# 纤维化（Fibrosis）

- 器官 / 系统：骨髓 / 造血系统（bone-marrow / hematopoietic-system）
- NTP 数据编号：ntp-0430
- 规范 URL：https://www.labsmart.cn/ntp/bone-marrow-fibrosis.html
- 中文图谱总页锚点：https://www.labsmart.cn/ntp-atlas.html#bone-marrow-fibrosis
- 原始出处：https://ntp.niehs.nih.gov/atlas/nnl/hematopoietic-system/bone-marrow/Fibrosis
- 授权：美国联邦政府作品，公有领域；引用请标注 NTP Nonneoplastic Lesion Atlas
- 适用说明：仅供科研使用，不用于临床诊断

## 一句话结论
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。

## 病变描述（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。

## 诊断与分级建议（NTP 共识，中文）
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。

## 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.

## 英文原文 · 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.”

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