Histological Characterization of Biliary Intraepithelial Neoplasia with respect to Pancreatic Intraepithelial Neoplasia

Abstract

Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of hilar/perihilar and extrahepatic cholangiocarcinoma. BilIN represents the process of multistep cholangiocarcinogenesis and is the biliary counterpart of pancreatic intraepithelial neoplasia (PanIN). This study was performed to clarify the histological characteristics of BilIN in relation to PanIN. Using paraffin-embedded tissue sections of surgically resected specimens of cholangiocarcinoma associated with BilIN and pancreatic ductal adenocarcinoma associated with PanIN, immunohistochemical staining was performed using primary antibodies against MUC1, MUC2, MUC5AC, cyclin D1, p21, p53, and S100P. For mucin staining, Alcian blue pH 2.5 was used. Most of the molecules examined here showed similar expression patterns in BilIN and PanIN, in which their expression tended to increase along with the increase in atypia of the epithelial lesions. Significant differences were observed in the increase in mucin production and the expression of S100P in PanIN-1 and the expression of p53 in PanIN-3, when compared with those in BilIN of a corresponding grade. These results suggest that cholangiocarcinoma and pancreatic ductal adenocarcinoma share, at least in part, a common carcinogenic process and further confirm that BilIN can be regarded as the biliary counterpart of PanIN.

Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma

“…BilIN has often been described as the biliary counterpart to pancreatic intraepithelial neoplasia (PanIN), partially due to the similar embryonal development and morphology of the pancreatic and biliary duct systems [12] . Grading of BilIN follows a similar 3-tiered pattern to that of PanIN, which has proven similar in several morphologic and immunohistochemical respects [13] . BilIN is subdivided into BilIN-1, BilIN-2 and BilIN-3 according to consensus criteria proposed in 2005 and accepted by an international group in 2007 [14,15] .…”

Comprehensive genomic profiling of extrahepatic cholangiocarcinoma reveals a long tail of therapeutic targets

“…Similarly, the presumed precursor lesion of cholangiocarcinoma, biliary intraepithelial neoplasia, was shown to share common carcinogenesis with pancreatic intraepithelial neoplasia 51. In fact, the initial systemic chemotherapy regimen for advanced cholangiocarcinoma, gemcitabine, has been devised based on regimen for advanced pancreatic cancer 52.…”

Pathology of intrahepatic cholangiocarcinoma

“…It is now recognized that iCC proceeds through multistepcarcinogenesis; three precursor lesions have been at present morphologically established (22)(23)(24)(25)(26)(27)(28)(29)(30)(31): (I) a flat intraepithelial bilirary neoplasia or BillN (discernible only at level of microscope) ( Figure 6A); (II) an IPNB (previously named papillomatosis) (discernible on radiologic imaging or at macroscopic examination ( Figures 4A and 6B); and (III) intraductal tubulo-papillary neoplasm (ITNB). These lesions are generally observed in large intrahepatic, hilar and extrahepatic BDs, and are infrequently observed in the septal or interlobular BDs.…”

“…IPNB are more and more admitted as the biliary counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, while intraductal tubular neoplasm of bile duct (ITNB) is considered as the biliary counterpart of intraductal tubular neoplasm of the pancreas (23). Both biliary and pancreatic duct derive embryonically from the foregut.…”