Predicting 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.
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.
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.
Certain DNA components are highly specific for high-grade dysplasia/invasive disease and may indicate aggressive lesions, requiring resection when cytology fails.
- DNA profile components predict malignant outcomes in select cases of intraductal papillary mucinous neoplasm with negative cytology
- Rachel E. Simpson - Indiana University School of MedicineNathan J. Cockerill - Indiana University School of MedicineMichele T. Yip-Schneider - Indiana University HealthEugene P. Ceppa - Indiana University HealthMichael G. House - Indiana University School of MedicineNicholas J. Zyromski - Indiana University School of MedicineAttila Nakeeb - Indiana University School of MedicineMohammad A. Al-Haddad - Indiana University HealthC. Max Schmidt - Indiana University Health
- Surgery, Vol.164(4), pp.712-718
- Elsevier Inc
- 7
- 991006261184502656
- Surgery
- English
- Journal article