Molecular Pathogenesis of Aids-Related Lymphomas

Abstract

Publisher Summary This chapter focuses on the molecular pathogenesis of acquired immunodeficiency syndrome (AIDS)-related lymphomas. Non-Hodgkin's lymphoma (NHL) is the second most frequent cancer associated with AIDS after Kaposi's sarcoma (KS), and in some AIDS-risk groups, such as the hemophiliacs, NHL overrates KS, thereby representing the most common AIDS-associated neoplasia. Various epidemiologic features distinguish AIDS-NHL from AIDS-related KS (AIDS-KS). First, AIDS-NHL is a relatively late event in AIDS natural history, whereas AIDS-KS is a frequent symptom. Second, AIDS-NHL displays a relatively uniform risk across all HIV-infected risk groups, whereas AIDS-KS is characterized by a strong association with male homosexuality. The detailed pathological classification of AIDS-NHL has been a matter of controversy, and it is continuously being remodeled. The development of B-cell NHL in the context of AIDS is often preceded by symptoms such as polyclonal hypergammaglobulinemia and persistent generalized lymphadenopathy (PGL), which indicate the presence of chronic B-cell stimulation and expansion. Host factors contributing to AIDS-related lymphoma genesis include Epstein–Barr virus (EBV), human immunodeficiency virus (HIV), and other viruses. Genetic lesions involved in AIDS-related lymphomas include dominantly acting oncogenes and tumor suppressor loci. AIDS-NHL is a strikingly heterogeneous disease. At least two major pathogenetic pathways can be identified in AIDS-related lymphomagenesis. Each of these pathogenetic pathways associates with peculiar clinical features and is restricted to distinct AIDS-NHL histological types.