Conjunctival Squamous Cell Carcinoma Masquerading as Orbital Cellulitis in a Patient With Relapsed Mixed Phenotype Acute Leukemia

Conjunctival squamous cell carcinoma (SCC) rarely presents as orbital cellulitis, creating a significant diagnostic challenge in profoundly immunocompromised patients. We report the case of a 40-year-old man with relapsed mixed phenotype acute leukemia (MPAL) receiving prolonged leukemia-directed therapy who developed progressive unilateral periorbital swelling, pain, and imaging findings consistent with orbital cellulitis. Despite broad-spectrum antimicrobial therapy, serial computed tomography and magnetic resonance imaging demonstrated persistent superior orbital soft tissue thickening without meaningful clinical resolution. Because of the atypical clinical course, ophthalmologic biopsy was performed and demonstrated invasive moderately differentiated conjunctival SCC with lymphovascular invasion. Peripheral blood flow cytometry excluded lymphomatous involvement, confirming a second primary epithelial malignancy rather than leukemic infiltration. This case illustrates how prolonged leukemia-associated immunosuppression and intensive chemotherapy may obscure the diagnosis of secondary ocular surface malignancy by mimicking orbital infection. In patients with persistent orbital inflammation despite appropriate antimicrobial therapy, particularly those with relapsed hematologic malignancies and profound neutropenia, failure to improve should prompt early tissue biopsy, even when radiographic findings remain suggestive of orbital cellulitis, to avoid delays in definitive diagnosis and management.