RICHTERS TRANSFORMATION OF CHRONIC LYMPHOCYTIC-LEUKEMIA WITH HODGKINS-LIKE CELLS IS ASSOCIATED WITH EPSTEIN-BARR-VIRUS INFECTION

The appearance of a high-grade lymphoma in the setting of B-cell chron ic lymphocytic leukemia (CLL) is termed Richter's syndrome. Usually th e high-grade component is a monomorphous, large cell lymphoma, but occ asionally the high-grade component takes the form of Hodgkin's disease or a Hodgkin's-like lymphoma. Although Richter's syndrome is thought to represent clonal evolution of the underlying B-cell neoplasm in mos t cases, such a progression is difficult to explain when the high-grad e component is Hodgkin's disease. We report two cases of Richter's syn drome in which the large cells had a morphology consistent with Reed-S ternberg cells and were found in a background of CLL. The large cells in both cases expressed the CD15 and CD30 antigens in a pattern charac teristic of Reed-Sternberg cells, and the large cells in one case also expressed monotypic cytoplasmic immunoglobulin of the same type as th at expressed by the underlying CLL. In both cases, Southern blot analy sis of DNA from lymph nodes that contained both CLL and the Hodgkin's- like component showed single immunoglobulin gene rearrangements. Using the polymerase chain reaction, we found Epstein-Barr virus DNA in lym ph nodes from both cases, and in peripheral blood lymphoid cells from one case 4 yr before the onset of Richter's syndrome. Immunoperoxidase staining showed expression of EBV latent membrane protein only in the Reed-Sternberg-like cells. By in situ hybridization, EBV RNA was foun d only in the Reed-Sternberg-like cells, whereas in CLL tissues obtain ed before the onset of Richter's syndrome, scattered EBV-positive CLL cells were identified. Our results provide further support for the clo nal association between CLL and a Hodgkin's-like large cell transforma tion, and strengthen the link between EBV infection and this form of R ichter's syndrome.