Abstract
Background and Clinical Significance: Methotrexate is widely used as a disease-modifying antirheumatic drug for rheumatoid arthritis (RA), yet prolonged immunosuppression may lead to rare complications, including Epstein-Barr virus (EBV)-positive lymphoproliferative disorders (LPDs). Case Presentation: We present the case of a 70-year-old woman with RA on chronic immunosuppressive therapy who developed symptoms resembling recurrent tonsillitis. CT imaging revealed bilateral necrotic palatine tonsils and extensive necrotic lymphadenopathy involving the cervical, mediastinal, and axillary regions. Bilateral tonsillectomy was performed due to concerns about malignancy or infection, and histopathology confirmed a polymorphic EBV-positive LPD with Hodgkin-like features, consistent with iatrogenic immunodeficiency-associated LPD. Methotrexate was subsequently discontinued, and the patient was managed conservatively without systemic chemotherapy. Clinical recovery was observed during follow-up. Conclusions: This case highlights the importance of considering methotrexate-associated LPDs in the differential diagnosis of atypical tonsillar infections in immunosuppressed patients, particularly when necrotic features or systemic lymphadenopathy are present. The pathogenesis may involve EBV reactivation under impaired immune surveillance due to methotrexate, leading to abnormal B-cell proliferation and clonal expansion. This case is contextualized through a comparative analysis of published reports, highlighting clinical features and treatment responses of methotrexate-associated EBV-positive LPDs in the form of a focused literature review.