Simpson, Rachel E.Cockerill, Nathan J.Yip-Schneider, Michele T.Ceppa, Eugene P.House, Michael G.Zyromski, Nicholas J.Nakeeb, AttilaAl-Haddad, Mohammad A.Schmidt, C. Max2019-05-102019-05-102018-10Simpson, R. E., Cockerill, N. J., Yip-Schneider, M. T., Ceppa, E. P., House, M. G., Zyromski, N. J., ... & Schmidt, C. M. (2018). DNA profile components predict malignant outcomes in select cases of intraductal papillary mucinous neoplasm with negative cytology. Surgery, 164(4), 712-718. https://doi.org/10.1016/j.surg.2018.05.033https://hdl.handle.net/1805/19234Predicting malignancy in intraductal papillary mucinous neoplasm remains challenging. Integrated molecular pathology combines pancreatic fluid DNA and clinical factors into a malignant potential score. We sought to determine the utility of DNA components alone in predicting high-grade dysplasia/invasive disease. Methods We reviewed prospectively the records from 1,106 patients with intraductal papillary mucinous neoplasm. We excluded non-intraductal papillary mucinous neoplasm cases and cases with definitive malignant cytology. A total 225 patients had 283 DNA profiles (98 followed by surgery, 185 followed by ≥23-month surveillance). High-grade dysplasia/invasive outcomes were high-grade dysplasia, intraductal papillary mucinous neoplasm-invasive, and adenocarcinoma on surgical pathology or mesenteric or vascular invasion, metastases, or biopsy with high-grade dysplasia or adenocarcinoma during surveillance. Results High-quantity DNA predicted (P = .004) high-grade dysplasia/invasive disease outcomes with sensitivity of 78.3%, but 52.7% specificity, indicating benign cases may exhibit high-quantity DNA. High clonality loss of heterozygosity of tumor suppressor genes was 98.0% specific, strongly predicted high-grade dysplasia/invasive disease but lacked sensitivity (20.0%). High-quantity DNA + high clonality loss of heterozygosity had 99.0% specificity for high-grade dysplasia/invasive disease. KRAS mutation alone did not predict high-grade dysplasia/invasive disease, but, when combined with high-quantity DNA (specificity 84.7%) and high clonality loss of heterozygosity (specificity 99.0%) strongly predicted high-grade dysplasia/invasive outcomes. Conclusion Certain DNA components are highly specific for high-grade dysplasia/invasive disease and may indicate aggressive lesions, requiring resection when cytology fails.enPublisher Policyintraductal papillary mucinous neoplasmdna profilenegative cytologyArticle