# Pancreatic Cancer Detection in Intraductal Papillary Mucinous Neoplasm (IPMN)—New Insights

## TL;DR

This paper reviews recent advances in diagnosing pancreatic cancer in intraductal papillary mucinous neoplasm, focusing on improved imaging and biomarker techniques.

## Contribution

The paper provides a comprehensive overview of the latest diagnostic tools and strategies for detecting malignancy in IPMN, emphasizing their clinical utility.

## Key findings

- MRI with radiomics achieves high sensitivity (91–96%) and specificity (78–81%) in detecting high-risk IPMN features.
- EUS-TTNB offers high diagnostic accuracy (sensitivity 90%, specificity 95%) but is limited by adverse events.
- miRNA panels in cyst fluid show promising diagnostic accuracy (89–91%) for malignant IPMN.

## Abstract

Intraductal papillary mucinous neoplasm is a precancerous form of pancreatic cancer and has posed a diagnostic challenge for years. In recent years, new guidelines, especially those from the International Association of Pancreatology, have been developed to systematize malignancy risk factors and propose management strategies. New techniques, particularly those based on artificial intelligence and radiomics, have significantly improved the diagnostic accuracy of magnetic resonance imaging and computed tomography, which remain the most commonly used modalities for assessing intraductal papillary mucinous neoplasm. New molecular and endoscopic techniques, such as pancreatoscopy and endoscopic ultrasound–confocal laser endomicroscopy, are also rapidly advancing. This paper aims to summarize the current state of knowledge in diagnosing malignancy in intraductal papillary mucinous neoplasm, with particular emphasis on the latest diagnostic advances, in order to serve as a valuable clinical resource for practicing physicians.

Early diagnosis of pancreatic cancer, particularly in intraductal papillary mucinous neoplasm (IPMN), remains challenging despite advances in imaging and biomarkers. Pancreatic adenocarcinoma (PDAC) has a high mortality rate; therefore, its early detection and adequate interventions are necessary to improve the disease outcome. Most IPMNs are asymptomatic and discovered incidentally. Magnetic resonance imaging (MRI) is a preferred tool for diagnosing malignant IPMNs, with a sensitivity of 90.7–94.1% and a specificity of 84.7–87.2% in detecting mural nodules > 5 mm, a strong predictor of high-risk lesions. Radiomics further enhances diagnostic accuracy (sensitivity 91–96%, specificity 78–81%), especially when combined with CA 19-9, which has lower sensitivity (73–90%) but higher specificity (79–95%). Computed tomography (CT), though less effective for small mural nodules, remains widely used; its accuracy improves with radiomics and clinical variables (sensitivity 90.4%, specificity 74%). Conventional endoscopic ultrasonography (EUS) shows lower performance (sensitivity 60%, specificity 80%), but its advanced variations have improved outcomes. Contrast-enhanced EUS (CE-EUS) visualizes mural nodules with more than 90% sensitivity and involvement of the main pancreatic duct, with a sensitivity of 83.5% and a specificity of 87%. EUS–fine-needle aspiration (EUS-FNA) allows cyst fluid analysis; however, CEA, glucose, and KRAS/GNAS mutations show poor value for malignancy risk. Cytology has low sensitivity (28.7–64.8%) but high specificity (84–94%) in diagnostic malignant changes and strongly affects further management. EUS–through-the-needle biopsy (EUS-TTNB) yields high diagnostic accuracy (sensitivity 90%, specificity 95%) but carries a range of 2–23% adverse events, which limits its wide use. EUS–confocal laser endomicroscopy (EUS-nCLE) provides real-time microscopic evaluation, detecting malignant IPMN with a sensitivity of 90% and a specificity of 73%, though its availability is limited. New emerging biomarkers available in cyst fluid or blood include mucins, miRNA panels (sensitivity 66.7–89%, specificity 89.7–100%), lipidomics, and cancer metabolite profiling, with diagnostic accuracy approaching 89–91%. Pancreatoscopy (POP) enables direct main pancreatic duct (MPD) visualization and biopsy with a sensitivity of 64–100% and a specificity of 75–100%, though adverse events occur in around 12% cases. Combining advanced imaging, EUS-based tissue acquisition, and novel biomarkers holds promise for earlier and more accurate detection of malignant IPMN, potentially improving PDAC outcomes.