• Liver tumours are benign or malignant; malignant tumours can be primary or secondary.
• In Europe and the USA, a solitary lesion in the liver is more likely to be a metastatic carcinoma than a primary liver tumour.¹
• In 2000, it was estimated that liver cancer was the 5th most common malignancy in men and the 8th most common in women worldwide.²
• The incidence of primary liver cancers in developed countries seems to be increasing. This is related to hepatitis B and hepatitis C infection, which peaked in incidence in the 1950s to 1980s.²
• Hepatitis B and hepatitis C infection account for over 80% of liver cancer worldwide. Introduction of hepatitis B vaccination programmes and blood and blood product screening for the viruses has the potential to reduce this.²

Benign liver tumours

Haemangioma

• The most common benign liver tumour in adults and children.^3,4
• In children:⁴
  • It commonly occurs within first 6 months of life.
  • Can be small and found incidentally on imaging for another reason. Large cavernous haemangiomas can also occur and may reach 8-10 cm in diameter.
  • A subgroup of haemangioma, known as haemangioendothelioma, is found in infants.
  • Can present with abdominal distension and high-output cardiac failure. Cutaneous haemangiomas may coexist.
  • Sequestration of platelets and a consumptive coagulopathy can rarely occur.
  • They usually regress within the first 2 years of life.
  • Treatment is only needed if there is high-output cardiac failure or platelet sequestration. Steroid and interferon treatment, surgical excision and hepatic artery embolisation are all treatment options.
• In adults:
  • They are usually small and found incidentally on imaging for another reason.
  • Rarely, they lead to symptoms which include abdominal pain. Also, they have potential to rupture, causing shock.
  • They are thought to be congenital and may enlarge under the influence of oral contraceptives.⁵ However, they usually regress when they are stopped. They can also grow during pregnancy.
  • They can bleed profusely if an attempt is made at liver biopsy.
  • If they require removal, they are not usually amenable to simple excision of the tumour and a whole lobe of the liver must be removed.
  • Thrombocytopenia, hypofibrinogenaemia and microangiopathic haemolytic anaemia can occur.³

Hepatic adenoma

• These are also usually asymptomatic and found incidentally, either as a mass on physical examination or during imaging for another reason.
• They can occur in adolescent girls.
• Occasionally, they present with abdominal pain and intraperitoneal bleeding.³
• Liver function is not usually affected.
• Most cases have occurred in women who have been taking the contraceptive pill for 5 years or more.³
• Hepatic adenoma and adenocarcinoma may also be associated with the use of anabolic steroids.⁶
• They can be seen as solitary, or sometimes multiple, vascular masses on hepatic arteriography.
• There is about a 5% chance of malignant change to hepatocellular carcinoma (HCC) and a risk of intraperitoneal bleeding so they are best removed.

Focal nodular hyperplasia

• These are more common in women.³ They can occur in adolescent girls.
• They are not prone to malignant change.⁴
• Rupture and haemorrhage have occasionally been reported.³ Because of this, some advocate excision. Others just monitor them regularly, using imaging.
• They can be distinguished from hepatic adenoma by careful imaging and liver biopsy.

Other benign tumours

They are very rare. They include:

• Fibroma
• Lipoma
• Leiomyoma
• Cystadenoma

Primary carcinoma of the liver

Hepatocellular carcinoma (HCC)⁷

See separate article Hepatocellular Carcinoma.

• There are about 1,500 deaths per year from HCC in the UK and its incidence appears to be rising.⁸
• The majority of cases worldwide are related to hepatitis B and hepatitis C viral infection. There are also associations with alcohol, haemochromatosis, primary biliary cirrhosis, contamination of foodstuff with aflatoxins, a group of mycotoxins produced by the fungi Aspergillus flavus and Aspergillus parasiticus, smoking and diabetes.⁹
• HCC is the second most common hepatic malignancy in children:⁴ It usually occurs in children with pre-existing liver disease (hepatic fibrosis and cirrhosis) secondary to, for example, metabolic liver disease, viral hepatitis, chemotherapy or total parenteral nutrition.
• Presentation is with abdominal pain, abdominal mass, weight loss and anaemia.
• Lung and lymph node metastases are common.
• The mainstay of treatment is resection and chemotherapy but many tumours are unresectable at presentation.
• Prognosis is generally poor.

