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-Hodgkin's lymphomas

This study was aimed at defining the histogenesis of the pathologic spectrum of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas (AIDS-NHL), including AIDS-related small noncleaved cell lymphoma (AIDS-SNCCL), AIDS-related large noncleaved cell lymphoma (AIDS-LNCCL), AIDS- related large cell immunoblastic lymphoma plasmacytoid (AIDS-IBLP), and AIDS- related primary effusion lymphoma (AIDS-PEL). Forty-six cases of AIDS-NHL were investigated for the expression pattern of BCL-6, a protein specifically expressed by germinal canter (GC) B-cells, and CD138/syndecan-1 (syn-1), a marker of post-GC B-cell differentiation. Expression of BCL-6 and syn-1 segregated two major phenotypic patterns among AIDS-NHL: (1) the BCL-6⁺/syn- 1^- pattern associated with AIDS-SNCCL and AIDS-LNCCL; (2) the BCL-6^-/syn- 1⁺ pattern associated with AIDS-IBLP and AIDS-PEL. Among systemic AIDS-NHL infected by Epstein-Barr virus (EBV), expression of the EBV-encoded latent membrane 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 stages of B-cell development, is, GC B-cells (BCL-6⁺/syn-1^-) and preterminally differentiated post-GC B-cells (BCL6^-/syn-1⁺). Thus, BCL-6⁺/syn-1^- AIDS- NHL reflects a GC stage of differentiation, whereas AIDS-NHL which are BCL- 6^-/syn-1⁺, and LMP-1⁺ when infected by EBV, derive from B cells that have entered post-GC plasma-cell differentiation. These findings are relevant for the pathogenesis and differential diagnosis of AIDS-NHL.