梁变薄或缺失和/或骨皮质变薄（Figure 1、Figure 2、Figure 3、Figure 4）。可见微骨折。在伴有活跃骨吸收的病变中，沿骨小梁呈扇贝状、不规则表面可见破骨细胞数量增多，这代表破骨细胞对 Howship 陷窝（吸收陷窝）的作用。弥漫性骨量减少可能由代谢紊乱所致，而局灶性骨量减少可能由骨内局灶性发生的病理过程所致，如纤维骨性病变或骨髓炎。废用（萎缩），如受伤肢体或关节的情况，可导致特定骨内弥漫性骨量减少。多种化合物的治疗与骨生长减弱相关，包括大鼠中因糖皮质激素毒性对破骨细胞活性的影响所致的干骺端骨小梁减少，以及小鼠中因对软骨形成和软骨内骨化的影响所致者。甲状腺功能亢进与因破骨细胞生成和骨吸收增加所致的皮质骨和髓质骨变薄相关。膳食因素如维生素/矿物质和蛋白质摄入可显著影响骨生长；膳食蛋白质水平低导致骨缩短，而导致因饥饿所致体重下降的毒物可引起以干骺端骨小梁丢失及骺板变窄和变形为特征的骨病变。在老龄繁殖动物中，由于妊娠对钙和蛋白质需求增加，也可观察到髓质骨小梁丢失。该病变也曾被记录为萎缩、骨质疏松、骨量减少和吸收，但更通用的术语“骨量减少”更为可取。不建议使用术语“骨质疏松”，因为其在人类医学中具有更具体的定义，即与全身性年龄相关或激素相关骨密度丢失相关的临床状况。在人类中，骨量减少被认为是骨质疏松的前驱病变/状况，其中骨内蛋白质发生改变并伴有明显的骨量减少，与骨折风险增加相关。
诊断建议
“骨 - 骨量减少”当作为原发性病变发生时应当诊断并赋予严重程度分级。病变的位置（包括特定骨及骨内位置，例如干骺端）应在病理学叙述中描述。如有可能，病变过程的特征也应在叙述中讨论。
参考切片图（2 张）
查看英文原文
Comment
Decreased bone can result from either decreased bone formation or increased resorption of preexisting bone. The lesion is characterized by thin or absent bony trabeculae and/or thin cortices ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Microfractures may be observed. In lesions with active bone resorption, there are increased numbers of osteoclasts along a scalloped, irregular surface of trabecular bone, which represent osteoclastic effects on Howship''s lacunae (resorption bays). A diffuse decrease in bone may result from metabolic disturbances, whereas a focal decrease in bone may result from a pathologic process occurring focally within a bone, such as fibro-osseous lesion or osteomyelitis. Disuse (atrophy), as in the case of injured limbs or joints, may lead to a diffuse decrease within a particular bone. Treatment with various compounds has been associated with diminished bone growth, including a decrease of metaphyseal trabeculae in corticosteroid toxicity due to effects on osteoclastic activity in rats and chondrogenesis and enchondral ossification in mice. Hyperthyroidism has been associated with thinning of cortical and medullary bone due to increased osteoclastogenesis and bone resorption. Dietary factors such as vitamin/mineral and protein intake can significantly influence bone growth; low levels of dietary protein lead to bone shortening, and toxicants that lead to decreases in body weight due to inanition can cause bone lesions characterized by loss of metaphyseal trabeculae and a narrowed and distorted physis. Loss of medullary trabeculae may also be observed in aged breeding animals due to increased calcium and protein requirements of pregnancy. This lesion has also been recorded as atrophy, osteoporosis, osteopenia, and resorption, but the more general term, "decreased bone," is preferred. The term "osteoporosis" is not recommended due to its more specific definition in human medicine as a clinical condition related to a generalized age-related or hormone-related loss of bone density. In humans, osteopenia is referred to as a precursor lesion/condition to osteoporosis, in which there is alteration of the proteins in bone and marked osteopenia, associated with increased risk of bone fracture.
Recommendation
"Bone - Decreased bone" should be diagnosed and assigned a severity grade when it occurs as a primary lesion. The location of the lesion (both the particular bone and the location within the bone, e.g., metaphysis) should be described in the pathology narrative. A characterization of the process, if possible, should also be discussed in the narrative.
骨增多Increased Bone 骨其他
描述（中文）
骨量增多（Increased bone）定义为正常骨的过度生长。该病变的特征是成熟皮质骨（cortical bone，致密骨）和松质骨（cancellous bone，骨小梁、海绵骨）形成量增加，导致皮质骨和骨小梁普遍性增厚、骨髓腔缩小（Figure 1、Figure 2）。骨量增多源于破骨细胞（osteoclast）介导的骨吸收减少或成骨细胞（osteoblast）介导的骨形成增加。目前用于描述骨的非肿瘤性增殖的术语往往混乱且不一致，同一病变被描述为骨质增生症（hyperostosis）、骨增生（bony hyperplasia）、骨硬化症（osteopetrosis）、骨硬化（osteosclerosis）、反应性骨（reactive bone）、骨增殖（bony proliferation）和外生骨疣（exostoses）。推荐使用“骨量增多”这一术语，以避免命名上的冗余以及研究结果解释中的混淆。虽然作为治疗相关效应罕见观察到，但骨量增多是老年F344大鼠中偶尔可见的背景性病变，雌性比雄性更常受累。该病变更常累及颅骨而非长骨，导致骨髓腔缩小或消失，颅骨和鼻甲骨显著增厚且致密。在大鼠中，雌激素毒性导致干骺端骨小梁的骨吸收减少，引起髓质骨致密增厚及骨整体长度缩短。据报道，在涉及鼻腔慢性炎症的长期研究中，鼻腔鼻甲可出现骨量增多（Figure 3、Figure 4）。当少量纤维结缔组织沿骨质增生骨的骨小梁沉积时，错误地使用了“纤维性骨营养不良（fibrous osteodystrophy）”这一术语。纤维性骨营养不良与成熟骨的丢失相关，因此当存在骨沉积增加时不应作出该诊断。相反，在许多病例中，这种纤维化成分是骨量增多的正常组成成分。
诊断建议
虽然骨量增多通常是一种背景性病变，但应作出诊断并给出严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Increased bone is defined as excessive growth of normal bone. The lesion is characterized by increased amounts of mature cortical (compact) and cancellous (trabecular, spongy) bone formation, resulting in generalized thickening of the cortices and trabeculae with diminution of marrow spaces ( Figure 1 and Figure 2 ). Increased bone results from either decreased resorption of bone by osteoclasts or increased bone formation by osteoblasts. The current terminology used to describe the nonneoplastic proliferation of bone is often confusing and inconsistent, with the same lesion being described as hyperostosis, bony hyperplasia, osteopetrosis, osterosclerosis, reactive bone, bony proliferation, and exostoses. The use of the term "increased bone" is recommended to prevent redundancy in the nomenclature and confusion in interpretation of study findings. While rarely observed as a treatment-related effect, an increased amount of bone is an occasional background lesion seen in aged F344 rats, with females more commonly affected than males. This lesion more commonly affects the cranium than the long bones and results in diminished or nonexistent marrow cavities and markedly thickened and dense cranial and nasal turbinate bones. In rats, estrogen toxicity results in decreased bone resorption from metaphyseal trabeculae, leading to densely thickened medullary bone and overall shortened length of the bone. Increased bone in the nasal cavity turbinates has been reported to occur in long-term studies involving chronic inflammation of the nasal cavity ( Figure 3 and Figure 4 ). The term "fibrous osteodystrophy" is incorrectly used when there are small amounts of fibrous connective tissue deposited along trabeculae of hyperostotic bone. Fibrous osteodystrophy is associated with loss of mature bone and thus should not be diagnosed when there is increased deposition of bone. Rather, this fibrotic component is a normal constituent of an increase in bone in many cases.
