{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T04:58:56Z","timestamp":1782709136404,"version":"3.54.5"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>Combined hepatocellular\u2010cholangiocarcinoma (cHCC\u2010CC) is a rare type of liver tumour that exhibits both hepatocytic and biliary differentiation within the same tumour. The histology and genomic alterations of recurrent\/metastatic cHCC\u2010CC are poorly understood. We selected six patients with cHCC\u2010CC whose recurrent or metastatic tumours were histologically confirmed. Four patients with classic cHCC\u2010CCs and two with intermediate cell carcinomas (ICs) were included. The clinicopathological features were evaluated, and next\u2010generation sequencing was performed in 17 multiregional and longitudinal tumour samples. The histology of recurrent\/metastatic lesions of classic cHCC\u2010CCs was variable: hepatocellular carcinoma (HCC) was observed in one (25.0%) patient, cHCC\u2010CC in one (25.0%) patient, and cholangiocarcinoma (CC) in two (50.0%) patients. Among 13 samples from four classic cHCC\u2010CC patients, the most frequent pathological variants were <jats:italic>TP53<\/jats:italic> (46.2%), <jats:italic>TERT<\/jats:italic> promoter (38.5%), <jats:italic>ARID1A<\/jats:italic> mutations (23.1%), and <jats:italic>MET<\/jats:italic> amplification (30.8%). In the sequencing analysis of each HCC and CC component, three (75.0%) of the four classic cHCC\u2010CCs shared pathogenic variants. A large proportion of mutations, both pathogenic and those of undetermined significance, were shared by each HCC and CC component. Regarding ICs, the <jats:italic>ATM<\/jats:italic> mutation was detected in one patient. In conclusion, the histology of recurrent\/metastatic cHCC\u2010CCs was heterogeneous. Genomic profiling of classic cHCC\u2010CCs revealed similar genomic alterations to those of HCC. Considerable overlapping genomic alterations in each HCC and CC component were observed, suggesting a monoclonal origin. Genetic alterations in ICs were different from those in either HCC or CC, suggesting the distinct nature of this tumour.<\/jats:p>","DOI":"10.1111\/his.15081","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T03:04:33Z","timestamp":1698721473000},"page":"402-408","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Multiregional analysis of combined hepatocellular\u2010cholangiocarcinoma reveals histologic diversity and molecular clonality"],"prefix":"10.1111","volume":"84","author":[{"given":"Hee Young","family":"Na","sequence":"first","affiliation":[{"name":"Department of Pathology Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4205-9081","authenticated-orcid":false,"given":"Haeryoung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology Seoul National University Hospital, Seoul National University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jai Young","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Surgery Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho\u2010Seong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Surgery Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Sun","family":"Jang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Wook","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sook\u2010Hyang","family":"Jeong","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Internal Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayoon","family":"Heo","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Korea"},{"name":"Department of Internal Medicine National Health Insurance Service Ilsan Hospital  Goyang Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1979-4010","authenticated-orcid":false,"given":"Soomin","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Pathology Seoul National University Bundang Hospital, Seoul National University College of Medicine  Seongnam Korea"},{"name":"Department of Pathology and Translational Genomics, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,30]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"260","volume-title":"Digestive system tumours. 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