Evidence of clonal progression in a case of Richter syndrome.

BACKGROUND: The debate continues as to whether Richter syndrome should be defined as non-Hodgkin lymphoma (NHL) because of a more malignant clone of neoplastic cells superimposed on preexisting chronic lymphocytic leukemia (CLL) or as the chance occurrence of two unrelated tumors. The cellular characteristics of the neoplastic clone involved in the CLL phase and the subsequent NHL were investigated in a patient in whom Richter syndrome developed. METHODS: Cell analysis was performed with immunofluorescence, histologic analysis, DNA extraction, and Southern blot analysis. RESULTS: The separated CLL and NHL B-cells from blood and bone marrow, as well as the neoplastic cells in autopsy specimens of the organs affected by NHL, particularly the brain, were found to express the same light chain of surface immunoglobulin (SIg). The change MD-->M in the SIg heavy-chain expression and the appearance of cytoplasmic IgMk suggested isotype switching simulating that observed on the final phases of primary B-cell differentiation. This hypothesis was confirmed by Southern blot analysis of DNA from blood cells in the CLL phase and in Richter transformation, which showed that the two cell populations had identical Ig gene rearrangement. CONCLUSIONS: The NHL in the patient in this study represented a malignant progression of CLL, not a second lymphoid malignancy.