Department of Surgery, Kohnodai Hospital, National Center for Global Health and Medicine, 1-7-1 Konodai, Ichikawa-shi, Chiba, 272-8156, Japan.
World J Surg Oncol. 2021 Jan 2;19(1):4. doi: 10.1186/s12957-020-02114-0.
Methotrexate (MTX) is a frequently used drug in the treatment of rheumatoid arthritis (RA), but occurrences of lymphoproliferative disorders (LPD) have been reported in patients undergoing an MTX regimen. Almost half of the patients with methotrexate-associated lymphoproliferative disorders (MTX-LPD) have extranodal lesions; moreover, although extremely rare, digestive tract perforations resulting from the extranodal lesions of MTX-LPD have also been reported.
We describe the case of an 81-year-old woman with RA who had been prescribed MTX at 6 mg per week for the past 11 years. She was admitted to our hospital with occasional abdominal pain and was first diagnosed with enteritis. Her abdominal pain did not improve, and a computed tomography scan showed abdominal effusion and free air in the abdominal cavity. She was diagnosed with a digestive tract perforation and underwent emergency surgery. The perforation site was identified in the jejunum, and she underwent small intestinal resection around the perforated region. The pathological findings showed an ulcer in the jejunum and infiltration of large atypical lymphocytes around the perforated region. An immunohistochemical examination revealed the expression of a cluster of differentiation 20 and latent membrane protein 1. Considering the patient's history of RA treated with MTX, she was diagnosed as having Epstein-Barr virus (EBV)-related MTX-LPD with a histological diagnosis of EBVMCU. MTX was discontinued after the surgery, and her soluble interleukin-2 receptor (sIL-2R) levels had returned to normal 1 year later. She has had a good course for the 2 years since surgery and remains asymptomatic with no recurrence of MTX-LPD, as confirmed by the sIL-2R levels.
We experienced a rare case of the jejunum perforation induced by MTX-LPD. Since only a few cases have been reported of a patient with small intestinal perforation induced by MTX-LPD, further research is necessary to evaluate the clinicopathological features of MTX-LPD. The patient had disease remission after surgery and by discontinuing MTX treatment; our case did not require chemotherapy. EBV-positive patients, especially those with a pathological presentation of EBVMCU, could have a higher likelihood of remission, which could have been a factor in the present case.
甲氨蝶呤（MTX）是治疗类风湿关节炎（RA）的常用药物，但有报道称，在接受 MTX 治疗方案的患者中，会出现淋巴增生性疾病（LPD）。接受 MTX 治疗的淋巴增生性疾病（MTX-LPD）患者中几乎有一半存在结外病变；此外，尽管极为罕见，但 MTX-LPD 的结外病变也会导致消化道穿孔。
我们描述了一位 81 岁的 RA 女性患者，她在过去 11 年中每周接受 6mg MTX 治疗。她因间歇性腹痛入住我院，最初被诊断为肠炎。她的腹痛没有改善，计算机断层扫描显示腹腔积液和腹腔内游离气体。她被诊断为消化道穿孔，并接受了紧急手术。穿孔部位位于空肠，她在穿孔区域周围进行了小肠切除。病理结果显示空肠溃疡和穿孔区域周围大非典型淋巴细胞浸润。免疫组化检查显示分化簇 20 和潜伏膜蛋白 1 的表达。鉴于患者有 MTX 治疗的 RA 病史，她被诊断为 EBV 相关的 MTX-LPD，组织学诊断为 EBVMCU。手术后停用 MTX，1 年后她的可溶性白细胞介素-2 受体（sIL-2R）水平恢复正常。手术后 2 年来，她的病情一直很好，没有复发 MTX-LPD，sIL-2R 水平也证实了这一点。
我们遇到了一例罕见的 MTX-LPD 导致的空肠穿孔病例。由于仅有少数 MTX-LPD 导致小肠穿孔的病例报道，因此需要进一步研究来评估 MTX-LPD 的临床病理特征。该患者手术后和停用 MTX 治疗后疾病缓解；本病例不需要化疗。EBV 阳性患者，特别是 EBVMCU 病理表现阳性的患者，缓解的可能性更高，这可能是本病例的一个因素。
