Angioimmunoblastic T‑cell lymphoma (AITL) is classified as a nodal T‑follicular helper cell lymphoma, angioimmunoblastic type, and is an aggressive peripheral T‑cell lymphoma frequently accompanied by immune dysregulation. Because AITL can contain Hodgkin/Reed‑Sternberg‑like cells and other overlapping histopathological features, it may be misinterpreted as classical Hodgkin lymphoma on initial biopsy. Misdiagnosis can delay correct therapy and complicate management, particularly when complicated by secondary hemophagocytic lymphohistiocytosis (HLH).
A 72‑year‑old man presented with progressive fatigue, recurrent fever, severe pancytopenia, and splenomegaly. An outside inguinal lymph node biopsy had led to a diagnosis of classical Hodgkin lymphoma. The clinical picture—marked cytopenias, fever, and splenomegaly—prompted further evaluation given discordance between the initial pathological report and the severity of systemic inflammatory features.
Laboratory testing in this patient revealed hypertriglyceridemia and marked hyperferritinemia, findings consistent with secondary HLH. Plasma Epstein‑Barr virus (EBV) DNA was detectable at low levels. The combination of fever, pancytopenia, splenomegaly, hypertriglyceridemia, and very elevated ferritin supported a diagnosis of HLH complicating an underlying lymphoid malignancy.
Archived lymph node tissue was reexamined. Reevaluation demonstrated Epstein‑Barr virus‑encoded RNA positivity and T‑cell receptor gene rearrangement. Immunophenotyping and molecular findings were diagnostic of nodal T‑follicular helper cell lymphoma, angioimmunoblastic type (AITL), and identified scattered Hodgkin/Reed‑Sternberg‑like cells within the lymph node. These features clarified that the initial interpretation as classical Hodgkin lymphoma did not reflect the underlying T‑cell lymphoma.
The disease was staged as Lugano stage III and the patient had B symptoms. Risk stratification by the International Prognostic Index classified the case as high risk. The presence of systemic hyperinflammation and HLH further complicated the clinical assessment and therapeutic planning.
Given the life‑threatening hyperinflammatory state, treatment began with HLH‑directed therapy to rapidly suppress macrophage activation and cytokine‑driven organ dysfunction. The patient received etoposide and dexamethasone as initial therapy to control HLH. After achieving sufficient control of hyperinflammation, lymphoma‑directed chemotherapy was administered using cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP regimen) for systemic treatment of AITL.
After six cycles of CHOP chemotherapy the patient achieved partial remission. Despite this initial response, the disease later progressed. Clinically suspected recurrent HLH accompanied the progression; salvage therapy was attempted but did not prevent further deterioration. The patient died on March 29, 2025. The report does not provide detailed timelines of each intervention beyond sequence and outcomes summarized above.
This case illustrates several clinically relevant points:
Diagnostic pitfall: AITL can contain Hodgkin/Reed‑Sternberg‑like cells and show histological overlap with classical Hodgkin lymphoma, risking misdiagnosis when clinicopathologic correlation is limited.
Association with EBV: The lymph node demonstrated EBV‑encoded RNA positivity and plasma EBV DNA was detectable, consistent with known associations between EBV and AITL pathology in some cases.
Risk of HLH: Secondary HLH may complicate T‑cell lymphomas, producing severe systemic inflammation that should be recognized and treated promptly.
Stepwise treatment strategy: Prioritizing rapid control of hyperinflammation with HLH‑directed agents (etoposide, dexamethasone) before systemic lymphoma chemotherapy (CHOP) was used here and is emphasized when clinical and pathological findings are discordant.
Prognostic challenge: Even with initial partial remission after CHOP, progression and recurrent HLH can occur, and outcomes may be poor in high‑risk presentations.
Early pathological reassessment is important when clinical features—such as severe cytopenias, hyperferritinemia, and systemic inflammation—do not fit an initial diagnosis of classical Hodgkin lymphoma. Clinicians should consider AITL in the differential diagnosis of older patients with systemic inflammatory findings and atypical lymph node histology. The authors reported no funding or conflicts of interest. The case is indexed with PMID 42826277 and DOI 10.1097/MD.0000000000050979.