IPMN beyond the cyst: toward a broader framework of pancreatic and systemic cancer susceptibility.

Abstract

Introduction: Intraductal papillary mucinous neoplasms (IPMNs) are established precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Although current guidelines primarily focus on lesion morphology, emerging evidence suggests that IPMN may also be associated with broader pancreatic and extrapancreatic cancer risk.

Areas covered: This review examines pancreatic field cancerization, including concomitant and metachronous PDACs that may arise independently of the index IPMN. We evaluate reported associations between IPMN and extrapancreatic malignancies, including colorectal, gastric, and breast cancers, while considering surveillance bias, age, shared environmental factors, and hereditary susceptibility. We further discuss germline pathogenic variants, including BRCA1/2, PALB2, and ATM, and identify clinical features that may support risk-adapted genetic assessment. Emerging approaches, including liquid biopsy, radiomics, artificial intelligence, and multi-omics, are evaluated as potential tools for individualized surveillance.

Expert opinion: IPMN may represent more than an isolated pancreatic precursor lesion and may identify selected patients with broader cancer susceptibility. However, current evidence is predominantly observational and does not establish causality. Future management should complement established guidelines with risk-adapted, patient-centered assessment. Emerging technologies may refine individualized risk stratification but require prospective validation before routine clinical implementation.