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This narrative review synthesizes evidence on how histomolecular characteristics of PCLs support risk stratification and inform medical management, including the role of targeted therapy. High-risk precursor lesions such as high-grade intraductal papillary mucinous neoplasia (IPMN) and PanIN stage III are emphasized. Endoscopic ultrasound (EUS) is highlighted for detailed histomolecular characterization and for refining decisions, including in branch-duct IPMNs (BD-IPMN).",{"@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/clinical-perspectives-on-the-histomolecular-features-of-the-pancreatic-precursor-lesions-a-narrative-review/333895/",{"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/clinical-perspectives-on-the-histomolecular-features-of-the-pancreatic-precursor-lesions-a-narrative-review/333895.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is early detection of pancreatic cystic lesions (PCLs) important in pancreatic cancer?","Question",{"text":112,"@type":113},"Early identification of PCLs supports detection and follow-up planning and may help recognize pancreatic malignancy during the window period before progression to non-resectable disease.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which precursor lesions are described as high-risk for developing pancreatic cancer?",{"text":117,"@type":113},"High-grade intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasia (PanIN) stage III are identified as high-risk lesions for pancreatic cancer development.",{"name":119,"@type":110,"acceptedAnswer":120},"How does endoscopic ultrasound (EUS) contribute to risk assessment and management?",{"text":121,"@type":113},"EUS enables direct visualization of lesion connections and supports biopsy or fine-needle aspiration to determine histological and molecular characteristics, which can change management decisions such as those in branch-duct IPMNs.","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},333895,1790156655,{"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":39,"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,"preview_page_count":4},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","Middle East J Dig Dis. July 2024;16(3):136-146  \ndoi  10.34172/mejdd.2024.387  \n[http://mejdd.org](http://mejdd.org)  \nReview Article   \nClinical Perspectives on the Histomolecular Features of the Pancreatic Precursor Lesions: A Narrative Review  \nSayedeh-Zahra Kazemi-Harikandei1 ID , Amirali Karimi1, Seyed Mohammad Tavangar2,3* ID  \n1School of Medicine, Tehran University of Medical Sciences, Tehran, Iran  \n2 Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran  \n3Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran  \nAbstract  \nPancreatic cancer (PC) is a lethal cancer with poor prognoses. Identifying and characterizing pancreatic cystic lesions (PCLs) in the early detection and follow-up plans is thought to help detect pancreatic malignancy. Besides, the molecular features of PCLs are thought to unravel potentials for targeted therapies. We present a narrative review of the existing literature on the role of PCLs in the early detection, risk stratification, and medical management of PC. High-grade intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasia (PanIN) stage III are high-risk lesions for developing PC. These lesions often require thorough histomolecular characterization using endoscopic ultrasound (EUS), before a surgical decision is made. EUS is also useful in the risk assessment of PCLs with tentative plans–for instance, in branch-duct IPMNs (BD-IPMN) -where the final decision might change. Besides the operative decisions, recent improvements in the application of targeted therapies are expected to improve survival measures. Knowledge of molecular features has helped develop targeted therapies. In summary, the histomolecular characterization of PCLs is helpful in optimizing management plans in PC. Further improvements are still needed for the broad application of this knowledge in the clinical setting.  \nKeywords: Pancreatic cystic lesions (PCL), Pancreatic ductal adenocarcinoma, Intraductal papillary mucinous neoplasms (IPMN), Pancreatic intraepithelial neoplasms (PanIN), Mucinous cystic neoplasms (MCN), Early detection of cancer, Targeted therapy  \nCite this article as: Kazemi-Harikandei SZ, Karimi A, Tavangar SM. Clinical perspectives on the histomolecular features of the pancreatic precursor lesions: a narrative review. Middle East J Dig Dis 2024;16(3):136-146 . doi: 10.34172/mejdd.2024.387 .  \nReceived: October 20, 2023, Accepted: June 7, 2024, ePublished: July 31, 2024  \nIntroduction  \nPancreatic cancer (PC) is the seventh leading cause of cancer mortality worldwide.1 Achieving an earlier diagnosis and implementing more effective oncological treatments are two significant problems that need to be addressed in tackling the current low survival rates.2 Targeting early neoplastic lesions seems beneficial due to the long window period before developing non-resectable lesions.3  \nIntraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasm (MCN), and pancreatic intraepithelial neoplasia (PanIN) are the main precursor lesions to the pancreatic ductal adenocarcinoma (PDAC)4 –called PC in this paper. Pancreatic cystic lesions (PCLs) possess specific histological and molecular characteristics that have both diagnostic and prognostic significance. The diagnostic markers include histological features for resemblance to other gastrointestinal cancers –for instance, in IPMNs-and the expression of surface markers –glycoprotein mucin 1 to 6 (MUC1-6) and estrogen and progesterone receptors (ER and PR) .4 The genetic landscape of each lesion is the most direct indicator for determining the risks of malignant conversion for PCLs. Using specific genetic aberrations, including KRAS, TP53, p16/CDKN2A, and SMAD4, enables the differentiation of  \nhigh-risk neoplastic lesions.5,6 Moreover, the designation of the precursor lesions based on their histomole","cbCaiulaZcUBiWw2","https://ap.wps.com/l/cbCaiulaZcUBiWw2","pdf",494244,11,"English","# Introduction\n# Precursor Lesions and Histomolecular Markers\n# Management Debates and the Role of EUS\n# Operative Decisions and Risk–Benefit Considerations\n# Targeted Therapies and Future Needs","[{\"question\":\"Why is early detection of pancreatic cystic lesions (PCLs) important in pancreatic cancer?\",\"answer\":\"Early identification of PCLs supports detection and follow-up planning and may help recognize pancreatic malignancy during the window period before progression to non-resectable disease.\"},{\"question\":\"Which precursor lesions are described as high-risk for developing pancreatic cancer?\",\"answer\":\"High-grade intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasia (PanIN) stage III are identified as high-risk lesions for pancreatic cancer development.\"},{\"question\":\"How does endoscopic ultrasound (EUS) contribute to risk assessment and management?\",\"answer\":\"EUS enables direct visualization of lesion connections and supports biopsy or fine-needle aspiration to determine histological and molecular characteristics, which can change management decisions such as those in branch-duct IPMNs.\"}]","Clinical Perspectives on the Histomolecular Features of the Pancreatic Precursor Lesions - A Narrative Review | PDF",1790004498,28]