Complete Absence of KSHV/HHV8 in Post-Transplant Lymphoproliferative Disorders: An Immunohistochemical and Molecular Study of 52 Cases
W Chen, Q Huang, CW Zuppan, EH Rowsell, JD Cao, LM Weiss, J Wang. City of Hope National Medical Center, Duarte, CA; Loma Linda University Medical Center, Loma Linda, CA; Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Background: Kaposi sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV8), is lymphotropic and has been associated with primary effusion lymphoma, multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma. KSHV/HHV8-associated lymphomas occur mostly in HIV-positive and other immunosuppressed patients, suggesting an association of immunosuppression, KSHV/HHV8 infection and lymphomagenesis. Post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoproliferative disorders that occur exclusively in iatrogenically immunosuppressed recipients following solid organ or bone marrow transplantation, and represent a spectrum of diseases ranging from early EBV driven polyclonal B-cell proliferation to full-fledged lymphoma. The clear relationship between KSHV/HHV8 infection and pathogenesis of PTLDs remains largely unknown. In the present study, we investigate the role of KSHV/HHV8 in various forms of PTLD in 43 organ transplant patients.
Design: 52 formalin-fixed, paraffin-embedded PTLD tissue specimens from 43 patients were analyzed for EBV status by EBER in situ hybridization and for expression of KSHV/HHV8 LNA-1 protein by immunohistochemistry, as well as for KSHV/HHV8 genome by PCR analysis on most cases.
Results: The 43 patients ranged from 1 to 64 years old (median age 9 years). Most PTLDs developed after heart (79%), kidney (11.5%), and liver (9.5%) transplantation. Diagnosis and classification were based on the current WHO criteria. The PTLD subtypes included 12 early changes (1 plasmacytic hyperplasia and 11 infectious-monoinucleosis-like), 10 polymorphic, 23 monomorphic (5 Burkitt, 14 diffuse large B cell lymphoma, 1 plasmacytoma, 1 multiple myeloma, and 2 T-cell), 1 Hodgkin lymphoma (HL), 5 HL-like lesions, and one unclassified. 92% of tested cases (46/50) were EBER+. None of the tested specimens (0/51) showed expression of KSHV/HHV8 LNA-1 protein. Furthermore, all specimens tested (46/46) were negative for KSHV/HHV8 genome by PCR analysis.
Conclusions: Despite the strong association of KSHV/HHV8 with lymphoma in patients with HIV infection and other forms of immune dysregulation, our results indicate that KSHV/HHV8 is not associated with lymphoproliferative disorders in the post-transplantation setting.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 166, Wednesday Morning