Carbone Antonino
Division of Pathology and Scientific Direction, Centro di Riferimento Oncologico-IRCCS, National Cancer Institute, Aviano, Italy.
Hum Pathol. 2002 Apr;33(4):392-404. doi: 10.1053/hupa.2002.124723.
In the highly active antiretroviral therapy (HAART) era, AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) and their treatment still represent an open issue, because HAART may not be sufficient to prevent the development of NHL. The present spectrum of AIDS-NHL includes systemic lymphomas, primary central nervous system lymphomas, and 2 rare entities, primary effusion lymphomas (PEL) and plasmablastic lymphomas of the oral cavity. The vast majority of systemic AIDS-NHL belongs to 3 high-grade B-cell lymphomas: Burkitt's lymphoma (BL), immunoblastic lymphoma (IBL), and large-cell lymphoma (LCL). The pathologic heterogeneity of AIDS-NHL is correlated with the heterogeneity of the molecular lesions associated with these lymphomas. The molecular lesions associated with AIDS-BL involve activation of c-MYC inactivation of p53, and infection by Epstein-Barr virus (EBV). EBV infection occurs in 40% of LCL cases and in 90% of IBL cases. Rearrangements of BCL-6 are detected in 20% of AIDS-LCL cases. In the presence of EBV infection, BCL-6 expressing AIDS-LCL fails to express the latent membrane protein 1 (LMP1) antigen. Conversely, AIDS-IBL are characterized by absent BCL-6 expression, absence of BCL-6 rearrangements, and frequent expression of LMP1. Consistently, the molecular pathways of viral infection and lesions of cancer-related genes associated with AIDS-NHL vary substantially in different clinicopathologic categories of the disease. The marked degree of biologic heterogeneity of AIDS-NHL is highlighted by their histogenetic differences, because AIDS-NHL are related to distinct B cell subsets (ie, germinal center [GC] or post-GC B cells). The phenotypic pattern of AIDS-BL and systemic AIDS-LCL closely reflects B cells residing in the GC, namely centroblasts and centrocytes. Conversely, the phenotype of AIDS-IBL, either systemic or localized primarily to the central nervous system, and AIDS-PEL reflects post-GC B cells in all cases. New information on the molecular and virologic pathogenesis of AIDS-NHL may serve as a point of attack for pathogenic-driven therapies. Moreover, a greater knowledge of other biologic features of these tumors may help investigators identify new potential targets for "intelligent" therapies.
在高效抗逆转录病毒治疗（HAART）时代，艾滋病相关非霍奇金淋巴瘤（AIDS-NHL）及其治疗仍是一个未解决的问题，因为HAART可能不足以预防NHL的发生。目前AIDS-NHL的范围包括系统性淋巴瘤、原发性中枢神经系统淋巴瘤，以及2种罕见类型，即原发性渗出性淋巴瘤（PEL）和口腔浆母细胞淋巴瘤。绝大多数系统性AIDS-NHL属于3种高级别B细胞淋巴瘤：伯基特淋巴瘤（BL）、免疫母细胞淋巴瘤（IBL）和大细胞淋巴瘤（LCL）。AIDS-NHL的病理异质性与这些淋巴瘤相关分子病变的异质性相关。与AIDS-BL相关的分子病变涉及c-MYC激活、p53失活以及爱泼斯坦-巴尔病毒（EBV）感染。EBV感染在40%的LCL病例和90%的IBL病例中出现。在20%的AIDS-LCL病例中检测到BCL-6重排。在存在EBV感染的情况下，表达BCL-6的AIDS-LCL不表达潜伏膜蛋白1（LMP1）抗原。相反，AIDS-IBL的特征是BCL-6表达缺失、BCL-6重排缺失以及LMP1频繁表达。一致地，与AIDS-NHL相关的病毒感染分子途径和癌症相关基因病变在该疾病的不同临床病理类别中差异很大。AIDS-NHL显著的生物学异质性通过它们的组织发生学差异得以凸显，因为AIDS-NHL与不同的B细胞亚群（即生发中心[GC]或GC后B细胞）相关。AIDS-BL和系统性AIDS-LCL的表型模式紧密反映了驻留在GC中的B细胞，即中心母细胞和中心细胞。相反，AIDS-IBL的表型，无论是系统性的还是主要局限于中枢神经系统的，以及AIDS-PEL在所有情况下都反映GC后B细胞。关于AIDS-NHL分子和病毒发病机制的新信息可能成为针对致病驱动疗法的攻击点。此外，对这些肿瘤其他生物学特征的更多了解可能有助于研究人员识别“智能”疗法的新潜在靶点。
