Chornenkyy Yevgen, LaBoy Carissa, De Hoyos Sergei Xavier, Hu Jingjing, Pezhouh Maryam
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Department of Pathology, Northwestern Feinberg School of Medicine, Chicago, Illinois, USA.
J Clin Pathol. 2025 Aug 18;78(9):583-590. doi: 10.1136/jcp-2024-209621.
Widespread use of immune checkpoint inhibitors (ICIs) for treatment of advanced malignancies led to an increase in number of immune-related adverse events such as ICI gastrointestinal (GI) injury (ICIGI). The resulting immune dysregulation of the GI mucosa is believed to predispose patients to viral infections. We characterised the histopathological features of ICIGI and the frequency of viral infections such as cytomegalovirus (CMV), adenovirus, and Epstein-Barr virus (EBV).
Single-centre retrospective study (2011-2020).
81 GI biopsies from 31 patients with ICIGI (65% male (20/31), 35% female (11/31)) with advanced malignancies were reviewed. Most patients received ipilimumab and nivolumab (14/31, 45%), followed by pembrolizumab (9/31, 29%), ipilimumab (4/31, 13%), nivolumab (2/31, 6%) and combination of all three medications (2/31, 6%). Average regimen prior to incidence of diarrhea was three cycles. Evidence of colitis or erythema by endoscopy was present in 77% of cases, while 23% showed normal endoscopy. Histologically, the predominant ICIGI findings were active inflammation (84%), including cryptitis (77%), crypt abscesses (65%), lymphocytic colitis-like (LCL) pattern (61%), increase in epithelial apoptosis (74%) and/or surface injury (81%). Only one case showed diffuse CMV positivity (3%) with characteristic CMV viral cytopathic effects present on H&E stain and four cases were positive for rare EBV (13%). Adenovirus infection was not identified.
While our cohort is small, ICIGI generally demonstrates active inflammation including cryptitis and crypt abscesses in the colon, LCL pattern, and an increase in epithelial apoptosis. Upfront immunohistochemistry for viral infection without high-degree of clinical and histologic suspicion is not recommended.
免疫检查点抑制剂（ICI）在晚期恶性肿瘤治疗中的广泛应用导致免疫相关不良事件数量增加，如ICI胃肠道（GI）损伤（ICIGI）。胃肠道黏膜由此产生的免疫失调被认为使患者易患病毒感染。我们对ICIGI的组织病理学特征以及巨细胞病毒（CMV）、腺病毒和爱泼斯坦-巴尔病毒（EBV）等病毒感染的频率进行了表征。
单中心回顾性研究（2011 - 2020年）。
对31例患有ICIGI的晚期恶性肿瘤患者（65%为男性（20/31），35%为女性（11/31））的81份胃肠道活检标本进行了回顾。大多数患者接受了伊匹木单抗和纳武单抗（14/31，45%），其次是帕博利珠单抗（9/31，29%）、伊匹木单抗（4/31，13%）、纳武单抗（2/31，6%）以及三种药物联合使用（2/31，6%）。腹泻发生前的平均疗程为三个周期。77%的病例通过内镜检查有结肠炎或红斑的证据，而23%的内镜检查结果正常。组织学上，ICIGI的主要表现为活动性炎症（84%），包括隐窝炎（77%）、隐窝脓肿（65%）、淋巴细胞性结肠炎样（LCL）模式（61%）、上皮细胞凋亡增加（74%）和/或表面损伤（81%）。仅1例显示弥漫性CMV阳性（3%），在苏木精-伊红（H&E）染色上有特征性的CMV病毒细胞病变效应，4例罕见EBV阳性（13%）。未发现腺病毒感染。
虽然我们的队列规模较小，但ICIGI通常表现为活动性炎症，包括结肠隐窝炎和隐窝脓肿、LCL模式以及上皮细胞凋亡增加。不建议在没有高度临床和组织学怀疑的情况下对病毒感染进行预先免疫组化检查。
