Evidence for a Mesothelial Origin of Body Cavity Effusion Lymphomas

David Sanchez-Martin, Thomas S. Uldrick, Hyeongil Kwak, Hidetaka Ohnuki, Mark N. Polizzotto, Christina M. Annunziata, Mark Raffeld, Kathleen M. Wyvill, Karen Aleman, Victoria Wang, Vickie A. Marshall, Denise Whitby, Robert Yarchoan, Giovanna Tosato*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Background: Primary effusion lymphoma (PEL) is a Kaposi's sarcoma herpes virus (KSHV)-induced lymphoma that typically arises in body cavities of HIV-infected patients. PEL cells are often co-infected with Epstein-Barr virus (EBV). "PEL-like" lymphoma is a KSHV-unrelated lymphoma that arises in body cavities of HIV-negative patients. "PEL-like" lymphoma is sometimes EBV positive. The derivation of PEL/"PEL-like" cells is unclear. Methods: Mesothelial cells were cultured from body cavity effusions of 23 patients. Cell proliferation, cytokine secretion, marker phenotypes, KSHV/EBV infection, and clonality were evaluated by standard methods. Gene expression was measured by quantitative polymerase chain reaction and immunoblotting. A mouse model of PEL (3 mice/group) was used to evaluate tumorigenicity. Results: We found that the mesothelia derived from six effusions of HIV-infected patients with PEL or other KSHV-associated diseases contained rare KSHV+ or EBV+ mesothelial cells. After extended culture (16-17 weeks), some mesothelial cells underwent a trans-differentiation process, generating lymphoid-type CD45+/B220+, CD5+, CD27+, CD43+, CD11c+, and CD3- cells resembling "B1-cells," most commonly found in mouse body cavities. These "B1-like" cells were short lived. However, long-term KSHV+EBV- and EBV+KSHV- clonal cell lines emerged from mesothelial cultures from two patients that were clonally distinct from the monoclonal or polyclonal B-cell populations found in the patients' original effusions. Conclusions: Mesothelial-to-lymphoid transformation is a newly identified in vitro process that generates "B1-like" cells and is associated with the emergence of long-lived KSHV or EBV-infected cell lines in KSHV-infected patients. These results identify mesothelial cultures as a source of PEL cells and lymphoid cells in humans.

Original languageEnglish
Article numberdjx016
JournalJournal of the National Cancer Institute
Issue number9
Publication statusPublished - 1 Sept 2017
Externally publishedYes


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