High-grade pancreatic intraepithelial lesions: prevalence and implications in pancreatic neoplasia.

Background: High-grade pancreatic intraepithelial neoplasia (PanIN-3), a precursor of pancreatic ductal adenocarcinoma (PDAC), is not universally detected in resected pancreatic neoplasms. We sought to determine the prevalence and prognostic relevance of PanIN-3 lesions in primary surgical resections of PDACs and intraductal papillary mucinous neoplasms (IPMNs).

Methods: A retrospective review of a tertiary care center pathology database (1/2000-6/2014) was performed. Demographics, imaging, pathology, disease-recurrence, and survival data were reviewed.

Results: A total of 458 patients who underwent primary pancreatic resection were included. "PanIN-3" lesions were found in 74 (16.2%) patients who either had PDAC (n=67) or main duct (MD)-IPMN (n=7). Among IPMN-MDs, PanIN-3 lesions were exclusively found in those with pathological evidence of chronic pancreatitis. For PDACs, the median overall survival (OS) for pancreata with PanIN-3 lesions was significantly better than those without (OS 1.12 years, inter-quartile range [IQR] 0.72, 2.05 years vs OS 0.86 years, IQR 0.64, 1.60 years respectively; P=0.04). Multivariate Cox regression analysis demonstrated that the presence of PanIN-3 lesions was associated with a reduced risk of death (HR=0.43; 95% CI: 0.23-0.82; P=0.01).

Conclusions: Following primary resection of pancreatic adenocarcinoma, the lower survival observed in patients without PanIN-3 lesions might suggest a state of complete or accelerated transformation. Further investigations are necessary to validate these findings that might impact disease prognosis and management.