Case Presentation: We present a case of a 65-year-old Caucasian male with T2 N3 nasopharyngeal carcinoma (EBV-positive), status post concurrent gentamicin/cisplatin and radiation therapy, Parkinson’s disease, chronic kidney disease stage 3a, and pancytopenia, who initially presented with fever, altered mental status, abdominal pain, and generalized weakness.Patient was recently admitted for fever and abdominal pain. Evaluation at the time was notable for chronic anemia and ferritin of 14,274, which were attributed to anemia of chronic disease. Abdominal ultrasound was notable for distended gallbladder but without clinical findings consistent with cholecystitis. Patient was treated empirically for a gastrointestinal infection with ceftriaxone and metronidazole and later discharged home.He presented again 2 weeks later with continued fever and abdominal pain and progressive somnolence and functional decline. He was febrile (38.4° Celsius), tachycardic (110 beats/min), tachypneic (20 breaths/min), hypotensive (99/43 mmHg with mean arterial pressure of 62 mmHg), and had an oxygen saturation (SatO2) of 94% on room air. On physical exam, he was somnolent, cachectic, and alert and oriented to name and place only.He was started empirically on intravenous (IV) piperacillin/tazobactam, vancomycin, and fluids. A complete blood count panel revealed hemoglobin of 4.1 g/dL, and he was given two units of packed red blood cells. Labs demonstrated markedly elevated ferritin of 11,304 and triglyceride of 453. Computed tomography abdomen/pelvis showed splenomegaly.Presentation of recurrent fever, progressive multiorgan dysfunction, progressive pancytopenia, and markedly elevated ferritin, was concerning for HLH. Soluble IL-2 receptor levels were elevated at 2,931. Plasma quantitative EBV polymerase chain reaction (EBV viral load) was elevated. HLH taskforce at our institution was contacted, and patient was treated with IV acyclovir, etoposide, and methylprednisolone. Bone marrow biopsy was deferred as the clinical suspicion of HLH was confirmed through lab testing and imaging. However, due to continued clinical deterioration and poor prognosis, patient was transitioned to hospice and passed away four days later.
Discussion: The diagnosis of HLH is difficult due to its broad presentation, and diagnostic criteria have not been established for adults with majority of published studies derived from pediatric cases [1]. Our patient did meet 6/8 of the HLH-2004 diagnostic criteria from the Histiocyte Society [2,3]. Bone marrow biopsy, once considered the diagnostic gold standard for HLH, may be inconclusive due to possibly only revealing erythroid hyperplasia and causing clinicians to reject HLH [3].Solid tumors least commonly account for 1.4% of HLH cases in the setting of diffuse metastatic disease with bone marrow infiltrates and aggressive histology [4]. Review of literature only reported 6 cases of nasopharyngeal carcinoma-associated HLH. EBV-induced HLH have an overall survival rate of 41.1% at 6 months, further signifying the need for early diagnosis and intervention [5].
Conclusions: In this case report, we present a rare and poor prognostic diagnosis of EBV positive nasopharyngeal carcinoma-associated HLH that was initially missed. Our case portrays the importance of high index of suspicion for early diagnosis of HLH and the nonspecific signs and symptoms of EBV-induced HLH, as well as the management of this disease.