Hepatocellular adenoma (ORPHA:54272)
Hepatocellular adenoma (HA) is a rare benign tumor of the liver.
Epidemiology
Annual incidence is estimated at one case per million.
Clinical description
Mean age at diagnosis is 34 years (ranging from 15 to 64 years). HA rarely occurs in children. Most patients with HA are asymptomatic and lesions are found incidentally during laparotomy or radiologic studies performed for other reasons. Pain or discomfort in the right upper quadrant or epigastric region is common, but not always related to the adenoma. HA may be revealed by spontaneous rupture or hemorrhage (leading to acute abdominal pain and possibly progressing to hemorrhagic shock, hypotension and even death). These complications are estimated to occur in 30% of patients with an adenoma over 5 cm in diameter. HA patients have normal liver function and no elevation of serum tumor markers. Serum aminotransferases and gamma-glutamyl transpeptidase may be mildly elevated. HA is typically solitary, although multiple lesions have been reported under the denomination `hepatocellular adenomatosis'. Size varies from about 1 cm (the detection limit for usual imaging methods) to over 20 cm. There appears to be a zero risk of complications for patients with a HA below 5 cm in diameter. In rare cases, and more frequently in males, the largest tumors may harbor malignant features. Histologically, adenoma cells are larger than normal hepatocytes but do not show cytonuclear atypia. Few or no portal tracts, central veins or bile ducts are present but there are isolated arteries. Kupffer cells are less numerous or absent.
Etiology
In most cases, adenomas develop for unclear reasons in an otherwise healthy liver. Some predisposing conditions have been identified: prolonged oral contraceptive use, glycogenosis type III and IV, congenital portocaval shunt and, in males, use of anabolic steroids. Molecular analysis has disclosed specific mutations in adenomatous cells, each associated with specific histological features: HNF1 mutations are associated with fatty hepatocytes, and mutations in beta-catenin are associated with dysplasia and malignant transformation. An additional type of hepatic adenoma has recently been characterized as telangiectatic adenoma. This type of adenoma features sinusoidal dilatation and inflammatory infiltrates.
Diagnostic methods
Diagnosis is made by a characteristic pattern of enhancement after injection of intravascular contrast medium, using contrast enhanced ultrasound, multiphasic computed tomography, or gadolinium-enhanced MRI. Biopsy and/or resection may be necessary to confirm the diagnosis.
Differential diagnosis
Differential diagnosis includes some forms of angiomas, focal nodular hyperplasia, hepatocellular carcinoma (see these terms), and certain types of liver metastases.
Management and treatment
Oral contraceptives are contraindicated and should be stopped. Surgical resection is advocated in most patients with a HA greater than 5 cm in diameter. When diagnosis is certain, and the tumor is less than 5 cm in diameter and asymptomatic, it can be left in place but surveillance is required.
Prognosis
Malignant transformation is rare and the long-term prognosis is good.

                            Last update: 
                            April 2008


                            - Expert reviewer(s): 
                            Pr Dominique VALLA