Integrated Molecular Pathology as a Predictor of Malignant Transformation of Pancreatic Cysts With up To 11-Year Follow-Up

Background and Study Aims The 2018 ACG guidelines recommend surgical evaluation for pancreatic cysts with high-risk features. Integrated Molecular Pathology (IMP) combines molecular and biochemical analysis with cytology to assess malignant potential of pancreatic cysts. We aim to characterize the long-term diagnostic utility of IMP for pancreatic cysts. Patients and Methods Pancreatic cystic lesions from prospective patients with EUS-FNA and IMP (PancraGEN, Interpace Diagnostics) from 9/2010 to 9/2013 were retrospectively analyzed in this study for maximum 11 years of follow-up. Data on patient demographics, EUS and cross-sectional imaging, cyst fluid biochemical and molecular analysis, and cytology were collected. Final diagnosis was based on surgical pathology, repeat biopsy or imaging, and on length of clinical follow up. Results 69 patients with mean age 69.9; 36.2% male were included. Median follow-up was 72.3 months (IQR 89.67); 7 patients were lost to follow-up. Average cyst size was 2.3cm (0.2-15.3). Using 2018 ACG EUS criteria 43/69 (62.2%) of cysts were classified as benign and 13/69 (18.8%) were classified as highrisk. All 5 malignancies were detected for a sensitivity of 100% and specificity of 82% combining IMP results with 2018 ACG EUS high-risk criteria. Among cysts followed long term, no additional transformations into adenocarcinoma were detected within the cohort. Conclusions The absence of high-risk features based on ACG guidelines and IMP is a strong negative predictor of malignant transformation of pancreatic cysts, based on up to 11-years of follow-up. In our study, high-risk features based on ACG guidelines or IMP identified all malignancies.