Intraductal Papillary Mucinous Neoplasms of the Pancreas: Performance of Pancreatic Fluid Analysis for Positive Diagnosis and the Prediction of Malignancy

Abstract

The preoperative diagnosis of intraductal papillary mucinous neoplasms (IPMN) of the pancreas must be as reliable as possible because large or even total pancreatectomy may be necessary. Early diagnosis of malignant forms is important to improve prognosis. The diagnostic accuracy of fluid analysis using endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been confirmed in cystic lesions of the pancreas. It is not known if these results can be applied to IPMN. To determine the levels of biochemical and tumor markers in fluid from EUS-FNA in patients with IPMN and to assess the impact on the diagnosis of IPMN. In total, 41 patients (14 men, median age 64 yr) underwent EUS-FNA before surgical resection of IPMN in our center. Levels of amylase, lipase, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19.9, and CA 72.4 were measured in the cyst fluid. The performance of the markers was retrospectively evaluated for: (a) a positive diagnosis of IPMN, using cutoffs validated in the literature for mucinous pancreatic lesions and (b) an assessment of malignancy (i.e., high-grade dysplasia or invasive carcinoma) compared with the final pathological examination of the surgical specimen. EUS-FNA was performed in dilated branch ducts (BD) in 39 cases and in the main pancreatic duct in 2 cases. No serious complications occurred. The median fluid levels of amylase, lipase, CEA, CA 19.9, and CA 72.4 were 20,155 U/mL, 59,500 U/mL, 173 ng/mL, 6,400 U/mL, and 11.5 U/mL, respectively. A CEA level >200 ng/mL and a CA 72.4 >40 U/mL had a 44% and a 39% sensitivity, respectively, for the diagnosis of IPMN. The levels of CEA, CA 19.9, and CA 72.4 were significantly different between benign and malignant IPMN. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of a CEA level >200 ng/mL for the diagnosis of malignant IPMN were 90%, 71%, 50%, and 96%, respectively. The sensitivity, specificity, PPV, and NPV of a CA 72.4 level >40 U/mL for this purpose were 87.5%, 73%, 47%, and 96%, respectively. CEA and CA 72.4 in pancreatic cyst fluid have excellent NPVs in the preoperative differential diagnosis of benign versus malignant IPMN, and might reinforce the decision of not to operate on patients with BD-type without predictive factors of malignancy.