A 65-year-old woman with a 3-year history of chronic lymphocytic leukemia (CLL) presented with rapidly progressing lymphadenopathy without lymphocytosis over the course of 2 months. Positron emission tomography-computed tomography scans showed hypermetabolism in the neck, axilla, and subpectoral regions and mediastinum with standardized uptake values ranging from 2 to 6. The patient underwent mediastinoscopy and biopsy. The specimen demonstrated sheets of large cells (70%) segregated from areas of small cell lymphoma/CLL (30%). Panel A shows distinct demarcation between CLL (top) and diffuse large B-cell lymphoma (bottom); inset shows large cells in detail. The small cells exhibited weak staining for CD20, as expected for CLL, compared with the population of large cells (panel B). The transformed population of large cells demonstrated loss of CD5 (panel C) and gain of C-MYC (panel D). By B-cell gene rearrangement, this tumor was identical to the patient’s prior biopsy. Diagnosis was diffuse large B-cell lymphoma, arising from CLL/small lymphocytic lymphoma (SLL) (Richter’s transformation).

Pathologic diagnosis of Richter’s transformation typically shows isolated large cell lymphoma in a patient with known history of CLL/SLL. This case demonstrates the coexistence of the small and large cell components, classic immunophenotypic alterations, and evidence of amplification of a strong proto-oncogene. C-MYC abnormalities are one of the most frequent genetic lesions in Richter’s syndrome, often acquired at transformation.