Proposed model for the histogenesis of HIV-related lymphomas.

This model is based on the physiologic stages of mature B-cell development identified by histogenetic markers, such as mutation pattern of immunoglobulin variable region genes (IgV) andBCL-6 gene and expression profile of BCL-6, MUM1, and CD138/syn-1 proteins (rectangles). Virgin B cells do not display immunoglobulin or BCL-6 mutations and lack protein expression of BCL-6, MUM1, and syn-1. At the time of B-cell transit through the GC, B cells acquire IgV and BCL-6 mutations, which are maintained during further differentiation, thus constituting genotypic markers of GC transit.10,11,13 B cells within the GC (ie, centroblasts and centrocytes) express BCL-6 but not syn-1.1 Post-GC B cells undergoing maturation toward the plasma cell stage switch off BCL-6 expression and stain positive for syn-1. Based on the results of this study, the histogenetic model presented in the figure has been enriched by the addition of the MUM1 marker, which is expressed by late stages of intra-GC differentiation (centrocytes) and by post-GC B cells undergoing plasma cell maturation. GC B cells are identified as follows: centroblasts, large open circles; MUM1⁻ centrocytes, small open circles; MUM1⁺ centrocytes, small striped circles; FDC, follicular dendritic reticulum cell. The major HIV-lymphoma categories are indicated as BL (Burkitt lymphoma), DLCL, IBL, PEL, PBL, and HL. The putative histogenetic derivation of each lymphoma category is indicated by an arrow originating from the relevant B-cell compartment. The common phenotypic patterns exhibited by the different categories of HIV-lymphomas are indicated in the lower part of the figure. Some lymphoma categories, namely IBL, are characterized by histogenetic heterogeneity.