Richter's syndrome: Diffuse histiocytic lymphoma in patients with chronic lymphocytic leukemia: A report of five cases and review of the literature

Abstract

The development of diffuse “histiocytic” lymphoma in patients with chronic lymphocytic leukemia (CLL), Richter's syndrome, occurs infrequently, but it is a distinct clinicopathologic phenomenon. In this report we describe five new cases of Richter's syndrome and summarize data on an additional 41 patients. Information from three separate series suggests a 3 to 10 per cent incidence of diffuse histiocytic lymphoma in patients with CLL. There were no features of CLL in these 46 patients in whom diffuse histiocytic lymphoma subsequently developed which would have distinguished them from patients with typical CLL in whom diffuse histiocytic lymphoma never developed. The median interval between the diagnosis of CLL and the recognition of diffuse histiocytic lymphoma in these 46 patients was 24 months (range, less than one month to 156 months). Fever (65 per cent), increasing lymphadenopathy (46 per cent), weight loss (29 per cent) and abdominal pain (26 per cent) were the clinical features which characterized the development of diffuse histiocytic lymphoma. Median durations of survival from the diagnosis of CLL and diffuse histiocytic lymphoma were 28 months and four months, respectively. Thirty-four per cent of the patients had received no treatment for CLL prior to the diagnosis of diffuse histiocytic lymphoma. Cytotoxic therapy for diffuse histiocytic lymphoma was generally unsuccessful in patients with Richter's syndrome (14 per cent complete remission rate). Clinical features of diffuse histiocytic lymphoma, which have been associated with poor response to combination chemotherapy (bulky lymph node masses, gastrointestinal or bone involvement and previous exposure to cytotoxic drugs), were common in these patients and may have contributed to the poor therapeutic response. Morphologic and immunologic studies suggest that the diffuse histiocytic lymphoma seen in patients with CLL arises as a proliferation and “dedifferentiation” of the lymphocytes of the preexisting CLL. Absolute proof that diffuse histiocytic lymphoma arises as a clonal progression of CLL cells is lacking, however, and further study of the genesis of diffuse histiocytic lymphoma in CLL is required.