Hepatocellular adenoma pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
The exact [[pathogenesis]] of hepatocellular adenoma is still unknown, however, its [[Association (statistics)|association]] with [[Oral contraceptive|oral contraceptive use]] is well established. It has also been [[Association (statistics)|associated]] with long term use of [[anabolic]] [[Androgen|androgenic]] [[Steroid|steroids]] and [[Glycogen storage disease|glycogen storage diseases]]. | The exact [[pathogenesis]] of hepatocellular adenoma is still unknown, however, its [[Association (statistics)|association]] with [[Oral contraceptive|oral contraceptive use]] is well established. It has also been [[Association (statistics)|associated]] with long term use of [[anabolic]] [[Androgen|androgenic]] [[Steroid|steroids]] and [[Glycogen storage disease|glycogen storage diseases]]. It has been linked to [[Mutation|mutations]] in [[HNF1A]] and [[beta-catenin]] [[Gene|genes]]. On [[gross pathology]], it appears as a [[solitary]] or multiple, unencapsulated and well demarcated mass, which can occasionally be [[pedunculated]] or encapsulated and also form multiple masses. The [[Tumoral|intratumoral]] [[hemorrhage]] can give rise to soft, [[Necrosis|necrotic]], and red brown [[lesion]] on [[Gross examination|gross]] appearance. The [[microscopic]] features of hepatocellular adenoma include [[benign]] [[Hepatocyte|hepatocytes]] arranged in mildly thickened [[Cell plate|cell plates]], with a preserved [[reticulin]] network and thin walled [[Artery|arteries]]. The [[Artery|arteries]] and [[Arteriole|arterioles]] are not accompanied by other [[portal]] tract elements such as [[Bile duct|bile ducts]], [[Portal vein|portal veins]], or fibroconnective [[Tissue (biology)|tissue]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
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}}</ref> | }}</ref> | ||
* Hepatocellular adenoma has also been [[Association (statistics)|associated]] with long term use of [[anabolic]] [[Androgen|androgenic]] [[Steroid|steroids]] and [[Glycogen storage disease|glycogen storage diseases]]. | * Hepatocellular adenoma has also been [[Association (statistics)|associated]] with long term use of [[anabolic]] [[Androgen|androgenic]] [[Steroid|steroids]] and [[Glycogen storage disease|glycogen storage diseases]]. | ||
* Other rare [[Causality|causal]] [[Association (statistics)|associations]] include | * Other rare [[Causality|causal]] [[Association (statistics)|associations]] include [[familial adenomatous polyposis]], [[maturity onset diabetes of the young]], [[obesity]], [[metabolic syndrome]], and [[vascular disorders]] like [[portal vein]] [[agenesis]], [[Budd chiari syndrome]], and [[hereditary hemorrhagic telangiectasia]].<ref name="KhanBegum2018">{{cite journal|last1=Khan|first1=MuhammadRizwan|last2=Begum|first2=Saleema|title=Hepatocellular adenoma: Review of contemporary diagnostic and therapeutic options|journal=IJS Short Reports|volume=3|issue=1|year=2018|pages=1|issn=2468-7332|doi=10.4103/ijssr.ijssr_4_18}}</ref><ref name="VédieSutter2018">{{cite journal|last1=Védie|first1=Anne-Laure|last2=Sutter|first2=Olivier|last3=Ziol|first3=Marianne|last4=Nault|first4=Jean-Charles|title=Molecular classification of hepatocellular adenomas: impact on clinical practice|journal=Hepatic Oncology|volume=5|issue=1|year=2018|pages=HEP04|issn=2045-0923|doi=10.2217/hep-2017-0023}}</ref> | ||
==Genetics== | ==Genetics== | ||
