骨髓活检组织淋巴瘤的病理诊断和分型

Pathologic diagnosis and subtyping of lymphoma in bone marrow biopsies using histologic examination,inununohistochemistry and gene rearrangement studies

目的 探讨组织形态改变、免疫组织化学、基因重排在淋巴瘤骨髓侵犯的病理诊断和分型中的作用。材料与方法 对62例甲醛固定、石蜡包埋的骨髓活检组织,分别做了组织学、EnVision法观察和免疫球蛋白重链(IgH)基因和TCRγ基因重排检测。结果慢性淋巴细胞性白血病/小淋巴细胞淋巴瘤(CLL/SLL)的异型淋巴细胞呈小梁间结节状或散在分布,有时可见假滤泡结构。滤泡型淋巴瘤(FCL)表现为结节性小梁旁或小梁间的浸润,结节内小淋巴样细胞松散聚集。淋巴浆细胞性淋巴瘤(LPL)主要为小梁间弥散浸润,在小而圆的淋巴细胞间可见散在数量不等的浆细胞样淋巴细胞。边缘区淋巴瘤(MZL)则见模糊的或界限不清的小梁间或小梁旁结节,一些细胞胞质透明。套细胞性淋巴瘤(MCL)异型细胞小到中等大小,缺乏副免疫母细胞和假滤泡。毛细胞性淋巴瘤(HCL)瘤细胞胞膜多清晰,胞质丰富透明,常形成荷包蛋样表现。霍奇金病可见大核瘤细胞,核仁明显。T-非霍奇金淋巴瘤(NHL)浸润骨髓主要为小粱间间质性散在或弥漫分布,胞质多透明,核有芋艿样或脑回状改变,DLBL造血细胞间体积大的瘤细胞散在或弥漫分布。CD3对T细胞来源、CD20和CD79对B细胞来源淋巴瘤有鉴别诊断价值,cyclin D1和CD5阳性对MCL具有诊断性价值,bcl-2和CD10阳性则对FCL具有诊断性意义,而CLL/

Objective To assess the value of histologic examination, immunohistochemistry and gene rearrangement studies in the diagnosis and subtyping of lymphoma with bone marrow involvement (BMI) . Methods Sixty-two formalin fixed, paraffin embedded bone marrow biopsy specimens were studied. Immunohistochemical and immunoglobulin heavy chain ( IgH ) and T-cell receptor gene rearrangement studies were performed in each case. Results Chronic lymphocytic leukemia/small lymphocytic lymphoma ( CLL/SLL ) demonstrated mainly an interstitial infiltration by dysplastic lymphocytes, with intertrabecular nodular arrangement or in dispersion. Sometimes, pseudofollicles may be noted. A predominantly para- or intertrabecular infiltration by nodules of lymphoma cells was characteristic of follicle center cell lymphoma ( FCL) cases. In most lymphoplasmacytoid lymphoma (LPL) cases, there was infiltration by small lymphocytes and plasma cells between bony trabeculae. In marginal zone cell lymphoma (MZL) , vague inter- or para-trabecular nodules of polymorphic lymphoma cells with clear cytoplasm might be noted. Small to medium-sized dysplastic lymphocytes, with absence of paraimmunoblasts or pseudofollicles, were the most frequent findings in mantle cell lymphoma ( MCL) . Hairy cell leukemia (HCL) might be identified by the presence of distinct cell membrane and abundant clear cytoplasm, resulting in a ' fried-egg' appearance. Tumor cells with large nuclei and eosinophilic nucleoli were characteristically seen in lymphomatosis diffusa (Hodgkin's disease, HD). In T-cell non-Hodgkin lymphoma with BMI, dispersed or clusters of intertrabecular neoplastic lymphoid cells with clear cytoplasm and gyriform nuclei were often observed. In diffuse large B-cell lymphoma ( DLBL) , the tumor cells were large and isolated or arranged in diffuse pattern. Immunohistochemically, a panel of markers, including CD3, CD20, and CD79 are valuable for the differential diagnosis of T- and B-cell lymphomas. The neoplastic cells in MCL were cyclin D1- and CD5-positive, while BCL2- and CD10-positivity was characteristic for FCL. CLL/SLL cells might be stained with CD5 and CD23, in addition to CD20 and CD79. CD25 expression might be noted in HCL; the positivity for GD15, CD30 and fascin suggests HD. There was a higher positively rate for IgH gene rearrangement in CLL/SLL, LPL, MZL and DLBL (80% ,60% ,66. 7% ,70% respectively) and for T-cell receptor γ gene rearrangement in T-cell lymphoma ( 66.7% ) . Conclusion A combination of histopathology, immunohistochemistry and IgH / T-cell receptor γ gene rearrangement studies may be of aid to the diagnosis and subtyping of lymphoma with BMI, especially if there is only a small number of tumor cells present in the specimen.