Table 1 Summary of clinical features, demographics, histopathology, immunohistochemistry and molecular genetics of major subtypes of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH)

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 %

–

–

–

–