Epstein-Barr virus-related lymphomagenesis in a child with Wiskott-Aldrich syndrome

Epstein-Barr virus (EBV) DNA was detected in immunoblastic lymphoma arising in a child with the primary immunodeficiency, Wiskott-Aldrich syndrome. Southern blot analysis of the structure of the EBV genome revealed that the lymphoma was monoclonal and contained episomal EBV DNA. The EBV latent genes, latent membrane protein 1 (LMP1) and the EBV nuclear antigen 2 (EBNA2), were detected by immunohistochemistry in the Wiskott-Aldrich lymphoma but not in an EBV-positive Burkitt's lymphoma, implying that host immune factors could influence EBV gene expression. Hybridization in situ demonstrated expression of EBV-encoded RNA (EBER), the cellular c-fgr protooncogene, and CD23 B-cell activation transcripts in the Wiskott-Aldrich lymphoma whereas EBER and c-fgr but not CD23 were expressed in the Burkitt's lymphoma. These data suggest that in primary immunodeficiency-related lymphoma, LMP1 and EBNA2 are expressed and that this expression correlates with expression of CD23. This supports previous in vitro studies showing that CD23 is specifically induced by LMP1 or EBNA2 genes. In contrast, expression of c-fgr may be independent of expression of these EBV latent genes.