{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:18:06Z","timestamp":1788369486168,"version":"build-2803163510"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Epstein\u2013Barr 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.<\/jats:p>","DOI":"10.3389\/fped.2025.1662074","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T06:32:11Z","timestamp":1762842731000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hemophagocytic lymphohistiocytosis as the initial manifestation of Epstein\u2013Barr virus-related T\/NK-cell lymphoproliferative disorders in a pediatric patient: a case report and literature 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