Endoscopic Ultrasound-Guided Pancreatic Cystic Fluid Biochemical and Genetic Analysis for the Differentiation Between Mucinous and Non-Mucinous Pancreatic Cystic Lesions

Pancreatic cystic lesions (PCLs) are increasingly identified via computerized tomography (CT) and magnetic resonance (MR), with a prevalence of 2–45%. Distinguishing mucinous PCLs (M-PCLs), which include intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) that can progress to pancreatic ductal adenocarcinoma, from non-mucinous PCLs (NM-PCLs) is essential. Carcinoembryonic antigen (CEA) remains widely used but often demonstrates limited sensitivity and specificity. In contrast, endoscopic ultrasound-guided measurement of intracystic glucose more accurately differentiates PCL subtypes, as tumor-related metabolic changes lower cyst fluid glucose in mucinous lesions. Numerous prospective and retrospective studies suggest a glucose cut-off between 30 and 50 mg/dL, yielding a sensitivity of 88–95% and specificity of 76–91%, frequently outperforming CEA. Additional benefits include immediate point-of-care assessment via standard glucometers and minimal interference from blood contamination. DNA-based biomarkers, including KRAS and GNAS mutations, enhance specificity (up to 99%) but exhibit moderate sensitivity (61–71%) and necessitate specialized, expensive platforms. Molecular analyses can be crucial in high-risk lesions, yet their uptake is constrained by technical challenges. In practice, combining glucose assessment with targeted molecular assays refines risk stratification and informs the choice between surgical resection or active surveillance. Future investigations should establish standardized glucose thresholds, improve the cost-effectiveness of genetic testing, and integrate advanced biomarkers into routine protocols. Ultimately, these strategies aim to optimize patient management, limit unnecessary interventions for benign lesions, and ensure timely therapy for lesions at risk of malignant transformation.