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Liver tumours—primary and secondary 

Liver tumours—primary and secondary

Liver tumours—primary and secondary

William J.H. Griffiths

and Simon M. Rushbrook


November 28, 2012: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

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date: 23 April 2017

A number of benign and malignant tumours may arise in the liver, the most important of which are:

Hepatocellular carcinoma (HCC)

HCC is the fifth most common cancer worldwide, but with great geographical variation in incidence, ranging from around 2 per 100 000 population in western Europe to 100 per 100 000 population in some parts of Africa. Most tumours arise on the background of cirrhosis, commonly due to hepatitis B, hepatitis C, or alcohol.

Symptoms may not be apparent until the cancer is already advanced, patients typically presenting with a triad of pain in the right upper quadrant, hepatomegaly, and weight loss. Decompensation in patients with cirrhosis may be precipitated by tumour and is signified by worsening ascites, variceal bleeding, jaundice, and/or encephalopathy.

The diagnosis of HCC is made primarily on contrast imaging (CT or MRI) where arterial enhancement and portal venous washout are characteristically seen. The tumour marker α‎-fetoprotein (AFP) is elevated in 80% of cases and is diagnostic when greater than 200 ng/ml in the presence of cirrhosis and a suspicious mass. Biopsy is reserved for indeterminate cases and immunohistochemical staining may help distinguish from adenocarcinoma.

Symptomatic presentation carries a poor prognosis, with less than 10% of patients surviving 3 years. However, ultrasound surveillance programmes of patients at risk (for example, those with cirrhosis or active hepatitis B infection) enable one-third of patients to be diagnosed at an early stage, when curative treatments are possible including (1) surgical resection, (2) ethanol/radiofrequency ablation, or (3) liver transplantation. Transarterial chemoembolization is an established palliative treatment. Cytotoxic drugs are generally not effective though new multikinase inhibitors appear promising.


Cholangiocarcinoma is an epithelial malignancy of the biliary tree that accounts for 7 to 10% of primary liver malignancies. Bile duct cancer is thought to be induced by chronic inflammation within the biliary tree, with risk factors including biliary infection by particular endemic trematodes and flukes, and primary sclerosing cholangitis.

Patients with peripheral intrahepatic masses typically present with upper abdominal pain, anorexia, malaise, and weight loss: jaundice is an early feature of those with hilar or extrahepatic tumours.

It can be difficult to establish the diagnosis of cholangiocarcinoma. Blood concentrations of CA19-9, a glycoprotein secreted by bile duct cells, are often elevated. Depending on tumour location, cross-sectional imaging or magnetic resonance cholangiopancreatography (MRCP) may be suggestive but not diagnostic. Options for obtaining tissue include (1) percutaneous biopsy if peripheral; (2) biliary brushings and/or intraductal biopsy at ERCP; (3) endoscopic ultrasound fine needle aspiration of hilar lesions where the differential includes inflammatory pseudotumour and metastasis.

Surgical resection can offer cure for a few patients, but results are generally disappointing. Useful palliation may be offered by photodynamic therapy, conventional radiotherapy and high-dose local irradiation, and biliary stenting.

Benign liver tumours

Haemangiomas are usually discovered incidentally during abdominal imaging and have a prevalence of 2 to 5% in the general population. Large symptomatic haemangiomas can be managed by surgical enucleation or embolization, but most do not require treatment and patients can be reassured.

Focal nodular hyperplasia (FNH) has a prevalence of 0.4 to 0.8% in the general population. FNH is usually found in women (female:male 9:1) and is typically discovered as an incidental solitary lesion during abdominal imaging. Appearances on MRI may be diagnostic, but biopsy is required if there is uncertainty particularly to differentiate from adenoma. The importance of diagnosing FNH is that it is a truly benign lesion.

Hepatic adenomas are associated with long-term use of the oral contraceptive pill, often incidental, but can present with abdominal pain. Lesions more than 5 cm in size should be considered for resection because of the risk of bleeding and malignant transformation. A conservative approach involves discontinuation of the oral contraceptive pill and surveillance imaging. Adenomas are currently being subclassified according to histopathological features and presence of somatic mutations (HNF1alpha, gp130, beta-catenin) with associated distinct prognosis.

Secondary liver tumours

Secondaries are commonly discovered as part of the staging process for primary malignancy (synchronous) or during follow-up (metachronous), or indeed may be the initial presentation. Symptoms and signs include abdominal pain and hepatomegaly; jaundice and ascites may occur with extensive infiltration. If the primary is not apparent, a targeted liver biopsy under ultrasound guidance usually confirms malignancy, with immunohistochemical assessment helpful in determining type.

For most primary cancers with liver involvement the prognosis is poor and treatment palliative. Surgical resection and other treatments have been shown to improve survival in the setting of colorectal liver metastases, neuroendocrine malignancies, and gastrointestinal stromal tumours (GISTs).

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