Morphometric and immunohistochemical study of cholangiolocellular carcinoma: comparison with non-neoplastic cholangiole, interlobular duct and septal duct

BACKGROUND/PURPOSE: The origin of cholangiolocellular carcinoma (CoCC) is still controversial. To solve this problem, morphometric and immunohistochemical features of CoCC were examined. MATERIALS AND METHODS: Cancerous ducts: 15 CoCC lesions from 13 resected and two autopsied cases. Non-neoplastic ducts: 20 specimens of non-cancerous areas of eight resected CoCC cases and of 12 resected hepatocellular carcinoma (HCC) cases. From these specimens, cholangioles, interlobular ducts of small size (ILD-S), interlobular ducts of medium size (ILD-M) and septal ducts were randomly selected. MORPHOMETRY: The outer and inner diameters of these ducts were measured. Immunohistochemistry: two hepatocyte markers [Hep Par 1 and α-fetoptotein (AFP)], two cholangiocyte markers (cytokeratin CK7, CK19), a marker for mucin (Muc1), a hepatic stem/progenitor cell marker (c-Kit) and epithelial membrane antigen (EMA) were used. RESULTS: Morphometry: both mean values of the outer and inner diameters of CoCC were far larger than those of cholangioles, and showed intermediate values between those of ILD-S and ILD-M. Immunohistochemistry: all ducts of CoCCs were negative for the two hepatocyte markers and positive for CK 7. Most CoCC ducts were positive for CK 19. Positive rate of c-Kit of cholangiole was most remote from that of CoCC. The positive rates of EMA in the membranous area of ducts were similarly very high in CoCC, cholangiole and ILD-S. CONCLUSION: These results suggest that CoCCs may originate from ILDs.