Phenotypic Characterisation of Richter Transformation and De Novo Diffuse Large B-Cell Lymphoma With or Without Monoclonal B-cell Lymphocytosis

Richter transformation diffuse large B-cell lymphoma type (DLBCL-RT) is a biologically complex process that requires a comprehensive work-up for an accurate diagnosis. Detailed information regarding DLBCL-RT immunophenotype is limited. We used multiparametric flow cytometry and immunohistochemistry to assess the phenotypic profile of 63 patients diagnosed with DLBCL-RT. Cases partially retained the immunophenotype of the previous chronic lymphocytic leukemia (CLL), although modulation of markers such as CD43, CD5, CD200, CD23, and CD38 was common. Moreover, the phenotype of DLBCL-RT differed according to prior exposure or not to CLL therapy, with treatment-naïve patients showing more immunophenotypic variations against prior CLL compared to those who received therapy before transformation. With respect to the prognostic impact of antigenic markers, cases expressing CD20 exhibited higher overall survival compared to those CD20-negative, whereas CD43 expression was associated with worse prognosis. DLBCL-RT cases exhibited several antigenic differences in CLL-associated markers compared with an independent cohort of non-transformed DLBCL without concurrent CLL-like monoclonal B-cell lymphocytosis (MBL) (n = 28). In contrast, a separate cohort of patients with de novo DLBCL and concomitant CLL-like MBL (n = 25) exhibited biological similarities to DLBCL-RT, including comparable phenotypic profiles and a high rate of clonal relatedness between MBL and DLBCL. We conclude that DLBCL-RT is associated with a CLL-like immunophenotype influenced by pre-existing CLL characteristics, and we propose that, in some cases, de novo DLBCL with concomitant MBL may be considered as RT.