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度伐利尤单抗诱导的弥漫性肺泡出血:一例尸检病例报告

Durvalumab-Induced Diffuse Alveolar Hemorrhage: An Autopsy Case Report.

作者信息

Kanaoka Kensuke, Ikebe Saori, Ihara Shouichi, Tsuji Hiromi, Yasuoka Hironao, Minami Seigo

机构信息

Department of Respiratory Medicine, Osaka Police Hospital, Osaka, Japan.

Department of Pathology, Osaka Police Hospital, Osaka, Japan.

出版信息

Case Rep Oncol. 2020 Jun 22;13(2):696-701. doi: 10.1159/000507848. eCollection 2020 May-Aug.

Abstract

Durvalumab, a programmed cell death ligand 1 inhibitor, induces various immune-related adverse events (irAEs), including lung injury. However, diffuse alveolar hemorrhage (DAH) is a rare type of lung injury due to immune checkpoint inhibitors. A 76-year-old man with c-stage IIIA squamous cell carcinoma of the lung received maintenance durvalumab therapy after chemoradiotherapy. He developed dyspnea and malaise after 11 cycles of durvalumab. Chest computed tomography showed rapidly spreading bilateral ground-glass opacity in the lungs. We diagnosed DAH by hemosiderin-laden macrophages in bloody bronchoalveolar lavage fluid. Despite mechanical ventilation, steroids, and cyclophosphamide, he died of respiratory failure. The autopsy revealed that fresh and old bleeding areas coexisted, and neither pulmonary vasculitis nor diffuse alveolar damage was detected microscopically. Furthermore, CD3+ and CD8+ lymphocytes were observed in the lung interstitium, whereas CD20+ and CD4+ lymphocytes were scarcely detected. We report the first case of durvalumab-induced DAH. We should be alert to irAEs with DAH as a potential differential diagnosis of lung injury during durvalumab treatment.

摘要

度伐利尤单抗是一种程序性细胞死亡配体1抑制剂,可引发包括肺损伤在内的多种免疫相关不良事件(irAEs)。然而,弥漫性肺泡出血(DAH)是一种由免疫检查点抑制剂导致的罕见肺损伤类型。一名76岁的男性,患有c期IIIA肺鳞状细胞癌,在放化疗后接受了度伐利尤单抗维持治疗。在接受11个周期的度伐利尤单抗治疗后,他出现了呼吸困难和不适。胸部计算机断层扫描显示肺部双侧磨玻璃影迅速扩散。我们通过血性支气管肺泡灌洗液中含铁血黄素巨噬细胞诊断为DAH。尽管进行了机械通气、使用了类固醇和环磷酰胺,他仍死于呼吸衰竭。尸检显示新鲜和陈旧出血区域并存,显微镜下未检测到肺血管炎或弥漫性肺泡损伤。此外,在肺间质中观察到CD3 +和CD8 +淋巴细胞,而CD20 +和CD4 +淋巴细胞几乎未检测到。我们报告了首例度伐利尤单抗诱导的DAH病例。在度伐利尤单抗治疗期间,我们应警惕DAH这种可能作为肺损伤鉴别诊断的irAEs。

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