Department of Pathology, Weill Cornell College of Medicine, New York, NY, USA.
Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Histopathology. 2020 Mar;76(4):531-539. doi: 10.1111/his.14029. Epub 2020 Feb 18.
Immune check-point inhibitors are frequently used in the treatment of a variety of solid tumours. The mechanism of action of these drugs involves up-regulation of cytotoxic T cells, which can lead to a lack of self-tolerance and immune-related adverse events, including those involving the gastrointestinal tract. This study was performed to characterise the histological features of immune check-point inhibitor therapy-associated gastritis.
Gastric biopsies from patients on immune check-point inhibitor therapy with clinical suspicion of drug-associated gastrointestinal injury were identified. The predominant histological pattern of injury, distribution of injury, degree of tissue eosinophilia and prominence of apoptosis were recorded. Presenting symptoms, treatment and follow-up data were obtained by medical chart review. The 12 patients included in the study group were treated with ipilimumab, nivolumab or pembrolizumab for a variety of tumours. Symptoms at presentation included nausea, vomiting and diarrhoea. Chronic active gastritis with intra-epithelial lymphocytosis and prominent apoptosis was seen in eight of 12 patients, and was the most useful combination for the diagnosis of drug-induced gastritis in these patients. Four patients showed focal enhancing gastritis with a lymphohistiocytic cuff around inflamed glands reminiscent of Crohn's disease. One of those four patients was homozygous for the ATG16L1 Crohn's disease-associated gene variant, but had no history of inflammatory bowel disease. Ten patients responded to medication withdrawal and steroid therapy, while two required treatment with infliximab.
Awareness of the morphological spectrum of immune check-point inhibitor therapy-associated gastritis is important for the accurate diagnosis and prompt management of these patients.
免疫检查点抑制剂常用于治疗多种实体瘤。这些药物的作用机制涉及细胞毒性 T 细胞的上调，这可能导致自身耐受缺失和免疫相关的不良反应，包括胃肠道受累。本研究旨在描述免疫检查点抑制剂治疗相关胃炎的组织学特征。
从接受免疫检查点抑制剂治疗且临床怀疑与药物相关胃肠道损伤的患者中获取胃活检。记录损伤的主要组织学模式、损伤分布、组织嗜酸性粒细胞增多程度和凋亡突出程度。通过病历回顾获取患者的临床表现、治疗和随访数据。本研究纳入了 12 例患者，均因不同肿瘤接受了依匹单抗、纳武单抗或帕博利珠单抗治疗。患者的主要表现为恶心、呕吐和腹泻。12 例患者中有 8 例表现为慢性活动性胃炎伴上皮内淋巴细胞增多和明显凋亡，这是这些患者诊断药物相关性胃炎最有用的组合。4 例患者表现为局灶性增强性胃炎，炎症腺体周围有淋巴组织细胞袖套，类似于克罗恩病。这 4 例患者中有 1 例携带 ATG16L1 克罗恩病相关基因突变，但无炎症性肠病病史。10 例患者对停药和皮质类固醇治疗有反应，2 例需要英夫利昔单抗治疗。
了解免疫检查点抑制剂治疗相关胃炎的形态谱对于这些患者的准确诊断和及时治疗非常重要。
