Intraductal papillary neoplasm of bile duct is associated with a unique intraepithelial spreading neoplasm

Cholangiocarcinoma is not infrequently associated with intraepithelial spread of neoplastic biliary cells in the biliary mucosa around the main carcinoma which is called here "intraepithelial spreading neoplasm (IESN)". Herein, the pathological features and significance of IESN of intraductal papillary neoplasm of bile duct (IPNB) were examined by using 52 cases of IPNB with reference to those of IPNB itself. As a control, 23 cases of nodular sclerosing cholangiocarcinoma (NS-CCA) with IESN were used. It was found that IPNB were constantly associated with IESN, and IESN and IPNB showed the similar biological and pathological features in individual cases. Interestingly, invasive lesion(s) were found at IESN in 22 of and also at IPNB in 32 of 52 cases, and invasion was tended to be found at both lesions in the same cases. IESN of IPNB was classifiable histologically into flat (52 cases), and lower and higher micropapillary types (52 and 43 cases, respectively), while IESN(s) in NS-CCA were only classifiable into flat (23 cases) and low micropapillary (12 cases) types. Intestinal, gastric, pancreatobiliary (PB) and oncocytic phenotypes were found similarly in IPNB and IESN of IPNB, while PB type was predominant in NS-CCA and in LSIN of NS-CCA. These findings suggest that IPNB and IESN compose a unique intraepithelial neoplasm of the biliary tree with imminent potential of invasion along any place.