{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:36:05Z","timestamp":1787621765541,"version":"build-2736575974"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"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:p>\n                    We report the case of a 75-year-old woman with a pancreatic body mass. Pathological findings from endoscopic ultrasonography-guided fine-needle aspiration revealed medullary carcinoma of the pancreas (MCP). Deficient mismatch repair (dMMR) and high microsatellite instability (MSI-H) were identified through immunohistochemistry and next generation sequencing, respectively. While immunohistochemistry suggested MLH1 abnormality, no\n                    <jats:italic>MLH1<\/jats:italic>\n                    mutation was; hypermethylation of the\n                    <jats:italic>MLH1<\/jats:italic>\n                    promoter was later confirmed via bisulfite sequencing. The patient initially received nab-paclitaxel plus gemcitabine, achieving tumor shrinkage. Upon tumor regrowth, she was treated with the anti-programmed cell death-1 immune checkpoint inhibitor (ICI) pembrolizumab, which resulted in significant tumor reduction. This is the first case report of MCP with dMMR\/MSI-H due to\n                    <jats:italic>MLH1<\/jats:italic>\n                    promoter hypermethylation, effectively treated with an ICI.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2025.1551038","type":"journal-article","created":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T22:14:32Z","timestamp":1743113672000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case Report: Medullary carcinoma of the pancreas with MLH1 promoter hypermethylation, induced deficient mismatch repair, successfully treated with an immune checkpoint inhibitor"],"prefix":"10.3389","volume":"15","author":[{"given":"Koushiro","family":"Ohtsubo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Sakaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kotani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaname","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Yano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihito","family":"Toshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Gabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Notohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Fujisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Yoshino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunio","family":"Miyake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Miwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e318258055c","article-title":"Japan Pancreatic Cancer Registry; 30th year anniversary: Japan Pancreas Society","volume":"41","author":"Egawa","year":"2012","journal-title":"Pancreas"},{"key":"B2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J Clin"},{"key":"B3","doi-asserted-by":"publisher","first-page":"375","DOI":"10.3322\/caac.21626","article-title":"Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma","volume":"70","author":"Grossberg","year":"2020","journal-title":"CA Cancer J Clin"},{"key":"B4","first-page":"295","article-title":"WHO classification of tumours","volume-title":"Digestive System Tumours, 10 Tumours of the Pancreas","year":"2019"},{"key":"B5","article-title":"Pancreatic adenocarcinomas with DNA replication errors (RER+) are associated with wild-type K-ras and characteristic histopathology. 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