{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T09:43:08Z","timestamp":1792489388437,"version":"4.5.0"},"reference-count":17,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"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"],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Hybrid lesions containing distinct components of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) within a single nodule are exceptionally rare. This study aimed to investigate the biological nature of these unusual lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      The two cases identified to date were examined by histopathological, immunohistochemical and targeted next\u2010generation sequencing analyses. In case 1, the hybrid tumour (6.0\u2009cm) consisted of approximately equal proportions of HNF1\u03b1\u2010inactivated HCA and FNH, which were intimately admixed but remained histologically distinct. In case 2, the tumour (9.5\u2009cm) consisted predominantly of HNF1\u03b1\u2010inactivated HCA but contained a small peripheral nodule of FNH, resulting in a nodule\u2010in\u2010nodule appearance. The HCA components in both cases showed loss of FABP1 expression, whereas the FNH components retained FABP1 expression and showed a map\u2010like pattern of glutamine synthetase expression. Next\u2010generation sequencing in case 1 demonstrated that the mutations were not shared between the HCA and FNH components, with\n                      <jats:italic>HNF1A<\/jats:italic>\n                      and\n                      <jats:italic>FLT1<\/jats:italic>\n                      mutations identified only in the HCA component. In case 2, the same\n                      <jats:italic>HNF1A<\/jats:italic>\n                      splice\u2010site mutation was identified in both the HCA and FNH components, but was also present in the non\u2010neoplastic gallbladder, confirming its germline origin. The HCA component, but not the FNH component, additionally harboured somatic mutations in\n                      <jats:italic>ATM<\/jats:italic>\n                      and\n                      <jats:italic>FAT4<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HCA, particularly the HNF1\u03b1\u2010inactivated subtype, rarely coexists with FNH. The distinct molecular and immunohistochemical profiles of the two components support a collision mechanism, indicating that the FNH component represents a separate non\u2010neoplastic lesion and arguing against one component arising from the other.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70305","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T09:25:55Z","timestamp":1792488355000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hybrid lesions of hepatocellular adenoma and focal nodular hyperplasia: a clinicopathological and molecular study of two cases"],"prefix":"10.1111","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 UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0950-3339","authenticated-orcid":false,"given":"Peter","family":"Schirmacher","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1111\/his.14605","article-title":"Hepatocellular adenoma: what we know, what we do not know, and why it matters","volume":"80","author":"Bioulac\u2010Sage P","year":"2022","journal-title":"Histopathology"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.humpath.2020.11.016","article-title":"Hepatocellular adenomas: review of pathological and molecular features","volume":"112","author":"Beaufr\u00e8re A","year":"2021","journal-title":"Hum. 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Hepatol."},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/j.1478-3231.2008.01849.x","article-title":"Over\u2010expression of glutamine synthetase in focal nodular hyperplasia: a novel easy diagnostic tool in surgical pathology","volume":"29","author":"Bioulac\u2010Sage P","year":"2009","journal-title":"Liver Int."},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1097\/PAS.0b013e3182653ece","article-title":"Immunohistochemical markers on needle biopsies are helpful for the diagnosis of focal nodular hyperplasia and hepatocellular adenoma subtypes","volume":"36","author":"Bioulac\u2010Sage P","year":"2012","journal-title":"Am. J. Surg. Pathol."},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"314","DOI":"10.4254\/wjh.v4.i11.314","article-title":"Co\u2010existence of hepatocellular adenoma and focal nodular hyperplasia in a young female","volume":"4","author":"Dimitroulis D","year":"2012","journal-title":"World J. Hepatol."},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1046\/j.1440-1746.2003.02840.x","article-title":"Simultaneous occurrence of adenoma, focal nodular hyperplasia, and hemangioma of the liver: are they derived from a common origin","volume":"18","author":"Di Carlo I","year":"2003","journal-title":"J. Gastroenterol. Hepatol."},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1097\/PAS.0000000000000477","article-title":"Simultaneous occurrence of focal nodular hyperplasia and HNF1A\u2010inactivated hepatocellular adenoma: a collision tumor simulating a composite FNH\u2010HCA","volume":"39","author":"Shih A","year":"2015","journal-title":"Am. J. Surg. Pathol."},{"key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1053\/j.gastro.2004.02.005","article-title":"Telangiectatic focal nodular hyperplasia: a variant of hepatocellular adenoma","volume":"126","author":"Paradis V","year":"2004","journal-title":"Gastroenterology"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1053\/j.gastro.2005.02.004","article-title":"Clinical, morphologic, and molecular features defining so\u2010called telangiectatic focal nodular hyperplasias of the liver","volume":"128","author":"Bioulac\u2010Sage P","year":"2005","journal-title":"Gastroenterology"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1159\/000543217","article-title":"High frequency of CTNNB1 variants associated with benign and malignant liver tumors in patients with congenital Porto\u2010systemic shunts","volume":"14","author":"Tyraskis A","year":"2025","journal-title":"Liver Cancer."},{"key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1365-2559.2005.02250.x","article-title":"Multiple mixed adenoma\u2010focal nodular hyperplasia of the liver associated with spontaneous intrahepatic porto\u2010systemic shunt: a new type of vascular malformation associated with the multiple focal nodular hyperplasia syndrome?","volume":"48","author":"Handra\u2010Luca A","year":"2006","journal-title":"Histopathology"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhepr.2026.101778","article-title":"New histopathological terminology for well\u2010differentiated hepatocellular lesions in unusual clinico\u2010pathological scenarios: HCA\u2010like and FNH\u2010like","volume":"8","author":"Sempoux C","year":"2026","journal-title":"JHEP Rep."},{"key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/0016-5085(87)90273-3","article-title":"Liver adenoma and focal nodular hyperplasia in a man with high endogenous sex steroids","volume":"93","author":"Grang\u00e9 JD","year":"1987","journal-title":"Gastroenterology"},{"key":"e_1_2_11_18_1","doi-asserted-by":"crossref","DOI":"10.1186\/1476-5926-2-6","article-title":"Association of adenoma and focal nodular hyperplasia: experience of a single French academic center","volume":"2","author":"Laurent C","year":"2003","journal-title":"Comp. Hepatol."}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70305","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.70305","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70305","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T09:25:58Z","timestamp":1792488358000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.70305"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":17,"alternative-id":["10.1111\/his.70305"],"URL":"https:\/\/doi.org\/10.1111\/his.70305","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"assertion":[{"value":"2026-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"his.70305"}}