An 84-year-old male with no previous hematologic diagnosis presented with 3 weeks of anorexia, weight loss, bilateral cervical adenopathy and hepatosplenomegaly. Complete blood counts showed hemoglobin 11.3 g/dL, platelets 27 x10^9/L and white blood cells 274.6 x 10^9/L with lymphocyte count of 260.9 x10^9/L. Serum LDH was 1,792. Peripheral blood film (shown here) displayed two discrete populations: one population of smaller B cells CD5+, CD19+, dim CD20+, CD200+, CD10- and expressing dim lambda light chains and a second population of large B-cells with dim CD5+, dim CD19+, CD20 bright, dim CD10+, CD200+ and expressing lambda light chains. Bone marrow biopsy was 90% diffusely infiltrated with neoplastic lymphocytes with large, distinct nuclei and a small number of neoplastic small lymphocytes seen in the background. The larger lymphocyte population were positive by immunohistochemistry for CD20, PAX5, CD10, BCL2, MUM-1 and weak CD5 and negative for BCL-6 and Cyclin-D1. KI-67 index was high at 80%. Based on these two distinct lymphoid populations, a probable diagnosis of diffuse large B-cell lymphoma (DLBCL), germinal center phenotype, with Richter transformation (RT) from CLL was made. FISH confirmed the presence of 13q deletion in 90% of nuclei of CLL cells and subsequent molecular testing reported IGHV unmutated status and TP53 mutation consistent with this patient’s transformed disease.  

      First described by Maurice Richter in 1928, RT occurs in 2-3% of CLL patients and refers most commonly to the development of aggressive large-cell lymphoma [1]. However, RT can lead to the development of Hodgkin lymphoma and other aggressive lymphomas have been described. In 80% of cases of RT-DLBCL, the B cells are clonally related to the underlying CLL and is associated with poor prognosis with median overall survival of 1 year. Conversely, in 20% of cases the two diseases remain clonally unrelated with a similar prognosis to de-novo DLBCL [2]. Combination chemoimmunotherapy approaches such as R-CHOP and DA-EPOCH-R have been adapted from the de-novo DLBCL setting and remain first line treatment for RT-DLBCL. Randomized controlled trials are needed to determine the optimal treatment approach for RT particularly in the era of novel agents. 

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References:

1.    Parikh SA, Rabe KG, Call TG, Zent CS, Habermann TM, Ding W, Leis JF, Schwager SM, Hanson CA, Macon WR, Kay NE, Slager SL, Shanafelt TD. Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): a cohort study of newly diagnosed patients. Br J Haematol. 2013 Sep; 162(6):774-82.

2.    Parikh SA, Kay NE, Shanafelt TD. How we treat Richter syndrome. Blood. 2014 Mar 13; 123(11): 1647-57.