Hepatocellular Carcinomas: Towards a pathomolecular approach

Abstract

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.

Quercetin Regulates Key Components of the Cellular Microenvironment during Early Hepatocarcinogenesis

“…Hepatocarcinogenesis is a complex process involving at least three well-categorized stages, initiation, promotion, and progression [ 3 ]. The early HCC stages are characterized by the development of preneoplastic lesions promoted by chronic liver damage, which eventually progress to established tumors [ 4 , 5 ]. It has been described that the tumor microenvironment (TME) plays a key role during hepatocarcinogenesis.…”

Hepatocellular Neoplasm of Uncertain Potential of Malignancy or Well-Differentiated Hepatocellular Carcinoma Arising within Hepatocellular Adenoma

“…However, because HCA can progress to malignancy, borderline hepatocellular lesions can be expected. These HCA do not have a definite pathomolecular subtype, but are examples of an uncertain diagnosis between HCA and HCC [4].…”

“…Hepatocellular adenoma (HCA) is a rare solid, solitary, benign liver lesion that develops in an otherwise normalappearing liver [1][2][3][4]. Often, they are found in young women in association with use of estrogen-containing medications.…”

“…The most important complications of HCA are hemorrhage (25-64%) and malignant transformation into hepatocellular carcinoma (HCC; 4-10%), which are the two main reasons for surgical treatment. Risk factors for malignant transformation include advanced age, male gender, use of anabolic steroids, metabolic syndrome, lesion size >5 cm, and beta-catenin activation subtype [2,[4][5][6].…”

“…The highest risk of malignant transformation into HCC is found with HCA with beta-catenin activation (b-HCA) [4]. Inflammatory HCA (I-HCA) may also exhibit marked WNT signaling pathway activation in 10% of cases, constituting a subset of tumors prone to undergo a malignant transformation, called I-HCA with beta-catenin activation (b-IHCA) [1,4,8,9]. b-IHCA have features of both I-HCA and b-HCA and they carry the same risk of malignant transformation as b-HCA [10].…”