hepatocellular adenoma

{{short description|Hepatocellular adenoma (HA) is a rare benign tumor of the liver}}

{{distinguish|Hepatocellular carcinoma}}

{{Infobox medical condition (new)

| name = Hepatocellular adenoma

| image = Hepatic_adenoma_low_mag.jpg

| caption = Micrograph of a hepatic adenoma (bottom of image). H&E stain

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Hepatocellular adenoma (also known as hepatic adenoma or hepadenoma) is a rare, benign liver tumor. It most commonly occurs in people with elevated systemic levels of estrogen, classically in women taking estrogen-containing oral contraceptive medication.{{cite journal|year=1979|title=Epidemiology of hepatocellular adenoma. The role of oral contraceptive use.|journal=JAMA|volume=242|issue=7|pages=644–8|doi=10.1001/jama.242.7.644|pmid=221698|vauthors=Rooks J, Ory H, Ishak K, Strauss L, Greenspan J, Hill A, Tyler C}}

Signs and symptoms

About 25–50% of hepatic adenomas cause pain in the right upper quadrant or epigastric region of the abdomen.{{cite web|url=http://emedicine.medscape.com/article/170205-overview|title=Hepatocellular Adenoma: eMedicine Gastroenterology|date=14 June 2021 }} Since hepatic adenomas can be large (8–15 cm), patients may notice a palpable mass. However, hepatic adenomas are usually asymptomatic, and may be discovered incidentally on imaging ordered for some unrelated reason. Large hepatic adenomas have a tendency to rupture and bleed massively inside the abdomen. If not treated, there is a 30% risk of bleeding.{{cite book|url=http://www.accessmedicine.com/content.aspx?aID=9116285|title=Harrison's principles of internal medicine|publisher=McGraw-Hill Medical|year=2008|isbn=978-0071466332|edition=17th|location=New York|pages=Chapter 92 (benign liver tumors)|author1=Anthony S. Fauci|author2=Eugene Braunwald|author3=Dennis L. Kasper|author4=Stephen L. Hauser|author5=Dan L. Longo|author6=J. Larry Jameson|author7=Joseph Loscalzo}} Bleeding may lead to hypotension, tachycardia, and sweating (diaphoresis).{{cn|date=March 2022}}

Hepatic adenomas are associated with glycogen storage diseases, type 1 diabetes, as well as anabolic steroid use.

Diagnosis

Hepatic adenoma is usually detected by imaging, typically an ultrasound or CT, as a hyperenhancing liver nodule. Given that several liver tumors appear similarly on these imaging modalities, a multi-phase contrast-enhanced imaging study such as CT or MRI may be used to provide more information.{{cite journal|year=2006|title=Hepatocellular adenoma: findings at state-of-the-art magnetic resonance imaging, ultrasound, computed tomography and pathologic analysis.|journal=Eur Radiol|volume=16|issue=9|pages=1873–86|doi=10.1007/s00330-006-0292-4|pmid=16708218|vauthors=Hussain S, van den Bos I, Dwarkasing R, Kuiper J, den Hollander J|s2cid=27821347 }} The significance of making a specific diagnosis is that, unlike other benign liver tumors such as hemangioma and focal nodular hyperplasia, hepatic adenomas have a small but meaningful risk of progressing into a malignancy. Although imaging provides supportive information, a definitive diagnosis of hepatic adenoma requires biopsy of the tissue.{{cn|date=March 2022}}

= Radiologic differential diagnosis =

=Subtypes=

Hepatic adenomas may be sub-classified according to morphologic appearance by microscopy, immunohistochemical staining, and genetic mutational analysis:{{Cite journal|last1=Bioulac-Sage|first1=Paulette|last2=Sempoux|first2=Christine|last3=Balabaud|first3=Charles|date=June 2017|title=Hepatocellular Adenomas: Morphology and Genomics|journal=Gastroenterology Clinics of North America|volume=46|issue=2|pages=253–272|doi=10.1016/j.gtc.2017.01.003|issn=1558-1942|pmid=28506364}}{{cite journal|last1=Nault|first1=JC|last2=Couchy|first2=G|last3=Balabaud|first3=C|last4=Morcrette|first4=G|last5=Caruso|first5=S|last6=Blanc|first6=JF|last7=Bacq|first7=Y|last8=Calderaro|first8=J|last9=Paradis|first9=V|last10=Ramos|first10=J|last11=Scoazec|first11=JY|last12=Gnemmi|first12=V|last13=Sturm|first13=N|last14=Guettier|first14=C|last15=Fabre|first15=M|last16=Savier|first16=E|last17=Chiche|first17=L|last18=Labrune|first18=P|last19=Selves|first19=J|last20=Wendum|first20=D|last21=Pilati|first21=C|last22=Laurent|first22=A|last23=De Muret|first23=A|last24=Le Bail|first24=B|last25=Rebouissou|first25=S|last26=Imbeaud|first26=S|last27=GENTHEP|first27=Investigators.|last28=Bioulac-Sage|first28=P|last29=Letouzé|first29=E|last30=Zucman-Rossi|first30=J|title=Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation.|journal=Gastroenterology|date=March 2017|volume=152|issue=4|pages=880–894.e6|doi=10.1053/j.gastro.2016.11.042|pmid=27939373|url=https://hal.archives-ouvertes.fr/hal-01797602/file/GASTRO-D-16-02075_R1%20submission.pdf|doi-access=free}}{{Cite journal|last1=Larson|first1=Brent K.|last2=Guindi|first2=Maha|title=A Limited Immunohistochemical Panel Can Subtype Hepatocellular Adenomas for Routine Practice|journal=American Journal of Clinical Pathology|language=en|volume=147|issue=6|pages=557–570|doi=10.1093/ajcp/aqx010|pmid=28472207|year=2017|doi-access=free}}

