Knowles D M
Department of Pathology, Cornell University Medical College, New York, New York, USA.
Hematol Oncol Clin North Am. 1996 Oct;10(5):1081-109. doi: 10.1016/s0889-8588(05)70386-5.
The incidence of NHL is greatly increased in HIV-infected individuals. The vast majority are clinically aggressive B cell-derived neoplasms exhibiting BL, IBL, or LCL histology. Approximately 80% arise systemically (nodal and/or extranodal), and the remaining 20% arise as primary CNS lymphomas. A small proportion are body cavity-based lymphomas associated with KSHV infection. Possible factors contributing to lymphoma development include HIV-induced immunosuppression, chronic antigenic stimulation, and cytokine overproduction. These alterations are associated with the development of oligoclonal B-cell expansions. The appearance of NHL is characterized by the presence of a monoclonal B-cell population displaying a variety of genetic lesions, including EBV infection, c-myc gene rearrangement, bcl-6 gene rearrangement, ras gene mutations, and p53 mutations/deletions. The number and type of genetic lesions varies according to the anatomic site and histopathology. In the case of BL, virtually 100% exhibit c-myc gene rearrangements, two thirds display p53 gene mutations, one third contain EBV, and none exhibit bcl-6 gene rearrangements. In contrast, in the case of IBL, virtually 100% contain EBV, 25% display c-myc gene rearrangements, 20% display bcl-6 gene rearrangements, and very few exhibit p53 gene mutations. These findings suggest that more than one pathogenetic mechanism is operational in the development and progression of AIDS-related NHLs. Further work will be necessary to develop a complete understanding of the etiology and pathogenesis of NHL in the setting of HIV infection. AIDS-related NHL remains an important biologic model for investigating the development and progression of high-grade NHLs as well as NHLs that develop in immune-deficient hosts.
在感染HIV的个体中，非霍奇金淋巴瘤（NHL）的发病率大幅上升。绝大多数是临床上具有侵袭性的B细胞源性肿瘤，表现为伯基特淋巴瘤（BL）、免疫母细胞淋巴瘤（IBL）或淋巴母细胞淋巴瘤（LCL）组织学特征。约80%为全身性发病（淋巴结和/或结外），其余20%为原发性中枢神经系统淋巴瘤。一小部分是与卡波西肉瘤相关疱疹病毒（KSHV）感染相关的体腔淋巴瘤。导致淋巴瘤发生的可能因素包括HIV诱导的免疫抑制、慢性抗原刺激和细胞因子过度产生。这些改变与寡克隆B细胞扩增的发生有关。NHL的出现特征是存在一个显示多种基因损伤的单克隆B细胞群体，包括EB病毒感染、c-myc基因重排、bcl-6基因重排、ras基因突变和p53突变/缺失。基因损伤的数量和类型因解剖部位和组织病理学而异。在BL病例中，几乎100%表现出c-myc基因重排，三分之二显示p53基因突变，三分之一含有EB病毒，且无bcl-6基因重排。相比之下，在IBL病例中，几乎100%含有EB病毒，25%显示c-myc基因重排，20%显示bcl-6基因重排，很少有p53基因突变。这些发现表明，不止一种致病机制在艾滋病相关NHL的发生和发展中起作用。有必要开展进一步研究，以全面了解HIV感染情况下NHL的病因和发病机制。艾滋病相关NHL仍然是研究高级别NHL以及免疫缺陷宿主中发生的NHL的发生和发展的重要生物学模型。