Recommendation
While it is usually a background lesion, increased bone should be diagnosed and given a severity grade.
骨折Fracture 骨其他
描述（中文）
骨折（Figure 1、Figure 2）的特征是皮质骨不连续和/或髓质骨小梁中断（微骨折）。根据病变的严重程度和慢性程度，骨折常伴有不同程度的出血、炎症和纤维化。在急性骨折中，大量出血是常见的，随着慢性化，炎症细胞数量增加并引发纤维组织反应，最终形成机化性纤维化、骨重塑并通过骨痂形成进行修复。骨折可能继发于严重的炎症性、肿瘤性或代谢性疾病。骨折也已被注意到继发于由某些化合物治疗引起的骨病。例如，过量的维生素A治疗导致大鼠骨形成减少和退行性骺板病变，从而导致纵向骨生长减少。偶尔，切片伪影可能表现为骨折，必须与真性骨折相鉴别。伪影性骨折，或假性骨折，将缺乏真性骨折中可能见到的出血、纤维蛋白沉积、纤维化和骨痂形成。
诊断建议
原发性骨折存在时应予以诊断，但无需分级。当骨折继发于其他病症时，如肿瘤、炎症或代谢性疾病，则不应诊断，而应在病理学叙述中描述为原发病变成分及其严重程度的指征。微骨折无需诊断，但应在叙述中作为其伴随的原发病变成分加以讨论。
参考切片图（2 张）
查看英文原文
Comment
Bone fractures ( Figure 1 and Figure 2 ) are characterized by discontinuity of cortical bone and/or disruption of medullary trabeculae (microfracture). They are often associated with variable hemorrhage, inflammation, and fibrosis, depending on the severity and chronicity of the lesion. In acute fractures large amounts of hemorrhage are common, and with chronicity increased numbers of inflammatory cells and fibrous tissue response are elicited, with eventual organized fibrosis, bony remodeling, and repair through callus formation. Fractures may be secondary to severe inflammatory, neoplastic, or metabolic disease. Fractures have been also noted secondary to bone disease due to treatment with some compounds. For example, excessive vitamin A treatment leads to decreased bone formation and degenerative physeal lesions in rats, which result in decreased longitudinal bone growth. Occasionally, sectioning artifacts can appear as fractures and must be differentiated from true fractures. Artifactual fractures, or pseudofractures, will lack the hemorrhage, fibrin deposition, fibrosis, and callus formation that might be seen with a true fracture.
Recommendation
Primary fractures should be diagnosed when present but need not be graded. When a fracture is secondary to another condition, such as neoplasia, inflammation, or metabolic disease, it should not be diagnosed but should be described in the pathology narrative as a component and indication of the severity of the primary lesion. Microfractures need not be diagnosed but should be discussed in the narrative as a component of the primary lesion with which they occur.
骨痂Callus 骨其他
描述（中文）
骨折后不久，随着出血的消退，骨折部位邻近的成纤维细胞开始增殖并形成疏松的肉芽组织（Figure 1、Figure 2、Figure 3）。肉芽组织形成后，骨折部位内以及沿骨膜分布的成纤维细胞分化为成软骨细胞，形成透明软骨，而位于骨折部位远端的成纤维细胞则分化为成骨细胞，形成编织骨。随着这些组织群体形成桥接骨折部位的新生结缔组织团块，骨痂即告形成。骨痂形成后，透明软骨和纤维组织通过现有胶原基质的矿化而被骨小梁取代（Figure 4）。在重塑阶段，骨痂和板层骨沉积被塑形以贴合原有骨结构。一般而言，在因肿瘤、持续存在的炎症或感染性疾病或代谢性骨病所致的继发性骨折病例中，骨折骨痂是不完整的或紊乱的。
诊断建议
骨——骨痂，观察到时，应当诊断但不进行分级。当与继发于肿瘤、持续存在的炎症或感染或代谢性疾病的骨折同时观察到时，骨折骨痂不应诊断，但应在叙述中讨论。相关病变，如炎症或纤维化，除非其严重程度足以支持，否则不应单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Shortly after fracture and resolution of hemorrhage, fibroblasts adjacent to the fracture site begin to replicate and form loose granulation tissue ( Figure 1 , Figure 2 , and Figure 3 ). Following granulation tissue formation, fibroblasts within the fracture site, as well as along the periosteum, differentiate into chondroblasts to form hyaline cartilage, while those distal to the fracture site develop into osteoblasts to form woven bone. As these populations of tissue form a new mass of connective tissue bridging the fracture site, a callus is formed. Following callus formation, hyaline cartilage and fibrous tissue are replaced by trabecular bone through mineralization of existing collagenous matrix ( Figure 4 ). During a remodeling phase, the callus and lamellar bone deposition is contoured to the original bone structure. Generally, fracture callus is incomplete or disordered in cases of secondary fracture due to neoplasia, ongoing inflammatory or infectious disease, or metabolic bone disease.
Recommendation
Bone - callus, when observed, should be diagnosed but not graded. When observed in conjunction with a fracture secondary to neoplasia, ongoing inflammation or infection, or metabolic disease, fracture callus should not be diagnosed but should be discussed in the narrative. Associated lesions, such as inflammation or fibrosis, should not be diagnosed separately unless warranted by their severity.
骨软骨病Osteochondrosis 骨其他
描述（中文）
骨软骨病（osteochondrosis）（Figure 1）被定义为软骨内骨化的局灶性（focal）性障碍。该病变的特征是关节软骨局灶性性增厚，并伴有软骨向软骨下骨延伸。软骨肥大由矿化缺陷和软骨吸收减少所致，导致增大的软骨细胞持续存在。裂隙在增厚软骨的基底层内形成，并且在这些裂隙下方发生纤维性结缔组织增生。最终，软骨发生分离，形成关节瓣。该病变可进展为软骨下骨塌陷所致的关节软骨糜烂。骨软骨病发生于多种家养动物，主要作为年轻、快速生长动物的病变，并被认为受饮食、激素、解剖和遗传因素影响。骨软骨病在老年大鼠中作为自发性病变发生，尽管病变可能在生命早期散发性出现。骨软骨病的早期组织学证据包括关节软骨基底层的增厚或碎裂，并可在Sprague-Dawley大鼠中早至六周龄时观察到。该病变倾向于发生在关节软骨较厚的区域，例如股骨内侧髁和肱骨头的尾侧。骨软骨病的病变本质上是局灶性的，尽管它们可能在同一动物中multifocally或双侧发生。历史上，骨软骨病也曾被记录为骨软骨炎（osteochondritis）和分离性骨软骨炎（osteochondritis dissecans）。术语“osteochondritis”不恰当，因为炎症不是该病变的特征性表现。术语“dissecans”不恰当，因为它意味着贯穿关节软骨的裂隙形成，而骨软骨病是一系列组织学特征，裂隙形成是终末期或进展性表现。
诊断建议
尽管骨软骨病是一种自发性病变，但无论何时存在，都应予以诊断并给出严重程度分级。
参考切片图（1 张）
查看英文原文
Comment
Osteochondrosis ( Figure 1 ) is defined as a focal disturbance of enchondral ossification. The lesion is characterized by focal thickening of articular cartilage with extension of the cartilage into the subchondral bone. Hypertrophy of cartilage results from defective mineralization and decreased cartilage resorption, leading to a persistence of enlarged chondrocytes. Fissures form within the basal layers of the thickened cartilage, and fibrous connective tissue proliferation occurs subjacent to these fissures. Eventually, separation of the cartilage occurs, with formation of an articular flap. The lesion may progress to erosion of articular cartilage due to subchondral bone collapse. Osteochondrosis occurs in a variety of domestic species, primarily as a lesion of young, rapidly growing animals, and is thought to be influenced by dietary, hormonal, anatomic, and genetic factors. Osteochondrosis occurs as a spontaneous lesion in aged rats, although lesions may sporadically occur earlier in life. Early histologic evidence of osteochondrosis includes thickening or fragmentation of the basal layer of articular cartilage and may be observed in Sprague-Dawley rats as early as six weeks of age. This lesion tends to occur in regions of articular cartilage that are thicker, such as the caudal aspect of the medial femoral condyles and humeral head. Lesions of osteochondrosis are focal in nature, although they may occur multifocally or bilaterally in the same animal. Historically, osteochondrosis has also been recorded as osteochondritis and osteochondritis dissecans. The term "osteochondritis" is not appropriate since inflammation is not a characteristic feature of the lesion. The term "dissecans" is inappropriate since it implies cleft formation through the articular cartilage, while osteochondrosis is a spectrum of histologic features, cleft formation being an end-stage or progressed manifestation.
