CORRELATIVE MORPHOLOGIC AND MOLECULAR GENETIC ANALYSIS OF 75 AIDS-RELATED SYSTEMIC NON-HODGKIN LYMPHOMAS

Abstract

Background: Non-Hodgkin lymphoma (NHL) is the second most common neoplasm occurring in AIDS. The vast majority of AIDS-related NHLs have been reported to be of B-cell origin and to exhibit clonal immunoglobulin (Ig) gene rearrangements. However, some recent studies have described the absence of clonal Ig gene rearrangements among 40% or more of AIDS-NHLs from the west coast of the USA, suggesting a new entity called "polyclonal AIDS-related lymphomas". Furthermore, prior studies have suggested that different histopathologic categories of AIDS-related NHL are characterized by specific molecular alterations. The goals of this study were to resolve the controversy surrounding the clonal nature of AIDS-related NHLs and to further investigate the relationship between their morphology and molecular genetic alterations. Methods: We collected 75 AIDS-related systemic NHLs from the east coast (38) and the west coast (37) of the USA and performed a comprehensive molecular analysis, including the evaluation of Ig heavy and light chain gene and T-cell receptor β-chain(TCR-β) gene rearrangements, and the presence of c-myc, bel-6, ras oncogene and p53 tumor suppressor gene alterations and viral infection (EBV, KSHV/HHV 8). Furthermore, we independently reviewed their histopathology and correlated the morphologic and molecular genetic findings. Results: We classified the lymphomas into the following morphologic categories: classical Burkitt lymphoma (BL) (6/75). Burkitt-like lymphoma (BLL) (20/75), large cell lymphoma(LCL) (12/75), immunoblastic lymphoma (IBL) (26/75), polymorphic lymphoproliferative disorder (PLD) (10/75) and peripheral T-cell lymphoma (PTCL) (1/75). The clonal EBV infection patterns and molecular genetic lesions were similar on the east and west coasts of the USA. A dominant clonal B-cell population was demonstrated in 36/37 (98%) east coast and 35/38 (92%) west coast cases by Ig heavy and light chain gene rearrangement and/or EBV terminal repeat analysis. Among the four germline cases one exhibited immunoblastic, two polymorphic and one peripheral T-cell lymphoma morphology. The presence and type of viral infection and the specific molecular genetic alterations associated with each histopathologic category were: Table 1Conclusions: First, AIDS-related systemic NHLs lacking detectable clonal Ig and TCR β chain gene rearrangements and clonal EBV infection exist but are rare, accounting for only 2% and 8% of our cohort of east and west coast cases of AIDS-related NHL, respectively. Second, whether these morphologically malignant NHLs are truly polyclonal or the Ig gene rearrangements are simply not detectable with the methods employed remains to be determined. Third, EBV infection and specific molecular genetic alterations do not appear to correlate with distinct histopathologic categories of AIDS-related NHL as suggested previously.