{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:11:19Z","timestamp":1791976279599,"version":"4.4.0"},"reference-count":126,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T00:00:00Z","timestamp":1771718400000},"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":[[2026,6]]},"abstract":"<jats:p>The 6th Edition of the WHO Classification of Digestive System Tumours represents a significant update to the 5th edition. It integrates pathological, new molecular, and clinical insights to refine the taxonomy of digestive system neoplasms. The revised classification continues to emphasise standardisation in terminology, coding, and diagnostic criteria to facilitate global consistency in diagnosis, treatment, epidemiological reporting and research. Structural reorganisation of book chapters describes epithelial tumours by anatomical site, while separating neuroendocrine, mesenchymal and haematolymphoid tumours into dedicated chapters that are aligned with other WHO tumour volumes. Genetic tumour syndromes are classified by mechanisms, pathways and genes, whereas metastatic disease is comprehensively covered under other tumours and metastases. Key structural and diagnostic refinements include consolidation of gastric dysplasia entities; separation of duodenal\/ampullary from jejuno\u2010ileal tumours; clearer categorisation of colorectal serrated polyps and novel carcinoma grading; introduction of small\u2010 and large\u2010duct intrahepatic cholangiocarcinoma as separate entities, and redefinition of undifferentiated carcinoma to include \u2018carcinoma with mesenchymal differentiation\u2019. Several new entities are introduced, including oesophageal epidermoid metaplasia, colorectal intramucosal adenocarcinoma, low\u2010grade tubuloglandular adenocarcinoma and lymphoglandular complex\u2010like adenocarcinoma, intraductal tubulopapillary and intraductal oncocytic papillary neoplasms of the bile ducts and sonic hedgehog hepatocellular adenoma. The concept of amphicrine\u2010like carcinoma (ALC) is distinguished from MiNEN and broadens the understanding of tumours with dual neuroendocrine\u2013non\u2010neuroendocrine differentiation. Grading systems are simplified to two\u2010tier classifications (low\/high grade) across precursor lesions, with enhanced criteria for neuroendocrine tumour grading. Anal canal neoplasia terminology is harmonised with human papillomavirus (HPV) related Lower Anogenital Squamous Terminology (LAST) and mass\u2010forming biliary and gallbladder cancer precursors share similar terminology. Finally, carcinoma of unknown primary (CUP) is included in a separate section for the first time, classified by molecular and immunophenotypic profiles to guide therapy. Overall, the 6th edition strengthens tumour diagnostic precision and molecular alignment across the digestive system.<\/jats:p>","DOI":"10.1111\/his.70116","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:05:01Z","timestamp":1771805101000},"page":"1295-1314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Changes in the 6th edition of the World Health Organization classification of tumours of the digestive\u00a0system"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6826-8770","authenticated-orcid":false,"given":"Mark J","family":"Arends","sequence":"first","affiliation":[{"name":"Edinburgh Pathology, Institute of Genetics &amp; Cancer University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-2402","authenticated-orcid":false,"given":"Irene","family":"Esposito","sequence":"additional","affiliation":[{"name":"Institute of Pathology Heinrich Heine University and University Hospital of Dusseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-1967","authenticated-orcid":false,"given":"Anthony J","family":"Gill","sequence":"additional","affiliation":[{"name":"NSW Health Pathology, Department of Anatomical Pathology Royal North Shore Hospital St Leonards  Sydney New South Wales Australia"},{"name":"Sydney Medical School University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4554-5672","authenticated-orcid":false,"given":"Ralph H","family":"Hruban","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Oncology, The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2621-3584","authenticated-orcid":false,"given":"Joseph D","family":"Khoury","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Kyoto Prefectural University of Medicine Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9788-8218","authenticated-orcid":false,"given":"Elizabeth A","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Miami Miller School of Medicine  Miami Beach Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9626-5086","authenticated-orcid":false,"given":"Fatimah","family":"Abdulkareem","sequence":"additional","affiliation":[{"name":"Department of Anatomic &amp; Molecular Pathology College of Medicine, University of Lagos  Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1964-1006","authenticated-orcid":false,"given":"F\u00e1tima","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Ipatimup\/i3S, Faculdade de Medicina da Universidade do Porto and Unidade Local de Sa\u00fade S\u00e3o Jo\u00e3o  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Costamagna","sequence":"additional","affiliation":[{"name":"Centre of Excellence of Gastrointestinal and Endocrine Metabolic Diseases Ospedale Isola Tiberina \u2013 Gemelli  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0897-5385","authenticated-orcid":false,"given":"Gregory","family":"Lauwers","sequence":"additional","affiliation":[{"name":"Department of Pathology H. 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