Non-Hodgkin's Lymphoma

B-cell lymphoma frequently occurs in immunosuppressed individuals. Genetic disorders of the immune system such as Wiskott-Aldrich syndrome, as well as immunosuppressive therapy used in organ transplantation, are associated with malignant transformation of B cells and an oligoclonal or monoclonal lymphoma. Non-Hodgkin's B-cell lymphoma is a frequent manifestation of HIV infection, occurring in 4 to 10% of the affected population. The relative risk of lymphoma in HIV-infected individuals compared with matched uninfected controls is 60- to 100-fold. The incidence of B-cell lymphoma in this population appears stable despite the introduction of potent antiretroviral therapy and may increase as survival lengthens and control of opportunistic infections improves.

Causative factors operative in the development of lymphoma in AIDS are likely to be multiple. HIV provides a permissive environment in which lymphoma develops. Lymphoma in this setting may be regarded as an opportunistic neoplasm and is considered an AIDS-defining illness. Proliferative signals to B cells, whether from dysfunctional T cells, aberrant cytokine production, or infections (such as Epstein-Barr virus or HIV-1 itself), may induce polyclonal expansion of the B-cell population. This expanded population may provide targets for genetic abnormalities that lead to malignant transformation and emergence of several dominant clones.

The oligoclonal populations of malignant B cells seen in some HIV-infected individuals with lymphoma support such a model. Ultimately, a single malignant clone may emerge, leading to a monoclonal neoplasm. The chromosomal abnormalities frequently seen in B-cell lymphoma involve translocation of loci encoding the immunoglobulin genes with the c-myc oncogene. Over 75% of AIDS-related lymphomas manifest alterations in at least one proto-oncogene, and a large fraction also have alterations in at least one tumor-suppressor gene. Genetic evidence of Epstein-Barr virus is found in about one half of B-cell lymphomas in AIDS patients and virtually all primary CNS lymphomas in AIDS. A number of interacting factors are likely to be important in the pathogenesis of lymphoma in those patients with HIV infection united by the disorganization of immune function induced by HIV. Recently, KSHV or HHV-8 infection has been associated with a distinct subset of B-cell lymphomas that presents with body cavity effusions. These aggressive lymphomas also frequently have genomic material from Epstein-Barr virus.

Clinically, B-cell lymphoma in AIDS patients tends to be of high-grade histologic pattern and follows an aggressive clinical course. Small, noncleaved or large cell histologies account for nearly all lymphomas in this setting. The low-grade lymphomas are uncommon and may represent background rather than a neoplasm directly associated with immunosuppression. Rarely, B-cell acute lymphoblastic leukemia or T-cell neoplasms have been reported.
Most patients have extranodular disease involving the gastrointestinal tract, CNS, liver, soft tissues, or bone marrow. In one large series, nearly 80% of all patients diagnosed with B-cell lymphoma in AIDS had extra-nodal involvement. Lymphoma strictly confined to lymph nodes is uncommon.