# 细胞减少（Hypocellularity）

- 器官 / 系统：骨髓 / 造血系统（bone-marrow / hematopoietic-system）
- NTP 数据编号：ntp-0432
- 规范 URL：https://www.labsmart.cn/ntp/bone-marrow-hypocellularity.html
- 中文图谱总页锚点：https://www.labsmart.cn/ntp-atlas.html#bone-marrow-hypocellularity
- 原始出处：https://ntp.niehs.nih.gov/atlas/nnl/hematopoietic-system/bone-marrow/Hypocellularity
- 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。

## 病变描述（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。

## 诊断与分级建议（NTP 共识，中文）
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。

## 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.

## 英文原文 · 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.

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