Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8-associated polyclonal body cavity effusions that mimic primary effusion lymphomas

Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) is involved in the pathogenesis of Kaposi's sarcoma (KS) and 2 lymphoproliferative diseases, primary effusion lymphoma (PEL) and the plasmablastic variant of multicentric Castleman's disease (MCD). PEL is defined as a liquid-phase lymphoma harboring monoclonal rearrangements of immunoglobulin (Ig) variable genes or, more rarely, of T-cell receptor (TCR) genes. As a rule, these elements are used for PEL diagnosis together with the demonstration of HHV-8 infection of the tumor clone. We report here a group of five patients with MCD and KS (n = 2) or MCD only (n = 2) or KS only (n = 1); subjects with KS showed cutaneous and visceral involvement. All 5 patients developed recurrent and massive HHV-8-positive body cavity effusions, often in multiple sites, and died shortly after diagnosis. Cytological examination of effusion specimens disclosed the absence of lymphoma cells in all cases. In the context of MCD or MCD and KS, the effusion cell population was found to include 5–30% of atypical lymphoid cells with plasmacytic features and reminiscent of PEL. Our observations suggest that patients with MCD and/or KS (not exclusively in association with HIV infection) may develop recurrent HHV-8-positive body cavity effusions other than PEL, although with a similar poor outcome. Their common morphologic and molecular features appear to identify a nonlymphomatous entity. The identification of HHV-8 in polyclonal effusions that mimic PEL is notable in light of the association between HHV-8 and PEL, and suggests a putative model of PEL lymphomagenesis.