Hepatosplenic T‑cell lymphoma (HSTCL) is a rare and aggressive mature T‑cell lymphoma characterized by sinusoidal infiltration of neoplastic lymphocytes — typically positive for CD2, CD3, and CD7 and negative for CD4, CD5, and CD8 — within the spleen and/or liver. HSTCL shows a strong predilection for male adolescents, with only rare occurrences in younger pediatric patients.

We describe a case involving a 2‑year‑old male with no significant past medical history who presented with refractory hemolytic anemia, pancytopenia, hepatosplenomegaly, and hyperinflammatory features following a recent viral infection, raising concern for hemophagocytic lymphohistiocytosis (HLH). Steroid therapy was initiated for presumed HLH. A bone marrow biopsy was initially performed, but atypical lymphocytes were not observed on the aspirate nor by flow cytometry. A liver biopsy was subsequently performed, from which HSTCL was diagnosed. The diagnostic microscopic and flow cytometry findings are in the accompanying image set. Flow cytometric analysis of a repeat bone marrow biopsy obtained 8 days later for staging purposes revealed 0.7% neoplastic T lymphocytes. Bone marrow cytogenetic and molecular next-generation sequencing studies did not yield findings, likely due to the low disease burden in the bone marrow.

This case illustrates an unusually subtle presentation of HSTCL in a very young pediatric patient, marked by minimal morphologic abnormalities and rare CD8 expression. Interpretation is further complicated by the biopsy having been obtained after steroid therapy, which may attenuate histologic features and obscure diagnostic clues. Given the aggressive nature of HSTCL, it is essential to maintain a high index of suspicion in patients presenting with hepatosplenomegaly, cytopenias, and HLH. For such patients, HSTCL should be included in the differential diagnosis. Submission of tissue for flow cytometry is also critical, as it was crucial for establishing the diagnosis in this challenging case.