Hepatocellular adenoma classification
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zahir Ali Shaikh, MD[2]
Overview
The hepatocellular adenomas are classified on the basis of molecular patterns called phenotypic-genotypic classification into 4 major groups, including HNF1-alpha inactivated adenoma, beta-catenin activated adenoma, inflammatory hepatic adenoma and unclassified type adenoma.
Classification
- In 2007, Bioulac-Sage and associates from Bordeaux, classified the hepatocellular adenomas based on molecular patterns called phenotypic-genotypic classification. They classified hepatocellular adenomas into 4 main groups.[1][2][3][4]
| Hepatocellular Adenoma | |||||||||||||||||||||||||||||||||||||||||||
| HNF-1 alpha inactivated adenoma | Beta catenin activated adenoma | Inflammatory hepatic adenoma | Unclassified type adenoma | ||||||||||||||||||||||||||||||||||||||||
HNF-1 Alpha Inactivated Hepatocellular Adenoma (35 - 40%)
- This group of hepatocellular adenomas is defined by the somatic inactivation of HNF1A (hepatocyte nuclear factor 1 A) gene by a mutational mechanism in tumor cells.[5]
- HNF1A is a transcription factor controlling hepatocyte metabolism.[6]
- Most of these variants show macrovesicular steatosis of variable extent and no atypical hepatocytes and are associated with metabolic syndrome.
- This type occurs mostly in women and is often associated with maturity onset diabetes of young (MODY3).
- Expression of liver fatty acid binding protein (LFABP) involved in lipid trafficking, usually expressed in normal liver, is specifically down-regulated in these cases as a consequence of HNF1A mutation.
Inflammatory Hepatocellular Adenoma (40 - 50%)
- The most important feature of these tumors is activation of JAK/STAT pathway.[7]
- Inflammatory hepatocellular adenoma also exhibits over expression of serum amyloid alpha (SAA) and C-reactive protein (CRP) induced by STAT3.
- They show greater morphological pleomorphism as they may show pseudo portal tracts, sinusoidal dilatation, dystrophic arteries, hemorrhage, and inflammatory infiltrate.
- Inflammatory syndrome, obesity, and alcohol consumption are reported in these patients.
- Five different molecular drivers, IL6 signal transducer, FRK, STAT3, GNAS, and JAK1 have been reported.[8]
Beta-catenin Mutated Hepatocellular Adenoma (10 - 15%)
- These are frequently associated with exposure to male hormones, glycogenolysis, and familial adenomatous polyposis.[9]
- This group has a higher risk of malignant potential.[10]
- Morphologically, these tumors have cytological and architectural atypical features of tumoral hepatocytes as well as that of cholestasis.
- On immunohistochemical staining, these adenomas tend to stain for glutamine synthetase rather than beta catenin, which stains patchily.
Unclassified Hepatocellular Adenoma (10%)
- By definition, they lack characteristics of other sub-types and their identification relies on a silent phenotype and by exclusion of criteria featuring other sub-types.
- The exact underlying pathogenesis is not completely understood.
