Hepatocellular adenoma in the paediatric population: Molecular classification and clinical associations

Table 1 Clinicopathologic characteristics of different hepatocellular adenoma subtypes

HCA subtype	Risk factors	Specific clinical features	Histologic features	IHCs
HHCA	HNF1A germline mutations, MODY type 3, microsatellite instability	Hepatic adenomatosis	Intralesional steatosis	LFABP (absent/decreased)
IHCA	Obesity, alcohol, glycogenosis	Inflammatory syndrome	Sinusoidal dilatation, inflammatory infiltrate	CRP, SAA
bex3HCA	Male, liver vascular disease, androgen therapy	Frequent malignant transformation	Pseudoacinar formation, mild nuclear atypia	beta-catenin (nuclear staining), GS (diffuse and strong)
bex7,8HCA	No specific risk factors	No specific clinical features	No specific features	GS (weak, heterogeneous)
shHCA	Obesity	Symptomatic bleeding	Intratumoural hemorrhage	Prostaglandin D2 synthase
UHCA	No specific risk factors	No specific clinical features	No specific features	None

HCA: Hepatocellular adenoma; IHCs: Immunohistochemical stains; HNF1A: hepatocyte nuclear factor 1 homeobox alpha; HHCA: HNF1A-inactivated hepatocellular adenoma; IHCA: Inflammatory hepatocellular adenoma; b^ex3HCA: Beta-catenin-mutated hepatocellular adenoma (exon 3); b^ex7,8HCA: Beta-catenin-mutated hepatocellular adenoma (exon 7/8); shHCA: Sonic hedgehog-activated hepatocellular adenoma; UHCA: Unclassified hepatocellular adenoma; MODY: Maturity-onset diabetes of the young; LFABP: Liver fatty acid binding protein; CRP: C-reactive protein; SAA: Serum amyloid A; GS: Glutamine synthetase.

Table 2 Various clinical associations of pediatric hepatocellular adenomas

Sex hormone dysregulation

Oral contraceptive use

Obesity

Klinefelter’s syndrome

Polycystic ovary syndrome

Sex hormone producing tumours (e.g., ertoli-Leydig cell tumours)

Androgen therapy (Turner’s syndrome, Fanconi anemia, Glanzmann's thrombasthenia)

Antiepileptic therapies with sodium ion channel modulation

Metabolic disorders

Glycogen storage diseases type I, III, and IV

Galactosemia

Hurler syndrome (mucopolysaccharidosis type 1)

Fanconi Anemia (with or without androgen therapy)

Diabetes mellitus type II

Immunodeficiency

Congenital portosystemic shunts

Cardiac hepatopathy (status-post Fontan procedure)

Other syndromes

Alagille syndrome

Familial adenomatous polyposis syndrome

Maturity-onset diabetes of the young type 3

McCune-Albright syndrome

Noonan syndrome with multiple lentigines

Prader Willi syndrome

Wolf-Hirschhorn syndrome