* | * Hepatocellular adenoma has been linked to [[Mutation|mutations]] in the [[HNF1A|hepatocyte nuclear factor 1 alpha (HNF1a)]] [[gene]] and [[Beta-catenin|beta catenin]] [[gene]].<ref name="NaultParadis2017">{{cite journal|last1=Nault|first1=Jean-Charles|last2=Paradis|first2=Valérie|last3=Cherqui|first3=Daniel|last4=Vilgrain|first4=Valérie|last5=Zucman-Rossi|first5=Jessica|title=Molecular classification of hepatocellular adenoma in clinical practice|journal=Journal of Hepatology|volume=67|issue=5|year=2017|pages=1074–1083|issn=01688278|doi=10.1016/j.jhep.2017.07.009}}</ref> | ||
==Gross Pathology== | ==Gross Pathology== | ||
* On [[Gross pathology|gross pathological appearance]], | * On [[Gross pathology|gross pathological appearance]], hepatocellular adenoma is a [[solitary]] or multiple, unencapsulated and well demarcated mass [[lesion]], which can occasionally be [[pedunculated]] or encapsulated, which can also form multiple masses.<ref name="pmid18333188">{{cite journal| author=Barthelmes L, Tait IS| title=Liver cell adenoma and liver cell adenomatosis. | journal=HPB (Oxford) | year= 2005 | volume= 7 | issue= 3 | pages= 186-96 | pmid=18333188 | doi=10.1080/13651820510028954 | pmc=PMC2023950 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18333188 }} </ref><ref name="pmid11452062">{{cite journal| author=Grazioli L, Federle MP, Brancatelli G, Ichikawa T, Olivetti L, Blachar A| title=Hepatic adenomas: imaging and pathologic findings. | journal=Radiographics | year= 2001 | volume= 21 | issue= 4 | pages= 877-92; discussion 892-4 | pmid=11452062 | doi=10.1148/radiographics.21.4.g01jl04877 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11452062 }} </ref> | ||
* The mass has a soft and fleshy consistency and size ranges from 1 to 30 cm. | * The mass has a soft and [[Flesh|fleshy]] consistency and size ranges from 1 to 30 cm. | ||
* The cut surface may be solid tan or yellow depending upon the presence or absence of [[steatosis]]. | * The cut surface may be solid tan or yellow depending upon the presence or absence of [[steatosis]]. | ||
* The [[Tumoral|intratumoral]] [[hemorrhage]] can give rise to a soft, [[Necrosis|necrotic]], red brown lesion. | * The [[Tumoral|intratumoral]] [[hemorrhage]] can give rise to a soft, [[Necrosis|necrotic]], red brown [[lesion]]. | ||
* [[Tumor]] [[Hepatocyte|hepatocytes]] have [[cytoplasm]] that may be normal, clear ([[Glycogen|glycogen rich]]), [[Steatosis|steatotic]] or contain [[pigment]] in the [[Lysosome|lysosomes]] | |||
==Microscopic Pathology== | |||
* The [[microscopic]] features of hepatocellular adenoma include [[benign]] [[Hepatocyte|hepatocytes]] arranged in mildly thickened [[Cell plate|cell plates]], with a preserved [[reticulin]] network and thin walled [[Artery|arteries]].<ref name="pmid18333188">{{cite journal| author=Barthelmes L, Tait IS| title=Liver cell adenoma and liver cell adenomatosis. | journal=HPB (Oxford) | year= 2005 | volume= 7 | issue= 3 | pages= 186-96 | pmid=18333188 | doi=10.1080/13651820510028954 | pmc=PMC2023950 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18333188 }} </ref> | |||
* [[Tumor]] [[Hepatocyte|hepatocytes]] have [[cytoplasm]] that may be normal, clear ([[Glycogen|glycogen rich]]), [[Steatosis|steatotic]], or contain [[pigment]] in the [[Lysosome|lysosomes]].<ref name="NaultParadis2017">{{cite journal|last1=Nault|first1=Jean-Charles|last2=Paradis|first2=Valérie|last3=Cherqui|first3=Daniel|last4=Vilgrain|first4=Valérie|last5=Zucman-Rossi|first5=Jessica|title=Molecular classification of hepatocellular adenoma in clinical practice|journal=Journal of Hepatology|volume=67|issue=5|year=2017|pages=1074–1083|issn=01688278|doi=10.1016/j.jhep.2017.07.009}}</ref><ref>{{Cite journal | |||
