Hepatic Tumors

This is a benign proliferation of hepatocytes. It is a rare tumor that occurs largely in female patients. Its incidence has increased since the 1960s, probably related to the introduction and increased use of oral contraceptives.

Hepatic adenoma is a multifactorial disease. Although oral contraceptive (OCP) use, female sex, anabolic androgens, and age are major risk factors, hepatic adenoma can still occur in males and females who are not taking OCPs.

There are four major molecular subgroups according to their genetic and phenotype characteristics: Hepatocyte nuclear factor (HNF)–1α mutated, β-catenin activated, inflammatory, and unclassified hepatic adenoma.

Hepatic adenoma with β-catenin activated mutation has a high risk of malignant transformation.

Inflammatory hepatic adenoma includes telangiectatic hepatic adenoma (THA), previously classified as “telangiectatic focal nodular hyperplasia.” Risk factors for THA include OCP use, hormonal therapy, and obesity. Some inflammatory hepatic adenomas may also have β-catenin activation, making them at increased risk of malignant transformation.

Adenomas are usually single but may be multiple, rarely with more than five lesions. The size is variable but typically greater than 5 cm in diameter at diagnosis and sometimes massive.

Hepatic adenomatosis is a rare condition characterized by large numbers of adenomas (>10) in the liver with a high rate of recurrence. Patients with metabolic syndrome may also have associated hemangioma and focal nodular hyperplasia (FNH) in addition to adenomatosis.

Patients typically present with pain or discomfort in the right upper quadrant, although occasional tumors are found incidentally. Adenomas, especially telangiectatic hepatic adenomas, may rupture, resulting in hemoperitoneum.

Complications include hemorrhage and malignant transformation. Risk factors for malignant transformation include male sex, large size (>10 cm), and β-catenin activated mutation. Malignancy associated with hepatic adenoma carries a good prognosis after surgery.

The presence of a mass in the liver may be confirmed by computed tomography (CT), ultrasonography, or magnetic resonance imaging (MRI). Technetium ( ^99m Tc) radioisotope scan may show a defect within the liver. The diagnosis may be confirmed by liver biopsy. Histologic examination of hepatic adenoma shows benign hepatocytes organized in cords but with no portal tracts.

Treatment includes discontinuing the use of estrogens. Surgical resection is usually recommended for adenomas >5 cm in diameter, in men, and for telangiectatic and unclassified adenomas because of an increased risk of complications. Liver transplantation may be considered for adenomas found in association with type I glycogen storage disease.

Focal nodular hyperplasia (FNH) represents an abnormal proliferation of hepatocytes around an abnormal hepatic artery. The artery is usually embedded in a characteristic “spoke-wheel” central stellate scar.

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  FNH is usually clinically silent and is typically found incidentally, often at the time of imaging or abdominal surgery for another reason.

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  In comparison with adenoma, FNH tends to be smaller and carries little risk of rupture. Multiple lesions are found in approximately 20% of patients.

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  The gold standard diagnosis is contrast-enhanced CT or MRI. However, some FNH may not have typical radiographic features, and a biopsy may be required to confirm the diagnosis. A hepatic arteriogram may suggest the diagnosis if a tumor is found surrounding a large hepatic artery.

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  The diagnosis may be difficult to make on needle biopsy. Excisional biopsy may be required and is usually curative.

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  Asymptomatic cases do not need intervention. For symptomatic patients, other diagnoses need to be ruled out before treatment is started. Embolization and radiofrequency ablation seem to have fewer complications and lower morbidity compared with surgical resection.

Nodular regenerative hyperplasia (NRH) is characterized by the formation of small regenerative nodules composed of hepatocytes throughout the liver. The pattern is similar to cirrhosis, except that these nodules do not have a surrounding rim of fibrosis.

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  NRH is often associated with identifiable systemic diseases such as autoimmune disorders, rheumatoid arthritis (including Felty syndrome), and myeloproliferative disorders (see Chapter 24 ).

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  The pathogenesis is believed to be related to obliterative portal venopathy associated with thrombosis or phlebitis causing ischemia.

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  The incidence of NRH increases with age and is found most commonly in persons >60 years old.

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  Symptomatic NRH is often complicated by the development of presinusoidal portal hypertension. Patients may present with splenomegaly and hypersplenism or bleeding esophageal varices.

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  In general, patients with NRH tolerate variceal bleeding better than those with cirrhosis, presumably because they have relatively well-preserved hepatic synthetic function.

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  Liver biopsy is required for the definitive diagnosis of NRH.

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  Asymptomatic NRH does not require intervention. For symptomatic patients, treat portal hypertension. Beta receptor antagonist therapy, endoscopic therapy, or rarely, portal decompression can be used to prevent rebleeding from varices.

Adenomatous hyperplasia (macroregenerative nodule, dysplastic nodule)

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  This term is used for regenerative nodules of hepatocytes >1 cm in diameter found in association with cirrhosis or, rarely, submassive hepatic necrosis. Adenomatous hyperplasia represents a form of dysplastic nodule.

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  In the context of cirrhosis, adenomatous hyperplasia is considered to be premalignant and is strongly associated with the development of HCC.

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  No specific therapy is needed, but percutaneous ablation therapy may be considered. In patients with cirrhosis, the presence of adenomatous hyperplasia should signal the need for intensive surveillance for the development of HCC (see discussion later in chapter).

Partial nodular transformation: This rare condition is characterized by the presence of nodules of hepatocytes located in the perihilar region and associated with portal hypertension.