Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Histopathology. 2020 Jan;76(2):233-243. doi: 10.1111/his.13963. Epub 2019 Nov 13.
AIMS: Immune checkpoint inhibitors (ICIs) improve survival across a range of malignancies but are also associated with a spectrum of gastrointestinal (GI) immune-related adverse events (GI-irAEs). The aims of this study were to explore the diagnostic value of gastric and duodenal biopsies and to address considerations in the differential diagnosis. METHODS AND RESULTS: We identified 39 patients who were treated with ICIs and had a subsequent upper GI biopsy. We recorded clinical data and endoscopic findings, and reviewed their gastric, duodenal and colonic biopsies. Twenty-one (54%) patients were treated with an anti-programmed cell death protein 1 (PD-1)/anti-programmed cell death ligand 1 antibody alone, and 17 (44%) patients were treated with a combination of anti-cytotoxic T-lymphocyte-associated protein-4 and anti-PD-1 antibodies. Thirty-two (82%) patients presented with diarrhoea. Gastric alterations included periglandular inflammation and granulomas, and duodenal changes included villous blunting, intraepithelial lymphocytosis, granulomas, and neutrophilic activity. We recognised four patterns of colonic injury: (i) acute self-limiting colitis; (ii) lymphocytic colitis; (iii) collagenous colitis; and (iv) apoptosis-only. Twenty-nine (74%) and 10 (26%) patients were diagnosed clinically as positive and negative for GI-irAEs, respectively. Gastric periglandular inflammation (P = 0.004) and an increased number of colonic lamina propria mononuclear cells (P = 0.04) correlated with the clinical diagnosis of a GI-irAE. Histological alterations associated with ICI injury were more often identified in upper GI biopsies (71%) than in colonic biopsies (65%). CONCLUSIONS: The morphological spectrum of ICI-related GI disease is broad, and mimics a range of infectious and inflammatory diseases. Gastric periglandular inflammation represents one of the more characteristic histological features of GI-irAEs. The study underscores the importance of a comprehensive review of upper and lower GI biopsies for the diagnosis of GI-irAEs.
目的：免疫检查点抑制剂 (ICI) 改善了多种恶性肿瘤的生存率，但也与一系列胃肠道 (GI) 免疫相关不良事件 (GI-irAE) 相关。本研究旨在探讨胃和十二指肠活检的诊断价值，并解决鉴别诊断中的注意事项。
方法和结果：我们确定了 39 名接受 ICI 治疗且随后进行上 GI 活检的患者。我们记录了临床数据和内镜发现，并回顾了他们的胃、十二指肠和结肠活检。21 名（54%）患者单独接受抗程序性细胞死亡蛋白 1 (PD-1)/抗程序性细胞死亡配体 1 抗体治疗，17 名（44%）患者接受抗细胞毒性 T 淋巴细胞相关蛋白 4 和抗 PD-1 抗体联合治疗。32 名（82%）患者出现腹泻。胃改变包括腺周炎症和肉芽肿，十二指肠改变包括绒毛变钝、上皮内淋巴细胞增多、肉芽肿和中性粒细胞活性。我们识别出四种结肠损伤模式：（i）急性自限性结肠炎；（ii）淋巴细胞性结肠炎；（iii）胶原性结肠炎；和（iv）仅凋亡。29 名（74%）和 10 名（26%）患者的临床诊断分别为 GI-irAE 阳性和阴性。胃腺周炎症（P=0.004）和结肠固有层单核细胞数量增加（P=0.04）与 GI-irAE 的临床诊断相关。与 ICI 损伤相关的组织学改变在上 GI 活检中比在结肠活检中更常见（71% vs 65%）。
结论：ICI 相关 GI 疾病的形态谱广泛，模仿一系列感染性和炎症性疾病。胃腺周炎症是 GI-irAE 的更具特征性组织学特征之一。该研究强调了全面审查上消化道和下消化道活检对 GI-irAE 诊断的重要性。
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