Benign liver tumours

Haemangioma

• The most common benign liver tumour in adults and children.^[3][4] They are more common in the right lobe of the liver than in the left lobe.
• Hepatic haemangiomas can occur as part of a clinical syndrome, eg Klippel-Trenaunay-Weber syndrome, Osler-Rendu-Weber disease and Von Hippel-Lindau disease.^[3]
• Large cavernous haemangiomas may reach 8-10 cm in diameter.
• They are thought to be congenital and may enlarge under the influence of oral contraceptives.^[5] However, they usually regress when oral contraceptives are stopped. They can also grow during pregnancy.
• Hepatic haemangiomas may be seen in up to 10% of children aged 1 year but they usually regress within the first two years of life.^[4]
• Presentation:^[3]
  • Usually small and asymptomatic; they most often present as incidental findings at the time of imaging of the liver, laparotomy or postmortem.
  • Right upper quadrant pain or fullness is the most common symptom.
  • Examination is usually normal but there may be hepatomegaly and/or an arterial bruit over the right upper quadrant.
  • Rare presentations include a large abdominal mass, high-output cardiac failure, obstructive jaundice, gastrointestinal haemorrhage or fever. Thrombocytopenia, hypofibrinogenaemia and microangiopathic haemolytic anaemia may rarely occur.
  • Large lesions may cause obstruction to gastric emptying and so present with vomiting.
  • Rupture is rare but may occur spontaneously, following trauma or at the time of attempted biopsy.
• Imaging techniques include ultrasound, contrast-enhanced CT scanning, nuclear medicine studies using technetium ^99m Tc-labelled red blood cells, MRI, hepatic arteriography and digital subtraction angiography.^[3]
• Surgical resection is the treatment of choice. Minimally invasive therapies include arterial embolisation, radiofrequency ablation and hepatic irradiation. Liver transplantation is required on rare occasions.^[3] Steroids and interferon treatment are other treatment options.^[4]

Hepatic adenoma

• Hepatic adenomas are rare, benign tumours. Approximately 90% of cases occur in females, mostly aged 15-45 years.They occur most often in women of childbearing age and are strongly associated with the use of oral contraceptives.^[6]
• Other conditions associated with hepatic adenomas include anabolic steroids,^[7] beta-thalassaemia, tyrosinaemia, type 1 diabetes mellitus and glycogen storage diseases (types 1 and 3). Multiple hepatic adenomas are more common in glycogen storage disease.^[6]
• The risk of malignant transformation is not completely known and may be as high as 13%.^[6]
• Presentation:^[6]
  • Often asymptomatic and found incidentally on physical examination or during imaging for another reason.
  • May present with pain in the right upper quadrant or epigastric region.
  • A palpable mass may be noticed by the patient.
  • May present with severe, acute abdominal pain with bleeding into the abdomen, leading to shock.
  • Other rare presentations include obstructive jaundice.
• Investigations:
  • Liver function is not usually affected but aminotransferase levels may be mildly elevated or there may be features suggestive of obstructive jaundice.
  • Appropriate imaging investigations include ultrasound, CT and MR angiography.
  • Immediate abdominal imaging is required for patients with hepatocellular adenomas who present with new or worsened abdominal pain or signs of haemodynamic instability.
• Management:^[6]
  • Patients should stop using oral contraceptives or anabolic steroids. Pregnancy should be avoided until resection of the tumour because of the risk of growth and rupture.
  • Symptomatic tumours should be resected. Due to the increased risk of spontaneous life-threatening haemorrhage and the possible malignant transformation associated with larger-sized tumours, asymptomatic hepatic hepatomas approaching 4 cm and those requiring hormonal therapy should also be resected.^[8]
  • Yearly ultrasound imaging and serum alpha-fetoprotein (AFP) levels for patients with hepatocellular adenomas who do not have a resection of the tumour.
  • Emergency hepatic arteriography and embolisation should be considered to control bleeding in high-risk surgical candidates.

