Are hepatolithiasis and cholangiocarcinoma aetiologically related?

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Abstract
A few cases of cholangiocarcinoma (CC) related to hepatolithiasis have been reported to date, but the aetiological relationship remains unclear. In an attempt to clarify the relationship between two phenomena, we examined morphologically 12 cases of hepatolithiasis associated with CC and 26 cases of hepatolithiasis without CC, with the aid of immunohistochemical staining for carcinoembryonic antigen (CEA). In the livers where both hepatolithiasis and CC were found, the carcinoma spread along the lumenal surface of the stone-containing bile ducts and invaded the ductal walls. Features of “chronic proliferative cholangitis” which was a basic feature of hepatolithiasis, were found within the bile duct walls where carcinoma was invading. In some cases of chronic proliferative cholangitis with hepatolithiasis in the absence of CC, atypical epithelial hyperplasia was noted. Atypical epithelial hyperplasia was also found in bile ducts adjacent to and remote from CC. Atypical epithelial hyperplasia was positive for CEA. The data lead us to speculate that chronic proliferative cholangitis in the presence of hepatolithiasis can undergo progressive changes to atypical epithelial hyperplasia which may in turn progress to CC.