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This study characterizes clinicopathological and molecular profiles of 19 MCNs and 4 SMCs with associated invasive carcinoma using multiregional DNA/RNA sequencing. Concomitant genomic alterations link SMC to invasive cancer in 95.7% of cases. SMC-derived carcinomas appear more aggressive than MCN-derived, show shared PDAC-like KRAS/TP53 alterations, exhibit intracystic heterogeneity, and display progression-associated transcriptomic subtype switching.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mucinous-cystic-neoplasms-and-simple-mucinous-cysts-are-two-distinct-precursors-of-pancreatic-cancer-clinicopathological-genomic-and-transcriptomic-characterization/361945/",{"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/mucinous-cystic-neoplasms-and-simple-mucinous-cysts-are-two-distinct-precursors-of-pancreatic-cancer-clinicopathological-genomic-and-transcriptomic-characterization/361945.png","ImageObject",300,407,{"name":92,"@type":93},"Aria","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What makes simple mucinous cysts (SMCs) clinically and biologically distinct from mucinous cystic neoplasms (MCNs)?","Question",{"text":112,"@type":113},"SMCs resemble MCNs but lack the ovarian-type subepithelial stroma. The study finds SMCs share specific genomic alterations with associated invasive carcinoma, supporting SMCs as true precursors of pancreatic cancer.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the study designed to link cyst lesions to invasive carcinoma?",{"text":117,"@type":113},"It used a multiregional sequencing approach with two samples from each cystic lesion and one from the adenocarcinoma, combining DNA and RNA sequencing to compare molecular changes across regions and stages.",{"name":119,"@type":110,"acceptedAnswer":120},"Which molecular alterations were most commonly observed in both cyst types?",{"text":121,"@type":113},"Both cyst types showed significant similarities to conventional PDAC, with KRAS and TP53 being the most commonly altered genes.","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},361945,1790453099,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"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},2336464648322,"https://ap-avatar.wpscdn.com/avatar/2200025388227c56fec?_k=1778556882303663488","Journal of Pathology  \nJ Pathol August 2025; 266: 421–434  \nPublished online 15 May 2025 in Wiley Online Library (wi[leyonlinelibrary.com](leyonlinelibrary.com) DOI: 10.1002/path.6437)[)](leyonlinelibrary.com) DOI: 10.1002/path.6437)[ DOI:](leyonlinelibrary.com) DOI: 10.1002/path.6437)[ 10.1002/path.6437](leyonlinelibrary.com) DOI: 10.1002/path.6437)  \nORIGINAL ARTICLE  \nMucinous cystic neoplasms and simple mucinous cysts are two distinct precursors of pancreatic cancer: clinicopathological, genomic, and transcriptomic characterization  \nAntonio Pea 1 †, Michele Bevere2†, Anastasios Gkountakos2†, Davide Pasini3,4†, Denise Fiorini5, Andrea Mafficini2,3, Stela Golovco2, Michele Simbolo5, Serena Pedron5, Concetta Sciammarella5, Paola Mattiolo5, Aldo Mombello5, Manuela Villanova5, Carlotta Franzina5, Francesca Masetto2, Calogero Ciulla5, Nicola Sperandio2, Kohei Fujikura6, Masha S. Ahadi7,8,9, Jaswinder S. Samra7,8, Amber L. Johns 10, Joanne Verheij 11 , Martijn W.J. Stommel 12,  \nHjalmar van Santvoort 13, Leonor Schubert Santana 14, Giuseppe Malleo 1 , Michele Milella3,  \nLodewijk A. A. Brosens 15, Laura D. Wood6,16, David K. Chang 14,17, Riccardo De Robertis 18, Mirko D’Onofrio 18, Anthony J. Gill7,8,9, Roberto Salvia 1 , Vincenzo Corbo3, Rita T. Lawlor2,3‡, Aldo Scarpa2,5‡ and Claudio Luchini2,5*‡  \n1 Department of General and Pancreatic Surgery–The Pancreas Institute, Verona University Hospital Trust, Verona, Italy  \n2 ARC-Net Research Center, University of Verona, Verona, Italy  \n3 Department of Engineering for Innovation Medicine, University of Verona, Verona, Italy  \n4 Department of Medicine, University of Verona, Verona, Italy  \n5 Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy  \n6 Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, USA  \n7 Royal North Shore Hospital, St Leonards, NSW, Australia  \n8 Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia  \n9 Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, and Department of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia  \n10 The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, Australia  \n11 Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands  \n12 Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands  \n13 Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht and St Antonius Hospital, Utrecht, Netherlands  \n14 Wolfson Wohl Cancer Research Centre, Research Institute of Cancer Sciences, University of Glasgow, Glasgow, UK  \n15 Department of Pathology, UMC Utrecht, Utrecht University, Utrecht, and Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands  \n16 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA  \n17 West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK  \n18 Department of Diagnostics and Public Health, Section of Radiology, University of Verona, Verona, Italy  \n*Correspondence to: C Luchini, Department of Diagnostics and Public Health, Section of Pathology, and ARC-Net Research Center, University of Verona, Piazzale Scuro, 10, 37134, Verona, Italy. E-mail: [claudio.luchini@univr.it](claudio.luchini@univr.it)  \n†Co-first authors.  \n‡Co-last authors.  \nAbstract  \nMucinous cystic neoplasms (MCNs) of the pancreas are macroscopic precursors of pancreatic cancer. A similar cystic lesion but lacking the ovarian-type subepithelial stroma has been recently defined as a simple mucinous cyst (SMC);  \nhowever, its nature remains unclear. This study aims to define the clinicopathological and molecular profiles of a cohort of MCNs and SMCs of the pancreas and their associated invasive carcinoma. Overall, 23 cases were identified, comprising 19 MC","cbCaijalYMxZTX69","https://ap.wps.com/l/cbCaijalYMxZTX69","pdf",5137490,14,"English","# Abstract\n## Study aims and cohort\n## Key molecular, clinical, and transcriptomic findings","[{\"question\":\"What makes simple mucinous cysts (SMCs) clinically and biologically distinct from mucinous cystic neoplasms (MCNs)?\",\"answer\":\"SMCs resemble MCNs but lack the ovarian-type subepithelial stroma. The study finds SMCs share specific genomic alterations with associated invasive carcinoma, supporting SMCs as true precursors of pancreatic cancer.\"},{\"question\":\"How was the study designed to link cyst lesions to invasive carcinoma?\",\"answer\":\"It used a multiregional sequencing approach with two samples from each cystic lesion and one from the adenocarcinoma, combining DNA and RNA sequencing to compare molecular changes across regions and stages.\"},{\"question\":\"Which molecular alterations were most commonly observed in both cyst types?\",\"answer\":\"Both cyst types showed significant similarities to conventional PDAC, with KRAS and TP53 being the most commonly altered genes.\"}]","Mucinous cystic neoplasms and simple mucinous cysts are two distinct precursors of pancreatic cancer - clinicopathological, genomic, and transcriptomic characterization | PDF",1790146084,35]