Comparison of Preoperative Cytopathology, Tumor Markers and Molecular Analysis for the Diagnosis of Mucinous Pancreatic Cysts in Patients Undergoing Surgical Resection: 2010 Presidential Poster

Abstract

Purpose: To prospectively evaluate the individual or combined accuracy of cytopathology, cyst fluid tumor markers (CEA) and molecular analysis to differentiate mucinous from non-mucinous cysts. Methods: Consecutive patients with pancreatic cysts referred to our institution for EUS-FNA who were determined have suspected MPCs and subsequently underwent surgical resection at our institution. Cyst fluid was aspirated for cytopathology, DNA analysis (RedPath®, Pittsburgh, PA) and CEA when quantity was sufficient. DNA quantity ≥40ng/ul and/or k-rasmutation and/or ≥2 allelic imbalance mutations and/or CEA>192 ng/ml were all criteria for a MPC. Surgical pathology from pancreas resection was considered the gold standard for diagnosis. Results: 27 patients underwent surgery following EUS-FNA. Final surgical pathology revealed mucinous lesions in 22 (all were intraductal papillary mucinous neoplasms (IPMN)), and non-mucinous lesions in 5 (serous cystadenoma in 2, retention cyst in 1, and pancreatic intraepithelial neoplasia (PanIN) in non-mucinous background in 2). Only one patient had invasive malignancy and another had high grade dysplasia on final pathology. Cytopathology was highly specific in MPC but with low sensitivity of 9%. Mean CEA levels in cyst fluid were numerically higher in the mucinous compared to the non-mucinous group but the difference didn't reach statistical significance due to small sample size (11799 ng/ml vs. 59 ng/ml, p=0.49). Molecular analysis (any criterion) had a sensitivity of 46% and specificity of 100% to detect mucinous lesions. K-ras mutation alone was the single most reliable molecular criterion with a specificity of 100%. K-ras mutation identified one additional mucinous cyst not identified as such by CEA. Combining all molecular markers with CEA improved sensitivity to 74% (table 1). Conclusion: In this series, the sensitivity of pancreatic cyst fluid CEA outperforms any of the individual molecular criteria evaluated for the diagnosis of MPCs. Therefore, we advocate initial screening of cyst fluid CEA prior to obtaining molecular studies. Molecular markers combined with cyst fluid CEA marginally increase sensitivity for MPC and could add diagnostic value in suspected malignant cysts; however, the limited number of malignant cysts in this study precludes a definitive conclusion. A larger sample size with more malignant cysts is required.Table