Giovanni Izzo, Pietro Tralongo, Marina Cerreto, Gabriele Ricciardi, Mariagiovanna Ballato, Walter Giuseppe Giordano, Emanuela Germanà, Rosa Scarfì, Antonio Ieni, Valeria Zuccalà, Vincenzo Fiorentino, Carmine Carbone, Maurizio Martini, Giuseppe Giuffrè
Intraductal papillary mucinous neoplasms (IPMNs) are a heterogeneous group of pancreatic cysts with the potential to transform into invasive pancreatic cancer. These cysts result from alterations in the epithelial cells of the pancreatic ducts, leading to the overproduction of mucin and duct dilation. Based on ductal involvement, IPMNs can be classified into three types: Main Duct (MD)-IPMN if located in the main duct, Branch Duct (BD)-IPMN if located in one or more secondary ducts, and Mixed Type (MT)-IPMN if it involves both the main and secondary ducts. Advances in abdominal imaging techniques have enabled more frequent identification and characterization of IPMNs. Second-level examinations, such as endoscopic ultrasound (EUS) or cystic fluid analysis, are essential for determining the risk of malignancy and implementing timely interventions for curative purposes. Considering that these precursor lesions are asymptomatic in most cases, and bearing in mind the extremely high mortality rate of pancreatic cancer, searching for new biomarkers with predictive value for malignant transformation appears essential. By integrating histopathological features, molecular alterations, and emerging cyst fluid biomarkers, this review aims to frame IPMN as a biologically heterogeneous disease and highlights how a molecularly informed approach may enable more precise, personalized risk stratification beyond current guideline-based management.