Hepatocellular adenoma classification: Difference between revisions
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{{CMG}}; {{AE}} {{ZAS}} | {{CMG}}; {{AE}} {{ZAS}} | ||
==Overview== | ==Overview== | ||
The [[ | The hepatocellular adenomas are [[Classification|classified]] on the basis of [[Molecule|molecular]] patterns called [[Phenotype|phenotypic]]-[[Genotype|genotypic]] [[classification]] into 4 major groups, including [[HNF1A|HNF1-alpha]] inactivated [[adenoma]], [[Beta-catenin|beta-catenin]] activated [[adenoma]], [[Inflammation|inflammatory]] [[Liver|hepatic]] [[adenoma]] and [[Classification|unclassified]] type [[adenoma]]. | ||
==Classification== | ==Classification== | ||
* In 2007, Bioulac-Sage and associates from Bordeaux | * In 2007, Bioulac-Sage and associates from Bordeaux, [[Classification|classified]] the hepatocellular adenomas based on [[Molecule|molecular]] patterns called [[Phenotype|phenotypic]]-[[Genotype|genotypic]] [[classification]]. They [[Classification|classified]] hepatocellular adenomas into 4 main groups.<ref>{{Cite journal | ||
| author = [[Kun Jiang]], [[Sameer Al-Diffhala]] & [[Barbara A. Centeno]] | | author = [[Kun Jiang]], [[Sameer Al-Diffhala]] & [[Barbara A. Centeno]] | ||
| title = Primary Liver Cancers-Part 1: Histopathology, Differential Diagnoses, and Risk Stratification | | title = Primary Liver Cancers-Part 1: Histopathology, Differential Diagnoses, and Risk Stratification | ||
| Line 63: | Line 63: | ||
'''[[HNF1A|HNF-1 | '''[[HNF1A|HNF-1 Alpha]] Inactivated Hepatocellular Adenoma (35 - 40%)''' | ||
* This group of | * This group of hepatocellular adenomas is defined by the [[somatic]] inactivation of [[HNF1A|HNF1A (hepatocyte nuclear factor 1 A)]] [[gene]] by a [[Mutation|mutational]] mechanism in [[Tumor cell|tumor cells]].<ref>{{Cite journal | ||
| author = [[Aparna P.. Shreenath]] & [[Arslan Kahloon]] | | author = [[Aparna P.. Shreenath]] & [[Arslan Kahloon]] | ||
| title = Hepatic (Hepatocellular) Adenoma | | title = Hepatic (Hepatocellular) Adenoma | ||
| Line 83: | Line 83: | ||
| pmid = 21883740 | | pmid = 21883740 | ||
}}</ref> | }}</ref> | ||
* Most of these variants show macrovesicular [[steatosis]] of variable extent and no atypical [[Hepatocyte|hepatocytes]] and are [[Association (statistics)|associated]] | * Most of these variants show macrovesicular [[steatosis]] of variable extent and no atypical [[Hepatocyte|hepatocytes]] and are [[Association (statistics)|associated]] with [[metabolic syndrome]]. | ||
* This type occurs mostly in women and is often associated with [[Maturity onset diabetes of the young|maturity onset diabetes of young (MODY3)]]. | * This type occurs mostly in women and is often associated with [[Maturity onset diabetes of the young|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 [[Downregulation|down-regulated]] in these cases as a consequence of [[HNF1A]] [[mutation]]. | * Expression of [[liver]] [[fatty acid]] [[binding protein]] (LFABP) involved in [[lipid]] trafficking, usually expressed in normal [[liver]], is specifically [[Downregulation|down-regulated]] in these cases as a consequence of [[HNF1A]] [[mutation]]. | ||
'''Inflammatory | '''Inflammatory Hepatocellular Adenoma (40 - 50%)''' | ||
* The most important feature of these [[Tumor|tumors]] is activation of [[Janus kinase|JAK]]/[[STAT protein|STAT]] pathway.<ref>{{Cite journal | * The most important feature of these [[Tumor|tumors]] is activation of [[Janus kinase|JAK]]/[[STAT protein|STAT]] pathway.<ref>{{Cite journal | ||
| author = [[Jean-Charles Nault]], [[Paulette Bioulac-Sage]] & [[Jessica Zucman-Rossi]] | | author = [[Jean-Charles Nault]], [[Paulette Bioulac-Sage]] & [[Jessica Zucman-Rossi]] | ||
| Line 99: | Line 99: | ||
| pmid = 23485860 | | pmid = 23485860 | ||
}}</ref> | }}</ref> | ||
* Inflammatory | * Inflammatory hepatocellular adenoma also exhibits over expression of [[Serum amyloid A|serum amyloid alpha (SAA)]] and [[C-reactive protein|C-reactive protein (CRP)]] induced by [[STAT3]]. | ||
* They show greater [[Morphology|morphological]] [[pleomorphism]] as they may show pseudo portal tracts, [[Sinusoid (blood vessel)|sinusoidal]] [[Dilation|dilatation]], [[Dystrophy|dystrophic]] [[Artery|arteries]], [[hemorrhage]] and [[Inflammation|inflammatory]] infiltrate. | * They show greater [[Morphology|morphological]] [[pleomorphism]] as they may show pseudo portal tracts, [[Sinusoid (blood vessel)|sinusoidal]] [[Dilation|dilatation]], [[Dystrophy|dystrophic]] [[Artery|arteries]], [[hemorrhage]], and [[Inflammation|inflammatory]] infiltrate. | ||
