Carbone Antonino
Centro di Riferimento Oncologico-IRCCS, Aviano, Italy.
Lancet Oncol. 2003 Jan;4(1):22-9. doi: 10.1016/s1470-2045(03)00957-4.
The clinicopathological range of AIDS-related non-Hodgkin lymphomas (NHLs) includes systemic lymphomas, primary central-nervous-system lymphomas, primary effusion lymphoma, and plasmablastic lymphoma of the oral cavity. Most AIDS-related NHLs belong to one of three categories of high-grade B-cell lymphomas: Burkitt's lymphoma, centroblastic lymphoma, and immunoblastic lymphoma. The pathological heterogeneity of AIDS-related NHL reflects the heterogeneity of their associated molecular lesions. In AIDS-related Burkitt's lymphoma, the molecular lesions involve activation of c-MYC, inactivation of p53, and infection with Epstein-Barr virus (EBV). AIDS-related immunoblastic lymphomas infected with EBV are characterised by frequent expression of latent membrane protein 1-an EBV oncoprotein. The biological heterogeneity of AIDS-related NHLs is highlighted by their histogenetic differences; AIDS-related NHLs are related to distinct B-cell subgroups (eg, germinal-centre or post-germinal-centre B cells). The phenotypic pattern of AIDS-related Burkitt's lymphomas and systemic AIDS-related centroblastic lymphomas closely reflects that of B cells in germinal centres. Conversely, the phenotype of AIDS-related immunoblastic lymphomas and AIDS-related primary effusion lymphomas reflects post-germinal-centre B cells in all cases. Despite their clinicopathological, genetic, and phenotypic heterogeneity, most lymphomas in patients with AIDS carry somatic mutations of immunoglobulin and BCL-6 genes. However, the somatic hypermutation mechanism functions aberrantly in a significant proportion of AIDS-related NHLs, causing the mutation of many genes, and possibly favouring chromosomal translocation, which may be a powerful contributor to malignant transformation. New molecular and virological evidence of such pathways and a greater knowledge of other biological features of AIDS-related NHLs may lead to new targets for pathogenetically and biologically oriented therapies.
艾滋病相关非霍奇金淋巴瘤（NHL）的临床病理范围包括系统性淋巴瘤、原发性中枢神经系统淋巴瘤、原发性渗出性淋巴瘤和口腔浆母细胞淋巴瘤。大多数艾滋病相关NHL属于高级别B细胞淋巴瘤的三类之一：伯基特淋巴瘤、中心母细胞淋巴瘤和免疫母细胞淋巴瘤。艾滋病相关NHL的病理异质性反映了其相关分子病变的异质性。在艾滋病相关伯基特淋巴瘤中，分子病变涉及c-MYC激活、p53失活以及感染爱泼斯坦-巴尔病毒（EBV）。感染EBV的艾滋病相关免疫母细胞淋巴瘤的特征是潜伏膜蛋白1（一种EBV癌蛋白）频繁表达。艾滋病相关NHL的生物学异质性通过其组织发生学差异得以凸显；艾滋病相关NHL与不同的B细胞亚群（如生发中心或生发中心后B细胞）相关。艾滋病相关伯基特淋巴瘤和系统性艾滋病相关中心母细胞淋巴瘤的表型模式密切反映生发中心B细胞的表型模式。相反，艾滋病相关免疫母细胞淋巴瘤和艾滋病相关原发性渗出性淋巴瘤的表型在所有病例中均反映生发中心后B细胞。尽管存在临床病理、遗传和表型异质性，但艾滋病患者的大多数淋巴瘤携带免疫球蛋白和BCL-6基因的体细胞突变。然而，体细胞超突变机制在相当一部分艾滋病相关NHL中异常发挥作用，导致许多基因发生突变，并可能有利于染色体易位，这可能是恶性转化的一个重要因素。这些途径的新分子和病毒学证据以及对艾滋病相关NHL其他生物学特征的更多了解可能会为基于发病机制和生物学的治疗带来新靶点。
