{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:54:19Z","timestamp":1790812459584,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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:p>\n                    To trace the historical evolution of gastrointestinal mixed epithelial\u2013neuroendocrine tumour terminology, clarify current diagnostic criteria, histological features and approach to reporting these lesions in accordance with the latest classification of gastrointestinal tumours, a narrative overview was undertaken on mixed neuroendocrine\u2013non\u2010neuroendocrine neoplasia (MiNEN). The review traces terminology from early descriptions and successive World Health Organization (WHO) classifications culminating in the 2026 WHO classification and recommendations. Definitions, histological grading, immunohistochemistry, molecular evidence and morphological mimics are reviewed. In the 2026 classification, MiNEN remains a mixed tumour composed of two morphologically recognizable components; each component constituting \u226530% of the neoplasm, with clear neuroendocrine marker expression in the neuroendocrine component. It is clarified that neoplasms with a non\u2010neuroendocrine component that is solely a precursor or intramucosal lesion are not MiNEN. For example, appropriate terminology would be a \u2018\n                    <jats:italic>neuroendocrine carcinoma arising from an adenoma<\/jats:italic>\n                    \u2019 rather than a \u2018\n                    <jats:italic>MiNEN (mixed adenoma\u2010neuroendocrine carcinoma)<\/jats:italic>\n                    \u2019 or even a MANET (\n                    <jats:italic>\u2018mixed adenoma neuroendocrine tumour\u2019<\/jats:italic>\n                    ). In the WHO 6th edition, to capture another class of tumours with mixed differentiation, the concept of \u2018amphicrine\u2010like carcinoma\u2019 (ALC) is introduced. ALC refers to a tumour where the neuroendocrine and non\u2010neuroendocrine differentiation is intimately intermixed (either in the same cells or morphologically similar cells) rather than forming distinct zones as in MiNEN. Both ALC and MiNEN represent a family of tumours rather than a distinct diagnosis and invariably require confirmation with immunohistochemistry. Molecular data support a clonal origin from a common precursor rather than collision.\n                  <\/jats:p>","DOI":"10.1111\/his.70291","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:54:19Z","timestamp":1790808859000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mixed neuroendocrine\u2010non\u2010neuroendocrine neoplasms, amphicrine\u2010like carcinoma and related lesions: a review of changes in classification and current concepts"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-515X","authenticated-orcid":false,"given":"Runjan","family":"Chetty","sequence":"first","affiliation":[{"name":"Diagnexia Pty Ltd  Oxford UK"}],"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":"Royal North Shore Hospital University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"WHO Classification of Tumours of the Digestive System","author":"Inzani F","year":"2026"},{"key":"e_1_2_7_3_1","first-page":"59","article-title":"Les cellules argentaffines dans les tumeurs intestinales","volume":"1","author":"Cordier R","year":"1924","journal-title":"Arch. Int. Med. Exp."},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/00000478-198700111-00007","article-title":"Carcinoid tumors and the mixed (composite) glandular endocrine cell carcinomas","volume":"11","author":"Lewin K","year":"1987","journal-title":"Am. J. Surg. Pathol."},{"key":"e_1_2_7_5_1","first-page":"13","volume-title":"WHO Classification of Tumours of the Digestive System","author":"Rindi G","year":"2010"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3390\/cancers4010011","article-title":"Mixed adenoneuroendocrine carcinomas (MANECs) of the gastrointestinal tract: an update","volume":"4","author":"La Rosa S","year":"2012","journal-title":"Cancers (Basel)"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s12022-016-9432-9","article-title":"Mixed neuroendocrine\u2013nonneuroendocrine neoplasms (MiNENs): Unifying the concept of a heterogeneous group of neoplasms","volume":"27","author":"La Rosa S","year":"2016","journal-title":"Endocr. Pathol."},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s00428-006-0306-2","article-title":"The grey zone between pure (neuro)endocrine and non\u2010(neuro)endocrine tumours: a comment on concepts and classification of mixed exocrine\u2013endocrine neoplasms","volume":"449","author":"Volante M","year":"2006","journal-title":"Virchows Arch."},{"key":"e_1_2_7_9_1","first-page":"188","volume-title":"WHO Classification of Tumours Editorial Board Digestive System Tumours","author":"Rindi G","year":"2019"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/his.14172","article-title":"Why did they change that? Practical implications of the evolving classification of neuroendocrine tumours of the gastrointestinal tract","volume":"78","author":"Gill AJ","year":"2021","journal-title":"Histopathology"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1097\/00000478-200207000-00004","article-title":"Increased endocrine cells in treated rectal adenocarcinomas: a possible reflection of endocrine differentiation in tumor cells induced by chemotherapy and radiotherapy","volume":"26","author":"Shia J","year":"2002","journal-title":"Am. J. Surg. Pathol."},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1097\/PAS.0000000000001123","article-title":"Mixed adenoma well\u2010differentiated neuroendocrine tumor (MANET) of the digestive system: an indolent subtype of mixed neuroendocrine\u2010nonneuroendocrine neoplasm (MiNEN)","volume":"42","author":"La Rosa S","year":"2018","journal-title":"Am. J. Surg. Pathol."},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/00000478-200402000-00009","article-title":"Patterns of morphologic alteration in residual rectal carcinoma following preoperative chemoradiation and their association with long\u2010term outcome","volume":"28","author":"Shia J","year":"2004","journal-title":"Am. J. Surg. Pathol."},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1111\/his.70116","article-title":"Changes in the 6th edition of the World Health Organization classification of tumours of the digestive system","volume":"88","author":"Arends MJ","year":"2026","journal-title":"Histopathology"},{"key":"e_1_2_7_15_1","first-page":"16","volume-title":"Introduction to Tumours of the Digestive System. WHO Classification of Tumours Editorial Board Digestive System Tumours","author":"Klimstra DS","year":"2019"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1159\/000445165","article-title":"The clinicopathologic heterogeneity of grade 3 Gastroenteropancreatic neuroendocrine neoplasms: Morphological differentiation and proliferation identify different prognostic categories","volume":"104","author":"Milione M","year":"2017","journal-title":"Neuroendocrinology"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","DOI":"10.3390\/jcm9010273","article-title":"Mixed neuroendocrine non neuroendocrine neoplasms: A systematic review of a controversial and underestimated diagnosis","volume":"9","author":"Frizziero M","year":"2020","journal-title":"J. Clin. Med."},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s00428-025-04241-z","article-title":"MiNEN, amphicrine carcinomas, and conventional carcinomas with neuroendocrine differentiation: Diagnostic criteria, open questions, and future perspectives","volume":"488","author":"Jesinghaus M","year":"2026","journal-title":"Virchows Arch."},{"key":"e_1_2_7_19_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12935-019-1031-7","article-title":"Amphicrine carcinoma of the stomach and intestine: a clinicopathologic and pan\u2010cancer transcriptome analysis of a distinct entity","volume":"19","author":"Huang D","year":"2019","journal-title":"Cancer Cell Int."}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70291","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.70291","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70291","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:54:22Z","timestamp":1790808862000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.70291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":18,"alternative-id":["10.1111\/his.70291"],"URL":"https:\/\/doi.org\/10.1111\/his.70291","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"assertion":[{"value":"2026-09-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"his.70291"}}