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In unresectable cases, the survival period is short despite combination therapy with cytotoxic anticancer agents and immune checkpoint inhibitors. The usefulness of immune checkpoint inhibitors against malignant tumors with microsatellite instability-high (MSI-H) mutations was shown in the KEYNOTE158 study; however, data for intrahepatic cholangiocarcinoma are insufficient. In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. A comprehensive cancer genomic profiling (CGP) test showed <jats:italic>MLH1<\/jats:italic> pathogenic mutation and MSI-H. When pembrolizumab was administered, the tumor shrinkage effect was rapidly observed, which was sustained even after 30\u00a0months. No pathogenic mutations were observed in the germline test, and MSI-high was considered to be due to the <jats:italic>MLH1<\/jats:italic> pathogenic mutation occurring sporadically in somatic cells. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed.<\/jats:p>","DOI":"10.1007\/s12328-025-02103-4","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T03:14:44Z","timestamp":1741058084000},"page":"363-368","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Microsatellite-high intrahepatic cholangiocarcinoma with favorable treatment outcome using pembrolizumab"],"prefix":"10.1007","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-8262","authenticated-orcid":false,"given":"Shigeru","family":"Horiguchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironari","family":"Kato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosaku","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Matsumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Terasawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyuki","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehiro","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoyuki","family":"Otsuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"2103_CR1","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","volume":"362","author":"J Valle","year":"2010","unstructured":"Valle J, Wasan H, Palmer DH, et al. 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