Genetic unrelatedness of co-occurring pancreatic adenocarcinomas and IPMNs challenges current views of clinical management

Intraductal papillary mucinous neoplasms (IPMN) represent the most common cystic pre-invasive lesion in the pancreas. The clinical management of patients with radiologic findings of IPMN may go from surgical resection for cases with “high-risk features” to a simple follow-up for small and “low-risk” lesions. Recent research has indicated the potential role of genetic analysis of cyst fluid for patients in follow-up, to individuate cases with a “high-risk” molecular profile, suggesting surgical resection also for those cases. The lack of a “high risk” molecular profile of the cyst fluid of an IPMN, however, does not guarantee the lack of malignant transformation in the entire pancreas. Indeed, recent evidences indicated: 1) the existence of a so-called “field-effect” of pancreatic carcinogenesis, and 2) the existence of pancreatic ductal adenocarcinomas (PDACs) genetically independent from co-occurring IPMNs (about 20% of cases). Thus, the general assumption of an absolute relatedness of IPMN and PDAC must be abandoned, in order to avoid a potential underestimation of the risk of malignant transformation in patients with IPMN.