Cholangioscopic biopsy sample detection of bile duct invasion by hepatocellular carcinoma: an underappreciated entity

Background and Aims: Bile duct invasion (BDI) by hepatocellular carcinoma (HCC) is rare and poorly characterized. Our aim was to elucidate clinical, cholangioscopic, and pathologic features of HCC with BDI and to compare them with features of cholangiocarcinoma (CC). Methods: Seven cases of HCC with BDI (6 HCC and 1 combined HCC-CC) and 7 cases of CC diagnosed by cholangioscopic biopsy sampling between 2016 and 2020 were compared. Results: The median age of HCC patients was 64 years (range, 49-77), and 6 patients were men. The median age of CC patients was 73 years (range, 58-75), and 4 patients were men. Obstructive jaundice was the presenting sign in 86% of HCC and 100% of CC cases. Cirrhosis was present in 77% of HCC cases but only 28% of CC cases. α-Fetoprotein was elevated in 57% of HCC cases and none of the CC cases. Both groups had biliary strictures; however, cholangioscopic features of HCC were more likely to show noncircumferential strictures with a mass and were less likely to include ulceration. Villiform formation and frond-like projections were more common in CC. Both showed increased vascularity and friability. Imaging showed a mass in 100% of HCC and in 57% of CC cases. The histopathology of HCC with BDI included trabecular or pseudoglandular architecture, granular eosinophilic cytoplasm, absence of mucin, and atypical nuclear features. Immunohistochemical staining in all HCC cases confirmed a hepatocyte phenotype. Immunohistochemical markers were required to distinguish cases of BDI caused by poorly differentiated HCC or CC because of overlapping clinicopathologic features between the 2 groups. Conclusions: Cholangioscopic findings of a noncircumferential stricture with a luminal mass are indicative of HCC with BDI. Pathologists should routinely use a panel of hepatocyte and cholangiocyte biomarkers to differentiate BDI by HCC from CC and metastases in poorly differentiated carcinoma that lack mucin.