Phenotypic and molecular changes in nodule-in-nodule hepatocellular carcinoma with pathogenetic implications.

Major phenotypic changes take place in the INC of N/N HCC. TERT promoter mutations take place frequently and very early, and, in contrast to β-catenin mutations, do not appear to be acquired during N/N growth. These findings suggest that inner nodules represent a step further along the pathway of tumour progression, in contrast to earlier, simply initiated, lesions, and that complete neovascularisation predicts a change in HCC biology.