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 [[hepatocellular adenoma]] have been linked to [[Mutation|mutations]] in [[HNF1A|HNF1a]] and [[Beta-catenin|beta catenin]] [[Gene|genes]]. On [[gross pathology]] it appears as a [[solitary]] or multiple, unencapsulated and well demarcated [[mass]] [[lesion]], which can occasionally be [[pedunculated]] or encapsulated that can also form multiple [[Mass|masses]]. The [[Tumoral|intratumoral]] [[hemorrhage]] can give rise to soft, [[Necrosis|necrotic]], red brown lesion on 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 this 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]].
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==
* The exact [[pathogenesis]] of [[hepatocellular adenoma]] is still unknown, however, its [[Association (statistics)|association]] with [[Oral contraceptive|oral contraceptive use]] is well established.<ref>{{Cite journal
* The exact [[pathogenesis]] of hepatocellular adenoma is still unknown, however, its [[Association (statistics)|association]] with [[Oral contraceptive|oral contraceptive use]] is well established.<ref>{{Cite journal
  | author = [[J. K. Baum]], [[J. J. Bookstein]], [[F. Holtz]] & [[E. W. Klein]]
  | author = [[J. K. Baum]], [[J. J. Bookstein]], [[F. Holtz]] & [[E. W. Klein]]
  | title = Possible association between benign hepatomas and oral contraceptives
  | title = Possible association between benign hepatomas and oral contraceptives
Line 25: Line 25:
  | pmid = 4126557
  | pmid = 4126557
}}</ref>
}}</ref>
* In 1973, Baum et al first described the [[Causality|causal]] [[Association (statistics)|association]] of [[hepatocellular adenoma]] with [[Oral contraceptive|oral contraceptive use]].
* In 1973, Baum et al first described the [[Causality|causal]] [[Association (statistics)|association]] of hepatocellular adenoma with [[Oral contraceptive|oral contraceptive use]].
* In 1979, Rooks et al reported the relationship with [[Oral contraceptive|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.<ref>{{Cite journal
* In 1979, Rooks et al reported the relationship with [[Oral contraceptive|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.<ref>{{Cite journal
  | author = [[L. Rosenberg]]
  | author = [[L. Rosenberg]]
Line 37: Line 37:
  | pmid = 1651205
  | pmid = 1651205
}}</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; [[familial adenomatous polyposis]], [[maturity onset diabetes of the young]], [[obesity]], [[metabolic syndrome]] and [[vascular disorders]] like [[portal vein]] [[agenesis]], [[Budd-Chiari syndrome|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>
* 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==
* The [[Hepatocellular adenoma|hepatocellular adenomas]] have 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>
* 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]], the [[hepatocellular adenoma]] is a [[solitary]] or multiple, un encapsulated and well demarcated [[mass]] [[lesion]], which can occasionally be [[pedunculated]] or encapsulated, which can also form multiple [[Mass|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>
* 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]]. [[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
 
==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
Line 60: Line 63:
  | 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
==Microscopic Pathology==
| 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]]
* 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>
| 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; 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>
| 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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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

Genetics

Gross Pathology

Microscopic Pathology

  • Low magnification micrograph of a hepatic adenoma. H&E stain.[12]

    Low magnification micrograph of a hepatic adenoma. H&E stain.[12]

  • High magnification micrograph of a hepatic adenoma. H&E stain.[13]

    High magnification micrograph of a hepatic adenoma. H&E stain.[13]

References

  1. ↑ 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)
  2. ↑ 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)
  3. ↑ 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.
  4. ↑ 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. ↑ 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. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ Hepatic adenoma. Librepathology (2015). http://librepathology.org/wiki/index.php/File:Hepatic_adenoma_low_mag.jpg Accessed on November 3, 2015
  13. ↑ Hepatic adenoma. Librepathology (2015). http://librepathology.org/wiki/index.php/File:Hepatic_adenoma_high_mag.jpg Accessed on November 7, 2015

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