Management of hepatocellular adenoma

Hepatocellular adenomas (HCAs) are rare benign liver tumors that usually develop in otherwise healthy livers in young women exposed to estrogen. HCAs can also occur in the context of liver diseases such as vascular liver disease or glycogenosis. These tumors can be complicated by bleeding (10–20% of cases) or malignant transformation into hepatocellular carcinoma (HCC) (4–5% of cases). HPCs are classified into five subtypes according to molecular alterations and histological and clinical features: HNF1A-inactivated adenomas, inflammatory adenomas, adenomas with mutation in exon 3 of the CTNNB1 gene, adenomas with mutation in exon 7/8 of the CTNNB1 gene, and adenomas with activation of the Sonic Hedgehog pathway due to INHBE/GLI1 fusion. Among these subtypes, HCAs with mutation in exon 3 of the CTNNB1 gene are associated with an increased risk of malignant transformation into HCC, whereas HCAs with Sonic Hedgehog activation present a significant risk of tumoral bleeding. Weight loss and the withdrawal of estrogen-based contraception/androgen therapy should be prioritized, and the surgical management of HCAs must be discussed in a multidisciplinary team meeting in which gender, tumor size, and molecular subtype are considered. HCAs of less than 5 cm in size developed in women without a CTNNB1 exon 3 mutation can be monitored by annual MRI. Conversely, surgery should be performed for HCAs developed in men and be considered for women with HCAs larger than 5 cm, as well as for HCAs with Sonic Hedgehog activation or harboring a CTNNB1 exon 3 mutation.