  • Inflammatory (40%–50%)
  • HNF1α-inactivated (35%–40%)
  • β-catenin–activated - with exon 3 versus exon 7/8 mutation
  • β-Catenin–activated inflammatory - with exon 3 versus exon 7/8 mutation
  • Unclassified

Although the significance of this categorization is still under research, the subtypes may indicate differential risk of hemorrhage or malignant transformation.{{cn|date=March 2022}}

=Pathologic diagnosis=

Image:Hepatic adenoma high mag reticulin.jpg of a hepatic adenoma demonstrating a regular reticulin scaffold. Reticulin stain]]

Hepatic adenomas are, typically, well-circumscribed nodules that consist of sheets of hepatocytes with a bubbly vacuolated cytoplasm. The hepatocytes are on a regular reticulin scaffold and less or equal to three cell thick.

The histologic diagnosis of hepatic adenomas can be aided by reticulin staining. In hepatic adenomas, the reticulin scaffold is preserved and hepatocytes do not form layers of four or more hepatocytes, as is seen in hepatocellular carcinoma.

Cells resemble normal hepatocytes and are traversed by blood vessels but lack portal tracts or central veins.

Image:Hepatic adenoma high mag.jpg|Micrograph of hepatic adenoma. H&E stain

Image:Hepatic adenoma low mag reticulin.jpg|Micrograph of hepatic adenoma. Reticulin stain

File:Histopathology of inflammatory hepatocellular adenoma.jpg|Inflammatory hepatocellular adenoma

Treatment

Some authors feel that all hepatocellular adenoma should be resected, because of the risk of rupture causing bleeding and because they may contain malignant cells.{{cite journal |vauthors=Toso C, Majno P, Andres A, Rubbia-Brandt L, Berney T, Buhler L, Morel P, Mentha G | title = Management of hepatocellular adenoma: solitary-uncomplicated, multiple and ruptured tumors. | journal = World J Gastroenterol | volume = 11 | issue = 36 | pages = 5691–5 | year = 2005 | pmid = 16237767 | pmc = 4481490 | doi=10.3748/wjg.v11.i36.5691 | doi-access = free }} Current recommendations are that all hepatic adenomas should be resected, as long as they are surgically accessible and the patient is a reasonable operative candidate.{{cite journal|last=Cho|first=S|author2=Marsh J |author3=Steel J |title=Surgical management of hepatocellular adenoma: take it or leave it?|journal=Ann Surg Oncol|volume=15|year=2008|issue=10|pages=2795–2803|display-authors=etal|doi=10.1245/s10434-008-0090-0|pmid=18696154|s2cid=207173531}} Patients with adenomas should avoid oral contraceptives or hormonal replacement therapy.{{cn|date=March 2022}}

Pregnancy could cause the adenoma to grow faster, so patients with hepatic adenomas should avoid pregnancy.{{cite web|title=Hepatocellular Adenoma Treatment & Management|url=http://emedicine.medscape.com/article/170205-treatment|work=WebMD|publisher=Medscape|access-date=11 July 2012}}

Epidemiology

File:Liver tumor types in adults by relative incidence.png

The majority of hepatic adenomas arise in women aged 20–40, most of whom use oral contraceptives. Other medications which also alter circulating hormone levels, such as anabolic or androgenic steroids, Barbiturates, clomifene, have also been implicated as risk factors.

Incidence of adenomas may be increased in metabolic diseases, including tyrosinemia and type 1 diabetes mellitus, and glycogen storage diseases (types 1 and 3), as well as in beta-thalassemia and hemochromatosis.

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References

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