{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:50:55Z","timestamp":1789411855937,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24ama221222"],"award-info":[{"award-number":["24ama221222"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"Abstract<\/jats:title>\n \n Bile duct tumor thrombus (BDTT), a tumor cluster occupying the luminal space in the large bile duct, is rare in intrahepatic cholangiocarcinoma (iCCA). Most studies on BDTT in iCCA to date are case reports, and the clinicopathological characteristics remain unknown. This study aimed to characterize iCCA with BDTT clinicopathologically and genetically. We analyzed 223 surgically resected iCCA cases, including 102 small duct type (SDT) and 121 large duct type (LDT) cases. BDTT was found in 19.6% (20\/102) of SDT cases. Histological and immunohistochemical features of BDTT\u2010positive SDT were comparable with those of conventional SDT (MUC1\n +<\/jats:sup>\n MUC2\n \u2212<\/jats:sup>\n MUC5AC\n \u2212<\/jats:sup>\n MUC6\n +\/\u2212<\/jats:sup>\n CDX\u20102\n \u2212<\/jats:sup>\n ). BDTT\u2010positive SDT showed female predominance and higher T factors compared with conventional SDT. SDT was associated with a significantly longer survival in iCCA. SDT patients with BDTT had significantly shorter survival than those without BDTT and survival rates similar to those of LDT patients; the presence of BDTT in SDT was an independent unfavorable prognostic factor (HR\u2009=\u20092.601,\n p<\/jats:italic>\n \u2009=\u20090.006). Whole\u2010exome sequencing analysis revealed recurrent altered gene expression: those more frequent in SDT compared with LDT (\n BAP1<\/jats:italic>\n ,\n IDH1\/2<\/jats:italic>\n ,\n ZNF717<\/jats:italic>\n ,\n FGFR2<\/jats:italic>\n ,\n NRAS<\/jats:italic>\n ); those more frequent in LDT (\n KRAS<\/jats:italic>\n ,\n TP53<\/jats:italic>\n ,\n SMAD4<\/jats:italic>\n ,\n MUC6<\/jats:italic>\n ,\n CACNA1A<\/jats:italic>\n ,\n MLL2<\/jats:italic>\n ,\n MDM2<\/jats:italic>\n ,\n TGFBR1\/2)<\/jats:italic>\n ; and those found comparably in both SDT and LDT (\n MUC4<\/jats:italic>\n ,\n ARID1A<\/jats:italic>\n ,\n EPHA2<\/jats:italic>\n ,\n PIK3CA<\/jats:italic>\n ,\n MUC17<\/jats:italic>\n ,\n MAP3K4<\/jats:italic>\n ,\n MUC2<\/jats:italic>\n ,\n BRAF<\/jats:italic>\n ,\n NF1<\/jats:italic>\n ). Genetic landscapes were similar in SDT iCCA with and without BDTT; recurrent mutations in\n MUC2<\/jats:italic>\n and\n MUC17<\/jats:italic>\n and\n FGFR2<\/jats:italic>\n fusion genes were more frequent in BDTT\u2010positive SDTs.\n PTPRK<\/jats:italic>\n ::\n RSPO3<\/jats:italic>\n fusion gene was found in one LDT case. Intraglandular papillary and tubular proliferation is a unique and rare histology of SDT. BDTT was frequently found in SDT with this pattern, and\n FGFR2<\/jats:italic>\n gene rearrangement was frequent. These results highlight the importance of evaluating BDTT in SDT, as it may be the main route of hilar extension in aggressive cases. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n <\/jats:p>","DOI":"10.1002\/path.70038","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T07:22:02Z","timestamp":1769844122000},"page":"100-111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Bile duct tumor thrombus (intraductal polypoid growth)\u2013positive intrahepatic cholangiocarcinoma: clinicopathologic and genomic analysis"],"prefix":"10.1002","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3448-8115","authenticated-orcid":false,"given":"Ayaka","family":"Mitsui","sequence":"first","affiliation":[{"name":"Division of Molecular Pathology National Cancer Center Research Institute Tokyo Japan"},{"name":"Division of Innovative Pathology and Laboratory Medicine National Cancer Center EPOC Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Esaki","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Surgery National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Nara","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Surgery National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Arai","sequence":"additional","affiliation":[{"name":"Division of Cancer Genomics National Cancer Center Research Institute Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Division of Cancer Genomics National Cancer Center Research Institute Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhiro","family":"Shibata","sequence":"additional","affiliation":[{"name":"Division of Cancer Genomics National Cancer Center Research Institute Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Ban","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Surgery National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Mizui","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Pancreatic Surgery National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4215-4385","authenticated-orcid":false,"given":"Nobuyoshi","family":"Hiraoka","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology National Cancer Center Research Institute Tokyo Japan"},{"name":"Division of Innovative Pathology and Laboratory Medicine National Cancer Center EPOC Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0310-z"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.157"},{"key":"e_1_2_8_4_1","first-page":"254","volume-title":"World Health Organization Classification of Tumours 5th Edition Digestive System Tumours","author":"Nakanuma Y","year":"2019"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v2.i12.419"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhbp.154"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.22"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000670"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000957"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12328-020-01275-5"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-007-0307-8"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijscr.2017.08.059"},{"key":"e_1_2_8_13_1","volume-title":"TNM Classification of Malignant Tumours","author":"Brierley JD","year":"2017"},{"key":"e_1_2_8_14_1","volume-title":"The General Rules for the Clinical and Pathological Study of Primary Liver Cancer","author":"Liver_Cancer_Study_Group_of_Japan","year":"2019"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2020.12.005"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.55418\/9781933477411-07"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/pin.13226"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3375"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10606"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26890"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-020-01735-2"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/bimj.201700067"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780030207"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.244"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1216097"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2022.07.019"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-322983"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2022-0343-OA"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14133156"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002347"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.16015"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.01.009"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1137510"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4709"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16466"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.70038","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.70038","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.70038","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T03:18:24Z","timestamp":1775445504000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.70038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/path.70038"],"URL":"https:\/\/doi.org\/10.1002\/path.70038","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"assertion":[{"value":"2025-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}