Molecular Pathology of Hepatic Neoplasms: Classification and Clinical Significance

Abstract

Recent technological advances have enabled investigators to characterize the molecular genetics and genomics of hepatic neoplasia in remarkable detail. From these studies, an increasing number of molecular markers are being identified that correlate with clinically important tumor phenotypes. This paper discusses current knowledge relevant to the molecular classification of epithelial primary hepatic tumors that arise in adults, including focal nodular hyperplasia (FNH), hepatocellular adenoma (HCA), hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC. Genetic analysis has defined molecular subtypes of HCA that are clinicopathologically distinct and can be distinguished through immunohistochemistry. Gene expression studies have identified molecular signatures of progression from dysplastic nodules (DNs) to early HCC in cirrhosis. Analyses of the mutational spectra, chromosomal aberrations and instability, transcriptomics, and microRNA profiles of HCC have revealed the existence of biologically distinct subtypes of this common malignancy, with prognostic implications. Molecular characterization of biliary and hepatic progenitor cell phenotypes in liver cancer has shed new light on the histogenesis of these tumors and has focused attention on novel therapeutic targets. In coming years, the molecular classification of hepatic neoplasms will be increasingly valuable for guiding patient care, as targeted therapies for liver cancer are developed and brought into clinical practice.

Diagnostic utility and limitations of glutamine synthetase and serum amyloid-associated protein immunohistochemistry in the distinction of focal nodular hyperplasia and inflammatory hepatocellular adenoma

“…This zonation is thought to be the result of b-catenin activation in the centrizonal hepatocytes, which may be the result of Wnt signaling from the central vein. 12,13 In focal nodular hyperplasia, there is expansion of the b-catenin-activated centrizonal region, which leads to overexpression in a characteristic geographic map-like pattern. [14][15][16] Diffuse cytoplasmic expression of glutamine synthetase is seen in a small subset of b-cateninactivated hepatocellular adenomas, but the map-like pattern typical of focal nodular hyperplasia is not observed in hepatocellular adenomas.…”

Primary and Metastatic Tumours of the Liver: Expanding Scope of Morphological and Immunohistochemical Details in the Biopsy

“…Liver cell adenoma was rare before the era of oral contraceptives [27]. At present, the incidence has increased but is still low: 3-4 /100 000 per year in long-term users of oral contraception [27][28][29]. The patients mostly are 20-39 years old.…”

“…Abdominal fullness can be attributed to the presence of mass lesion; pain can be caused by necrosis [27]. Rupture and bleeding (40%) represent dangerous complications [27,[29][30][31]; the risk of these events is increased in pregnant ladies affected by liver cell adenoma due to prior use of hormonal contraceptives. Risk of malignant transformation also is recognised [29,32].…”

“…Rupture and bleeding (40%) represent dangerous complications [27,[29][30][31]; the risk of these events is increased in pregnant ladies affected by liver cell adenoma due to prior use of hormonal contraceptives. Risk of malignant transformation also is recognised [29,32]. By literature analysis, Farges and Dokmak concluded that 5% of resected hepatic adenomas bear HCC foci [32].…”

HAb18G/CD147 Promotes Radioresistance in Hepatocellular Carcinoma Cells: A Potential Role for Integrin β1 Signaling

“…Most patients are not surgical candidates at the time of diagnosis because of vascular invasion, multifocality, and large tumor size, and liver shortage has been the rate-limiting step in the expansion of hepatic transplantation for patients with HCC (1,2). Therefore, nonresectional therapies, including radiotherapy combined with other locoregional treatments, have been introduced to improve survival in patients with advanced HCC (3).…”