Placke Jan-Malte, Rawitzer Josefine, Reis Henning, Rashidi-Alavijeh Jassin, Livingstone Elisabeth, Ugurel Selma, Hadaschik Eva, Griewank Klaus, Schmid Kurt Werner, Schadendorf Dirk, Roesch Alexander, Zimmer Lisa
Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Front Oncol. 2021 Aug 11;11:725549. doi: 10.3389/fonc.2021.725549. eCollection 2021.
Gastritis induced by checkpoint inhibitors (CPI) is a rare but severe drug-related side effect. The reference standard for confirming CPI-associated gastritis (CPI-assGastritis) is histopathological assessment; however, the histopathological features of CPI-assGastritis are not yet adequately defined.
Gastric biopsies of melanoma patients with histopathologically suspected CPI-assGastritis were compared with gastric biopsies of patients with inflammation free gastric mucosa (IFGM), type A, B, and C gastritis with respect to apoptosis count and predominant histopathological features. Immunohistochemical anti-caspase-3 staining was performed to identify apoptosis. Quantification was performed by manually counting the number of apoptotic events per 10 high-power fields (HPF). Clinical symptoms, treatment, and follow-up data of patients with CPI-assGastritis were examined. The nonparametric Mann-Whitney test was used for statistical testing.
Five melanoma patients (three women, two men; median age: 45 years) were treated with PD-1-based CPI. The patients reported epigastric pain, weight loss, nausea, and vomiting. Histologically, the patients with CPI-assGastritis showed a partly lymphocytic, partly granulocytic inflammatory infiltrate. Manual counting of apoptotic cells in biopsy tissue slides stained against caspase 3 revealed a median of 6 apoptotic events/10 HPF (95% CI, 2.75-17.30) in the patients with CPI-assGastritis. Results for the comparison cohort (patients n = 21) were a median of 1 apoptotic event/10 HPF (95% CI, 0.5-4.5) for type-A gastritis (six patients), a median of 2 apoptotic events/10 HPF (95% CI, 0-4.5) for type-B gastritis (five patients), and no apoptosis for IFGM and type-C gastritis (five patients). Patients with CPI-assGastritis had a significantly higher apoptosis count than patients with IFGM (p<0.01), type A (p<0.05), B (p<0.05), and C gastritis (p<0.01). None of the CPI-assGastritis biopsies showed evidence of . All CPI-assGastritis patients responded to systemic treatment with corticosteroids.
CPI-assGastritis manifests with nonspecific symptoms but histologically shows a high number of apoptotic events, which can best be visualized by anti-caspase-3 immunohistochemistry. This histopathological feature may help to histologically differentiate CPI-assGastritis from other forms of gastritis and inform decision-making regarding its optimal management.
检查点抑制剂（CPI）诱发的胃炎是一种罕见但严重的药物相关副作用。确认CPI相关胃炎（CPI - assGastritis）的参考标准是组织病理学评估；然而，CPI - assGastritis的组织病理学特征尚未得到充分界定。
将组织病理学怀疑为CPI - assGastritis的黑色素瘤患者的胃活检组织与胃黏膜无炎症（IFGM）、A型、B型和C型胃炎患者的胃活检组织在凋亡计数和主要组织病理学特征方面进行比较。进行免疫组织化学抗半胱天冬酶 - 3染色以识别凋亡。通过手动计数每10个高倍视野（HPF）中的凋亡事件数量进行定量分析。检查CPI - assGastritis患者的临床症状、治疗和随访数据。采用非参数曼 - 惠特尼检验进行统计学检验。
5例黑色素瘤患者（3例女性，2例男性；中位年龄：45岁）接受了基于PD - 1的CPI治疗。患者报告有上腹部疼痛、体重减轻、恶心和呕吐。组织学上，CPI - assGastritis患者表现为部分淋巴细胞、部分粒细胞炎性浸润。对用抗半胱天冬酶3染色的活检组织切片中的凋亡细胞进行手动计数，结果显示CPI - assGastritis患者的凋亡事件中位数为6个/10 HPF（95%CI，2.75 - 17.30）。比较队列（n = 21例患者）的结果为，A型胃炎（6例患者）凋亡事件中位数为1个/10 HPF（95%CI，0.5 - 4.5），B型胃炎（5例患者）凋亡事件中位数为2个/10 HPF（95%CI，0 - 4.5），IFGM和C型胃炎（5例患者）无凋亡。CPI - assGastritis患者的凋亡计数显著高于IFGM患者（p<0.01）、A型患者（p<0.05）、B型患者（p<0.05）和C型胃炎患者（p<0.01）。所有CPI - assGastritis活检组织均未显示……的证据。所有CPI - assGastritis患者对全身用皮质类固醇治疗均有反应。
CPI - assGastritis表现为非特异性症状，但组织学上显示大量凋亡事件，通过抗半胱天冬酶 - 3免疫组织化学可最佳显示。这一组织病理学特征可能有助于在组织学上将CPI - assGastritis与其他形式的胃炎区分开来，并为其最佳管理的决策提供依据。