Recommendation
Although osteochondrosis is a spontaneous lesion, it should be diagnosed and given a severity grade whenever present.
骺板发育不良Physeal Dysplasia 骨其他
描述（中文）
骨骺软骨发育不良（dysplasia）（Figure 1、Figure 2）由矿化缺陷和软骨吸收减少所致。抑制血管长入骨骺的药物可导致骨骺增厚和发育不良（Figure 1）；这是软骨吸收减少的一个示例。这导致增大的软骨细胞持续存在（Figure 2）以及肥厚带扩大，从而使生长板中央显著增宽、外周边缘逐渐变细。在大鼠的晚期病变中，骨骺变得不规则，未矿化软骨的增大延伸部深入干骺端内。病变最常见于生长最快的骨骼，包括桡骨、胫骨、跖骨和掌骨。当存在全身性矿化缺陷时，未矿化类骨质增多（hyperosteoidosis）可能是晚期病变的组成部分。在大鼠中，可沿肋骨外侧缘形成“佝偻病串珠（rachitic rosary）”，即显著增大的肋软骨交界。骨骺发育不良可作为营养缺乏、代谢性疾病或化学暴露继发矿化障碍的结果而发生。当这些病变由矿化过程中的营养障碍（维生素 D、钙或磷缺乏）所致，尤其是在生长板处时，被称为佝偻病（rickets）。通常，“骨软化（osteomalacia）”一词曾被用于描述骨骺软骨的矿化缺陷；然而，这并不是首选的命名，因为“骨软化”（见 Bone - Increased Osteoid）用于描述未矿化骨基质（类骨质）增多，导致骨小梁普遍增厚和骨密度总体降低，而不是像骨骺发育不良中所见的那样，表现为骨骺或骺软骨矿化延迟或受损。此外，“骨软化”一词表示大体形态学改变，应被认为不适用于组织学特征描述。干扰钙、磷或维生素 D 代谢的化合物可导致矿化障碍。软骨发育不良也可由化学暴露或代谢障碍诱导的矿化缺陷所致。
诊断建议
骨骺发育不良应予以记录并给出严重程度分级。可在描述中尝试将这些病变与营养性（佝偻病）、代谢性或化合物相关病因联系起来。相关链接：Bone - Increased Osteoid
参考切片图（2 张）
查看英文原文
Comment
Dysplasia of physeal cartilage ( Figure 1 and Figure 2 ) results from defective mineralization and decreased cartilage resorption. Pharmaceutical agents that inhibit vascular penetration of the physis can lead to physeal thickening and dysplasia ( Figure 1 ); this is an example of decreased cartilage resorption. This leads to a persistence of enlarged chondrocytes ( Figure 2 ) and an enlarged zone of hypertrophy, resulting in a growth plate that is markedly widened centrally and tapered at the peripheral margins. In advanced lesions in the rat, the physes become irregular, with enlarged extensions of unmineralized cartilage extending deep within the metaphysis. Lesions are most prevalent in the fastest-growing bones, including the radius, tibia, metatarsals, and metacarpals. Increased amounts of unmineralized osteoid (hyperosteoidosis) may be a component of advanced lesions when a systemic defect in mineralization is present. In rats, the formation of a "rachitic rosary," or markedly enlarged costochondral junctions, may occur along the lateral margins of the ribs. Physeal dysplasia may occur as a result of disturbances in mineralization secondary to nutritional deficiencies, metabolic disease, or chemical exposure. When these lesions occur as a result of a nutritional disturbance (deficiency in vitamin D, calcium, or phosphorus) in mineralization, particularly at the growth plate, they are referred to as rickets. Often, the term "osteomalacia" has been used to describe defective mineralization of epiphyseal cartilage; however, this is not the preferred nomenclature, since "osteomalacia" (see Bone - Increased Osteoid ) is used to describe increased amounts of unmineralized bone matrix (osteoid) causing generalized thickening of bony trabeculae, and an overall decrease in bone density, rather than delayed or impaired mineralization of physeal or epiphyseal cartilage, as seen in physeal dysplasia. Furthermore, the term "osteomalacia" denotes a gross morphologic change and should be considered inappropriate for histologic characterization. Compounds interfering with calcium, phosphorus, or vitamin D metabolism may result in disturbances in mineralization. Dysplasia of cartilage may also result from defective mineralization induced by chemical exposure or metabolic disturbances.
Recommendation
Physeal dysplasia should be recorded and given a severity grade. An attempt to associate these lesions with nutritional (rickets), metabolic, or compound-related etiologies can be made in the narrative. Related Links: Bone - Increased Osteoid
再生Regeneration 骨骼肌其他
描述（中文）
再生骨骼肌纤维的组织学特征为存在明显的（活化的）星状细胞、成排的内部肌母细胞核以及胞质嗜碱性（Figure 1、Figure 2）。虽然在大多数物种中，内部核在再生早期倾向于向周边迁移，但啮齿类动物往往会在一定时间内保留其内部核。这可作为先前发生过坏死和再生的纤维的标志。这些纤维常常失去活跃再生的肌管所特有的嗜碱性染色（Figure 3、Figure 4）。再生肌纤维通常存在于活动性坏死或变性区域内或附近，而再生的程度会受到损伤性刺激与样本采集之间间隔时间长短的影响。在先前或同时不存在肌毒性情况下出现的偶见成排细胞核，很可能反映背景性的细胞更新和修复，不需要作出诊断。营养性、劳力性和中毒性肌病可导致大范围的肌肉损伤；然而，修复往往极为有效。相比之下，缺血所致损伤后的修复过程往往无效。这很可能是由于卫星细胞和肌内膜细胞随后死亡所致。常导致大范围的纤维化。
诊断建议
当再生超过背景水平时，应记录并进行分级。当再生与伴随的肌纤维变性相关时，除非严重程度需要，否则不需要单独记录，但应在病理学叙述中加以描述。伴随的肌病性改变，如炎症或纤维化，在严重程度需要时也应单独记录并进行分级。相关链接：骨骼肌 - 坏死
参考切片图（2 张）
查看英文原文
Comment
Regenerating skeletal muscle fibers are histologically characterized by the presence of prominent (activated) stellate cells, rows of internal myoblast nuclei, and cytoplasmic basophilia ( Figure 1 and Figure 2 ). While in most species internal nuclei tend to peripheralize early in regeneration, rodents tend to retain their internal nuclei for some time. This can serve as a marker for fibers that had previously undergone necrosis and regeneration. These fibers often lose the characteristic basophilic staining of an actively regenerating myotube ( Figure 3 and Figure 4 ). Regenerating myofibers are commonly present within or near areas of active necrosis or degeneration, and the degree of regeneration present will be influenced by the amount of time that has passed between the injurious stimulus and sample collection. Occasional rowing of nuclei in the absence of prior or concurrent myotoxicity likely reflects background cellular turnover and repair and does not warrant a diagnosis. Nutritional, exertional, and toxic myopathies can result in extensive regions of muscle damage; however, repair is often extremely effective. In contrast, the reparative process following damage due to ischemia is often ineffective. This is likely due to the subsequent death of the satellite cells and endomysial cells. Extensive regions of fibrosis often result.
