Hepatocellular adenoma: Where are we now?

Table 1 Morpho-molecular features of the subtypes of hepatocellular adenoma

	Key pathogenesis	Histology	Immunohistochemical stains	Clinical features
H-HCA	HNF1A inactivating mutation: Negative regulation of glycolipid metabolism and L-FABP	Marked steatosis	L-FABP: Negative	Associated with maturity onset diabetes of the young (MODY3) and familial hepatic adenomatosis
I-HCA	IL-6/JAK/STAT3 pathway mutations: (1) Constitutive activation of inflammatory pathway; and (2) Upregulation of acute reactants and hepatocellular proliferation	(1) Inflammatory infiltration; (2) Pseudoportal tracts; (3) Ductular reaction; and (4) Sinusoidal dilatation/ peliosis	SSA and CRP: Diffuse positive	Obesity, metabolic syndrome, glycogen storage disease, high alcohol consumption, inflammatory syndrome
b-HCA	(1) CTNNB1 gene mutation: Activation of signaling pathway and upregulation of targeted genes including GS; and (2) Level of activation depends on mutation loci (Exon 3 Non-S45: Strong activation; S45: Weak activation, and T41: Moderate activation; Exon 7/8: Weak activation)	More atypical features: Pseudoacini and mild cytologic atypia	(1) β-catenin: Aberrant nuclear expression; and (2) GS: Positive	More in men, anabolic steroids use, glycogen storage disease, high risk of malignant transformation, and high risk of bleeding (exon 7/8)
b-IHCA	Share the features of both b-HCA and I-HCA
shHCA	INHBE-GLI1 gene fusion: Constitutive activation of Sonic hedgehog pathway	Hemorrhage	PTGSD and ASS1	High risk of bleeding and obesity
Unclassified	Not other specified
Uncommon subtypes	Myxoid HCA, pigmented HCA, atypical HCA, I-ICA in cirrhotic liver

HNF1A: Hepatocyte nuclear factor 1A; L-FABP: Liver fatty acid binding protein; SSA: Serum amyloid A; CRP: C-reactive protein; CTNNB1: Catenin beta 1; GS: Glutamine synthetase; INHBE-GLI1: Inhibin beta E chain/glioma-associated oncogene 1; PTGDS: Prostaglandin D synthase; ASS1: Argininosuccinate Synthase 1; HCA: Hepatocellular adenoma; I-HCA: Inflammatory HCA; H-HCA: HNF1A-inactivated HCA; shHCA: Sonic hedgehog HCA; b-HCA: β-catenin mutated HCA.