THE ASSOCIATION OF EPSTEIN-BARR-VIRUS WITH SMOOTH-MUSCLE TUMORS OCCURRING AFTER ORGAN-TRANSPLANTATION

Background. Epstein-Barr virus (EBV) has been associated with nasophar yngeal carcinoma, some lymphomas, and lymphoproliferative disease afte r organ transplantation. Many lymphoproliferative tumors that occur af ter transplantation are clonal, a property that classifies them as neo plastic. Clonality can be determined by analysis of the extrachromosom al circular DNA episomes produced by EBV infection. Methods. We descri be three young children in whom smooth-muscle tumors developed 18 mont hs to 5 1/2 years after liver transplantation with immunosuppression, We examined the tumors by microscopy and with immunohistochemical stud ies and molecular genetic analyses of the EBV DNA. Results. The tumors were composed of spindle cells with smooth-muscle features and resemb led those described in patients with the acquired immunodeficiency syn drome, Immunohistochemical analysis was negative for EBV latent membra ne protein and EBV receptor (CD21), but positive for EBV nuclear antig en 2. In situ hybridization revealed nuclear EBV sequences, and molecu lar genetic analysis showed the EBV genome to be clonal in all three p atients. Conclusions. Smooth-muscle tumors that developed after organ transplantation contained clonal EBV, suggesting that the virus has a role in the development of these neoplastic lesions.