Liver cell adenoma D13.4

Rare, monoclonal, 1-10 cm large, mostly solitary, yellow-brown, benign nodule of the liver, delimited by a pseudocapsule.

The adenoma cells carry specific somatic mutations that correlate with the histological characteristics (Thomeer MG et al. 2014):

• HNF1 mutations (hepatocyte nuclear factor 1α-mutated HCA); this type is associated with steatosis of adenomatous hepatocytes.
• Mutations in the gene for beta-catenin with dysplasia and malignant transformation
• Teleangiectatic adenoma (inflammatory adenoma) with dilated sinusoidal vessels and inflammatory infiltrates has been described as a 3rd type
• Unclassifiable hepatocellular adenomas

The annual incidence is estimated at 1:1,000,000.

Tumor growth probably hormone-induced. The adenoma not only occurs more frequently in women who take oestrogen-containing preparations, but also becomes larger (up to > 10 cm) and is associated with an increased risk of bleeding. Adenomas often regress after discontinuation of oestrogen-containing preparations. Other predisposing factors are long-term use of anabolic steroids, the presence of glycogenosis (glycogen storage diseases) type III and IV and a congenital porto-caval shunt. HA only rarely occurs in children (Dhingra S et al. 2014).

Mostly women of childbearing age. The average age at diagnosis is 34 years (range 15-64 years).

HA is typically solitary, but patients with multiple tumors have also been described as "hepatocellular adenomatosis". The size varies between about 1 cm (the detection limit for common imaging techniques) and > 10 cm. If the diameter of the HA is less than 5 cm, carriers do not appear to be at risk of complications. Rarely, and then more often in men, very large tumors may show features of malignancy.

Most patients with HCA do not experience any symptoms. The diagnosis is usually made incidentally during a laparatomy or routine abdominal imaging for other reasons. Pain or discomfort in the right upper abdomen or epigastrium is common but is not always related to the adenoma.

Liver value changes are rare, but occur more frequently than in focal nodular hyperplasia.

The diagnosis is often made using several imaging techniques (sonography, CT, MRI). Small adenomas are sonographically isoechogenic to the surrounding healthy liver tissue. A biopsy is rarely indicated due to the increased risk of bleeding and often very limited diagnostic value.

Possible infarction with acute abdominal symptoms; sometimes rupture of the tumor with life-threatening bleeding (10% of cases). Malignant degeneration of an adenoma is possible and occurs in 8-13% of cases. It is therefore recommended to surgically remove an adenoma that is symptomatic or has not regressed after discontinuation of hormone preparations.

Oral contraceptives must be discontinued. Surgical resection is recommended if the HCA is > 5 cm in diameter. If the diagnosis is confirmed, the tumor can be left in place if the tumor diameter is < 5 cm and the patient is symptom-free. Further monitoring (size growth?) is required. Malignant transformation is rare and the long-term prognosis is good. If an adenoma of the liver is suspected, oestrogen-containing preparations should be discontinued in any case.

1. Dhingra S et al (2014) Update on the new classification of hepatic adenomas: clinical, molecular, and pathologic characteristics. Arch Pathol Lab Med 138:1090-1097.
2. Thomeer MG et al (2014) Genotype-phenotype correlations in hepatocellular adenoma: an update of MRI findings. Diagn Interv Radiol 20:193-199.