title: Etiology and pathogenesis of AIDS-related non--Hodgkin's lymphoma.
abstract: 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.
authors.affiliation: Department of Pathology, Cornell University Medical College, New York, New York, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Knowles
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006678:HIV / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D016483:Lymphoma, AIDS-Related / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000821:virology; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000821:virology; D011519:Proto-Oncogenes / Q000502:physiology; D014481:United States
chemical_list: D016207:Cytokines; D006133:Growth Substances