Distinct Clinicopathologic and Genetic Features of 2 Histologic Subtypes of Intrahepatic Cholangiocarcinoma

Abstract

Previous studies have identified 2 clinically significant morphologic subtypes of intrahepatic cholangiocarcinoma (ICC) on the basis of anatomic location and/or histologic appearances. Recognizing that these classification schemes are not always applicable practically, this study aimed to establish a novel classification system based on mucin productivity and immunophenotype and to determine the rationale of this classification by examining the clinicopathologic and genetic characteristics of the 2 subtypes defined by this method. We retrospectively investigated 102 consecutive ICC cases and classified them on the basis of mucin productivity and immunophenotype (S100P, N-cadherin, and NCAM). We found that 42 and 56 cases were classified as type 1 and type 2 ICCs, respectively, and only 4 cases were of indeterminate type. Type 1 ICC, generally characterized by mucin production and diffuse immunoreactivity to S100P, arose less frequently in chronic liver diseases and showed higher levels of serum CEA and CA 19-9 than did type 2 ICC, which generally showed little mucin production and exhibited immunoreactivity to N-cadherin and/or NCAM. Type 1 ICC was characterized by several pathologic features, including higher frequencies of perineural invasion and lymph node metastasis. Although the log-rank test demonstrated that type 1 ICC had significantly worse survival, the multivariate Cox regression analysis showed no prognostic significance of this histologic subtype. Genetic analyses revealed that KRAS mutation was significantly more frequent in type 1 ICC, whereas IDH mutation and FGFR2 translocation were restricted to type 2 ICC. In conclusion, the present classification of ICC based on mucin productivity and immunophenotype identified 2 subtypes with clinicopathologic significance.

Transcriptomic and histopathological analysis of cholangiolocellular differentiation trait in intrahepatic cholangiocarcinoma

“…There is a various histological differentiation in iCCAs and recently cholangiolar type and bile duct type have been reported . However, iCCAs show an intratumoural histological heterogeneity and tumour components resembling cholangiole or bile duct are often mixed at various proportions.…”

Anatomical, histomorphological and molecular classification of cholangiocarcinoma

“…The gross and histological features of large bile duct type iCCA are similar to those of p/dCCA . Actually, the distinction between iCCA and pCCA at the second‐order biliary branches is somehow artificial and seems to take into account surgical implications more than anatomical, embryological and molecular aspects . Moreover, the precise anatomical origin of some large tumours can be challenging, as there is no clear evidence whether they are by definition intrahepatic or perihilar on gross examination .…”

Intrahepatic cholangiocarcinoma frequently shows loss of BAP1 and PBRM1 expression, and demonstrates specific clinicopathological and genetic characteristics with BAP1 loss

“…Cholangiocarcinoma is classified conventionally into intrahepatic, perihilar or distal type based on its anatomical location . Recently, it was proposed that intrahepatic cholangiocarcinoma (ICC) should be classified further into two subtypes, large‐duct and small‐duct types (or types 1 and 2), with distinct clinicopathological features based on histological or immunohistochemical features …”