Carbone A, Gaidano G, Gloghini A, Larocca L M, Capello D, Canzonieri V, Antinori A, Tirelli U, Falini B, Dalla-Favera R
Division of Pathology, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy.
Blood. 1998 Feb 1;91(3):747-55.
This study was aimed at defining the histogenesis of the pathologic spectrum of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas (AIDS-NHL), including AIDS-related small noncleaved cell lymphoma (AIDS-SNCCL), AIDS-related large noncleaved cell lymphoma (AIDS-LNCCL), AIDS-related large cell immunoblastic lymphoma plasmacytoid (AIDS-IBLP), and AIDS-related primary effusion lymphoma (AIDS-PEL). Forty-six cases of AIDS-NHL were investigated for the expression pattern of BCL-6, a protein specifically expressed by germinal center (GC) B-cells, and CD138/syndecan-1 (syn-1), a marker of post-GC B-cell differentiation. Expression of BCL-6 and syn-1 segregated two major phenotypic patterns among AIDS-NHL: (1) the BCL-6+/syn-1- pattern associated with AIDS-SNCCL and AIDS-LNCCL; (2) the BCL-6-/syn-1+ pattern associated with AIDS-IBLP and AIDS-PEL. Among systemic AIDS-NHL infected by Epstein-Barr virus (EBV), expression of the EBV-encoded latent membrane protein-1 (LMP-1) preferentially associated with the BCL-6-/syn-1+ profile. Analysis of nonneoplastic lymph nodes showed that the two phenotypic patterns detected in AIDS-NHL correspond to physiologic stages of B-cell development, i.e., GC B-cells (BCL-6+/syn-1-) and preterminally differentiated post-GC B-cells (BCL-6-/syn-1+). Thus, BCL-6+/syn-1- AIDS-NHL reflects a GC stage of differentiation, whereas AIDS-NHL which are BCL-6-/syn-1+, and LMP-1+ when infected by EBV, derive from B cells that have entered post-GC plasmacell differentiation. These findings are relevant for the pathogenesis and differential diagnosis of AIDS-NHL.
本研究旨在明确获得性免疫缺陷综合征相关非霍奇金淋巴瘤（AIDS-NHL）病理谱的组织发生情况，包括艾滋病相关小无裂细胞淋巴瘤（AIDS-SNCCL）、艾滋病相关大无裂细胞淋巴瘤（AIDS-LNCCL）、艾滋病相关大细胞免疫母细胞淋巴瘤浆细胞样型（AIDS-IBLP）以及艾滋病相关原发性渗出性淋巴瘤（AIDS-PEL）。对46例AIDS-NHL病例进行了研究，检测生发中心（GC）B细胞特异性表达的蛋白BCL-6以及GC后B细胞分化标志物CD138/多配体蛋白聚糖-1（syn-1）的表达模式。BCL-6和syn-1的表达在AIDS-NHL中区分出两种主要表型模式：（1）与AIDS-SNCCL和AIDS-LNCCL相关的BCL-6+/syn-1-模式；（2）与AIDS-IBLP和AIDS-PEL相关的BCL-6-/syn-1+模式。在感染爱泼斯坦-巴尔病毒（EBV）的系统性AIDS-NHL中，EBV编码的潜伏膜蛋白-1（LMP-1）的表达优先与BCL-6-/syn-1+谱相关。对非肿瘤性淋巴结的分析表明，在AIDS-NHL中检测到的两种表型模式对应于B细胞发育的生理阶段，即GC B细胞（BCL-6+/syn-1-）和GC后终末前分化的B细胞（BCL-6-/syn-1+）。因此，BCL-6+/syn-1-的AIDS-NHL反映了分化的GC阶段，而BCL-6-/syn-1+且在感染EBV时LMP-1+的AIDS-NHL来源于已进入GC后浆细胞分化的B细胞。这些发现与AIDS-NHL的发病机制和鉴别诊断相关。