Recommendation
Regeneration should be recorded and graded when above background levels. When regeneration is associated with concomitant myofiber degeneration, it does not need to be recorded separately unless warranted by severity, but it should be described in the pathology narrative. Concurrent myopathic changes, such as inflammation or fibrosis, should also be recorded and graded separately when warranted by severity. Related Links: Skeletal Muscle - Necrosis
出血Hemorrhage 骨骼肌出血
描述（中文）
肌肉内出血与其他组织中的出血一样，在组织学上以血液在血管外积聚为特征，就骨骼肌而言，积聚的血液分离并包绕（Figure 1、Figure 2、Figure 3）相邻的肌纤维，在某些情况下还会使其结构消失（Figure 4）。根据病变的原因和严重程度，受累区域的肌纤维可能相对不受影响（Figure 1、Figure 2、Figure 3），也可能发生变性和/或坏死性改变。病变范围可从局灶性（focal）、离散到广泛、弥漫。出血区域内出现含铁血黄素负载的巨噬细胞（Figure 5、Figure 6）提示存在一定程度的慢性化。肌内出血通常发生于肌肉受到损伤之后，如钝性创伤、肌内注射（注射部位）或炎症。原发性血管病变，如动脉瘤和血管炎，以及血小板或凝血因子异常，也可导致肌内出血。
诊断建议
当肌内出血作为原发性且显著的变化存在时，应予以诊断，并根据病变范围赋予严重程度分级。病理学家应全面评估组织，以尽可能确定出血的原发原因（例如原发性血管病变、创伤证据）。继发性肌病性改变无需单独记录，除非其严重程度足以需要记录，但应在病理学叙述中予以描述。
参考切片图（2 张）
查看英文原文
Comment
Hemorrhage in muscle, as in other tissues, is histologically characterized by the extravascular accumulation of blood, which in the case of skeletal muscle separates and surrounds ( Figure 1 , Figure 2 , and Figure 3 ), and in some instances effaces ( Figure 4 ), adjacent muscle fibers. Depending upon the cause and severity of the lesion, myofibers in affected regions may remain relatively unaffected ( Figure 1 , Figure 2 , and Figure 3 ) or undergo degenerative and/or necrotic changes ( Figure 4 ). Lesions can range from focal and discrete to extensive and widespread. The presence of hemosiderin-laden macrophages within a region of hemorrhage ( Figure 5 and Figure 6 ) implies some degree of chronicity. Intramuscular hemorrhage typically occurs following an insult to the muscle, such as blunt trauma, intramuscular injection (injection site), or inflammation. Primary vascular lesions, such as aneurysms and vasculitis, and abnormalities in platelets or coagulation factors can also result in intramuscular hemorrhage.
Recommendation
When present as a primary and significant change, intramuscular hemorrhage should be diagnosed and assigned a severity grade based on the extent of the lesion. The pathologist should thoroughly evaluate the tissue in an attempt to determine the primary cause of the hemorrhage (e.g., primary vascular lesions, evidence of trauma). Secondary myopathic changes do not need to be recorded separately unless warranted by severity but should be described in the pathology narrative.
变性Degeneration 骨骼肌变性
描述（中文）
变性的肌肉在大体上可表现为苍白或暗色。在组织学上，变性的肌纤维可表现出多种显微镜下变化，包括细胞肿胀、嗜酸性增强（hypereosinophilia）、空泡化、横纹消失、碎裂和纤维断裂（Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6、Figure 7）。断裂的纤维通常可通过“回缩帽”（retraction caps）的存在来识别，回缩帽是断裂纤维游离端的凹陷。巨噬细胞常可见与变性肌纤维密切相伴，因为它们在吞噬相关碎片中发挥重要作用（Figure 4）。由于肌纤维较长，变性通常仅累及纤维的一个或数个节段，而非整个肌纤维。变性区域可不同程度地伴有其他肌病性改变，如坏死、萎缩、代偿性肥大、再生和纤维化（Figure 5）。无论病因如何，变性都是肌纤维损伤的常见后果。常见病因包括化学刺激物/肌毒素、代谢异常、创伤和感染。与其他组织一样，变性可以是可逆的；然而，如果损伤性刺激持续存在，将达到“不可逆点”（point of no return）。当这种情况发生时，变性过程变为不可逆，随后出现肌纤维坏死。变性和坏死代表一个连续的病变谱系，因此在一个给定病变中二者常同时存在。由于骨骼肌反应方式有限，它们具有相似的形态学特征，因此在组织学上可能难以区分。这会造成诊断上的困难。在评估毒性研究时，病理学家必须为这两种病变建立明确的判定标准，并在应用时保持一致和审慎。标准应在叙述中加以描述。“肌病”（myopathy）一词通常用于描述以变性和坏死为关键特征的骨骼肌疾病。然而，由于肌病是一个通用术语，且通常涵盖一组病变而非某一独立病变，因此不建议使用该词。
诊断建议
当存在时，肌纤维变性应予以诊断并分级。如果一项研究中同时存在变性和坏死，应诊断占优势的病变，并在病理学叙述中描述另一病变。然而，如果同时记录两种病变最能描述所发生的变化，病理学家可以记录两者。伴随的再生应单独记录，当其存在达到显著程度时赋予严重程度分级。其他继发性病变，如炎症和出血，除非严重程度确有必要，否则不应单独诊断，但应在叙述中描述。相关链接：骨骼肌 - 坏死
参考切片图（2 张）
查看英文原文
Comment
Degenerated muscle can grossly appear either pale or dark. Histologically, degenerating myofibers can exhibit a variety of microscopic changes, including cell swelling, hypereosinophilia, vacuolation, loss of striation, fragmentation, and rupture of fibers ( Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 , and Figure 7 ). Ruptured fibers can often be identified by the presence of "retraction caps," which are concavities at the free ends of the ruptured fibers. Macrophages are often noted in close association with degenerating myofibers, as they play an important role in phagocytizing associated debris ( Figure 4 ). Due to the long length of muscle fibers, degeneration often only affects a segment or several segments of the fiber, as opposed to the entire myofiber. Regions of degeneration can be variably accompanied by additional myopathic changes, such as necrosis, atrophy, compensatory hypertrophy, regeneration, and fibrosis ( Figure 5 ). Degeneration is a common sequela of myofiber injury, regardless of the cause. Common causes include chemical irritants/myotoxins, abnormal metabolism, trauma, and infection. As in other tissues, degeneration can be reversible; however, if the injurious stimulus persists, a "point of no return" will be reached. When this occurs, the degenerative process becomes irreversible and myofiber necrosis follows. Degeneration and necrosis represent a continuum of lesions and therefore are often both present within a given lesion. Due to the limited repertoire of skeletal muscle responses, they share similar morphologic features and can thus be difficult to differentiate histologically. This can create a diagnostic challenge. When evaluating a toxicity study, it is important for the pathologist to establish distinct criteria for both lesions and to be consistent and careful when applying them. Criteria should be described in the narrative. The term "myopathy" is commonly used to describe disorders of skeletal muscle in which degeneration and necrosis are key features. However, since myopathy is a general term and one that typically encompasses a collection of lesions rather than one distinct lesion, its use is not recommended.
