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Intestinal (INT) and pancreato-biliary (PB) subtypes are emphasized, with molecular separation that influences diagnosis, treatment response, and post-surgical survival. PB is associated with a worse clinical outcome, while subtype assignment criteria remain insufficiently established. A triage of immune markers (CK7, CK20, CDX-2) is proposed as an effective compromise, using immunohistochemistry as the key approach with diagnostic, predictive, and prognostic value.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/ampullary-cancer-histological-subtypes-markers-and-clinical-behaviourstate-of-the-art-and-perspectives/381371/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/ampullary-cancer-histological-subtypes-markers-and-clinical-behaviourstate-of-the-art-and-perspectives/381371.png","ImageObject",300,407,{"name":92,"@type":93},"Maya Linwood","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What are the main histological subtypes of ampullary adenocarcinoma (AAC)?","Question",{"text":112,"@type":113},"The key AAC subtypes are intestinal (INT) and pancreato-biliary (PB). These reflect different cellular components and likely origins within the ampullary region.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which immune markers are proposed for distinguishing AAC INT vs PB groups?",{"text":117,"@type":113},"A triage of immune markers CK7, CK20, and CDX-2 is described as the best compromise for splitting AAC patients into INT and PB groups.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is immunohistochemical subtyping important for AAC?",{"text":121,"@type":113},"Immuno-histochemical classification provides diagnostic, predictive, and prognostic value, and it is linked to clinical management responses and survival after surgery.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},381371,1790485467,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Review  \nAmpullary Cancer: Histological Subtypes, Markers, and Clinical Behaviour—State of the Art and Perspectives  \nGennaro Nappo 1,2, *,†, Niccola Funel 3,†, Virginia Laurenti 1, Elisabetta Stenner 3, Silvia Carrara 4, Silvia Bozzarelli 5, Paola Spaggiari 6 and Alessandro Zerbi 1,2  \nCitation: Nappo, G.; Funel, N.; Laurenti, V.; Stenner, E.; Carrara, S.; Bozzarelli, S.; Spaggiari, P.; Zerbi, A. Ampullary Cancer: Histological Subtypes, Markers, and Clinical Behaviour—State of the Art and Perspectives. Curr. Oncol. 2023, 30, 6996–7006. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/curroncol30070507](10.3390/curroncol30070507)  \nReceived: 29 June 2023  \nRevised: 15 July 2023  \nAccepted: 20 July 2023  \nPublished: 22 July 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy;  \nalessandro.zerbi@humanitas.it (A.Z.)  \n2 Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy  \n3 USL Toscana Nordovest, Chemical-Clinical Analysis Laboratory, Department of Diagnostics, 56121 Pisa, Italy; [niccola.funel@uslnordovest.toscana.it](niccola.funel@uslnordovest.toscana.it) (N.F.); [elisabetta.stenner@uslnordovest.toscana.it](elisabetta.stenner@uslnordovest.toscana.it) (E.S.)  \n4 Endoscopic Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy  \n5 Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy  \n6 Pathology Unit, Humanitas Clinical and Research Center—IRCCS, 20089 Rozzano, Italy;  \npaola.spaggiari@humanitas.it  \n* Correspondence: gennaro.nappo@humanitas.it † These authors contributed equally to this work.  \nAbstract: There are different cancers in the peri-ampullary region, including pancreatic ductaladenocarcinoma (PDAC), duodenum cancers (DCs), and ampullary adenocarcinoma (AAC) . Here, significant morphological–molecular characterizations should be necessary for the distinction of primary tumours and classifications of their subtypes of cancers. The sub classification of AACs might include up to five different variants, according to different points of view, concerning the prevalence of the two more-cellular components found in the ampulla. In particular, regarding the AACs, the most important subtypes are represented by the intestinal (INT) and the pancreato-biliary (PB) ones. The subtyping of AACs is essential for diagnosis, and their identifications have been impacting clinical management responses to treatments and overall survival (os) after surgery. Pb is associated with a worse clinical outcome. Otherwise, the criteria, through which are possible to attribute its subtype classification, are not well established. A triage of immune markers represented by CK7, CK20, and CDX-2 seem to represent the best compromise in order to split the cohort of AAC patients in the INT and PB groups. The test of choice for the sub-classification of AACs is represented by the immuno-histochemical approach, in which its molecular classification acquires its diagnostic, predictive, and prognostic value for both the INT and PB patients.  \nKeywords: ampullary adenocarcinomas (AAC); subtypes; molecular markers; immuno-histochemistry; clinical behaviours; clinical management; CK7; CK20; CDX2  \n1. Introduction  \nAmpullary adenocarcinoma (AAC) is a rare disease, accounting for only 0.2% of gastrointestinal malignancies and 6% of periampullary tumours [1] . The ampullary region is a very complex anatomical region, representing the convergence of multiple structures. It can be divided into","cbCailpAtWrRmIJz","https://ap.wps.com/l/cbCailpAtWrRmIJz","pdf",826739,11,"English","# Introduction\n## Definition of Different Subtypes of AAC","[{\"question\":\"What are the main histological subtypes of ampullary adenocarcinoma (AAC)?\",\"answer\":\"The key AAC subtypes are intestinal (INT) and pancreato-biliary (PB). These reflect different cellular components and likely origins within the ampullary region.\"},{\"question\":\"Which immune markers are proposed for distinguishing AAC INT vs PB groups?\",\"answer\":\"A triage of immune markers CK7, CK20, and CDX-2 is described as the best compromise for splitting AAC patients into INT and PB groups.\"},{\"question\":\"Why is immunohistochemical subtyping important for AAC?\",\"answer\":\"Immuno-histochemical classification provides diagnostic, predictive, and prognostic value, and it is linked to clinical management responses and survival after surgery.\"}]","Ampullary Cancer: Histological Subtypes, Markers, and Clinical Behaviour—State of the Art and Perspectives | PDF",1790245037,28]