- These adenomas do not stain for the C-reactive protein (CRP), beta-catenin, or glutamine synthetase.[11]
References
- ↑ Kun Jiang, Sameer Al-Diffhala & Barbara A. Centeno (2018). "Primary Liver Cancers-Part 1: Histopathology, Differential Diagnoses, and Risk Stratification". Cancer control : journal of the Moffitt Cancer Center. 25 (1): 1073274817744625. doi:10.1177/1073274817744625. PMID 29350068. Unknown parameter
|month=ignored (help) - ↑ H. Dharmana, S. Saravana-Bawan, S. Girgis & G. Low (2017). "Hepatocellular adenoma: imaging review of the various molecular subtypes". Clinical radiology. 72 (4): 276–285. doi:10.1016/j.crad.2016.12.020. PMID 28126185. Unknown parameter
|month=ignored (help) - ↑ Paulette Bioulac-Sage, Christine Sempoux & Charles Balabaud (2017). "Hepatocellular adenoma: Classification, variants and clinical relevance". Seminars in diagnostic pathology. 34 (2): 112–125. doi:10.1053/j.semdp.2016.12.007. PMID 28131467. Unknown parameter
|month=ignored (help) - ↑ Paulette Bioulac-Sage, Sandra Rebouissou, Cristel Thomas, Jean-Frederic Blanc, Jean Saric, Antonio Sa Cunha, Anne Rullier, Gaelle Cubel, Gabrielle Couchy, Sandrine Imbeaud, Charles Balabaud & Jessica Zucman-Rossi (2007). "Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry". Hepatology (Baltimore, Md.). 46 (3): 740–748. doi:10.1002/hep.21743. PMID 17663417. Unknown parameter
|month=ignored (help) - ↑ Aparna P.. Shreenath & Arslan Kahloon (2018). "Hepatic (Hepatocellular) Adenoma". PMID 30020636. Unknown parameter
|month=ignored (help) - ↑ Motoko Sasaki, Norihide Yoneda, Seiko Kitamura, Yasunori Sato & Yasuni Nakanuma (2011). "Characterization of hepatocellular adenoma based on the phenotypic classification: The Kanazawa experience". Hepatology research : the official journal of the Japan Society of Hepatology. 41 (10): 982–988. doi:10.1111/j.1872-034X.2011.00851.x. PMID 21883740. Unknown parameter
|month=ignored (help) - ↑ Jean-Charles Nault, Paulette Bioulac-Sage & Jessica Zucman-Rossi (2013). "Hepatocellular benign tumors-from molecular classification to personalized clinical care". Gastroenterology. 144 (5): 888–902. doi:10.1053/j.gastro.2013.02.032. PMID 23485860. Unknown parameter
|month=ignored (help) - ↑ Motoko Sasaki, Norihide Yoneda, Yoshiyuki Sawai, Yasuharu Imai, Fukuo Kondo, Toshio Fukusato, Seiichi Yoshikawa, Satoshi Kobayashi, Yasunori Sato, Osamu Matsui & Yasuni Nakanuma (2015). "Clinicopathological characteristics of serum amyloid A-positive hepatocellular neoplasms/nodules arising in alcoholic cirrhosis". Histopathology. 66 (6): 836–845. doi:10.1111/his.12588. PMID 25318388. Unknown parameter
|month=ignored (help) - ↑ Kimberley J. Evason, James P. Grenert, Linda D. Ferrell & Sanjay Kakar (2013). "Atypical hepatocellular adenoma-like neoplasms with beta-catenin activation show cytogenetic alterations similar to well-differentiated hepatocellular carcinomas". Human pathology. 44 (5): 750–758. doi:10.1016/j.humpath.2012.07.019. PMID 23084586. Unknown parameter
|month=ignored (help) - ↑ Camilla Pilati, Eric Letouze, Jean-Charles Nault, Sandrine Imbeaud, Anais Boulai, Julien Calderaro, Karine Poussin, Andrea Franconi, Gabrielle Couchy, Guillaume Morcrette, Maxime Mallet, Said Taouji, Charles Balabaud, Benoit Terris, Frederic Canal, Valerie Paradis, Jean-Yves Scoazec, Anne de Muret, Catherine Guettier, Paulette Bioulac-Sage, Eric Chevet, Fabien Calvo & Jessica Zucman-Rossi (2014). "Genomic profiling of hepatocellular adenomas reveals recurrent FRK-activating mutations and the mechanisms of malignant transformation". Cancer cell. 25 (4): 428–441. doi:10.1016/j.ccr.2014.03.005. PMID 24735922. Unknown parameter
|month=ignored (help) - ↑ Paulette Bioulac-Sage, Gaelle Cubel, Said Taouji, Jean-Yves Scoazec, Emmanuelle Leteurtre, Valerie Paradis, Nathalie Sturm, Jeanne Tran Van Nhieu, Dominique Wendum, Brigitte Bancel, Jeanne Ramos, Francois Paraf, Marie Christine Saint Paul, Sophie Michalak, Monique Fabre, Catherine Guettier, Brigitte Le Bail, Jessica Zucman-Rossi & Charles Balabaud (2012). "Immunohistochemical markers on needle biopsies are helpful for the diagnosis of focal nodular hyperplasia and hepatocellular adenoma subtypes". The American journal of surgical pathology. 36 (11): 1691–1699. doi:10.1097/PAS.0b013e3182653ece. PMID 23060349. Unknown parameter
|month=ignored (help)