High-grade precursor lesions can be used as surrogate markers to identify the epicenter of periampullary carcinomas

Abstract

Identifying the accurate origin of periampullary cancers is important because different origins may trigger different clinicopathological behaviors. The presence of intraepithelial precursor lesions, including high-grade pancreatic intraepithelial neoplasias (PanINs) and/or high-grade biliary intraepithelial neoplasias (BilINs), may be suggestive of the origin of the periampullary carcinoma in challenging cases. To prove the usefulness of high-grade intraepithelial precursor lesions in identifying the origin of ambiguous periampullary cancers, the status and grades of PanINs and BilINs were evaluated in 256 periampullary carcinomas with a well-defined cancer origin as a test set, including 114 pancreatic cancers, 82 distal bile duct cancers, 54 ampullary cancers, and 6 duodenal cancers. One hundred twelve periampullary carcinomas with clinically equivocal epicenter either by radiologic imaging or by endoscopic finding used as a validation set. High-grade PanINs were found more commonly in pancreatic cancers than in distal bile duct, ampullary, and duodenal cancers both in test (P = .002) and validation sets (P < .001). Similarly, high-grade BilINs were identified more frequently in distal bile duct cancers than in ampullary, pancreatic, and duodenal cancers both in test (P < .001) and validation sets (P = .039). High-grade PanINs were found most commonly in pancreatic cancers, whereas high-grade BilINs were seen most frequently in distal bile duct cancers. In addition, both high-grade PanINs and high-grade BilINs are uncommonly noted in ampullary or duodenal cancers. The recognition of high-grade intraepithelial lesions can help identify the primary origin of periampullary cancers, especially when the epicenter of the periampullary cancer is ambiguous.