Title | Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD). |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Chadburn A, Hyjek EM, Tam W, Liu Y, Rengifo T, Cesarman E, Knowles DM |
Journal | Histopathology |
Volume | 53 |
Issue | 5 |
Pagination | 513-24 |
Date Published | 2008 Nov |
ISSN | 1365-2559 |
Keywords | Adult, B-Lymphocytes, Castleman Disease, Cell Differentiation, Female, Herpesviridae Infections, Herpesvirus 8, Human, HIV Infections, Humans, Immunohistochemistry, Immunophenotyping, In Situ Hybridization, Lymphoma, Primary Effusion, Male, Middle Aged |
Abstract | 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 lambda 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. |
DOI | 10.1111/j.1365-2559.2008.03144.x |
Alternate Journal | Histopathology |
PubMed ID | 18983461 |
Related Faculty:
Amy Chadburn, M.D. Ethel Cesarman, M.D., Ph.D.