Hepatocellular Benign Tumors—From Molecular Classification to Personalized Clinical Care  Jean–Charles Nault, Paulette Bioulac–Sage, Jessica Zucman–Rossi  Gastroenterology  Volume 144, Issue 5, Pages 888-902 (May 2013) DOI: 10.1053/j.gastro.2013.02.032 Copyright © 2013 AGA Institute Terms and Conditions

Figure 1 Composite algorithm for the diagnosis and treatment of FNH and HCAs. Clinical, radiologic, pathologic, and molecular data are combined in a step-by-step diagnostic and treatment algorithm stratified by the risk of complications (hemorrhage and malignant transformation for HCA, absence of complications for FNH). Diagnosis of FNH is usually at MRI. In atypical cases, a biopsy specimen showing glutamine synthase in a “map-like” pattern staining is very useful for diagnosis of FNH. CT, computed tomographic; CRP, C-reactive protein; OC, oral contraception; GS, glutamine synthase; SAA,serum amyloid A. *Surgery should be considered in the absence of adenoma regression after oral contraception or androgen withdrawal. Gastroenterology 2013 144, 888-902DOI: (10.1053/j.gastro.2013.02.032) Copyright © 2013 AGA Institute Terms and Conditions

Figure 2 Molecular classification of HCAs. Each molecular subgroup of HCA is related to specific pathologic and clinical features (genotype/phenotype relationship). They are identified using immunohistochemistry with 5 antibodies (FABP, SAA, C-reactive protein [CRP], β-catenin, and glutamine synthase) and/or specific features at MRI. Gastroenterology 2013 144, 888-902DOI: (10.1053/j.gastro.2013.02.032) Copyright © 2013 AGA Institute Terms and Conditions

Figure 3 Dysregulation of the metabolic and proliferative pathway in HNF1A-inactivated adenomas. Genes are down-regulated (green) and up-regulated (red) in HNF1A-inactivated HCAs. Biallelic inactivating mutations of HNF1A in hepatocytes leads to metabolic defects: activation of glycolysis (solid arrows), repression of gluconeogenesis (dashed arrows), and activation of fatty acid synthesis. In addition, this subtype of HCA harbors activation of the mTOR pathway and dysregulation of cell cycle genes. Abnormal estrogen metabolism with possible accumulation of 17β estradiol could explain the role of oral contraception in the development of HCA. Gastroenterology 2013 144, 888-902DOI: (10.1053/j.gastro.2013.02.032) Copyright © 2013 AGA Institute Terms and Conditions

Figure 4 Hepatocytes as a pivotal inflammatory cell involved in benign liver tumorigenesis. The driving oncogenes found recurrently mutated and responsible of the inflammatory phenotype are in red. The role of chronic inflammatory response in the genesis of dystrophic artery and sinusoidal dilatation remains unexplored. Gastroenterology 2013 144, 888-902DOI: (10.1053/j.gastro.2013.02.032) Copyright © 2013 AGA Institute Terms and Conditions

Figure 5 Clinical and genetic determinants of the occurrence of HCAs. Patients with germline mutations of HNF1A, McCune–Albright syndrome, or glycogenosis 1a should avoid the use of estrogen and should be screened for HCA. Moreover, patients with HNF1A germline mutations should be screened for MODY3 and genetic counseling should be proposed to the family. Gastroenterology 2013 144, 888-902DOI: (10.1053/j.gastro.2013.02.032) Copyright © 2013 AGA Institute Terms and Conditions