| author = [[L. M. Franco]], [[V. Krishnamurthy]], [[D. Bali]], [[D. A. Weinstein]], [[P. Arn]], [[B. Clary]], [[A. Boney]], [[J. Sullivan]], [[D. P. Frush]], [[Y.-T. Chen]] & [[P. S. Kishnani]] | | author = [[L. M. Franco]], [[V. Krishnamurthy]], [[D. Bali]], [[D. A. Weinstein]], [[P. Arn]], [[B. Clary]], [[A. Boney]], [[J. Sullivan]], [[D. P. Frush]], [[Y.-T. Chen]] & [[P. S. Kishnani]] | ||
| title = Hepatocellular carcinoma in glycogen storage disease type Ia: a case series | | title = Hepatocellular carcinoma in glycogen storage disease type Ia: a case series | ||
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| pmid = 15877204 | | pmid = 15877204 | ||
}}</ref> | }}</ref> | ||
*[[Cell nucleus|Nuclear]] [[atypia]] and [[mitosis]] are unusual but may be seen in specific variants.<ref name="NaultParadis2017">{{cite journal|last1=Nault|first1=Jean-Charles|last2=Paradis|first2=Valérie|last3=Cherqui|first3=Daniel|last4=Vilgrain|first4=Valérie|last5=Zucman-Rossi|first5=Jessica|title=Molecular classification of hepatocellular adenoma in clinical practice|journal=Journal of Hepatology|volume=67|issue=5|year=2017|pages=1074–1083|issn=01688278|doi=10.1016/j.jhep.2017.07.009}}</ref><ref>{{Cite journal | |||
| author = [[L. M. Franco]], [[V. Krishnamurthy]], [[D. Bali]], [[D. A. Weinstein]], [[P. Arn]], [[B. Clary]], [[A. Boney]], [[J. Sullivan]], [[D. P. Frush]], [[Y.-T. Chen]] & [[P. S. Kishnani]] | |||
* | | title = Hepatocellular carcinoma in glycogen storage disease type Ia: a case series | ||
* The arteries and arterioles are not accompanied by other portal tract elements such as [[Bile duct|bile ducts]], [[Portal vein|portal veins]] or fibroconnective [[Tissue (biology)|tissue]]. | | journal = [[Journal of inherited metabolic disease]] | ||
* Other variable features include | | volume = 28 | ||
| issue = 2 | |||
| pages = 153–162 | |||
| year = 2005 | |||
| month = | |||
| doi = 10.1007/s10545-005-7500-2 | |||
| pmid = 15877204 | |||
}}</ref> | |||
* The [[artery|arteries]] and [[artriole|arterioles]] are not accompanied by other portal tract elements, such as [[Bile duct|bile ducts]], [[Portal vein|portal veins]] or fibroconnective [[Tissue (biology)|tissue]]. | |||
* Other variable features include the presence of [[steatosis]], [[inflammation|inflammatory]] [[cell]] infiltrates, [[Dystrophy|dystrophic]] [[Blood vessel|blood vessels]], ductular reaction, [[Sinusoid (blood vessel)|sinusoidal]] [[Dilation|dilatation]], [[hemorrhage]], and peliosis.<ref name="DhingraFiel2014">{{cite journal|last1=Dhingra|first1=Sadhna|last2=Fiel|first2=M. Isabel|title=Update on the New Classification of Hepatic Adenomas: Clinical, Molecular, and Pathologic Characteristics|journal=Archives of Pathology & Laboratory Medicine|volume=138|issue=8|year=2014|pages=1090–1097|issn=0003-9985|doi=10.5858/arpa.2013-0183-RA}}</ref><ref name="NaultCouchy2017">{{cite journal|last1=Nault|first1=Jean-Charles|last2=Couchy|first2=Gabrielle|last3=Balabaud|first3=Charles|last4=Morcrette|first4=Guillaume|last5=Caruso|first5=Stefano|last6=Blanc|first6=Jean-Frederic|last7=Bacq|first7=Yannick|last8=Calderaro|first8=Julien|last9=Paradis|first9=Valérie|last10=Ramos|first10=Jeanne|last11=Scoazec|first11=Jean-Yves|last12=Gnemmi|first12=Viviane|last13=Sturm|first13=Nathalie|last14=Guettier|first14=Catherine|last15=Fabre|first15=Monique|last16=Savier|first16=Eric|last17=Chiche|first17=Laurence|last18=Labrune|first18=Philippe|last19=Selves|first19=Janick|last20=Wendum|first20=Dominique|last21=Pilati|first21=Camilla|last22=Laurent|first22=Alexis|last23=De