Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD).
OBJECTIVE
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.


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.
Chadburn
A
A
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10021, USA. achadbur@med.cornell.edu
Hyjek
E M
EM
Tam
W
W
Liu
Y
Y
Rengifo
T
T
Cesarman
E
E
Knowles
D M
DM
D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology*; D005871:Castleman Disease / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002454:Cell Differentiation; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006566:Herpesviridae Infections / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D054685:Lymphoma, Primary Effusion / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged