title: Primary effusion lymphoma in HIV-infected patients with multicentric Castleman's disease.
abstract: Multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL) are two B-cell lymphoproliferative diseases associated with Kaposi's sarcoma-associated herpes virus/human herpesvirus-8 (KSHV/HHV-8). Although MCD is considered a prelymphoma state, it is not known whether a pathogenetic link exists between MCD and PEL. This paper reports the clinico-pathological features of four cases of PEL (two pericardial, one pleural, and one peritoneal) developing in the context of HIV-associated MCD. Effusions, lymph nodes, spleen, and additional tissues from three autopsies were examined for morphology/immunophenotype, search for HHV-8 DNA, and assessment of immunoglobulin 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 polyclonal. Light-chain immunostaining confirmed B-cell clonality in PEL (two lambda, one kappa, one not tested) and polyclonality in MCD. The autopsies revealed different morphological variants of visceral KS and multi-organ atypical infiltrates exhibiting immunoblastic/plasmablastic features reminiscent of 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 identical junctional size to the PEL clone; however, further analysis with PEL-derived clonotypic primers and sequencing of PCR products showed no amplification 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 association between these two HHV-8-related disorders. Although a definite clonal relationship between MCD and PEL was not demonstrated, it is hypothesized that in some MCD cases, within expanded polyclonal B-cell populations secondary to HHV-8 infection, clonal expansions may occur that localize into a body cavity, i.e. PEL.
authors.affiliation: Anatomia Patologica, Dipartimento di Medicina Sperimentale e Patologia, Università La Sapienza, Roma, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Ascoli
authors.forename: S
authors.initials: S
authors.lastname: Signoretti
authors.forename: A
authors.initials: A
authors.lastname: Onetti-Muda
authors.forename: E
authors.initials: E
authors.lastname: Pescarmona
authors.forename: C
authors.initials: C
authors.lastname: Della-Rocca
authors.forename: F
authors.initials: F
authors.lastname: Nardi
authors.forename: C M
authors.initials: CM
authors.lastname: Mastroianni
authors.forename: R
authors.initials: R
authors.lastname: Gastaldi
authors.forename: A
authors.initials: A
authors.lastname: Pistilli
authors.forename: G
authors.initials: G
authors.lastname: Gaidano
authors.forename: A
authors.initials: A
authors.lastname: Carbone
authors.forename: F
authors.initials: F
authors.lastname: Lo-Coco
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes; D005871:Castleman Disease / Q000150:complications* / Q000276:immunology / Q000473:pathology; D004279:DNA, Viral / Q000032:analysis; D015321:Gene Rearrangement; D006679:HIV Seropositivity / Q000150:complications* / Q000276:immunology / Q000473:pathology; D019288:Herpesvirus 8, Human / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D016130:Immunophenotyping; D008223:Lymphoma / Q000150:complications* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D004279:DNA, Viral; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains