Authors
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis, representing the 3rd leading cause of cancer mortality worldwide. HCC is a heterogeneous tumor, both morphologically and molecularly. The aim of this update is to address this heterogeneity by describing the different histological and molecular subtypes of HCC. Morphologically, eight subtypes have been described according to the WHO classification: steatohepatitic, massive macrotrabecular (MTM), clear-cell, chromophobe, squirrelly, fibrolamellar, lymphocyte-rich and neutrophil-rich. Other HCCs are classified as HCC without specificity. Certain subtypes are associated with a different prognosis, notably MTM, which has a shorter survival rate than the other subtypes. On the genomic level, most HCCs present mutations of the TERT promoter, while other mutations are observed later in the carcinogenesis, such as TP53 and CTNNB1 mutations. TP53-mutated HCCs are associated with poor prognosis and the MTM subtype. In terms of transcriptomics, two classifications are particularly informative, as they are associated with prognosis (proliferative versus non-proliferative classes) and clinical, morphological and genomic tumor characteristics (G1-G6 classification). In conclusion, morphological heterogeneity in HCC, directly related to molecular heterogeneity, correlates with prognosis. This underlines the importance of specifying the different HCC subtypes in histological reports.