Recommendation
When present, myofiber degeneration should be diagnosed and graded. If both degeneration and necrosis are present in a study, the predominant lesion should be diagnosed and the other described in the pathology narrative. However, the pathologist may record both lesions if it best describes the changes that are occurring. Concomitant regeneration should be recorded separately and assigned a severity grade when present to a significant extent. Other secondary lesions, such as inflammation and hemorrhage, should not be diagnosed separately unless warranted by severity but should be described in the narrative. Related Links: Skeletal Muscle - Necrosis
囊肿Cyst 骨骼肌囊肿
描述（中文）
骨骼肌内可发生上皮衬覆的囊肿（Figure 1、Figure 2、Figure 3、Figure 4）。根据其大小，可发生相邻肌纤维的压迫。囊性结构可为空虚，或含有数量不等的角蛋白、毛发碎片和/或细胞碎片。关节是囊性病变发生的常见部位；然而，滑膜囊肿在这些区域更为常见。滑膜囊肿由滑膜细胞衬覆，含液体，并可能与相邻关节相通。寄生虫性囊肿有时存在于骨骼肌内。虽然鼠肉孢子虫（Sarcocystis muris）确实感染大鼠和小鼠的骨骼肌，但在管理良好的啮齿动物种群中并不常见，且通常不伴有炎症。若存在伴随病变，其性质主要为退行性。
诊断建议
虽然骨骼肌囊肿常为偶然性病变，但其存在应当记录。不需要赋予严重程度分级。伴随的肌病性改变不需要单独诊断，除非严重程度确有必要。应在描述中说明衬覆细胞的性质、腔内容物的存在及性质，以及对相邻骨骼肌纤维的局部影响。
参考切片图（2 张）
查看英文原文
Comment
Epithelium-lined cysts can develop in skeletal muscle ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Depending upon their size, compression of adjacent myofibers can occur. The cystic structures can be empty or contain variable amounts of keratin, hair fragments, and/or cellular debris. Joints are a common place for cystic lesions to occur; however, synovial cysts are more common in these regions. Synovial cysts are lined with synovial cells, contain fluid, and may communicate with the adjacent joint. Parasitic cysts are sometimes present within skeletal muscle. While Sarcocystis muris does infect skeletal muscle in rats and mice, it is not common in well-managed rodent colonies and is generally not associated with accompanying inflammation. If accompanying lesions are present, they are primarily degenerative in nature.
Recommendation
While skeletal muscle cysts are often incidental lesions, their presence should be recorded. A severity grade does not need to be assigned. Accompanying myopathic changes do not need to be diagnosed separately unless warranted by severity. The nature of the lining cells, presence and nature of luminal contents, and regional effects on adjacent skeletal muscle fibers should be addressed in the narrative.
坏死Necrosis 骨骼肌坏死
描述（中文）
多种类型的损伤，包括创伤、缺血、感染因子和肌毒素，均可引起肌纤维坏死。肌纤维坏死（myonecrosis）的组织学特征为肿胀、深嗜酸性、均质化的肌纤维，横纹消失（透明化）。受累纤维常呈空泡化并碎裂，伴核固缩（Figure 1）。常并发炎症。营养不良性矿化（Figure 2、Figure 3）也可发生。肌纤维变性和再生的不同阶段也常同时存在（见 Skeletal Muscle - Degeneration 和 Skeletal Muscle - Regeneration）。变性和坏死代表病变的一个连续过程，因此二者常同时存在于同一病变中。由于骨骼肌反应方式有限，二者具有相似的形态学特征，因而在组织学上难以区分。这会给诊断带来挑战。在评价毒性研究时，病理学家必须为这两种病变建立明确的判定标准，并在应用时保持一致和审慎。标准应在描述中予以说明。“肌病（myopathy）”一词通常用于描述以变性和坏死为主要特征的骨骼肌疾病。然而，由于肌病是一个笼统的术语，且通常涵盖一组病变而非某一独立病变，故不推荐使用该词。
诊断建议
当坏死被视为主要病变时，例如梗死，应作出诊断并赋予严重程度分级。如果一项研究中同时存在变性和坏死，应诊断占优势的病变，并在病理学描述中描述另一病变。然而，如果同时记录两种病变最能描述所发生的变化，病理学家可同时记录两种病变。伴随的再生通常不应单独记录，除非其程度显著，但应在描述中予以说明。其他继发性病变，如炎症和出血，除非严重程度足以支持，否则不应单独诊断，但应在描述中予以说明。相关链接：Skeletal Muscle - Degeneration Skeletal Muscle - Regeneration
参考切片图（2 张）
查看英文原文
Comment
Numerous types of injury, including trauma, ischemia, infectious agents, and myotoxins, can cause myofiber necrosis. Myofiber necrosis (myonecrosis) is histologically characterized by swollen, deeply eosinophilic, homogeneous myofibers that lack cross striations (hyalinization). Affected fibers are often vacuolated and fragmented with pyknotic nuclei ( Figure 1 ). Concurrent inflammation is common. Dystrophic mineralization ( Figure 2 and Figure 3 ) can also occur. Various stages of myofiber degeneration and regeneration are also often present (see Skeletal Muscle - Degeneration and Skeletal Muscle - Regeneration ). Degeneration and necrosis represent a continuum of lesions and therefore are often both present within a given lesion. Due to the limited repertoire of skeletal muscle responses, they share similar morphologic features and can thus be difficult to differentiate histologically. This can create a diagnostic challenge. When evaluating a toxicity study, it is important for the pathologist to establish distinct criteria for both lesions and to be consistent and careful when applying them. Criteria should be described in the narrative. The term "myopathy" has commonly been used to describe disorders of skeletal muscle in which degeneration and necrosis are key features. However, since myopathy is a general term and one that typically encompasses a collection of lesions rather than one distinct lesion, its use is not recommended.
Recommendation
When necrosis is considered the primary lesion, such as with infarction, the lesion should be diagnosed and assigned a severity grade. If both degeneration and necrosis are present in a study, the predominant lesion should be diagnosed and the other described in the pathology narrative. However, the pathologist may record both lesions if it best describes the changes that are occurring. Concomitant regeneration should generally not be recorded separately unless present to a significant extent but should be described in the narrative. Other secondary lesions, such as inflammation and hemorrhage, should not be diagnosed separately unless warranted by severity but should be described in the narrative. Related Links: Skeletal Muscle - Degeneration Skeletal Muscle - Regeneration
水肿Edema 骨骼肌水肿
描述（中文）
骨骼肌中的水肿与其他组织中的水肿一样，在组织学上表现为间质组织被无定形至纤维状、透明至淡嗜酸性物质所扩张，这些物质分隔并环绕单个肌纤维（Figure 1、Figure 2、Figure 3、Figure 4）。重要的是要将因水肿而扩张的间质间隙与正常组织中因固定或切片伪影而形成的间隙区分开来（Figure 5）。由伪影导致的分离在肌纤维和肌束之间缺乏淡嗜酸性纤维状物质的存在。虽然水肿可以作为原发性病变发生（Figure 1、Figure 2、Figure 3、Figure 4），但它最常见的是继发于坏死和炎症；出血区域常伴有水肿。肌内水肿可见于自身免疫性疾病，如多发性肌炎和皮肌炎；轻度损伤；感染性肌炎；亚急性失神经支配；骨筋膜室综合征；以及横纹肌溶解症；它也可作为肌肉运动期间及运动后短暂的生理性表现而被观察到。
诊断建议
当肌内水肿是唯一或原发性病变时，应予以诊断并分级。在肌内水肿为继发性病变（例如继发于炎症）的情况下，除非因严重程度而有必要，否则不应单独记录，但应在病理学叙述中加以描述。
参考切片图（2 张）
查看英文原文
Comment
Edema in skeletal muscle, as in other tissues, is histologically identified by the expansion of interstitial tissue by amorphous to fibrillar, clear to pale eosinophilic material that separates and surrounds individual myofibers ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). It is important to distinguish interstitial spaces that are expanded due to edema from those created in normal tissue as a result of fixation or sectioning artifact ( Figure 5 ). Separation as a result of artifact lacks the presence of pale eosinophilic fibrillar material between muscle fibers and bundles. While edema can occur as a primary lesion ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ), it most commonly occurs secondary to necrosis and inflammation; regions of hemorrhage are often accompanied by edema. Intramuscular edema can be seen in association with autoimmune conditions, such as polymyositis and dermatomyositis; mild injuries; infectious myositis; subacute denervation; compartment syndrome; and rhabdomyolysis; it can also be seen as a transient, physiologic finding during and briefly following muscle exercise.
