Larocca L M, Capello D, Rinelli A, Nori S, Antinori A, Gloghini A, Cingolani A, Migliazza A, Saglio G, Cammilleri-Broet S, Raphael M, Carbone A, Gaidano G
Institute of Pathology, Catholic University of the Sacred Heart, Rome, Italy.
Blood. 1998 Aug 1;92(3):1011-9.
Primary central nervous system lymphoma (PCNSL) is a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals. The precise histogenetic derivation and the molecular pathogenesis of PCNSL is poorly understood. In an attempt to clarify the histogenesis and pathogenesis of these lymphomas, 49 PCNSL (26 acquired immunodeficiency syndrome [AIDS]-related and 23 AIDS-unrelated) were analyzed for multiple biologic markers, which are known to bear histogenetic and pathogenetic significance for mature B-cell neoplasms. PCNSL associated frequently (50.0%) with mutations of BCL-6 5' noncoding regions, which are regarded as a marker of B-cell transition through the germinal center (GC). Expression of BCL-6 protein, which is restricted to GC B cells throughout physiologic B-cell maturation, was detected in 100% AIDS-unrelated PCNSL and in 56.2% AIDS-related cases. Notably, among AIDS-related PCNSL, expression of BCL-6 was mutually exclusive with expression of Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP)-1 and, with few exceptions, also of BCL-2. All but one PCNSL expressed hMSH2, which among mature B cells selectively stains GC B cells. These data suggest that PCNSL may be frequently related to GC B cells and may be segregated into two major biologic categories based on the expression pattern of BCL-6, LMP-1, and BCL-2. BCL-6(+)/LMP-1(-)/BCL-2(-) PCNSL occur both in the presence and in the absence of HIV infection and consistently display a large noncleaved cell morphology. Conversely, BCL-6(-)/LMP-1(+)/BCL-2(+) PCNSL are restricted to HIV-infected hosts and are represented by lymphomas with immunoblastic features. These data are relevant for the pathogenesis and histogenesis of PCNSL and may be helpful to segregate distinct biologic and prognostic categories of these lymphomas.
原发性中枢神经系统淋巴瘤（PCNSL）是人类免疫缺陷病毒（HIV）感染个体发病和死亡的主要原因。PCNSL的确切组织发生来源和分子发病机制尚不清楚。为了阐明这些淋巴瘤的组织发生和发病机制，对49例PCNSL（26例与获得性免疫缺陷综合征[AIDS]相关，23例与AIDS无关）进行了多种生物学标志物分析，这些标志物对成熟B细胞肿瘤具有组织发生和发病学意义。PCNSL常（50.0%）与BCL-6 5'非编码区突变相关，该区域被视为B细胞通过生发中心（GC）转变的标志物。在整个生理性B细胞成熟过程中，BCL-6蛋白的表达仅限于GC B细胞，在100%与AIDS无关的PCNSL和56.2%与AIDS相关的病例中均检测到。值得注意的是，在与AIDS相关的PCNSL中，BCL-6的表达与EB病毒（EBV）编码的潜伏膜蛋白（LMP）-1的表达相互排斥，并且除少数例外，与BCL-2也是如此。除1例PCNSL外，所有PCNSL均表达hMSH2，在成熟B细胞中，hMSH2选择性地标记GC B细胞。这些数据表明，PCNSL可能常与GC B细胞相关，并可能根据BCL-6、LMP-1和BCL-2的表达模式分为两个主要生物学类别。BCL-6(+)/LMP-1(-)/BCL-2(-) PCNSL在有和没有HIV感染的情况下均会出现，并且始终表现出大的无裂细胞形态。相反，BCL-6(-)/LMP-1(+)/BCL-2(+) PCNSL仅限于HIV感染的宿主，并且以具有免疫母细胞特征的淋巴瘤为代表。这些数据与PCNSL的发病机制和组织发生相关，可能有助于区分这些淋巴瘤不同的生物学和预后类别。
