BackgroundMalignancy-associated hemophagocytic lymphohistiocytosis (M-HLH) is a syndrome of life-threatening inflammation that can arise in the context of cancer or cancer-directed therapy. While commonly associated with leukemias/lymphomas, M-HLH cases related to solid tumors, particularly neuroblastoma, a sympathetic nervous system malignancy, are rarely described. Five prior neuroblastoma-associated HLH cases are reported, wherein the HLH was primarily attributed to rapid lysis of the neuroblastoma initiating a massive systemic cytokine release (Table 1). Here we report a case of HLH as a presenting sign of neuroblastoma. Case DiscussionA 13-month-old male presented with fever, hypoxia and abdominal distention. Labs were notable for hemoglobin 5.8 (G/dL), platelets 13 (cells/µL), hypofibrinogenemia 63 (mg/dL), AST >6000 (U/L), ALT 2777 (U/L), ammonia 135 (uM/L), INR 4.8, LDH 33 000 (U/L), uric acid 14.4(mg/dL), ferritin 56,198(ng/mL), soluble IL2-receptor 10,1128(pg/mL). Imaging demonstrated numerous bulky abdominal masses. He was admitted to the PICU in the setting of multiple organ dysfunction requiring intubation, vasopressors and CRRT. Presumed M-HLH was diagnosed on the basis of bicytopenia, hypofibrinogenemia, fever, elevated ferritin and liver dysfunction.He was started on anakinra (2 mg/kg q6hrs), however his ferritin continued to escalate with no significant clinical improvement. On day 3 of hospitalization and prior to surgical biopsy results, emergent chemotherapy was initiated with dexamethasone (3 mg/m2 BID) and cyclophosphamide (300 mg/m2). Further workup with urine catecholamines and biopsy confirmed a diagnosis of neuroblastoma. On day 5, he transitioned from cyclophosphamide to cisplatin (19.5 mg or 40 mg/m2) due to concern cyclophosphamide was inadequately hepatically activated. On day 6, due to ongoing multiorgan failure, ruxolitinib (2.5 mg BID or 5 mg/m2) therapy was initiated. On day 9 of hospitalization ferritin improved to 22050 however due to worsening multiorgan failure he was also given a dose of alemtuzumab (10 mg or 20 mg/m2). He experienced neurological decline and died on day 9. Of note, he underwent genome-wide sequencing with no HLH-related variants identified. ConclusionThis case is a rare presentation of the M-HLH occurring pre-therapy as a presenting sign of neuroblastoma with auto-necrosis of the neuroblastoma likely precipitating the uncontrolled inflammatory cascade. Screening for neuroblastoma via urine catecholamines in children presenting with HLH should be strongly considered, particularly in those with abdominal, thoracic, or paravertebral masses.