{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:57:07Z","timestamp":1787770627052,"version":"build-2784847793"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020258","name":"Department of Molecular Medicine, University of Pavia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020258","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Gastrointestinal medullary carcinoma is a rare histologic subtype of adenocarcinoma. As nonampullary small bowel medullary carcinomas (SB\u2010MCs) are poorly characterized, we aimed to analyse their clinicopathologic and immunohistochemical features and to compare them with nonmedullary small bowel adenocarcinomas (NM\u2010SBAs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Surgically resected SBAs collected through the Small Bowel Cancer Italian Consortium were classified as SB\u2010MCs (carcinomas with \u226550% of tumour fulfilling the typical histologic criteria of MC) or NM\u2010SBAs. Immunohistochemistry for cytokeratin (CK)7, CK20, CDX2, programmed death\u2010ligand 1 (PD\u2010L1) and mismatch repair proteins was performed in both SB\u2010MCs and NM\u2010SBAs. SB\u2010MCs were also tested for CK8\/18, synaptophysin, SMARCB1, SMARCA2, SMARCA4, and ARID1A and for Epstein\u2013Barr virus (EBV)\u2010encoded RNAs by <jats:italic>in\u2010situ<\/jats:italic> hybridization. <jats:italic>MLH1<\/jats:italic> promoter methylation status was evaluated in MLH1\u2010deficient cases. Eleven SB\u2010MCs and 149 NM\u2010SBAs were identified. One (9%) SB\u2010MC was EBV\u2010positive, while 10 (91%) harboured mismatch repair deficiency (dMMR). <jats:italic>MLH1<\/jats:italic> promoter hypermethylation was found in all eight dMMR SB\u2010MCs tested. Switch\/sucrose nonfermentable deficiency was seen in two (18%) SB\u2010MCs, both with isolated loss of ARID1A. Compared with NM\u2010SBAs, SB\u2010MCs exhibited an association with coeliac disease (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), higher rates of dMMR (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), and PD\u2010L1 positivity by both tumour proportion score and combined positive score (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001 for both), and a lower rate of CK20 expression (<jats:italic>P<\/jats:italic>\u2009=\u20090.024). Survival analysis revealed a better prognosis of SB\u2010MC patients compared to NM\u2010SBA cases (<jats:italic>P<\/jats:italic>\u2009=\u20090.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SB\u2010MCs represent a distinct histologic subtype, with peculiar features compared to NM\u2010SBAs, including association with coeliac disease, dMMR, PD\u2010L1 expression, and better prognosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15307","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T07:40:40Z","timestamp":1724830840000},"page":"236-246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Medullary carcinomas of the nonampullary small intestine: association with coeliac disease, mismatch repair deficiency, PD\u2010L1 expression, and favourable prognosis"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2976-7032","authenticated-orcid":false,"given":"Alessandro","family":"Vanoli","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Unit of Anatomic Pathology IRCCS San Matteo Hospital Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6477-3182","authenticated-orcid":false,"given":"Federica","family":"Grillo","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino  Genoa Italy"},{"name":"Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DISC) University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"De Lisi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Guerini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7226-381X","authenticated-orcid":false,"given":"Giovanni","family":"Arpa","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Anatomic Pathology Unit of Pavia Institute Istituti Clinici Scientifici Maugeri IRCCS  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0314-8548","authenticated-orcid":false,"given":"Catherine","family":"Klersy","sequence":"additional","affiliation":[{"name":"Biostatistics and Clinical Trial Center Fondazione IRCCS Policlinico San Matteo  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6515-5482","authenticated-orcid":false,"given":"Matteo","family":"Fassan","sequence":"additional","affiliation":[{"name":"Department of Medicine (DIMED), Surgical Pathology &amp; Cytopathology Unit University of Padua  Padua Italy"},{"name":"Veneto Institute of Oncology IOV\u2010IRCCS  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0591-6723","authenticated-orcid":false,"given":"Paola","family":"Parente","sequence":"additional","affiliation":[{"name":"Unit of Pathology Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0193-5281","authenticated-orcid":false,"given":"Luca","family":"Mastracci","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale Policlinico San Martino  Genoa Italy"},{"name":"Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DISC) University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0093-7315","authenticated-orcid":false,"given":"Elena","family":"Biletta","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Surgery ASL BI Nuovo Ospedale degli Infermi  Ponderano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Nesi","sequence":"additional","affiliation":[{"name":"Pathology Section, Department of Health Sciences University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4199-5636","authenticated-orcid":false,"given":"Maria C","family":"Macciomei","sequence":"additional","affiliation":[{"name":"Pathology Unit San Camillo\u2010Forlanini Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6654-4911","authenticated-orcid":false,"given":"Marco V","family":"Lenti","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics University of Pavia  Pavia Italy"},{"name":"Department of Internal Medicine IRCCS San Matteo Hospital Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9099-5352","authenticated-orcid":false,"given":"Erica","family":"Quaquarini","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit Istituti Clinici Scientifici Maugeri IRCCS  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3924-2117","authenticated-orcid":false,"given":"Anna M","family":"Chiaravalli","sequence":"additional","affiliation":[{"name":"Department of Oncology Ospedale di Circolo, ASST\u2010Sette Laghi  Varese Italy"},{"name":"Hereditary Cancer Research Center University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5958-5379","authenticated-orcid":false,"given":"Daniela","family":"Furlan","sequence":"additional","affiliation":[{"name":"Department of Oncology Ospedale di Circolo, ASST\u2010Sette Laghi  Varese Italy"},{"name":"Hereditary Cancer Research Center University of Insubria  Varese Italy"},{"name":"Unit of Pathology, Department of Medicine and Technological Innovation University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1941-2403","authenticated-orcid":false,"given":"Stefano","family":"La Rosa","sequence":"additional","affiliation":[{"name":"Department of Oncology Ospedale di Circolo, ASST\u2010Sette Laghi  Varese Italy"},{"name":"Hereditary Cancer Research Center University of Insubria  Varese Italy"},{"name":"Unit of Pathology, Department of Medicine and Technological Innovation University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Paulli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Unit of Anatomic Pathology IRCCS San Matteo Hospital Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0302-8645","authenticated-orcid":false,"given":"Antonio","family":"Di Sabatino","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Therapeutics University of Pavia  Pavia Italy"},{"name":"Department of Internal Medicine IRCCS San Matteo Hospital Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Digestive system tumours. 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