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

Abstract

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are precancerous lesions with variable malignant potential, highlighting the importance of accurate diagnostic and treatment strategies. This review summarizes recent advancements in epidemiologic understanding, molecular pathogenesis, and international/society guidelines regarding IPMN management. The rising global incidence of IPMN, driven by aging populations and increased imaging, underscores the growing clinical significance of these tumors. Main-duct and mixed-type subtypes exhibit much higher malignant transformation rates (approximately 59%) than branch-duct IPMN (approximately 8%). Molecular analyses identified early dual KRAS and GNAS mutations as key drivers of IPMN, with subsequent RNF43, TP53, and SMAD4 mutations associated with its progression to invasive carcinoma. Diagnostic accuracy has improved with cyst fluid next-generation sequencing, demonstrating high sensitivity and specificity. International/society guidelines, such as Fukuoka guidelines, American Gastroenterological Association guidelines, European evidence-based guidelines on pancreatic cystic neoplasms, and the 2024 Kyoto guidelines, differ significantly regarding surgical indications and surveillance strategies. Notably, Kyoto guidelines incorporate molecular markers into risk assessment and suggest the discontinuation of surveillance for small (≤ 2 cm) branch-duct IPMNs that remain stable for 5 years. Innovations, such as artificial intelligence-driven radiomics, have rendered malignant transformation more predictable. However, standardizing these technologies and addressing cost-effectiveness remain challenging. Future research directions include validating integrated diagnostic models, refining surveillance intervals based on precise risk stratification, and exploring novel molecular and immune markers. Ultimately, adopting a comprehensive, personalized management approach for IPMN is critical to minimizing overtreatment, preventing invasive pancreatic cancer, and optimizing patient outcomes.