Combined hepatocellular carcinoma–intrahepatic cholangiocarcinoma
(cHCC–CCA) is a primary liver cancer with features of both hepatocellular carcinoma
(HCC) and intrahepatic cholangiocarcinoma (iCCA). This combined tumor represents
1% of all primary liver cancers, but recent studies have shown its increasing incidence
and incidence-based mortality. The risk factors (identifiable in about 30% of the cases)
are similar to those of HCC and CCA: cholestatic liver diseases, hepatobiliary flukes,
toxins, liver cirrhosis of any etiology, and metabolic diseases such as obesity and
diabetes mellitus. The first pathological classifications of cHCC-CCA described three
types of tumors: collision, transition and intermediate tumors. Intermediate tumors
develop from a cell intermediate between the hepatocyte and biliary epithelial cell. The
4th WHO classification of digestive system tumors (2010) was the first one to report
cHCC-CCA as a distinct entity, with two main subtypes: classical type and cHCC-CCA
with stem-cell features. The collision type was no longer accepted. In the 5th WHO
classification (2019), the tumors of the subtype with stem cell features were recategorized as either HCC or iCCA. Due to the cHCC-CCA mixture of phenotype
characteristics, the staging criteria have been also controversial. Presently, the cHCCCCA tumors are staged by a similar algorithm as for iCCA: the TNM staging of HCC
is used for clinical applications and prognosis, and the SEER staging is used for
epidemiological studies. The growing interest in molecular research, genetic
biomarkers identification, diagnosis and staging of these combined tumors will
eventually lead to the development of effective therapeutical approaches.
Keywords: Combined tumor, Epidemiology, Hepatocellular carcinoma, Intrahepatic cholangiocarcinoma, Pathology, Tumor staging.
