Splenic Diffuse Red Pulp Small B-cell Lymphoma: A Rare Diagnosis in a Patient With Incidental Abnormal Lymphocytosis

Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is an extremely rare form of non-Hodgkin lymphoma that has an indolent course and is characterized by splenomegaly, lymphocytosis, and hemocytopenia. Lymphomas with villous morphology are rare, with the least common subtype being SDRPL. Therefore, the diagnosis of SDPRL primarily hinges on a rigorous exclusion of other lymphoproliferative disorders, alongside a detailed correlation of histopathological features from bone marrow and spleen tissues, complemented by comprehensive immunophenotypic analysis. Adequate diagnosis is important to guide patient treatment and outcome. Here, we present a case of a 66-year-old male who presented with leukocytosis. At first, the patient was asymptomatic, though a peripheral blood smear revealed abnormal lymphocytes, and the presence of hairy cells led to a misdiagnosis of hairy cell leukemia (HCL), hence, no treatment was administered for six years. Subsequently, the patient was re-diagnosed with a splenic condition resembling a hairy cell variant, which later was found to be SDPRL. After minimal to no response on rituximab monotherapy, the patient was transitioned to cyclophosphamide and eventually to zanubrutinib, with subsequent hematologic improvement. This case underscores the diagnostic complexity of SDRPL, the importance of a multidisciplinary approach in distinguishing it from other splenic lymphomas, and highlights the therapeutic challenges in managing this rare entity.