Recommendation
When intramuscular edema is the sole or primary lesion, it should be diagnosed and graded. In instances where intramuscular edema is a secondary lesion (e.g., to inflammation), it should not be recorded separately unless warranted by severity but should be described within the pathology narrative.
炎症Inflammation 骨骼肌炎症
描述（中文）
骨骼肌炎症可由多种类型的损伤引起，包括物理性创伤（例如注射部位、咬伤和钝器伤）、暴露于肌毒素或感染性病原体，以及缺血、血栓形成或肌纤维坏死。炎症可表现为多种形态学模式。它可以是主要为间质性的，伴有很少或无肌纤维坏死，或者可以是主要特征，而炎症很少。在NTP研究中，炎症有五个标准类别：急性（急性（acute））、化脓性（化脓性（suppurative））、慢性（慢性（chronic））、慢性活动性（慢性活动性（chronic-active））和肉芽肿性（肉芽肿性（granulomatous））；脓肿诊断为化脓性炎症。在急性炎症（Figure 1、Figure 2）中，主要浸润细胞是中性粒细胞（neutrophil），尽管也可能存在较少的巨噬细胞（macrophage）和淋巴细胞（lymphocyte）。也可能有水肿或充血（hyperemia）的证据。中性粒细胞也是化脓性炎症（Figure 3、Figure 4）中的主要浸润细胞类型，但中性粒细胞聚集，其中许多发生变性（化脓性渗出物，化脓性 exudate）。细胞碎片（来自驻留细胞群和浸润白细胞）、含纤维蛋白（fibrin）的蛋白性液体、较少的巨噬细胞、偶见的淋巴细胞和/或浆细胞（plasma cell），以及可能的感染性病原体也可能存在于渗出物中。肉眼上，这些病变将以脓液的存在为特征。在渗出物周围的组织中，可能存在成纤维细胞（fibroblast）、纤维结缔组织和混合性炎症细胞，取决于病变的慢性程度。淋巴细胞在慢性炎症中占主导地位。淋巴细胞在慢性活动性炎症中也占主导地位，但也存在显著数量的中性粒细胞（Figure 5、Figure 6）。两种病变均可能含有巨噬细胞。肉芽肿性炎症是慢性炎症的另一种形式，但该诊断需要存在显著数量的聚集性、大的、活化的巨噬细胞、上皮样巨噬细胞（epithelioid macrophage）或多核巨细胞（multinucleated giant cell）（Figure 7、Figure 8）。由于炎症可响应于或导致肌纤维坏死，除水肿和/或出血外，肌病性改变常同时发生。炎症反应对于有效修复受损组织是必要的；然而，该反应的性质、持续时间和强度将关键性地影响修复的总体结局。
诊断建议
每当炎症被视为原发性病变时，应诊断并分级。如果炎症特别严重或相对于原发性病变的严重程度比预期更严重，则可诊断为继发性病变（例如继发于坏死）。诊断应包括炎症类型（例如急性、慢性、慢性活动性）作为修饰词。通常不需要包括部位修饰词，除非需要区分两个不同的病变。相关病变，如血管病变、异物或感染性病原体，应单独诊断。继发于炎症的病变（例如坏死）和属于炎症过程一部分的病变（例如水肿或出血）不应单独诊断，除非严重程度需要，但应在病理学叙述中描述。
参考切片图（2 张）
查看英文原文
Comment
Inflammation of skeletal muscle can occur as a result of numerous types of injury, including physical trauma (e.g., injection sites, bite wounds, and blunt trauma), exposure to myotoxins or infectious agents, and ischemia, thrombosis, or myofiber necrosis. Inflammation can exhibit various morphologic patterns. It can be primarily interstitial, with little or no myofiber necrosis, or can be the predominant feature, with little inflammation. In NTP studies, there are five standard categories of inflammation: acute, suppurative, chronic, chronic-active, and granulomatous; abscesses are diagnosed as suppurative inflammation. In acute inflammation ( Figure 1 and Figure 2 ), the predominant infiltrating cell is the neutrophil, though fewer macrophages and lymphocytes may also be present. There may also be evidence of edema or hyperemia. The neutrophil is also the predominant infiltrating cell type in suppurative inflammation ( Figure 3 and Figure 4 ), but the neutrophils are aggregated, and many of them are degenerate (suppurative exudate). Cell debris (both from the resident cell populations and from infiltrating leukocytes); proteinaceous fluid containing fibrin, fewer macrophages, occasional lymphocytes, and/or plasma cells; and possibly an infectious agent may also be present within the exudate. Grossly, these lesions would be characterized by the presence of pus. In the tissue surrounding the exudate, there may be fibroblasts, fibrous connective tissue, and mixed inflammatory cells, depending on the chronicity of the lesion. Lymphocytes predominate in chronic inflammation . Lymphocytes also predominate in chronic-active inflammation , but a significant number of neutrophils are also present ( Figure 5 and Figure 6 ). Both lesions may contain macrophages. Granulomatous inflammation is another form of chronic inflammation, but this diagnosis requires the presence of a significant number of aggregated, large, activated macrophages, epithelioid macrophages, or multinucleated giant cells ( Figure 7 and Figure 8 ). Since inflammation can occur in response to, or result in, myofiber necrosis, myopathic changes in addition to edema and/or hemorrhage often occur concurrently. An inflammatory response is necessary to effectively repair damaged tissues; however, the nature, duration, and intensity of this response will crucially influence the overall outcome of repair.
Recommendation
Inflammation should be diagnosed and graded whenever it is considered a primary lesion. It may be diagnosed as a secondary lesion (e.g., secondary to necrosis) if it is particularly severe or more severe than expected relative to the severity of the primary lesion. The diagnosis should include the type of inflammation (e.g., acute, chronic, chronic-active) as a modifier. Generally it is not necessary to include a site modifier unless it is needed to separate two distinct lesions. Associated lesions, such as vascular lesions, foreign bodies, or infectious agents, should be diagnosed separately. Lesions secondary to the inflammation (e.g., necrosis) and lesions that are part of the inflammatory process (e.g., edema or hemorrhage) should not be diagnosed separately unless warranted by severity but should be described in the pathology narrative.
矿化Mineralization 骨骼肌矿化
描述（中文）
矿化（mineralization）的组织学特征是存在深嗜碱性的细至粗颗粒状沉积物，钙组织化学染色呈阳性。还可能存在多核异物巨细胞、急性或慢性炎症和/或成纤维细胞反应。矿化既可作为局部创伤/坏死的结果（营养不良性）发生，也可由全身性钙磷失衡（转移性）引起。虽然营养不良性矿化在大鼠中不是常见的反应，但某些小鼠品系，尤其是 BALB/c、C3H 和 DBA，特别易感。骨骼肌的营养不良性或转移性钙化偶尔作为自发性变化被观察到；然而，饮食、激素变化、给予氢化可的松以及内源性皮质类固醇高分泌均被推测为促成因素。
诊断建议
当骨骼肌矿化显著或为主要病变（即转移性矿化）时，应进行诊断并分级。作为坏死组成部分发生的矿化无需单独记录（除非因严重程度而有必要），但应在病理学叙述中描述。
参考切片图（1 张）
查看英文原文
Comment
Mineralization is histologically characterized by the presence of deeply basophilic fine to coarse granular deposits that stain positively with histochemical stains for calcium. Multinucleated foreign-body giant cells, acute or chronic inflammation, and/or a fibroblastic response may also be present. Mineralization can occur either as a result of local trauma/necrosis (dystrophic) or due to systemic Ca:P imbalances (metastatic). While dystrophic mineralization is not a common response in rats, certain mouse strains, notably BALB/c, C3H, and DBA, are particularly susceptible. Dystrophic or metastatic calcification of skeletal muscle is sporadically observed as a spontaneous change; however, diet, hormonal changes, administration of hydrocortisone, and high endogenous secretion of corticosteroids have all been postulated as contributing factors.
