Angioimmunoblastic T-cell lymphoma with secondary hemophagocytic lymphohistiocytosis initially misdiagnosed as classical Hodgkin lymphoma

Rationale: Angioimmunoblastic T-cell lymphoma (AITL), classified as nodal T-follicular helper cell lymphoma, angioimmunoblastic type, is an aggressive lymphoma frequently complicated by immune dysregulation. Owing to overlapping histopathological features, particularly Hodgkin/Reed–Sternberg–like cells, AITL may be initially misdiagnosed as Hodgkin lymphoma, leading to delayed recognition and inappropriate management. Patient concerns: A 72-year-old man presented with progressive fatigue, recurrent fever, severe pancytopenia, and splenomegaly after an outside diagnosis of Hodgkin lymphoma based on inguinal lymph node biopsy. Diagnoses: Laboratory findings revealed hypertriglyceridemia and marked hyperferritinemia, consistent with secondary hemophagocytic lymphohistiocytosis (HLH). Reevaluation of archived lymph node tissue demonstrated Epstein–Barr virus–encoded RNA positivity, T-cell receptor gene rearrangement, and an immunophenotype diagnostic of nodal T-follicular helper cell lymphoma, angioimmunoblastic type with scattered Hodgkin/Reed–Sternberg–like cells. Plasma Epstein–Barr virus DNA was detected at low levels. The disease was staged as Lugano stage III with B symptoms and classified as high risk by the International Prognostic Index. Interventions: HLH-directed therapy with etoposide and dexamethasone was initiated for rapid disease control, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy for lymphoma treatment. Outcomes: Partial remission was achieved after 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. The patient later experienced disease progression with clinically suspected recurrent HLH despite salvage therapy and died on March 29, 2025. Lessons: This case underscores the diagnostic pitfalls of AITL complicated by HLH and highlights the importance of early pathological reassessment and a stepwise treatment approach prioritizing control of hyperinflammation in patients with discordant clinical and pathological findings.