THE NATURAL-HISTORY AND MOLECULAR HETEROGENEITY OF HIV-ASSOCIATED PRIMARY MALIGNANT LYMPHOMATOUS EFFUSIONS

Primary malignant lymphomatous effusions arising in individuals infect ed with the human immunodeficiency virus, type 1 (HIV-1) represent a r are subset of HIV-associated lymphomas. Previous studies have demonstr ated that the malignant cells are monoclonal (as defined by rearrangem ent of the immunoglobulin gene), express cell surface CD38, and are in fected with Epstein-Barr virus (EBV) and human herpes virus, type 8 (H HV-8). Despite these detailed molecular and immunophenotypic studies, clinical information on this disease entity is scant, prompting us to review the clinical features of eight cases seen at our institutions. All eight patients had total peripheral CD4 + lymphocytes <200/mu l an d presented with complaints related to body cavity distension. Routine laboratory values were nondiagnostic and yielded no prognostic inform ation. Only two patients could tolerate and thus received chemotherapy with no obvious impact on their clinical course. The mean overall sur vival after diagnosis was 60 days (range 6-166 days). Four patients we re examined at autopsy. The primary malignant lymphomatous effusion ei ther was the immediate cause of death or contributed significantly to the death of only two. All four patients examined post mortem, however , had lymphomatous infiltration of serosal surfaces adjacent to the si te of the primary malignant effusion. Molecular and immunologic studie s performed on the malignant cells and effusion fluids revealed univer sal expression of cell surface CD38 and the presence of HHV-8 gene seq uences, but in contrast with previous studies, only four had rearrange d immunoglobulin genes or EBV present; IL-6 and IL-10 levels in the ma lignant effusion fluids were markedly elevated, In summary, this rare subset of HIV-associated lymphomas in our eight patients arose late in the course of HIV-associated disease, had a rapid clinical course, an d was molecularly heterogeneous. A pathogenetic role for HHV-8 alone i n this disease process is strengthened by our observation of four case s lacking EBV but containing HHV-8.