Expression profile of MUM1/IRF4, BCL-6, and CD138/syndecan-1 defines novelhistogenetic subsets of human immunodeficiency virus-related lymphomas

This study was aimed at defining the histogenesis of the pathologic spectru m of lymphoma arising in the context of human immunodeficiency virus (HIV) infection. Toward this aim, 87 AIDS-related non Hodgkin lymphomas (AIDS-NHL ) and 16 Hodgkin lymphomas arising in HIV+ patients (HIV-HL) were comparati vely analyzed for the expression pattern of several B-cell histogenetic mar kers, including BCL-6 (expressed by centroblasts and centrocytes), MUM1/IRF 4 (expressed by late centrocytes and post-germinal center [GC] B cells), an d CD138/syn-1 (expressed by post-cc B cells). Expression of MUM1, BCL-6, an d syn-1 segregated 3 major phenotypic patterns among AIDS-NHL and HIV-HL: ( 1) the BCL-6(+)/MUM1(-)/ syn-1(-) pattern, selectively clustering with a la rge fraction of AIDS-Burkitt lymphoma (17 of 19) and of systemic AIDS-diffu se large cell lymphoma (12 of 16); (2) the BCL-6(-)/MUM1(+)/syn-1(-) patter n, associated with a fraction of AIDS-immunoblastic lymphoma (8 of 24); and (3) the BCL-6(-)/ MUM1(+)/syn-1(+) pattern, associated with systemic and p rimary central nervous system immunoblastic lymphoma (14 of 24) and with pr imary effusion lymphoma (10 of 10), plasmablastic lymphoma of the oral cavi ty (7 of 7), and HIV-HL (15 of 16), Analysis of nonneoplastic lymph nodes s howed that the 3 phenotypic patterns detected in AIDS-NHL and HIV-HL corres pond to distinct stages of physiologic B-cell developemtn-centroblasts (BCL -6(+)/MUM1(-)/syn1(-)), late GC/early post-cc B cells (BCL-6(-)/MUM1(+)/syn -1(-)), and post-GC B cells (BCL-6(-)/MUM1(+)/syn-1(+)). Expression of the Epstein-Barr virus-encoded latent membrane protein-1 clustered with the BCL -6(-)/MUM1(+)/syn-1(+) profile throughout the clinicopathologic spectrum of AIDS-NHL and HIV-HL, Overall, these results define novel histogenetic subs ets of AIDS NHL and HIV-HL and may provide novel tools for refining the dia gnosis of these disorders. (C) 2001 by The American Society of Hematology.