Methotrexate-related lymphoproliferative disease of the ileum with fistular formation between the small bowel and rectum:a case report

Abstract

Methotrexate (MTX), the first-line drug for rheumatoid arthritis, rarely causes malignant lymphomas, which have been reported as MTX-associated lymphoproliferative disorders (MTX-LPD). Herein, report a case of MTX-LPD in the ileum with fistula formation in the small bowel and rectum. At the end of January 2023, an 81-year-old man who had been taking MTX for rheumatoid arthritis since the age of 73 years complained of abdominal pain and was diagnosed with intestinal obstruction at a previous hospital. In the early February 2023, the patient was referred to our hospital for further examination and treatment. A computed tomography scan revealed a thickened terminal ileum wall and enlarged mesenteric lymph nodes. A retrograde double-balloon endoscopy (DBE) detected circumferential ulcerative lesions at the terminal ileum with deep depressions in parts of the ulcer base. In addition, submucosal tumor-like lesions with central depressions were observed in the rectum. Retrograde contrast imaging under DBE confirmed the presence of fistulae between the ileum and rectum. A biopsy of the ulcerative lesion revealed hyperplasia of germinal center cell-like cells, and immunohistochemistry demonstrated CD20 and CD79a positivity, but CD5, CD10, and cyclin D1 negativity. Ki-67 positivity was 90%, indicating B-cell lymphoma. Based on histopathological findings and patient's history, the patient was suspected to have MTX-LPD, resulting in ileal and high anterior rectal resection. Histopathological examination of the resected specimen revealed large atypical lymphocyte proliferation. Immunohistochemistry confirmed CD20 and CD79a positivity;CD5, CD10, and cyclin D1 negativity;a Ki-67 positivity rate of 70%;and Epstein-Barr virus-encoded small RNA in situ hybridization negativity, confirmming the MTX-LPD diagnosis, presenting as diffuse large B-cell lymphoma. Postoperatively, the patient was monitored with MTX discontinuation, and no recurrence occurred. The clinical course remained consistent with MTX-LPD.