Hepatoblastoma¹

• One study found that 79% of hepatic malignancies in children were hepatoblastomas (although still uncommon compared with other solid tumours).¹⁰
• It is associated with low birthweight.
• There are associations with hemihypertrophy, Beckwith-Wiedemann syndrome and familial adenomatous polyposis syndrome.
• Other associations noted include maternal oral contraceptive exposure, fetal alcohol syndrome and gestational exposure to gonadotropins.
• It is extremely rare in adults.¹¹
• It usually presents as abdominal mass and distension, vomiting, anaemia and failure to thrive in a child under the age of 3 years.
• Alpha-fetoprotein (AFP) levels are raised and can be used to monitor response to treatment.
• Other blood test findings may include a normochromic, normocytic anaemia and a high platelet count.
• Useful imaging techniques include plain abdominal X-ray, ultrasonography, CT, MRI, bone scanning and single positron emission tomography (SPECT).
• Pulmonary metastases are common.
• Treatment is with resection and chemotherapy (which may be required before surgery to shrink the tumour).
• Radiotherapy may be required if there is tumour in the resection margins or chemotherapy-resistant pulmonary secondaries.
• Liver transplantation has been used in children with nonresectable tumours.¹¹
• With complete tumour resection and the use of adjuvant chemotherapy, survival rate can be 100%.¹¹
• A poor prognosis is associated with large tumour size, multifocal disease, extrahepatic disease and metastatic spread.¹⁰

Cholangiocarcinoma

• This is a carcinoma that arises in the biliary tree anywhere from the small intrahepatic ducts to the distal common bile duct. It is most commonly found near the junction of the left and right hepatic ducts.
• It presents by causing obstruction to the flow of bile with subsequent obstructive jaundice, pale stools and dark urine.
• It is commonly associated with the liver flukes Opisthorchis viverrini and Clonorchis sinensis.⁹
• There is a separate article Cholangiocarcinoma.

Other tumours

Other rare primary malignant liver tumours include:

• Fibrosarcoma.
• Angiosarcoma (associated with occupational exposure to vinyl chloride).⁹
• Leiomyosarcoma.
• Lymphoma.

Secondary carcinoma of the liver⁴

• Lymph nodes are the most common site for metastatic malignant spread with the liver next in frequency.
• Autopsy studies have found 30-70% of patients dying from cancer have liver metastases, the frequency depending on the site of the primary.
• The vulnerability of the liver for metastatic disease may be related to the fact that it is the largest organ in the body and it filters blood from both the systemic and portal systems. Humoral factors promoting cell growth and blood flow are second only to the lungs.
• Most liver metastases are multiple and affect both lobes. Single metastases occur in only 10%.¹
• The most common primary sites for hepatic metastases are colorectal, stomach, pancreas, breast, lung and eye.¹
• In children the most common primaries are neuroblastoma, Wilm's tumour and leukaemia.¹
• Most tumours that have spread to the liver have metastasised to other sites as well.

Clinical features

• Hepatomegaly and ascites are present in about 50% of patients with liver metastases. Nodularity may be palpable along the enlarged liver edge. Ascites indicates wide dissemination and a poor prognosis.
• Large metastases may block bile ducts and cause jaundice, malaise, anorexia and loss of weight.

Investigations⁴

• Abnormal blood results may include anaemia and leukocytosis. Bilirubin, alkaline phosphatase and transaminase levels may be raised but liver function tests are not always abnormal.
• A number of tumour markers have been identified, including alpha-fetoprotein (AFP), protein induced by vitamin K absence (PIVKA-II), carcinoembryonic antigen (CEA) and CA19-9 but their diagnostic accuracy needs further evaluation.
• Chest X-rays and abdominal ultrasound may be helpful, plain abdominal X-rays less so.
• Ultrasound (especially when enhanced with Doppler or colour-flow imaging). CT, MRI and positron emission tomography may all be useful in varying circumstances.
• Angiography is essential if vascular intervention is planned.
• Biopsy is needed for an histological diagnosis. However, biopsy can lead to needle tract metastases and some argue that in Western populations where primary liver tumours are rare, investigation should focus on finding a primary source when investigating malignant liver lesions.¹² Liver biopsy is not advised if the tumour is operable.

