EPSTEIN-BARR-VIRUS AND PROGRESSION OF NON-HODGKINS-LYMPHOMA TO KI-1-POSITIVE, ANAPLASTIC LARGE-CELL PHENOTYPE

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a variety of lymphoproliferative disorders (LPDs) including endemic Burk itt's lymphoma, Hodgkin's disease (HD), HIV-associated non-Hodgkin's l ymphomas (NHLs), and LPDs arising in immunosuppressed transplant patie nts. More recently, EBV has been associated with Ki-1-positive anaplas tic large cell lymphoma (ALCL), a recently described NHL that shares w ith HD expression of the CD30 antigen Ki-1, Because EBV has been shown to induce Ki-1 expression in vitro, and ALCL has been diagnosed in pa tients with prior or concurrent HD or NHL, it has been proposed that E BV may mediate progression of a ''primary'' lymphoma to a ''secondary' ' ALCL. We report a case in which an AIDS-associated, Ki-1-negative, l arge-cell immunoblastic lymphoma progressed to a Ki-1-positive ALCL. A nalysis of the immunoglobulin heavy chain locus revealed a clonal rela tionship between these morphologically and immunophenotypically distin ct tumors. Although EBV was absent from the original large-cell immuno blastic lymphoma as assessed by in situ hybridization for EBV-encoded small RNA1 (EBER1), polymerase chain reaction for EBNA-1, immunocytoch emistry for latent membrane protein 1, and Southern blot hybridization for EBV terminal repeat sequences, all four techniques confirmed the presence of EBV in the secondary ALCL. Moreover, analysis of EBV termi nal repeat sequences indicated that the ALCL resulted from expansion o f a single EBV-infected clone. These data suggest that EBV may mediate progression of NHL to Ki-1-positive ALCL, and that in some instances, EBV may be involved in the later stages of clonal progression of NHL.