Diagnosis and Management of Intraductal Papillary Mucinous Neoplasms: Focusing on Precancerous Lesions

Abstract

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are precancerous lesions withvariable malignant potential, highlighting the importance of accurate diagnostic and treatmentstrategies. This review summarizes recent advancements in epidemiologic understanding, molecularpathogenesis, and international/society guidelines regarding IPMN management. Therising global incidence of IPMN, driven by aging populations and increased imaging, underscoresthe growing clinical significance of these tumors. Main-duct and mixed-type subtypesexhibit much higher malignant transformation rates (approximately 59%) than branch-ductIPMN (approximately 8%). Molecular analyses identified early dual KRAS and GNAS mutationsas key drivers of IPMN, with subsequent RNF43, TP53, and SMAD4 mutations associatedwith its progression to invasive carcinoma. Diagnostic accuracy has improved with cystfluid next-generation sequencing, demonstrating high sensitivity and specificity. International/society guidelines, such as Fukuoka guidelines, American Gastroenterological Associationguidelines, European evidence-based guidelines on pancreatic cystic neoplasms, and the 2024Kyoto guidelines, differ significantly regarding surgical indications and surveillance strategies. Notably, Kyoto guidelines incorporate molecular markers into risk assessment and suggest thediscontinuation of surveillance for small (≤ 2 cm) branch-duct IPMNs that remain stable for5 years. Innovations, such as artificial intelligence-driven radiomics, have rendered malignanttransformation more predictable. However, standardizing these technologies and addressingcost-effectiveness remain challenging. Future research directions include validating integrateddiagnostic models, refining surveillance intervals based on precise risk stratification, andexploring novel molecular and immune markers. Ultimately, adopting a comprehensive, personalizedmanagement approach for IPMN is critical to minimizing overtreatment, preventinginvasive pancreatic cancer, and optimizing patient outcomes.