DIFFERENTIAL EXPRESSION OF BCL-6, CD138 SYNDECAN-1, AND EPSTEIN-BARR VIRUS-ENCODED LATENT MEMBRANE PROTEIN-1 IDENTIFIES DISTINCT HISTOGENETIC SUBSETS OF ACQUIRED IMMUNODEFICIENCY SYNDROME-RELATED NON-HODGKINS-LYMPHOMAS/

This study was aimed at defining the histogenesis of the pathologic sp ectrum of acquired immunodeficiency syndrome-related non-Hodgkin's lym phomas (AIDS-NHL), including AIDS-related smalt noncleaved cell lympho ma (AIDS-SNCCL), AIDS-related large noncleaved cell lymphoma (AIDS-LNC CL), AIDS-related large cell immunoblastic lymphoma plasmacytoid (AIDS -IBLP), and AIDS-related primary effusion lymphoma (AIDS-PEL). Forty-s ix cases of AIDS-NHL were investigated for the expression pattern of B CL-6, a protein specifically expressed by germinal center (GC) B-cells , and CD138/syndecan-1 (syn-1), a marker of post-GC B-cell differentia tion. Expression of BCL-6 and syn-1 segregated two major phenotypic pa tterns among AIDS-NHL: (1) the BCL-6(+)/syn-1(-) pattern associated wi th AIDS-SNCCL and AIDS-LNCCL; (2) the BCL-6(-)/syn-1(+) pattern associ ated with AIDS-IBLP and AIDS-PEL. Among systemic AIDS-NHL infected by Epstein-Barr virus (EBV), expression of the EBV-encoded latent membran e protein-1 (LMP-1) preferentially associated with the BCL-6(-)/syn-1( +) profile. Analysis of nonneoplastic lymph nodes showed that the two phenotypic patterns detected in AIDS-NHL correspond to physiologic sta ges of B-cell development, ie, GC B-cells (BCL-6(+)/syn-1(-)) and pret erminally differentiated post-GC B-cells (BCL-6(-)/syn-1(+)). Thus, BC L-6(+)/syn-1(-) AIDS-NHL reflects a GC stage of differentiation, where as AIDS-NHL which are BCL-6(-)/syn-1(+), and LMP-1(+) when infected by EBV, derive from B cells that have entered post-GC plasmacell differe ntiation. These findings are relevant for the pathogenesis and differe ntial diagnosis of AIDS-NHL. (C) 1998 by The American Society of Hemat ology.