{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T21:08:27Z","timestamp":1773176907171,"version":"3.50.1"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>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\u2013Whitney <jats:italic>U<\/jats:italic> test was used for statistical testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u20134.5) for type-A gastritis (six patients), a median of 2 apoptotic events\/10 HPF (95% CI, 0\u20134.5) 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&amp;lt;0.01), type A (p&amp;lt;0.05), B (p&amp;lt;0.05), and C gastritis (p&amp;lt;0.01). None of the CPI-assGastritis biopsies showed evidence of <jats:italic>Helicobacter pylori<\/jats:italic>. All CPI-assGastritis patients responded to systemic treatment with corticosteroids.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.725549","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T07:44:04Z","timestamp":1628667844000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Apoptotic Gastritis in Melanoma Patients Treated With PD-1-Based Immune Checkpoint Inhibition \u2013 Clinical and Histopathological Findings Including the Diagnostic Value of Anti-Caspase-3 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