Presence of p16 hypermethylation and Epstein-Barr virus infection in transplant-associated hematolymphoid neoplasm of the skin.

Abstract

Epstein-Barr virus (EBV) is associated with the malignant transformation of B, T, and NK lymphocytes in humans, especially in immunosuppressed individuals. We describe an unusual case confined to the skin in a 39-year-old African American female following a renal transplant. Morphologically and immunophenotypically, the tumor was best classified as a plasmablastic lymphoma; however, the neoplastic population revealed rearrangements of both immunoglobulin heavy chain (IgG) and T cell receptor gamma (TCR-gamma). In situ hybridization demonstrated the presence of Epstein-Barr early RNA species (EBER) in the lymphoma cells, consistent with EBV infection. We have previously demonstrated that EBV-induced reactive oxygen is associated with hypermethylation of the tumor suppressor gene p16 in Burkitt lymphoma, and that p16 hypermethylation is nearly always associated with EBV infection in Burkitt lymphoma. Further studies are needed to determine whether p16 is widely suppressed in immunosuppression-induced lymphoma. In this study, we demonstrated high levels of hypermethylation of the tumor suppressor gene p16, thus supporting the role of EBV as a carcinogen in post-transplant lymphoproliferative disease.