Non-Hodgkin’s Lymphoma Mimicking Orbital Cellulitis: A Diagnostic Dilemma

We reported a rare case of disseminated diffuse large B-cell lymphoma (DLBCL) initially presenting as refractory orbital cellulitis in a 53-year-old male. The patient presented with acute periorbital swelling, pain, and restricted ocular motility, unresponsive to broad-spectrum antibiotics. Magnetic resonance imaging (MRI) revealed extensive sinusitis with a peripherally enhancing medial extraconal orbital mass and adjacent bony erosions. A prompt functional endoscopic sinus surgery and histopathology revealed a poorly differentiated malignant neoplasm. Immunohistochemistry confirmed DLBCL, non-germinal center B-cell subtype. Systemic evaluation with whole-body MRI and fluorodeoxyglucose-positron emission tomography demonstrated widespread dissemination involving the lungs, gastrointestinal tract, adrenal glands, and skeleton. The patient was initiated on required chemoimmunotherapy with central nervous system prophylaxis and remains under oncology follow-up. This case highlights the diagnostic challenge posed by orbital lymphoma mimicking infectious orbital cellulitis and underscores the need for early imaging and tissue diagnosis in culture-negative, non-resolving cases. A high index of suspicion and multidisciplinary collaboration are essential for timely diagnosis and effective management.