Etiology and pathogenesis of AIDS-related non-Hodgkin's lymphoma

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Epidemiology

The first cases of AIDS-related non-Hodgkin's lymphoma (NHL) were described in 1982 [5], [6], approximately 1 year after the initial reports of AIDS [7], [8]. The patients were young immunocompromised men who have sex with men (MSM) with advanced-stage Burkitt's-like lymphoma. The Centers for Disease Control (CDC) subsequently revised their initial diagnostic criteria for AIDS to include diffuse, undifferentiated (Burkitt's and Burkitt's-like) lymphoma occurring in an HIV-seropositive

Sites of disease

AIDS-related NHLs are divisible according to their anatomic site of origin into three broad categories: systemic (nodal or extranodal), primary central nervous system (CNS), and body cavity-based or primary effusion lymphomas [16].

The systemic NHLs comprise approximately 80% of all AIDS-related NHLs. Approximately two-thirds of individuals who have AIDS-related systemic NHL possess stage III or IV disease, and most of the remaining individuals have stage IE disease (usually bulky) at

Lineage and clonality

Many investigators [11], [12], [13], [28], [34], [50] have shown that the more than 90% of AIDS-related systemic and primary CNS lymphomas that display Burkitt's, immunoblastic, and large cell morphology express monotypic surface immunoglobulin (SIg) or B-cell lineage-associated antigens CD19, CD20, or CD22 in the absence of T-cell lineage-associated antigens. These AIDS-related B-cell NHLs express immunophenotypes similar to those expressed by NHLs of comparable morphology occurring in the

Molecular genetics

Several proto-oncogenes and tumor suppressor genes are believed to play a significant role in lymphomagenesis through chromosomal translocation, point mutation, and other mechanisms. Structural alterations involving these genes occur nonrandomly in association with specific histopathologic categories of conventional NHL [74]. Some of these same alterations also occur in AIDS-related NHLs [16], [73].

Reciprocal chromosomal translocations between the MYC oncogene on chromosome 8 and the

HIV

The inability to detect HIV sequences in the genome of freshly isolated AIDS-related lymphomas and in vitro cell lines by Southern blotting [64], [65], [118], [119] fails to support the hypothesis that HIV plays a direct role in AIDS lymphomagenesis. Furthermore, polymerase chain reaction (PCR) analysis of AIDS-related lymphoma tissue has demonstrated HIV levels that are consistent with the presence of benign T cells infiltrating within the tissues and inconsistent with HIV infection of the

Summary

The incidence of NHL is greatly increased in HIV-infected individuals; malignant lymphoma is the second most common neoplasm that occurs in association with AIDS. The vast majority of neoplasms are clinically aggressive, monoclonal B-cell neoplasms that exhibit Burkitt's, immunoblastic, large cell, or transitional histopathology. Approximately 80% arise systemically (nodal or extranodal) and 20% arise as primary CNS lymphomas. A small proportion of neoplasms are body cavity-based, primary

Acknowledgements

The author wishes to thank his colleagues and collaborators, Drs. Ethel Cesarman, Amy Chadburn, Yuan Chang, Riccardo Dalla-Favera, Gianluca Gaidano, Patrick Moore, and Pier-Giuseppe Pelicci, without whom portions of the studies discussed in this article would not have been possible.

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