Clonal γδ T-cell proliferation associated with Babesia infection: a rare and challenging diagnostic pitfall

A 60-year-old woman with history of mantle cell lymphoma in remission presented with night sweats, weight loss, hemolytic anemia (hemoglobin, 9.6 g/dL), thrombocytopenia (72 × 10³/μL), and elevated serum lactate dehydrogenase (1620 U/L). Positron emission tomography/computed tomography revealed splenomegaly (23.5 cm) without lymphadenopathy, raising suspicion for relapse. Bone marrow (BM) examination demonstrated an unexpected increased γδ T-cell population, histologically subtle (panel A; hematoxylin and eosin stain, 40× objective) but showing sinusoidal localization by immunohistochemistry (panel B; 40× objective). Flow cytometry on BM and peripheral blood (PB; panel C) showed significantly increased γδ T cells (without immunophenotypic aberrancy), and polymerase chain reaction (PCR) performed on PB detected clonal T-cell receptor γ (TRG) rearrangement (panel D), raising suspicion for a T-cell neoplasm such as hepatosplenic T-cell lymphoma. Although metaphases were unobtainable, interface fluorescence in situ hybridization analysis was negative for i(7q). The persistent symptomatology also prompted an infectious workup, with PCR confirming babesiosis, explaining the symptoms and suggesting an unusual γδ T-cell proliferation triggered by infection. After a 3-month antibiotic course, Babesia testing was negative, lactate dehydrogenase levels normalized, and both splenomegaly and hemolytic anemia resolved. PB flow cytometry showed marked reduction in γδ T cells, decreasing from 0.5 × 10⁹/L to 0.2 × 10⁹/L.

This highly unusual case underscores that clonal γδ T-cell expansions can occur in infections like Babesia, mimicking neoplastic conditions and creating diagnostic challenges. Recognizing this pitfall is critical for ensuring appropriate treatment.

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