ニボルマブ関連大腸炎の一剖検例

An Autopsy Case of Nivolumab-induced Colitis

要旨●患者は60歳代，男性．肺扁平上皮癌Stage IVに対してニボルマブによる治療中，下痢，血便，腹痛が出現した．大腸内視鏡検査では，直腸〜S状結腸にかけて血管透見像が消失した粗糙粘膜と不整形潰瘍を認めた．感染症による大腸病変は否定的であったため，免疫チェックポイント阻害薬関連副作用の大腸炎と診断した．ステロイド，インフリキシマブ治療を行うも難治性に経過し，ニボルマブ投与開始から173日目に永眠された．剖検所見では，最大径8cmの肺癌の約70%は壊死しており，治療が奏効したと考えられた．一方，遠位大腸では区域性全周性潰瘍と偽ポリポーシス様病変を認め，大腸炎に改善は認められなかった．ニボルマブの適応拡大に伴い，今後ニボルマブ関連大腸炎を経験する機会が増加することが予想される．

　A 60s man with advanced lung squamous cell carcinoma was treated with nivolumab, an immune checkpoint inhibitor. The patient was admitted to our hospital with diarrhea, hematochezia, and abdominal pain. Colonoscopy revealed friable erythematous mucosa and ulceration from the rectum to sigmoid colon. These findings were compatible with ulcerative colitis. Nivolumab-induced colitis, an immune-related adverse effect, was diagnosed. The patient was treated with prednisolone and infliximab, but he did not respond. The patient died 173 days after the first administration of nivolumab. A pathological autopsy was done. According to the autopsy, the lung tumor size was 8cm, with 70% necrosis. The effect of the immune checkpoint inhibitor was confirmed. However, the colitis grade score was severe because of the circumferential ulcer and pseudopolyposis of the distal colon. The number of cases of nivolumab-induced colitis is expected to increase because of the extension of indications.