Molecular Profiling in Mucinous Pancreatic Cystic Neoplasms: Implications for Surgical Decision-Making - A Narrative Review.

Pancreatic cystic lesions (PCLs) represent a heterogeneous group ranging from benign cysts to lesions with malignant potential. Despite advances in imaging and endoscopic evaluation, determining which lesions warrant surgical resection remains a major challenge in hepatobiliary and pancreatic surgery. Overtreatment exposes patients to substantial operative morbidity, whereas delayed intervention may permit progression to invasive cancer. Cyst-fluid molecular profiling can improve the classification of mucinous cysts and intraductal papillary mucinous neoplasms and may reduce diagnostic uncertainty during preoperative risk stratification. However, improved diagnostic classification does not necessarily establish an indication for surgery. KRAS and GNAS mutations primarily provide information about cyst identity and should not be interpreted as independent markers of malignant transformation. Conversely, negative molecular findings should not provide reassurance when radiologic or clinical features indicate substantial risk. Molecular results are therefore best considered within a multidimensional framework that incorporates imaging characteristics, cytology, clinical risk factors, patient comorbidities, and operative fitness. Additional alterations associated with advanced neoplasia may further modify risk when interpreted alongside established clinical and radiologic findings. Prospective validation and outcome-based modeling are needed to determine whether molecularly informed management reduces unnecessary surgery, improves detection of clinically significant disease, and ultimately improves patient outcomes.