Diagnostic performance of endoscopic ultrasound and conventional cyst fluid analysis in pancreatic cystic lesions without molecular testing: a real-world, guideline-based study.

BACKGROUND: Differentiating mucinous from non-mucinous pancreatic cystic lesions (PCLs) remains clinically challenging because of overlapping imaging features and heterogeneous malignant potential. Although molecular cyst fluid analysis improves diagnostic accuracy, its limited availability and high cost restrict routine use. This study aimed to evaluate the diagnostic performance of endoscopic ultrasound (EUS) morphology combined with conventional cyst fluid analysis in a real-world, guideline-based cohort without molecular testing. METHODS: In this retrospective cohort study, 100 consecutive patients with PCLs underwent EUS-guided cyst fluid sampling. EUS morphology and cyst fluid carcinoembryonic antigen (≥192 ng/mL), glucose (≤50 mg/dL), cytology, and string sign were systematically assessed. Final diagnoses were established through multidisciplinary clinical-radiological follow-up of at least 12 months. Of the included patients, 38 cysts were classified as mucinous and 62 as non-mucinous. RESULTS: Among individual biomarkers, cyst fluid glucose demonstrated the highest sensitivity for identifying mucinous cysts (89.5%), while cytology and the string sign showed the highest specificity (98.4 and 95.2%, respectively). EUS morphology alone achieved moderate diagnostic performance (sensitivity 71.1%, specificity 77.4%). Combining EUS morphology with cyst fluid analysis significantly improved diagnostic accuracy, with sensitivities and specificities of 92.1 and 88.7% for EUS plus greater than or equal to 1 marker, and 94.7 and 90.3% for EUS plus greater than or equal to 2 markers, respectively. CONCLUSION: A multimodal, guideline-based approach integrating EUS morphology with conventional cyst fluid analysis provides clinically meaningful diagnostic accuracy for differentiating PCLs in real-world settings without molecular testing. This pragmatic strategy is particularly valuable in centers where molecular diagnostics are unavailable.