CASE REPORT article
Front. Pediatr.
Sec. Pediatric Hematology and Hematological Malignancies
Volume 13 - 2025 | doi: 10.3389/fped.2025.1662074
This article is part of the Research TopicEBV Strategies to Counteract the Immune ResponseView all 9 articles
Hemophagocytic lymphohistiocytosis as the initial manifestation of Epstein–Barr virus-related T/NK-cell lymphoproliferative disorders in a pediatric patient: A case report and literature review
Provisionally accepted
- Second Affiliated Hospital of Dalian Medical University, Dalian, China
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Epstein-Barr virus-associated T/Natural Killer-cell lymphoproliferative disorders (EBV-T/NK-LPDs) are rare diseases that predominantly affect children and young adults. We report a case of a 12-year-old child who initially presented with EBV-associated hemophagocytic lymphohistiocytosis (HLH) and later progressed to aggressive NK-cell leukemia (ANKL). Both EBV-HLH and ANKL belong to the spectrum of EBV-T/NK-LPDs, which also includes chronic active EBV infection (CAEBV) of T-cell and NK-cell types, systemic EBV-positive T-cell lymphoma of childhood, extranodal NK/T-cell lymphoma (ENKTL), and primary EBV-positive nodal T/NK-cell lymphoma. The patient initially presented with recurrent high fever, pancytopenia, hepatosplenomegaly, hypertriglyceridemia, and hypofibrinogenemia with a significantly elevated EBV-DNA load. Bone marrow examination indicated a few histiocytes and hemophagocytic cells. Subsequent increases in ferritin and soluble CD25 (sCD25) levels were further consistent with the diagnosis of EBV-HLH. No lymphadenopathy or nasal primary lesion was identified. Further BM flow cytometry and BM cell morphology examination indicated abnormal NK-cell infiltration, leading to the exclusion of ENKTL, primary EBV-positive nodal T/NK-cell lymphoma, and systemic EBV-positive T-cell lymphoma of childhood. A diagnosis of ANKL was highly suspected. This case highlights that when EBV infection triggers a series of complex EBV-T/NK-LPDs occurring sequentially or simultaneously, the differential diagnosis and treatment become difficult, which can easily lead to delays in diagnosis and treatment. Developing optimized diagnostic algorithms and evidence-based treatment strategies is essential to improve outcomes of patients.
Keywords: Hemophagocytic lymphohistiocytosis (HLH), Epstein-Barr virus (EBV), Aggressive Natural Killer Cell Leukemia (ANKL), Lymphoproliferative disorders (LPDs), pediatric, DDX3X mutation, KMT2D mutation
Received: 08 Jul 2025; Accepted: 20 Oct 2025.
Copyright: © 2025 Ma, Xing, Liu and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yonge Liu, lye4@163.com
Wei Jiang, jiangqiang202210@126.com
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