Abstract
Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast-growing) non-Hodgkin lymphoma (NHL) that affects B-lymphocytes. We report a rare and diagnostically complex case of aggressive DLBCL manifesting in immune-privileged and atypical extranodal sites of the head and neck, including bilateral retrobulbar regions, optic nerves, zygomatic muscle, cervical soft tissues, and paraspinal musculature, in a 70-year-old male patient with multiple comorbidities including end-stage renal disease (ESRD) and prior cerebrovascular accident. The patient presented with rapidly progressive bilateral proptosis and systemic signs of sepsis. Diagnostic imaging, constrained by renal insufficiency, revealed multifocal soft tissue masses without intracranial involvement. Histopathology and immunohistochemistry confirmed nongerminal center subtype DLBCL (CD20+, BCL2+, MUM1+, MYC-, CD3-, CD7-). Bone marrow analysis excluded systemic leukemic-phase disease. Due to the patient's frailty and organ dysfunction, standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy was contraindicated; a modified immunochemotherapy with corticosteroids and rituximab was initiated, yielding a partial reduction in tumor size. Despite initial improvement, the patient succumbed to complications of multiorgan failure. This case highlights the clinical and therapeutic challenges in diagnosing and managing extranodal DLBCL in elderly, immunocompromised patients, especially when the disease involves immune-privileged sites and standard diagnostic tools are limited.