Tu1514 Limited Application of New International Consensus Diagnostic Criteria for Autoimmune Pancreatitis in Clinical Practice

Abstract

G A A b st ra ct s of patients with surgical pathology as the gold standard for outcome. Design: 137 patients underwent diagnostic analysis of EUS aspirated pancreatic cyst fluid. DNA was extracted from cyst fluid with quantity and quality (extent of degradation) measured by optical density and qPCR. Mutational analysis targeted KRAS point mutation and loss of heterogeneity (LOH) mutations of 16 markers at 1p, 3p, 5q, 9p, 10q, 17p, 17q, 18q, 21q, 22q. Molecular findings were integrated with results from EUS, chemistry and cytology. For each marker, presence or absence of mutation and clonality were determined, determined, with high clonality comprising 75% of more of cells affected by LOH and low clonality comprising 50-75% of cells. Interpretation of combined molecular, imaging, and chemistry results were classified and subsequently compared to surgical outcome or followup. Surgical pathology was classified into indolent biological behavior (benign or low grade disease), and aggressive biological behavior (high grade or malignant disease). Results: Surgical pathology was available on 81 of these patients. Outcomes included benign cystic neoplasms with low and high grade dysplasia, malignant ductal disease, endocrine neoplasms and pseudocysts. There were 32 aggressive outcomes and 49 indolent outcomes. Molecular findings, including elevated DNA level, and high numbers and clonality of mutations, correlated strongly with aggressive biological behavior. While KRAS mutation was highly specific for mucinous cyst formation, individual molecular parameters used in isolation showed limited sensitivity for detection of aggressive disease. Combining all molecular parameters together, sensitivity was 94%, and specificity was 100%, with overall accuracy of 97%. Conclusions: The molecular biology of pancreatic cystic disease involves multiple pathways that can each lead to cancer. The majority of pancreatic cysts do not progress to cancer and the diagnosis and biological potential of individual lesions can be effectively characterized by integrating broad panel molecular findings with information from first line testing. The presence or absence of aggressive molecular changes, taken in the context of overall findings provides an effective means to individualize patient management when first line results are unclear.