Hepatocellular Carcinomas: Towards a pathomolecular approach

Molecular analysis of primary liver malignancies has provided a refinement of the pathological diagnosis of this entity and the identification of an increasing number of tumor subtypes of hepatocellular proliferation, either malignant (hepatocellular carcinomas) or benign (hepatocellular adenomas). Besides the diagnosis, a combined pathomolecular approach can also provide further insights into patient prognosis, and help select patients who can benefit from targeted therapies. Hepatocellular carcinomas define a heterogeneous group of malignant hepatocellular proliferation at various levels: macroscopic, histological and molecular. While most carcinomas occur in patients with chronic liver diseases and advanced fibrosis in the background liver, some arise from the malignant transformation of a pre-existing hepatocellular adenoma. TERT promoter mutations are the most frequent genomic alterations observed in the process of malignancy, and they occur early in the process of liver carcinogenesis. Overall, a more active biopsy strategy should be considered a key step in the management of patients with HCC.