Muret|first23=Anne|last24=Le Bail|first24=Brigitte|last25=Rebouissou|first25=Sandra|last26=Imbeaud|first26=Sandrine|last27=Bioulac-Sage|first27=Paulette|last28=Letouzé|first28=Eric|last29=Zucman-Rossi|first29=Jessica|last30=Laurent|first30=Christophe|last31=Saric|first31=Jean|last32=Frulio|first32=Nora|last33=Castain|first33=Claire|last34=Dujardin|first34=Fanny|last35=Benchellal|first35=Zin|last36=Bourlier|first36=Pascal|last37=Azoulay|first37=Daniel|last38=Luciani|first38=Alain|last39=Pageaux|first39=Georges-Philippe|last40=Fabre|first40=Jean-Michel|last41=Vilgrain|first41=Valerie|last42=Belghiti|first42=Jacques|last43=Bancel|first43=Brigitte|last44=Boleslawski|first44=Emmanuel|last45=Letoublon|first45=Christophe|last46=Vaillant|first46=Jean Christophe|last47=Prévôt|first47=Sophie|last48=Castaing|first48=Denis|last49=Jacquemin|first49=Emmanuel|last50=Peron|first50=Jean Marie|last51=Quaglia|first51=Alberto|last52=Paye|first52=François|last53=Terraciano|first53=Luigi|last54=Mazzaferro|first54=Vincenzo|last55=Saint Paul|first55=Marie Christine|last56=Terris|first56=Benoit|title=Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation|journal=Gastroenterology|volume=152|issue=4|year=2017|pages=880–894.e6|issn=00165085|doi=10.1053/j.gastro.2016.11.042}}</ref> | |||
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Latest revision as of 22:12, 19 August 2019
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Hepatocellular adenoma Microchapters |
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Hepatocellular adenoma pathophysiology On the Web |
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Risk calculators and risk factors for Hepatocellular adenoma pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zahir Ali Shaikh, MD[2]
Overview
The exact pathogenesis of hepatocellular adenoma is still unknown, however, its association with oral contraceptive use is well established. It has also been associated with long term use of anabolic androgenic steroids and glycogen storage diseases. It has been linked to mutations in HNF1A and beta-catenin genes. On gross pathology, it appears as a solitary or multiple, unencapsulated and well demarcated mass, which can occasionally be pedunculated or encapsulated and also form multiple masses. The intratumoral hemorrhage can give rise to soft, necrotic, and red brown lesion on gross appearance. The microscopic features of hepatocellular adenoma include benign hepatocytes arranged in mildly thickened cell plates, with a preserved reticulin network and thin walled arteries. The arteries and arterioles are not accompanied by other portal tract elements such as bile ducts, portal veins, or fibroconnective tissue.
Pathophysiology
- The exact pathogenesis of hepatocellular adenoma is still unknown, however, its association with oral contraceptive use is well established.[1]
- In 1973, Baum et al first described the causal association of hepatocellular adenoma with oral contraceptive use.
- In 1979, Rooks et al reported the relationship with oral contraceptive use to be dose and duration dependent and is highest in women over 30 years of age after using oral contraceptive for more than 24 months.[2]
- Hepatocellular adenoma has also been associated with long term use of anabolic androgenic steroids and glycogen storage diseases.
