A Recently Recognized and Underdiagnosed Entity of Splenic Diffuse Red Pulp Small B-Cell Lymphoma: A Report of Two Cases.

Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is an extremely rare entity newly individualized in the WHO 2022 classification, following provisional recognition in 2008. It remains underrecognized in routine practice. Its diagnosis is challenging because it overlaps with other splenic lymphomas with villous lymphocytes, particularly splenic marginal zone lymphoma (SMZL) and hairy cell leukemia variants, with only a few cases reported due to recent recognition. We present two patients illustrating their distinctive diagnostic and therapeutic phenotypes. Case 1 was a 65-year-old woman diagnosed in 2017 with SMZL and treated with rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine), and prednisone (or prednisolone) (R-CHOP), achieving complete remission, who presented nine years later with recurrent hyperlymphocytosis at 10.8 × 109/L with villous appearance, massive splenomegaly, and systemic symptoms. Bone marrow evaluation demonstrated small-cell lymphoid infiltration, and flow cytometry showed CD19 positivity, CD5 negativity, strong FMC7 and CD11c expression, and a CD200/CD180 ratio of 0.3, consistent with SDRPL. Karyotype was normal. The patient was treated with rituximab-bendamustine and achieved complete remission. Case 2 was a 53-year-old man presenting for three months with splenic discomfort, systemic symptoms, and hyperlymphocytosis at 22.6 × 109/L with villous morphology. SDRPL diagnosis was confirmed by combining bone marrow aspiration showing a small-cell lymphomatous process and flow cytometry showing CD19 positivity, CD5 negativity, strong FMC7 and CD11c expression, and a CD200/CD180 ratio of 0.5. Karyotype was normal. Rituximab monotherapy was followed by rapid improvement, with normalization of the lymphocyte count to 2.13 × 109/L and regression of splenomegaly from the first cycle. These observations highlight the importance of combining lymphocyte immunophenotyping and bone marrow aspiration in isolated splenomegaly with villous lymphocytes on blood smear to avoid underdiagnosis of this new histopathological entity and therefore guide therapeutic management in the absence of guidelines.