Epstein-Barr Virus-Positive Lymphoproliferative Disorder in an HIV Patient Successfully Treated With Rituximab

Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) represent a heterogeneous group of conditions that occur most often in immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection, organ transplantation, autoimmune disease, and immune senescence. We report a case of a 55-year-old female with previously undiagnosed HIV, who presented with progressive throat pain, dysphagia, weight loss, and recurrent antibiotic-refractory tonsillitis, initially raising concern for squamous cell carcinoma. Imaging with contrast-enhanced CT of the neck revealed asymmetric oropharyngeal swelling with a rim-enhancing lesion, and biopsy demonstrated EBV-positive polymorphic LPD with clonal B-cell proliferation, confirmed by immunoglobulin heavy-chain gene rearrangement studies and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization (EBER-ISH). Despite initiation of antiretroviral therapy and <i>Pneumocystis jirovecii</i> prophylaxis, the patient's oropharyngeal symptoms and cervical lymphadenopathy progressed, accompanied by EBV viremia. Rituximab was introduced, resulting in rapid symptomatic relief, regression of lymphadenopathy, clearance of EBV viremia, and continued HIV viral suppression. This case highlights the diagnostic complexity of HIV-associated EBV-positive LPDs, which may mimic infection or malignancy and require biopsy with immunophenotyping, EBV detection, and clonality studies for accurate diagnosis. Furthermore, it underscores that while immune restoration with antiretroviral therapy is essential, it may not be sufficient to control EBV-driven lymphoproliferation, and targeted therapy with rituximab can be critical for achieving remission. Broader recognition of HIV-associated EBV-positive LPD within evolving classification frameworks is needed, along with standardized treatment strategies and prospective outcome studies to guide management of this rare but clinically significant disorder.