- Other rare causal associations include familial adenomatous polyposis, maturity onset diabetes of the young, obesity, metabolic syndrome, and vascular disorders like portal vein agenesis, Budd chiari syndrome, and hereditary hemorrhagic telangiectasia.[3][4]
Genetics
- Hepatocellular adenoma has been linked to mutations in the hepatocyte nuclear factor 1 alpha (HNF1a) gene and beta catenin gene.[5]
Gross Pathology
- On gross pathological appearance, hepatocellular adenoma is a solitary or multiple, unencapsulated and well demarcated mass lesion, which can occasionally be pedunculated or encapsulated, which can also form multiple masses.[6][7]
- The mass has a soft and fleshy consistency and size ranges from 1 to 30 cm.
- The cut surface may be solid tan or yellow depending upon the presence or absence of steatosis.
- The intratumoral hemorrhage can give rise to a soft, necrotic, red brown lesion.
Microscopic Pathology
- The microscopic features of hepatocellular adenoma include benign hepatocytes arranged in mildly thickened cell plates, with a preserved reticulin network and thin walled arteries.[6]
- Tumor hepatocytes have cytoplasm that may be normal, clear (glycogen rich), steatotic, or contain pigment in the lysosomes.[5][8]
- Nuclear atypia and mitosis are unusual but may be seen in specific variants.[5][9]
- The arteries and arterioles are not accompanied by other portal tract elements, such as bile ducts, portal veins or fibroconnective tissue.
- Other variable features include the presence of steatosis, inflammatory cell infiltrates, dystrophic blood vessels, ductular reaction, sinusoidal dilatation, hemorrhage, and peliosis.[10][11]
-
![Low magnification micrograph of a hepatic adenoma. H&E stain.[12]](/images/9/90/Hepatic_adenoma_low_magnification.jpg)
Low magnification micrograph of a hepatic adenoma. H&E stain.[12]
-
![High magnification micrograph of a hepatic adenoma. H&E stain.[13]](/images/4/42/Hepatocellular_adenoma_high_magnification.jpg)
High magnification micrograph of a hepatic adenoma. H&E stain.[13]
![Low magnification micrograph of a hepatic adenoma. H&E stain.[12]](/index.php/File:Hepatic_adenoma_low_magnification.jpg)
![High magnification micrograph of a hepatic adenoma. H&E stain.[13]](/index.php/File:Hepatocellular_adenoma_high_magnification.jpg)
References
- ↑ J. K. Baum, J. J. Bookstein, F. Holtz & E. W. Klein (1973). "Possible association between benign hepatomas and oral contraceptives". Lancet (London, England). 2 (7835): 926–929. PMID 4126557. Unknown parameter
|month=ignored (help) - ↑ L. Rosenberg (1991). "The risk of liver neoplasia in relation to combined oral contraceptive use". Contraception. 43 (6): 643–652. PMID 1651205. Unknown parameter
|month=ignored (help) - ↑ Khan, MuhammadRizwan; Begum, Saleema (2018). "Hepatocellular adenoma: Review of contemporary diagnostic and therapeutic options". IJS Short Reports. 3 (1): 1. doi:10.4103/ijssr.ijssr_4_18. ISSN 2468-7332.
- ↑ Védie, Anne-Laure; Sutter, Olivier; Ziol, Marianne; Nault, Jean-Charles (2018). "Molecular classification of hepatocellular adenomas: impact on clinical practice". Hepatic Oncology. 5 (1): HEP04. doi:10.2217/hep-2017-0023. ISSN 2045-0923.
- ↑ 5.0 5.1 5.2 Nault, Jean-Charles; Paradis, Valérie; Cherqui, Daniel; Vilgrain, Valérie; Zucman-Rossi, Jessica (2017). "Molecular classification of hepatocellular adenoma in clinical practice". Journal of Hepatology. 67 (5): 1074–1083. doi:10.1016/j.jhep.2017.07.009. ISSN 0168-8278.
