Epstein-Barr virus in a malignant lymphoproliferative disorder of B-cells occurring after thymic epithelial transplantation for combined immunodeficiency.

A fatal disseminated polyclonal malignant lymphoproliferative disorder of B-cells (immunoblastic sarcoma) developed shortly after a second thymic epithelial peritoneal implant in a 5-yr-old girl with combined immunodeficiency. The immunodeficiency was characterized by low T-cell numbers and function, very low levels of thymic hormone, dysgammaglobulinemia, and an inability to mount a primary antibody or cell-mediated response to new antigens. At necropsy, the thymus fulfilled morphological criteria for thymic dysplasia. Epstein-Barr virus (EBV) antigen and DNA were identified in neoplastic infiltrates in the lymph nodes and thymus by immunofluorescence for the EBV nuclear antigen and by EBV-specific complementary RNA/DNA hybridization. No antibodies to nuclear antigen, early antigen, or viral capsid antigen of EBV were identified in the serum. The concurrence of these events suggests that the thymic epithelial implant itself may have been instrumental in the pathogenesis of this neoplasm. It is proposed that the thymus may have provided factors which indirectly potentiated the proliferation of EBV-infected B-cells, possibly by induction of nonspecific T-helper cells and perhaps through other thymic humoral factors. It is suggested that some forms of immunoblastic sarcoma, even when polyclonal, and especially those which arise in immunocompromised hosts, may, in some instances, represent an opportunistic form of EBV-induced B-cell neoplasia.