EBV-driven hemophagocytic lymphohistiocytosis secondary to extranodal NK/T cell lymphoma: a case report
Materials and Methods/Case Presentation/Objective:
A previously healthy 29-year-old male presented with a 1-month history of right-sided neck swelling, a 40-pound weight loss, right ear discharge, and tinnitus. Initial labs revealed thrombocytopenia (platelets: 56 x 10^9/L), a normal white blood cell count (4.2 x10^9/L), and cholestatic transaminitis (ALP: 664 U/L, ALT: 106 U/L, AST: 229 U/L). CT and MRV of the neck demonstrated right oropharyngeal soft tissue fullness compressing the internal jugular vein (IJV) and a filling defect in the sigmoid sinus. Although there was an initial concern for septic thrombophlebitis, this possibility was eventually dismissed given the complete absence of bacterial growth across multiple sets of blood cultures and persistent heterophile antibody testing. For this reason, broad spectrum antibiotics were discontinued.
The patient later developed rapid clinical deterioration with massive oropharyngeal bleeding requiring intubation. His hospital course was further complicated by disseminated intravascular coagulation (DIC; PT: 18.9s, aPTT: 60.5s, fibrinogen: 93 mg/dL, D-dimer: 5.62 mg/L) and profound systemic inflammation. Further testing revealed an EBV viremia of 16,900 copies/mL, hyperferritinemia ( >20,000 ng/mL), and markedly elevated cytokine levels including soluble IL-2 receptor (8,375 pg/mL), CXCL9 (82,466 pg/mL), IL-6 (31 pg/mL), IL-18 (12,644 pg/mL), and CD163 (3,339 pg/mL). A liver biopsy confirmed Kupffer cell hyperplasia and hemophagocytosis. A PET-CT showed intense uptake in the right nasopharyngeal (SUV max 10.7) and tonsillar spaces.
Results/Description/Main Outcome Measure(s):
Definitive diagnosis of ENKTL was established via an excisional biopsy of a right cervical lymph node. Following diagnosis, the patient suffered an acute 300 mL hemoptysis event secondary to the angiodestructive nature of ENKTL, resulting in cardiopulmonary arrest. He also required emergent coil embolization of the right ascending pharyngeal artery to control bleeding. His course was further complicated by tumor lysis syndrome and acute kidney injury requiring hemodialysis. Due to multi-organ failure, he was initiated on a modified SMILE regimen consisting of dexamethasone and a 50% dose-reduced etoposide; methotrexate, ifosfamide, and pegasparagase were withheld. Concurrently, ruxolitinib was utilized to manage the HLH-driven cytokine storm. Despite aggressive interventions, the patient developed severe encephalopathy and was transitioned to comfort care.
Conclusion(s).: This case highlights a devastating diagnostic pitfall where the angioinvasive and necrotic properties of ENKTL at first simulated the clinical and radiographic features of Lemierre syndrome. In young patients presenting with atypical "septic" thrombophlebitis, persistent culture-negative states, and extreme hyperferritinemia ( >10,000 ng/mL), clinicians must maintain a high index of suspicion for underlying EBV-driven malignancies. Early tissue biopsy is paramount to breaking the diagnostic deadlock so that lymphoma therapy can be initiated before irreversible multi-organ failure and terminal hemorrhagic events occur.
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