Hepatocellular adenoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zahir Ali Shaikh, MD[2]

Overview

The exact pathogenesis of hepatocellular adenoma is still unknown, however, its association with oral contraceptive use is well established. It has also been associated with long term use of anabolic androgenic steroids and glycogen storage diseases. It has been linked to mutations in HNF1A and beta-catenin genes. On gross pathology, it appears as a solitary or multiple, unencapsulated and well demarcated mass, which can occasionally be pedunculated or encapsulated and also form multiple masses. The intratumoral hemorrhage can give rise to soft, necrotic, and red brown lesion on gross appearance. The microscopic features of hepatocellular adenoma include benign hepatocytes arranged in mildly thickened cell plates, with a preserved reticulin network and thin walled arteries. The arteries and arterioles are not accompanied by other portal tract elements such as bile ducts, portal veins, or fibroconnective tissue.

Pathophysiology

• The exact pathogenesis of hepatocellular adenoma is still unknown, however, its association with oral contraceptive use is well established.
• In 1973, Baum et al first described the causal association of hepatocellular adenoma with oral contraceptive use.
• In 1979, Rooks et al reported the relationship with oral contraceptive use to be dose and duration dependent and is highest in women over 30 years of age after using oral contraceptive for more than 24 months.
• Hepatocellular adenoma has also been associated with long term use of anabolic androgenic steroids and glycogen storage diseases.
• Other rare causal associations include familial adenomatous polyposis, maturity onset diabetes of the young, obesity, metabolic syndrome, and vascular disorders like portal vein agenesis, Budd chiari syndrome, and hereditary hemorrhagic telangiectasia.

Genetics

• Hepatocellular adenoma has been linked to mutations in the hepatocyte nuclear factor 1 alpha (HNF1a) gene and beta catenin gene.

Gross Pathology

• On gross pathological appearance, hepatocellular adenoma is a solitary or multiple, unencapsulated and well demarcated mass lesion, which can occasionally be pedunculated or encapsulated, which can also form multiple masses.
• The mass has a soft and fleshy consistency and size ranges from 1 to 30 cm.
• The cut surface may be solid tan or yellow depending upon the presence or absence of steatosis.
• The intratumoral hemorrhage can give rise to a soft, necrotic, red brown lesion.

Microscopic Pathology

• The microscopic features of hepatocellular adenoma include benign hepatocytes arranged in mildly thickened cell plates, with a preserved reticulin network and thin walled arteries.
• Tumor hepatocytes have cytoplasm that may be normal, clear (glycogen rich), steatotic, or contain pigment in the lysosomes.
• Nuclear atypia and mitosis are unusual but may be seen in specific variants.
• The arteries and arterioles are not accompanied by other portal tract elements such as bile ducts, portal veins or fibroconnective tissue.
• Other variable features include; the presence of steatosis, inflammatory cell infiltrates, dystrophic blood vessels, ductular reaction, sinusoidal dilatation, hemorrhage and peliosis.

• 

  _{Low magnification micrograph of a hepatic adenoma. H&E stain.}

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  _{High magnification micrograph of a hepatic adenoma. H&E stain.}

References