[Hepatocellular carcinoma: Histological and molecular classifications]

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumour, with a poor prognosis, ranking third for cancer mortality worldwide. HCC is a morphologically and molecularly heterogeneous tumour. This update aims 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, macrotrabecular massive (MTM), clear cell, chromophobe, scirrhous, fibrolamellar, lymphocyte-rich and neutrophil-rich. Other HCCs are classified as non-specific (not otherwise specified or NOS). These subtypes may be associated with a different prognosis, particularly the MTM, which displays a poorer survival than the other subtypes. Genomically, most HCCs present mutations in the TERT promoter, while other mutations occured later in carcinogenesis, such as TP53 and CTNNB1. TP53 mutated HCCs are associated with a poor prognosis and the MTM subtype. From a transcriptomic standpoint, two classifications are particularly noteworthy, as they are associated with both prognosis (proliferative vs. non-proliferative classification) and clinical, morphological and genomic tumour characteristics (G1-G6 classification). In conclusion, the morphological heterogeneity of HCC, directly linked to molecular heterogeneity, is associated with prognosis. This strongly supports the specification of the different HCC subtypes in our reports.