Proposal of progression model for intrahepatic cholangiocarcinoma: clinicopathologic differences between hilar type...

It is important to clarify the histologic progression of intrahepatic cholangiocarcinoma (ICC) in consideration of its origin from the intrahepatic large or small biliary ducts. On the basis of the gross and histologic assessment, we classified 87 cases of ICC smaller than 5 cm in diameter into hilar type (H-ICC, n=38) or peripheral type (P-ICC, n=49) to compare their clinical and histologic features. Biliary dysplasia was observed in 65.8% (25/38) of H-ICC cases, whereas hepatitis virus infection and liver cirrhosis were associated with 46.7% (21/45) and 28.6% (14/49) of P-ICC, respectively. The frequency of perineural invasion, lymph node metastasis, and extrahepatic recurrence of H-ICC was significantly higher than that of P-ICC (P<0.0001, 0.0106, and 0.0279, respectively). H-ICC cases showed frequent vascular invasion and intrahepatic metastasis even with small tumor size, compared with P-ICC cases. H-ICC showed large duct involvement within the tumor, and in the cases of large tumor size, intraductal spread was detected in the tumor periphery. P-ICC of small size contained preserved architecture of the portal tracts. The survival of patients with H-ICC was worse than that of patients with P-ICC (P=0.0121). The independent and best prognostic factor by multivariate analysis was intrahepatic metastasis for H-ICC and lymph node metastasis for P-ICC. Our results suggest that ICCs derived from a different level of biliary ducts were related to different premalignant conditions and different tumor progression. Some ICCs arising from the large biliary duct are likely to exhibit an aggressive course even in cases of small tumor size. The recognition of the above events induces the proper therapy.