Recommendation
When mineralization of skeletal muscle is significant or is a primary lesion (i.e., metastatic mineralization), it should be diagnosed and graded. Mineralization that occurs as a component of necrosis does not need to be recorded separately (unless warranted by severity) but should be described in the pathology narrative.
纤维化Fibrosis 骨骼肌纤维化
描述（中文）
在骨骼肌中，纤维化的主要组织学特征是数量增多的丰满的反应性成纤维细胞（伴有明显的泡状核），以及数量增多的淡嗜酸性纤维状物质（胶原沉积），这些物质分隔并环绕相邻的肌纤维（Figure 1、Figure 2、Figure 3、Figure 4）。受累的肌纤维可能表现出也可能不表现出萎缩、变性、坏死或再生的组织学特征。纤维化是一系列事件的最终结果，该过程始于组织损伤和炎症，终于永久性瘢痕形成。当组织受损时，浸润的炎症细胞释放促纤维化细胞因子，如转化生长因子β。这些细胞因子发出信号，使成纤维细胞迁移至受累区域，并开始产生和重塑细胞外基质。随后，基质成纤维细胞开始产生细胞因子、生长因子和蛋白酶，进一步触发并维持炎症/促纤维化状态。虽然成纤维细胞对于维持组织稳态和调控正常伤口修复至关重要，但它们也是慢性纤维化疾病形成过程中的关键中间环节。在慢性或广泛性肌肉损伤的情况下，持续性炎症、延长的成纤维细胞活化以及卫星细胞修复能力的减弱最终导致细胞外基质成分的过度积累。这抑制了肌源性修复，并导致肌肉被纤维化/瘢痕组织所取代。虽然营养性、劳力性和中毒性肌病可导致广泛的肌肉损伤区域，但修复往往极为有效，因此纤维化轻微至缺失。相比之下，缺血所致损伤后的修复过程往往无效，可能是由于随后卫星细胞和肌内膜细胞的死亡。因此，广泛的纤维化区域常常是主要特征。
诊断建议
当纤维化作为原发性改变存在时，应当进行诊断和分级。作为慢性或慢性活动性炎症的次要成分存在的纤维化，仅当其为该病变的显著成分或纤维化程度与炎症程度不相称时（即纤维化比根据炎症严重程度所预期的更为严重），才应当进行诊断。如果未单独诊断纤维化，则应在病理学叙述中对其进行描述。无论何时诊断纤维化，都应根据组织的总体受累程度以及基础架构被遮蔽的程度进行分级。由于纤维化通常是初始炎症过程的最终结果，应在病理学叙述中讨论纤维化的可能原因。其他肌病性改变（例如炎症、坏死、再生）不应单独记录，除非其严重程度足以支持单独记录。
参考切片图（2 张）
查看英文原文
Comment
In skeletal muscle, the predominant histologic features of fibrosis are increased numbers of plump reactive fibroblasts with prominent vesiculated nuclei, and increased amounts of pale eosinophilic fibrillar material (collagen deposition) separating and surrounding adjacent myofibers ( Figure 1 , Figure 2 , Figure 3 , and Figure 4 ). Affected myofibers may or may not exhibit histologic features of atrophy, degeneration, necrosis, or regeneration. Fibrosis is the end result of a cascade of events that begins with tissue injury and inflammation and ends in permanent scar formation. When tissue is damaged, profibrotic cytokines, such as transforming growth factor beta, are released by the infiltrating inflammatory cells. These cytokines signal the fibroblasts to migrate into the affected region and to begin producing and remodeling the extracellular matrix. The stromal fibroblasts then begin producing cytokines, growth factors, and proteases that further trigger and uphold the inflammatory/profibrotic conditions. While fibroblasts are fundamental for maintaining tissue homeostasis and regulating normal wound repair, they also serve as a crucial intermediate in the formation of chronic fibrotic diseases. During conditions of chronic or extensive muscle damage, persistent inflammation, prolonged fibroblastic activation, and attenuated reparative capacity of the satellite cells ultimately lead to excessive accumulation of extracellular matrix components. This inhibits myogenic repair and leads to the replacement of muscle with fibrotic/scar tissue. While nutritional, exertional, and toxic myopathies can result in extensive regions of muscle damage, repair is often extremely effective, and thus fibrosis is minimal to absent. In contrast, the reparative process is often ineffective following damage due to ischemia, likely due to the subsequent death of the satellite cells and endomysial cells. For this reason, extensive regions of fibrosis are often a dominant feature.
Recommendation
When present as a primary change, fibrosis should be diagnosed and graded. Fibrosis that is present as a minor component of chronic or chronic-active inflammation should be diagnosed only if it is a prominent component of that lesion or if the degree of fibrosis is not commensurate to that of the inflammation (i.e., the fibrosis is more severe than would be expected given the severity of the inflammation). If fibrosis is not diagnosed separately, it should be described in the pathology narrative. Whenever it is diagnosed, fibrosis should be graded based upon the overall involvement of the tissue and the degree to which the underlying architecture is obscured. Since fibrosis is often the end result of an initial inflammatory process, potential causes of the fibrosis should be discussed in the pathology narrative. Additional myopathic changes (e.g., inflammation, necrosis, regeneration) should not be recorded separately unless warranted by severity.
肥大Hypertrophy 骨骼肌肥大
描述（中文）
骨骼肌肥大（skeletal muscle hypertrophy）在组织学上的特征是肌纤维直径增大。这在组织学上有时难以检出。肥大由工作负荷增加所致，既可为局灶性（focal），即作为周围肌肉丧失或萎缩后的代偿性反应，也可范围更广，作为运动需求增加的生理性反应。此外，弥漫性（diffuse）肥大还可因长期暴露于过量生长因子（如生长激素或促生长性外源化学物）而发生。因肌病性或神经病性疾患而发生代偿性肥大的肌纤维，其直径可达发生生理性肥大纤维的两倍。这些纤维常为异常，可含一个或多个内移细胞核，发生纵向分裂（Figure 1、Figure 2），和/或表现出奇异的细胞构筑改变，如裂隙形成和漩涡状排列。在这些情况下，肥大的单个肌纤维常散在分布于萎缩的肌纤维之间。
诊断建议
凡存在肥大时，均应作出诊断并分级。当肥大发生于萎缩区域内时，不应单独诊断，除非其严重程度足以支持单独诊断。
参考切片图（2 张）
查看英文原文
Comment
Skeletal muscle hypertrophy is characterized histologically by an increase in myofiber diameter. This can sometimes be difficult to detect histologically. Hypertrophy occurs as a result of increased workload and can occur either focally, as a compensatory reaction following the loss or atrophy of surrounding muscle, or more extensively, as a physiologic response to increased exercise demands. In addition, diffuse hypertrophy can occur in response to prolonged exposure to excessive growth factors, such as growth hormones or growth-promoting xenobiotics. Myofibers undergoing compensatory hypertrophy due to a myopathic or neuropathic disorder can reach diameters up to twice that of fibers that have undergone physiologic hypertrophy. These fibers are often abnormal and can contain one or more internal nuclei, undergo longitudinal splitting ( Figure 1 and Figure 2 ), and/or exhibit bizarre cytoarchitectural alterations, such as clefting and whorling. In these instances, individual hypertrophic myofibers are often interspersed among atrophic ones.