Management¹

• Partial hepatectomy to remove a single deposit may prolong survival and even lead to cure in some cases.³ Patients must be carefully selected and be free from extrahepatic metastases.
• Minimally invasive treatments, including freezing, ethanol and lasers, have also been used in the treatment of metastatic hepatic deposits. Radiofrequency ablation is a popular technique.¹³ However, more trials are needed to look at its effectiveness.¹⁴ Transcatheter arterial chemoembolisation (TACE) can block the blood supply to hepatic tumours and microcatheters can be used to deliver chemotherapeutic agents.
• The National Institute for Health and Clinical Excellence (NICE) has advocated the use of laparoscopic liver resection for a solitary liver metastasis, hepatocellular carcinoma (HCC) and for benign liver tumours and cysts.¹⁵ Radiofrequency-assisted liver resection is supported by NICE.¹⁶ NICE also endorses the use of ex vivo hepatic resection (operation on the liver outside the body followed by reimplantation) in patients who would otherwise die and have tried all other appropriate treatments.¹⁷
• Chemotherapy may also be a treatment option depending on the primary site. However, if there is coexisting extensive extrahepatic disease, prognosis is usually guarded.

Prognosis⁴

• Deposits from colorectal cancer seem to have a better prognosis.³
• Studies have found a 20-40% five-year survival rate after hepatic resection in patients with metastases confined to the liver.
• People with secondary liver carcinoma do not usually die as a direct result of the liver metastases but for some other reason - for example, a chest infection or renal impairment.³

Document references

1. Khan AN; Liver, Metastases, eMedicine, Feb 2009
2. Bosch FX, Ribes J, Diaz M, et al; Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004 Nov;127(5 Suppl 1):S5-S16. [abstract]
3. Primary liver tumours. Chapter 5.38. Concise Oxford Textbook of Medicine, 2000
4. William KG; Liver Tumors, eMedicine, Feb 2009
5. Glinkova V, Shevah O, Boaz M, et al; Hepatic haemangiomas: possible association with female sex hormones. Gut. 2004 Sep;53(9):1352-5. [abstract]
6. Socas L, Zumbado M, Perez-Luzardo O, et al; Hepatocellular adenomas associated with anabolic androgenic steroid abuse in bodybuilders: a report of two cases and a review of the literature. Br J Sports Med. 2005 May;39(5):e27. [abstract]
7. Hepatocellular carcinoma (HCC): a global perspective, World Gastroenterology Organisation Global Guideline, 2009
8. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (HCC) in adults, British Society of Gastroenterology (2003)
9. Chuang SC, La Vecchia C, Boffetta P; Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV Cancer Lett. 2009 Dec 1;286(1):9-14. Epub 2008 Dec 16. [abstract]
10. Schnater JM, Kohler SE, Lamers WH, et al; Where do we stand with hepatoblastoma? A review. Cancer. 2003 Aug 15;98(4):668-78. [abstract]
11. Willert JR; Hepatoblastoma, eMedicine, Jan 2010
12. Metcalfe MS, Bridgewater FH, Mullin EJ, et al; Useless and dangerous--fine needle aspiration of hepatic colorectal metastases. BMJ. 2004 Feb 28;328(7438):507-8.
13. Radiofrequency ablation for the treatment of colorectal metastases in the liver, NICE (2004)
14. Garrean S, Hering J, Saied A, et al; Radiofrequency ablation of primary and metastatic liver tumors: a critical review of the literature. Am J Surg. 2008 Apr;195(4):508-20. [abstract]
15. Laparoscopic liver resection, NICE (2005)
16. Radiofrequency-assisted liver resection, NICE Interventional Procedure Guideline (2007)
17. Ex-vivo hepatic resection and reimplantation for liver cancer, NICE Interventional Procedure Guideline (April 2009)

Acknowledgements