Expression of MUM1/IRF4 selectively clusters with primary effusion lymphoma among lymphomatous effusions: implications for disease histogenesis and pathogenesis

Primary effusion lymphoma (PEL) is a peculiar B-cell lymphoma characterized by infection by human herpesvirus type-8/Kaposi sarcoma-associated herpesv irus (HHV-8/KSHV) and by preferential growth in the serous body cavities, H istogenetic studies have suggested that PEL originates from B cells at a la te stage of differentiation. In this study, we have investigated PEL for th e expression status of MUM1/IRF4 (multiple myeloma 1/interferon regulatory factor 4) protein, which is involved in physiological B-cell maturation and represents a histogenetic marker of late B-cell differentiation. Using mul tiple detection assays, all cases of PEL (n = 22) were found to express MUM 1/IRF4 molecules, MUM1/IRF4 expression was a selective feature of PEL among lymphomas involving the serous body cavities as secondary lymphomatous eff usions generally failed to express the protein. In reactive lymphoid tissue s, MUM1/IRF4 IRF4 expression clustered with advanced stages of B-cell diffe rentiation. Comparison of MUM1/IRF4 expression with that of other histogene tic markers defined two phenotypic variants of PEL, i.e, MUM1/IRF4(+), CD13 8/syndecan-1(+) B-cell antigen(-) (20 out of 22 cases) and MUM1/IRF4(+) CD1 38/syndecan-1(-), B-cell antigen(+) (2 out of 22 cases), suggesting a certa in degree of heterogeneity in the disease histogenesis. The implications of these data are threefold. First, MUM1/IRF4 expression corroborates the not ion that PEL originates from post-germinal centre, preterminally differenti ated B-cells. Second, MUM1/IRF4 may help in the differential diagnosis of P EL among other lymphomas involving the serous body cavities, Finally MUM1/I RF4 may interact with HHV-8/KSHV-encoded interferon regulatory factors (IRF s) and thus contribute to PEL escape from interferon-mediated control of vi ral infection.