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.
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.
Authors: Mark N Polizzotto; Thomas S Uldrick; Victoria Wang; Karen Aleman; Kathleen M Wyvill; Vickie Marshall; Stefania Pittaluga; Deirdre O'Mahony; Denise Whitby; Giovanna Tosato; Seth M Steinberg; Richard F Little; Robert Yarchoan Journal: Blood Date: 2013-10-30 Impact factor: 22.113
Authors: Thomas S Uldrick; Mark N Polizzotto; Karen Aleman; Deirdre O'Mahony; Kathleen M Wyvill; Victoria Wang; Vickie Marshall; Stefania Pittaluga; Seth M Steinberg; Giovanna Tosato; Denise Whitby; Richard F Little; Robert Yarchoan Journal: Blood Date: 2011-04-12 Impact factor: 22.113
Authors: Thomas S Uldrick; Mark N Polizzotto; Karen Aleman; Kathleen M Wyvill; Vickie Marshall; Denise Whitby; Victoria Wang; Stefania Pittaluga; Deirdre O'Mahony; Seth M Steinberg; Richard F Little; Robert Yarchoan Journal: Blood Date: 2014-10-20 Impact factor: 22.113
Authors: Kristen M Tamburro; Dongmei Yang; Jessica Poisson; Yuri Fedoriw; Debasmita Roy; Amy Lucas; Sang-Hoon Sin; Nadia Malouf; Vincent Moylan; Blossom Damania; Stephan Moll; Charles van der Horst; Dirk P Dittmer Journal: Virology Date: 2012-08-24 Impact factor: 3.616