* [[Inflammation|Inflammatory]] [[syndrome]], [[obesity]] and [[alcohol]] consumption are reported in these [[Patient|patients]]. | * [[Inflammation|Inflammatory]] [[syndrome]], [[obesity]], and [[alcohol]] consumption are reported in these [[Patient|patients]]. | ||
* Five different [[Molecule|molecular]] drivers, [[Interleukin 6|IL6]] signal transducer, FRK, [[STAT3]], [[GNAS-AS1|GNAS]] and [[Janus kinase|JAK1]] have been reported.<ref>{{Cite journal | * Five different [[Molecule|molecular]] drivers, [[Interleukin 6|IL6]] signal transducer, FRK, [[STAT3]], [[GNAS-AS1|GNAS]], and [[Janus kinase|JAK1]] have been reported.<ref>{{Cite journal | ||
| author = [[Motoko Sasaki]], [[Norihide Yoneda]], [[Yoshiyuki Sawai]], [[Yasuharu Imai]], [[Fukuo Kondo]], [[Toshio Fukusato]], [[Seiichi Yoshikawa]], [[Satoshi Kobayashi]], [[Yasunori Sato]], [[Osamu Matsui]] & [[Yasuni Nakanuma]] | | author = [[Motoko Sasaki]], [[Norihide Yoneda]], [[Yoshiyuki Sawai]], [[Yasuharu Imai]], [[Fukuo Kondo]], [[Toshio Fukusato]], [[Seiichi Yoshikawa]], [[Satoshi Kobayashi]], [[Yasunori Sato]], [[Osamu Matsui]] & [[Yasuni Nakanuma]] | ||
| title = Clinicopathological characteristics of serum amyloid A-positive hepatocellular neoplasms/nodules arising in alcoholic cirrhosis | | title = Clinicopathological characteristics of serum amyloid A-positive hepatocellular neoplasms/nodules arising in alcoholic cirrhosis | ||
| Line 114: | Line 114: | ||
| pmid = 25318388 | | pmid = 25318388 | ||
}}</ref> | }}</ref> | ||
'''[[Beta- | '''[[Beta-catenin]] [[Mutation|Mutated]] Hepatocellular Adenoma (10 - 15%)''' | ||
* These are frequently [[Association (statistics)|associated]] with exposure to male hormones, [[glycogenolysis]] and [[familial adenomatous polyposis]].<ref>{{Cite journal | * These are frequently [[Association (statistics)|associated]] with exposure to male [[hormones]], [[glycogenolysis]], and [[familial adenomatous polyposis]].<ref>{{Cite journal | ||
| author = [[Kimberley J. Evason]], [[James P. Grenert]], [[Linda D. Ferrell]] & [[Sanjay Kakar]] | | author = [[Kimberley J. Evason]], [[James P. Grenert]], [[Linda D. Ferrell]] & [[Sanjay Kakar]] | ||
| title = Atypical hepatocellular adenoma-like neoplasms with beta-catenin activation show cytogenetic alterations similar to well-differentiated hepatocellular carcinomas | | title = Atypical hepatocellular adenoma-like neoplasms with beta-catenin activation show cytogenetic alterations similar to well-differentiated hepatocellular carcinomas | ||
| Line 140: | Line 140: | ||
}}</ref> | }}</ref> | ||
* [[Morphology|Morphologically]], these [[Tumor|tumors]] have [[Cytology|cytological]] and architectural atypical features of [[Tumor|tumoral]] [[Hepatocyte|hepatocytes]] as well as that of [[cholestasis]]. | * [[Morphology|Morphologically]], these [[Tumor|tumors]] have [[Cytology|cytological]] and architectural atypical features of [[Tumor|tumoral]] [[Hepatocyte|hepatocytes]] as well as that of [[cholestasis]]. | ||
* On [[immunohistochemical staining]], these [[Adenoma|adenomas]] tend to stain for [[glutamine synthetase]] rather than [[Beta-catenin|beta catenin]], which [[ | * On [[immunohistochemical staining]], these [[Adenoma|adenomas]] tend to [[Staining|stain]] for [[glutamine synthetase]] rather than [[Beta-catenin|beta catenin]], which [[Staining|stains]] patchily. | ||
'''Unclassified | '''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. | * 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 [[Adenoma|adenomas]] do not [[stain]] for the [[C-reactive protein|C-reactive protein (CRP)]], [[Beta-catenin|beta-catenin]] or [[glutamine synthetase]].<ref>{{Cite journal | * These [[Adenoma|adenomas]] do not [[stain]] for the [[C-reactive protein|C-reactive protein (CRP)]], [[Beta-catenin|beta-catenin]], or [[glutamine synthetase]].<ref>{{Cite journal | ||
| author = [[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]] | | author = [[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]] | ||
| title = Immunohistochemical markers on needle biopsies are helpful for the diagnosis of focal nodular hyperplasia and hepatocellular adenoma subtypes | | title = Immunohistochemical markers on needle biopsies are helpful for the diagnosis of focal nodular hyperplasia and hepatocellular adenoma subtypes | ||
Latest revision as of 20:51, 19 August 2019
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Hepatocellular adenoma Microchapters |
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Hepatocellular adenoma classification On the Web |
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Risk calculators and risk factors for Hepatocellular adenoma classification |
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)