Presence of p16 hypermethylation and Epsteine Barr virus infection in transplant-associated hematolymphoid neoplasm of the skin Jack L. Arbiser, MD, PhD, a,c Karen P. Mann, MD, PhD, b Elizabeth M. Losken, MD, a Cynthia Cohen, MD, b Kalpana Reddy , a,c Kenneth Kokko, MD, d Brian Pollack, MD, PhD, a Chung-Yang Fan, PhD, e and Fiona O’Reilly, MD a Atlanta, Georgia, and Little Rock, Arkansas Background: EpsteineBarr virus (EBV) is associated with the malignant transformation of B, T, and NK lymphocytes in humans, especially in immunosuppressed individuals. Objective: We describe an unusual case confined to the skin in a 39-year-old African American female following a renal transplant. Methods: 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-g). In situ hybridization demonstrated the presence of EpsteineBarr early RNA species (EBER) in the lymphoma cells, consistent with EBV infection. Results: 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. Limitations: Further studies are needed to determine whether p16 is widely suppressed in immunosup- pression-induced lymphoma. Conclusion: 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. ( J Am Acad Dermatol 2006;55:794-8.) A 39-year-old African American female re- ceived a cadaveric renal transplant for hy- pertension-induced, end-stage renal disease in 1998. She was known to be EpsteineBarr virus (EBV)-positive at the time of the transplant. Syner- gistic immunosuppression with cyclosporin and rapamycin was complicated by early allograft nephropathy. Multiple surgical complications with renal obstruction secondary to a lymphocele neces- sitating a ureteroureterostomy contributed to a fur- ther decline in renal function. She presented 3 years posttransplant with renal insufficiency (creatinine = 7 mg/dl) and a 2-month history of multiple firm, asymptomatic nodules on the bilateral lower ex- tremities (Fig 1, A). Review of systems was negative, and no peripheral lymphadenopathy was detected. A biopsy of a leg lesion led to the diagnosis of hematolymphoid neoplasm. After the diagnosis was made, the patient was referred to the Department of Radiation Oncology for external beam radiation therapy, leading to resolution of the lower extremity lesions, but re-presented some months later with facial lesions. A biopsy of these lesions also revealed hematolymphoid neoplasm. She was started on chemo- therapy, part A of hyper-CVAD (cyclophosphamide, From the Departments of Dermatology, a Pathology and Labora- tory Medicine, b and Medicine, Atlanta VA Medical Center c ; the Division of Nephrology, d Emory University School of Medicine; and the Department of Pathology, e University of Arkansas Medical Center. Supported in part by research funding to J.L.A. (National Institutes of Health grants RO1 AR47901 and P30 AR42687 to the Emory Skin Disease Research Center) and a VA Merit Award to J.L.A. Conflicts of interest: None identified. Accepted for publication June 4, 2006. Reprints not available from the authors. Correspondence to: Jack L. Arbiser, MD, PhD, Department of Dermatology, Emory University School of Medicine, WMB 5309, 1639 Pierce Dr, Atlanta, GA 30322. E-mail: jarbise@emory.edu. Published online September 4, 2006. 0190-9622/$32.00 ª 2006 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2006.06.043 794