Primary effusion lymphoma in HIV-infected patients with multicentric Castleman's disease

Multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL) are two B-cell lymphoproliferative diseases associated with Kaposi's sarcom a-associated herpes virus/human herpesvirus-8 (KSHV/HHV-8). Although MCD is considered a prelymphoma state, it is not known whether a pathogenetic lin k exists between MCD and PEL, This paper reports the clinicopathological fe atures of four cases of PEL (two pericardial, one pleural, and one peritone al) developing in the context of HIV-associated MCD. Effusions, lymph nodes , spleen, and additional tissues from three autopsies were examined for mor phology/immunophenotype, search for HHV-8 DNA, and assessment of immunoglob ulin heavy chain gene (IgH) configuration using polymerase chain reaction ( PCR)-based techniques. MCD and PEL samples contained HHV-8 DNA, Clonal IgH rearrangements were detected only in PEL, whereas MCD tissues were polyclon al. Light-chain immunostaining confirmed B-cell clonality in PEL (two lambd a, one kappa, one not tested) and polyclonality in MCD, The autopsies revea led different morphological variants of visceral KS and multi-organ atypica l infiltrates exhibiting immunoblastic/plasmablastic features reminiscent o f PEL morphology, with a restriction of lambda-positive cells. In two cases , using microdissection and IgH PCR analysis, multiple/discrete bands were found in the infiltrates, compatible with polyclonality/oligoclonality. The case showing an oligoclonal IgH ladder contained a rearrangement of identi cal junctional size to the PEL clone; however, further analysis with PEL-de rived clonotypic primers and sequencing of PCR products showed no amplifica tion and nucleotide diversity, respectively, indicating that the two B-cell populations examined were clonally unrelated. These data show that MCD and PEL may co-exist in HIV-infected patients, suggesting a relevant associati on between these two HHV-8-related disorders. Although a definite clonal re lationship between MCD and PEL was not demonstrated, it is hypothesized tha t in some MCD cases, within expanded polyclonal B-cell populations secondar y to HHV-8 infection, clonal expansions may occur that localize into a body cavity, i.e. PEL, Copyright (C) 2000 John Wiley & Sons, Ltd.