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Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV‐8)‐infected B cells in HIV+ multicentric Castleman disease (MCD)
Author(s) -
Chadburn A,
Hyjek E M,
Tam W,
Liu Y,
Rengifo T,
Cesarman E,
Knowles D M
Publication year - 2008
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2008.03144.x
Subject(s) - primary effusion lymphoma , kaposi's sarcoma associated herpesvirus , biology , immunophenotyping , virology , immunohistochemistry , b cell , lymphoma , antibody , virus , microbiology and biotechnology , herpesviridae , immunology , flow cytometry , viral disease
Aims: Kaposi sarcoma herpesvirus (KSHV) is aetiologically related to Kaposi sarcoma, classical and extracavitary primary effusion lymphoma (PEL; EC‐PEL) and multicentric Castleman disease (MCD), entities preferentially occurring in HIV‐infected individuals. Characterization of HIV‐associated PELs/EC‐PELs suggests that the KSHV‐infected malignant cells originate from a pre‐terminal stage of B‐cell differentiation. However, only limited phenotypic studies have been performed on HIV+ MCD, including for PR domain containing 1 with zinc finger domain/B lymphocyte‐induced maturation protein 1 (PRDM1/BLIMP1), a key regulator of terminal B‐cell differentiation. The aim was to characterize KSHV‐infected cells in 17 cases of HIV+ MCD. Methods and results: Double immunohistochemistry and immunohistochemistry– in situ hybridization were used to characterize the KSHV‐infected cells in MCD; the results were compared with the phenotypic profiles of 39 PELs/EC‐PELs and seven PEL cell lines. Whereas the immunophenotype of KSHV‐infected cells in MCD and malignant KSHV+ PEL cells was similar (PAX5, Bcl‐6−; PRDM1/BLIMP1, IRF4/MUM1+; Ki67+), the MCD KSHV‐infected cells differed, as they expressed OCT2, cytoplasmic λ immunoglobulin; variably expressed CD27; lacked CD138; and were Epstein–Barr virus negative. Conclusions: Although both PEL and MCD originate from KSHV‐infected pre‐terminally differentiated B cells, these findings, with previously reported genetic studies, indicate HIV+ MCD may arise from extrafollicular B cells, whereas PELs may originate from cells that have traversed the germinal centre.