Focal nodular hyperplasia

• Focal nodular hyperplasia is the second most common tumour of the liver.^[1]
• It is a benign condition of the liver that is often discovered incidentally on radiological investigation. It is more common in women.
• It is not prone to malignant change.^[4]
• It is rarely symptomatic and surgical intervention is almost never required. However, symptomatic focal nodular hyperplasia does occur, may have rapid growth and may require resection.^[9]
• Duplex Doppler ultrasound may be sufficient but further confirmation may be required using CT, MRI, angiography or radionuclide imaging.^[1]
• Rupture and haemorrhage have occasionally been reported. Therefore, some authorities advocate excision but most patients can be monitored with imaging.

Other benign tumours

They are very rare. They include:

• Fibroma
• Lipoma
• Leiomyoma
• Cystadenoma

Primary carcinoma of the liver

Hepatocellular carcinoma (HCC)

See separate Hepatocellular carcinoma article.

Hepatoblastoma^[4][10]

• One study found that 79% of hepatic malignancies in children were hepatoblastomas (although still uncommon compared with other solid tumours).^[11] They usually affect children younger than 3 years. They are extremely rare in adults.
• 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 gonadotrophins.
• Hepatoblastomas are usually unifocal and affect the right lobe of the liver more often than the left lobe.
• They are usually asymptomatic at diagnosis but may present with an abdominal mass and distension, vomiting, anaemia and failure to thrive in a child under the age of 3 years. Disease is advanced at diagnosis in approximately 40% of cases. Approximately 20% have pulmonary metastases.
• 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 (may show calcification), ultrasound, CT, MRI, bone scanning and single positron emission computed tomography (SPECT).
• Management:
  • With complete surgical resection of the tumour at diagnosis followed by adjuvant chemotherapy, survival rate can be 100%.
  • Radiotherapy may be required when there is tumour in the resection margins or when there are chemotherapy-resistant pulmonary secondaries.
  • Liver transplantation has been used in children with nonresectable tumours.
• A poor prognosis is associated with large tumour size, multifocal disease, extrahepatic disease and metastatic spread.^[11] Older children and adults also tend to have a worse prognosis.

Cholangiocarcinoma

See separate article Cholangiocarcinoma.

Other tumours

Other rare primary malignant liver tumours include:

• Fibrosarcoma.
• Angiosarcoma (associated with occupational exposure to vinyl chloride).^[12]
• Leiomyosarcoma.
• Lymphoma.

Secondary carcinoma of the liver^[4]

See also separate articles Malignancy of unknown origin and Carcinomatosis.

• 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.

Investigations^[4]

• Abnormal blood results may include anaemia and leukocytosis. Bilirubin, alkaline phosphatase and transaminase levels may be raised but LFTs are not always abnormal.
• A number of tumour markers have been identified, including AFP, protein induced by vitamin K absence (PIVKA-II), carcinoembryonic antigen (CEA) and CA19-9 but their diagnostic accuracy needs further evaluation.
• CXRs 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.^[13] Liver biopsy is not advised if the tumour is operable.

Management^[1]

• Partial hepatectomy to remove a single deposit may prolong survival. 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.^[14] However, more trials are needed to look at its effectiveness.^[15] 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.^[16]
  
  Radiofrequency-assisted liver resection is supported by NICE.^[17]
  
  NICE also endorses the use of ex vivo hepatic resection (operation on the liver outside the body followed by re-implantation) in patients who would otherwise die and have tried all other appropriate treatments.^[18]
  
  NICE recommends that selective internal radiation therapy (SIRT) should be considered as a treatment option for non-resectable colorectal metastases in the liver.^[19]
• Chemotherapy may also be a treatment option depending on the primary site. However, if there is co-existing extensive extrahepatic disease, prognosis is usually guarded.

Prognosis^[4]

• Deposits from colorectal cancer seem to have a better prognosis.
• 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.