Recommendation
Whenever present, hypertrophy should be diagnosed and graded. When hypertrophy occurs within an area of atrophy, it should not be diagnosed separately unless warranted by severity.
萎缩Atrophy 骨骼肌萎缩
描述（中文）
骨骼肌萎缩可由起源于骨骼肌纤维内部的退行性过程引起，也可继发于去神经支配（去神经性萎缩），或在老龄啮齿类动物中自发发生。它是任何导致肌纤维细胞器降解和/或丢失的损伤的常见反应。示例包括废用、恶病质、营养或代谢紊乱、血管功能不全、激素生长控制机制紊乱以及给予肌毒性外源化学物。无论病因如何，常同时存在存活/未受累肌纤维的代偿性肥大。骨骼肌萎缩的主要组织学特征是肌纤维直径减小（Figure 1、Figure 2）。受累肌纤维常呈圆形至棱角状，肌浆嗜酸性增强。在去神经性萎缩中，特征性组织学表现为受压的棱角状肌纤维伴细胞核密集。非神经源性原因所致的萎缩，例如由给予肌毒性外源化学物所诱导者，通常缺乏这些纤维，而是伴有传统肌病性改变，如坏死性或玻璃样变肌纤维、撕裂或碎裂的肌纤维以及具有中央核的肌纤维。老龄啮齿类动物的自发性萎缩（常称为后肢肌病）的组织学特征为肌纤维大小和数量减少；肌纤维大小变异增加；退行性包涵体、脂褐素和脂滴蓄积增加；以及结缔组织增加。常存在棱角状肌纤维，提示脊髓退行性变可能在该过程中发挥作用。然而，并非在所有受累动物中均一致观察到脊神经病变；其发病机制仍不清楚。该病变主要见于受累大鼠的后肢。已在包括Wistar和Sprague-Dawley在内的多个大鼠品系中描述，但尚未在F344大鼠中记录。萎缩可均匀累及肌纤维，或选择性靶向特定肌纤维类型。当萎缩与废用、恶病质或营养不良相关时，II型纤维被选择性累及。在大鼠中长期给予皮质类固醇会导致II型快肌纤维的选择性萎缩。相反，在实验性诱导的甲状腺毒症中，I型纤维被选择性靶向。
诊断建议
当存在时，骨骼肌萎缩应当被诊断并分级。未受累纤维的代偿性肥大无需单独记录，除非其严重程度需要如此。萎缩的可能原因（例如原发性变性、继发于去神经支配，或老龄动物中的自发性）应在病理学叙述中讨论。受累肌纤维的组织学表现，特别是关于是否存在棱角状肌纤维，应纳入叙述中。当其严重程度需要时，其他肌病性改变，如肌纤维坏死或变性，应当单独记录并分级。
参考切片图（2 张）
查看英文原文
Comment
Skeletal muscle atrophy can occur due to degenerative processes originating within the skeletal muscle fibers, secondary to denervation (denervation atrophy), or spontaneously in aging rodents. It is a common reaction to any injury that results in the degradation and/or loss of myofiber organelles. Examples include disuse, cachexia, nutritional or metabolic derangements, vascular insufficiency, disturbances of hormonal growth control mechanisms, and administration of myotoxic xenobiotics. Compensatory hypertrophy of surviving/unaffected myofibers is often present concomitantly, regardless of the cause. The main histologic feature of skeletal muscle atrophy is a reduction in myofiber diameter ( Figure 1 and Figure 2 ). Affected myofibers are often rounded to angular with hypereosinophilic sarcoplasm. In denervation atrophy, the characteristic histologic feature is that of compressed angular myofibers with crowded nuclei. Atrophy due to nonneurogenic causes, such as that induced by the administration of myotoxic xenobiotics, often lacks these fibers and is instead accompanied by traditional myopathic changes, such as necrotic or hyalinized myofibers, split or fragmented myofibers, and myofibers with central nuclei. Spontaneous atrophy of aging rodents (often referred to as hind leg myopathy) is histologically characterized by decreased myofiber size and number; increased myofiber size variation; increased accumulation of degenerative inclusion bodies, lipofuscin, and lipid droplets; and increased connective tissue. Angulated myofibers are often present, suggesting a possible role of spinal degeneration within this process. However, spinal nerve lesions are not consistently observed in all affected animals; the pathogenesis remains unclear. This condition is predominately noted in the hind limbs of affected rats. It has been described in several strains of rats, including Wistar and Sprague-Dawley, but has not been recorded in the F344 rat. Atrophy can uniformly affect myofibers or selectively target specific muscle fiber types. Type II fibers are selectively affected when atrophy is associated with disuse, cachexia, or malnutrition. Chronic administration of corticosteroids in rats results in the selective atrophy of type II fast-twitch fibers. Conversely, type I fibers are selectively targeted during experimentally induced thyrotoxicosis.
Recommendation
When present, skeletal muscle atrophy should be diagnosed and graded. Compensatory hypertrophy of unaffected fibers does not need to be recorded separately unless warranted by severity. Potential causes of the atrophy (e.g., primary degeneration, secondary to denervation, or spontaneously in aging animals) should be discussed in the pathology narrative. The histologic appearance of the affected myofibers, specifically regarding the presence of angulated myofibers, should be included in the narrative. When warranted by severity, additional myopathic changes, such as myofiber necrosis or degeneration, should be recorded and graded separately.
血管扩张Angiectasis 骨骼肌扩张
描述（中文）
血管扩张（angiectasis）是一种非增殖性病变，其中原有的血管腔扩张并变得显著（Figure 1、Figure 2）。血管由单层扁平内皮细胞衬覆，内皮细胞在外观、数量和大小上均正常。血管扩张通常是一种偶然性病变，其病因学和发病机制往往不清楚。将血管扩张与血管瘤（hemangioma）区分开来很重要。这可能有难度，因为这种区分并不总是显而易见，而且血管扩张性病变可出现在血管瘤的区域。血管瘤往往是边界清楚、无包膜的肿块，由紧密排列的扩张血管腔组成，压迫周围组织。虽然血管腔由单层分化良好的内皮细胞衬覆，但内皮细胞核通常数量增多并轻度增大。一般来说，缺乏内皮细胞增殖和/或核异型性可将血管扩张与肿瘤性血管病变区分开来。此外，血管扩张通常不表现为边界清楚的肿块；扩张的血管通道常不规则地穿行于组织中。
诊断建议
血管扩张出现时，应当作出诊断并赋予严重程度分级。
参考切片图（2 张）
查看英文原文
Comment
Angiectasis is a nonproliferative lesion in which preexisting vascular spaces are dilated and prominent ( Figure 1 and Figure 2 ). The vessels are lined by a single layer of flat endothelium in which the endothelial cells are normal in appearance, number, and size. Angiectasis is typically an incidental lesion, and its etiology and pathogenesis are often obscure. It is important to distinguish angiectasis from a hemangioma. This can be difficult because the distinction is not always obvious and angiectatic lesions can appear in regions of hemangiomas. Hemangiomas tend to be well-circumscribed, unencapsulated masses composed of tightly packed, dilated vascular spaces that compress surrounding tissues. While the vascular spaces are lined by a single layer of well-differentiated endothelium, endothelial nuclei are typically increased in number and slightly enlarged. In general, the absence of endothelial cell proliferation and/or nuclear atypia differentiates angiectasis from a neoplastic vascular lesion. In addition, angiectasis does not typically present as a well-circumscribed mass; the dilated vascular channels often course irregularly through the tissue.
Recommendation
When present, angiectasis should be diagnosed and assigned a severity grade.
内容译自美国国家毒理学计划（NTP）Nonneoplastic Lesion Atlas，原文属美国联邦政府公有领域，可自由使用。本页为机器翻译并经术语表校正，仅供科研与病理读片参考，不作为临床诊断依据；如有疑问请以 NTP 英文原文为准。