{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:45:53Z","timestamp":1791395153273,"version":"4.3.3"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    Characterization of molecular features of cholangiocarcinoma (CCA) has questioned the traditional, anatomy\u2010based classification scheme and has alternatively suggested biology\u2010based classifications. Intrahepatic CCA has been classified into small\u2010duct and large\u2010duct types, and the latter is histologically and molecularly almost identical to perihilar CCA. Although distal and perihilar CCA have been classified together, they have different molecular abnormalities, with\n                    <jats:italic>MDM2<\/jats:italic>\n                    amplification observed in 15% of perihilar CCA cases but in none of the distal CCA cases.\n                    <jats:italic>FGFR2<\/jats:italic>\n                    and\n                    <jats:italic>IDH1<\/jats:italic>\n                    are two main drug targets in small\u2010duct intrahepatic CCA, and mismatch repair (MMR) deficiency is most common in small\u2010duct intrahepatic CCA. In contrast, HER2 is a promising target for extrahepatic CCA and gallbladder cancer, as HER2 overexpression is seen in 17%\u201330% of cases. Classification of intrahepatic CCA is often challenging on biopsy specimens; however, recognition of pitfalls (e.g., hybrid morphology) will help avoid misclassification. Staining for ancillary markers, including CRP, albumin\u2010ISH, and S100P, is also useful. Accurate distinction between distal CCA and pancreatic head cancer has become increasingly important, particularly in unresectable or borderline resectable cases, as systemic treatment strategies differ between these entities. Although these two neoplasms share many morphological and immunohistochemical features, the presence of clear or foamy cancer cells in biopsy specimens is uncommon in dCCA and may favour pancreatic ductal carcinoma.\n                  <\/jats:p>","DOI":"10.1111\/his.70157","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:15:37Z","timestamp":1776334537000},"page":"590-602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Understanding cholangiocarcinoma: molecular landscape, pathological classification, and challenges in biopsy diagnosis"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-6508","authenticated-orcid":false,"given":"Yoh","family":"Zen","sequence":"first","affiliation":[{"name":"Institute of Liver Studies, King's College Hospital King's College London  London 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