Table 1.

Summary of clinical features, demographics, histopathology, immunohistochemistry and molecular genetics of major subtypes of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH)

	Subtype	Frequency	Gender	Genetic mutation	Immunohistochemical marker	Histological phenotype	Clinical association	Complications
Focal nodular hyperplasia	Classic	80 %	F> > M	Angiopoietin 1 and 2. β-Catenin activation without mutation	Glutamine synthetase (perivenous)	Abnormal nodular architecture, malformed vessels and cholangiolar proliferation	Hereditary haemorrhagic telangiectasia, congenital absence of portal vein, haemangiomas	Very low risk of haemorrhage. No risk of malignant transformation
	Non-classic	20 %	F> > M	Angiopoietin 1 and 2. β-Catenin activation without mutation	Glutamine synthetase (perivenous)	Cholangiolar proliferation with either abnormal nodular architecture or malformed vessels	Multiple FNH syndrome associated with haemangiomas, cyst and adenoma	Slightly increased risk of bleeding in telangiectatic subtype. False risk of malignancy in inflammatory hepatic adenomas misclassified as ‘telangiectatic FNH’
Hepatocellular adenoma	Inflammatory HCA	40–55 %	F> > M	IL6ST (60 %), STAT3 (40 %)	Serum amyloid A (SAA) and C-reactive protein (CRP)	Intense polymorp infiltrates, marked sinusoidal dilatation and thick-walled arteries	Obesity. hepatic steatosis, high alcohol intake and inflammatory syndrome	Increased tendency to bleed. 10 % express β-catenin and are at risk of malignant transformation
	HNF1α-mutated HCA	30–35 %	Exclusively F	TCF1	Lack of LFABP1 expression	Intracellular lipid	Adenomatosis and MODY 3 diabetes	Lower tendency to bleed and very low risk of malignancy. Best prognosis.
	β-Catenin-mutated HCA	10–15 %	F > M	CTNNB1	Glutamine synthase (diffusely positive) and β-catenin	High nuclear-cytoplasmic ratio, nuclear atypia and acini formation	Male hormone and glycogen storage disease	Increased risk of malignant transformation
	Unclassified	10 %	–	–	–	–