B-cell lymphoma in severe combined immunodeficiency not associated with the Epstein-Barr virus

Patients with congenital and acquired immunodeficiencies are at increased risk for the development of B-cell lymphoproliferative disorders. When the appropriate tests have been performed, the Epstein-Barr virus (EBV) nuclear antigen (EBNA) or EBV DNA has been found in tissues from these tumors. These data have provided support for the idea that these tumors are associated with EBV. In this article we report about a child with severe combined immunodeficiency (SCID) who developed a malignant B-cell lymphoma that was not associated with EBV. The B-cell lymphoma in the patient proved to be, by hybridization analysis of immunoglobulin (Ig) heavy chain gene rearrangements of tumor-cell DNA, of clonal origin. However, neither EBNA nor EBV DNA could be detected in tumor tissue by anticomplement immunofluorescence or in situ cytohybridization with an EBV DNA probe. Furthermore, EBV DNA could not be detected by Southern blot hybridization using two EBV DNA hybridization probes on the same DNA blots that clearly contained the clonal Ig gene rearrangement. This case represents a clonal B-cell lymphoma occurring in a severely immunodeficient patient that was not associated with EBV. Antiviral chemoprophylaxis has been recommended for the prevention of EBV-related B-cell lymphoproliferations in transplant patients. Such prophylaxis may be ineffective in patients with B-cell lymphoproliferative disorders not associated with EBV.