Aggressive Natural Killer (NK)-Cell Leukemia Initially Presenting as Orbital Cellulitis: A Case Report

We report a case of aggressive natural killer cell leukemia (ANKL) presenting as orbital cellulitis, highlighting diagnostic challenges for ophthalmologists. A 50-year-old Japanese man presented with progressive right eyelid swelling and was initially diagnosed with orbital cellulitis. Antibiotics were ineffective. Given the antibiotic-refractory orbital inflammation without sinusitis, corticosteroids were initiated but provided only transient improvement. After hospitalization with pulse methylprednisolone, the patient developed fever, thrombocytopenia, and hepatic dysfunction, with markedly elevated ferritin, soluble interleukin-2 receptor, and plasma Epstein-Barr virus (EBV) DNA, and features suggestive of hemophagocytic lymphohistiocytosis. Bone marrow and liver biopsies subsequently demonstrated a natural killer (NK)-cell neoplasm positive for CD56 and for EBV-encoded small RNA by in situ hybridization, with expression of T-cell intracellular antigen-1 and granzyme B in the liver. Leukemic bone marrow infiltration, concurrent sinusoidal infiltration of the liver without a mass lesion, the absence of nasal involvement, and the fulminant systemic course favored a clinical diagnosis of ANKL over extranodal NK/T-cell lymphoma. Despite chemotherapy, the patient died 24 days after admission. ANKL can mimic orbital cellulitis or idiopathic orbital inflammation, even without nasal involvement. Refractory orbital inflammation should prompt early biopsy and hematological evaluation to exclude NK/T-cell neoplasms.