- ↑ 6.0 6.1 Barthelmes L, Tait IS (2005). "Liver cell adenoma and liver cell adenomatosis". HPB (Oxford). 7 (3): 186–96. doi:10.1080/13651820510028954. PMC 2023950. PMID 18333188.
- ↑ Grazioli L, Federle MP, Brancatelli G, Ichikawa T, Olivetti L, Blachar A (2001). "Hepatic adenomas: imaging and pathologic findings". Radiographics. 21 (4): 877–92, discussion 892-4. doi:10.1148/radiographics.21.4.g01jl04877. PMID 11452062.
- ↑ L. M. Franco, V. Krishnamurthy, D. Bali, D. A. Weinstein, P. Arn, B. Clary, A. Boney, J. Sullivan, D. P. Frush, Y.-T. Chen & P. S. Kishnani (2005). "Hepatocellular carcinoma in glycogen storage disease type Ia: a case series". Journal of inherited metabolic disease. 28 (2): 153–162. doi:10.1007/s10545-005-7500-2. PMID 15877204.
- ↑ L. M. Franco, V. Krishnamurthy, D. Bali, D. A. Weinstein, P. Arn, B. Clary, A. Boney, J. Sullivan, D. P. Frush, Y.-T. Chen & P. S. Kishnani (2005). "Hepatocellular carcinoma in glycogen storage disease type Ia: a case series". Journal of inherited metabolic disease. 28 (2): 153–162. doi:10.1007/s10545-005-7500-2. PMID 15877204.
- ↑ Dhingra, Sadhna; Fiel, M. Isabel (2014). "Update on the New Classification of Hepatic Adenomas: Clinical, Molecular, and Pathologic Characteristics". Archives of Pathology & Laboratory Medicine. 138 (8): 1090–1097. doi:10.5858/arpa.2013-0183-RA. ISSN 0003-9985.
- ↑ Nault, Jean-Charles; Couchy, Gabrielle; Balabaud, Charles; Morcrette, Guillaume; Caruso, Stefano; Blanc, Jean-Frederic; Bacq, Yannick; Calderaro, Julien; Paradis, Valérie; Ramos, Jeanne; Scoazec, Jean-Yves; Gnemmi, Viviane; Sturm, Nathalie; Guettier, Catherine; Fabre, Monique; Savier, Eric; Chiche, Laurence; Labrune, Philippe; Selves, Janick; Wendum, Dominique; Pilati, Camilla; Laurent, Alexis; De Muret, Anne; Le Bail, Brigitte; Rebouissou, Sandra; Imbeaud, Sandrine; Bioulac-Sage, Paulette; Letouzé, Eric; Zucman-Rossi, Jessica; Laurent, Christophe; Saric, Jean; Frulio, Nora; Castain, Claire; Dujardin, Fanny; Benchellal, Zin; Bourlier, Pascal; Azoulay, Daniel; Luciani, Alain; Pageaux, Georges-Philippe; Fabre, Jean-Michel; Vilgrain, Valerie; Belghiti, Jacques; Bancel, Brigitte; Boleslawski, Emmanuel; Letoublon, Christophe; Vaillant, Jean Christophe; Prévôt, Sophie; Castaing, Denis; Jacquemin, Emmanuel; Peron, Jean Marie; Quaglia, Alberto; Paye, François; Terraciano, Luigi; Mazzaferro, Vincenzo; Saint Paul, Marie Christine; Terris, Benoit (2017). "Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation". Gastroenterology. 152 (4): 880–894.e6. doi:10.1053/j.gastro.2016.11.042. ISSN 0016-5085.
- ↑ Hepatic adenoma. Librepathology (2015). http://librepathology.org/wiki/index.php/File:Hepatic_adenoma_low_mag.jpg Accessed on November 3, 2015
- ↑ Hepatic adenoma. Librepathology (2015). http://librepathology.org/wiki/index.php/File:Hepatic_adenoma_high_mag.jpg Accessed on November 7, 2015
