Massive hemorrhage and osteonecrosis of the jaw in the patient with methotrexate-associated lymphoproliferative disorder: Report of a case and review of literature

Introduction: Methotrexate-associated lymphopro-liferative disorder (MTX-LPD) is one of the adverse effects of methotrexate (MTX). We report a case of MTX-LPD that caused osteonecrosis and massive bleeding without regression following MTX withdrawal.\r\nCase Report: A 61-year-old woman was referred to our hospital because of delayed socket healing after dental extraction. She had been diagnosed with rheumatoid arthritis (RA) and received MTX treatment for six years. At the first visit, a 15 mm × 15 mm bone exposure and swelling of the surrounding gingiva in the right upper molar region were observed. We performed an incisional biopsy of the necrotic bone and surrounding mucosal tissue. The histopathological diagnosis was diffuse large B-cell lymphoma (DLBCL). Therefore, we referred the patient to the Department of Hematology in our hospital. She was diagnosed with MTX-LPD based on the history of MTX therapy for RA, and MTX was discontinued immediately. However, the lesion progressed and caused bleeding that required blood transfusion and hemostasis by microfibrous collagen and tie-over even after the withdrawal of MTX. Subsequently, rituximab, cyclophosphamide, vincristine, and prednisolone (R-COP) chemotherapy was initiated. After 3 courses of chemotherapy, sequestrectomy was performed under local anesthesia. She achieved complete remission after 8 courses of chemotherapy, and there was no recurrence of necrotic bone exposure or gingival swelling.\r\nConclusion: Approximately 80% of MTX-LPD cases occurring in the oral region show regression after MTX discontinuation, but we experienced a case in which bleeding occurred with progression of the lesion after discontinuation. Careful follow-up is required during the MTX discontinuation period.