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Tumours

Hepatobiliary tumours

Practitioners from all areas of medicine may be faced with
the evaluation of lesions arising in the liver or biliary tract.
Greater use and sensitivity of radiological imaging including
ultrasonography, computed tomography (CT) and magnetic
resonance imaging (MRI) has meant that an increasing number
of hepatobiliary tumours are identified incidentally, leading to
diagnostic and therapeutic difficulties. They can be classified
by their anatomical location, biological behaviour and cell of
origin (Table 1).

Charlie Imber
Brian Davidson

Benign liver tumours (Table 2)
Abstract

Benign focal liver masses are present in approximately 9% of
patients in the general community in developed countries.1

Greater use and sensitivity of radiological imaging including ultrasound,
computed tomography and magnetic resonance imaging has meant that an
increasing number of hepatobiliary tumours are identified incidentally, leading to diagnostic and therapeutic difficulties. They can be classified by their
anatomical location, biological behaviour and cell of origin. Haemangiomas
are the most common benign tumour of the liver. They have no potential
for malignant transformation, and can therefore be treated conservatively.
Liver cell adenoma has a strong association with the oral contraceptive pill
and most would recommend resection because of potential for rupture,
malignant transformation and misdiagnosis. Focal nodular hyperplasia has
no risk of malignancy and can also be treated conservatively if asymptomatic, although avoidance of oral contraception is recommended. Hepatocellular carcinoma accounts for 90% of all primary liver malignancy and
usually occurs on a background of chronic liver disease. Surgical resection
may be possible in well compensated cirrhotics, but transplantation treats
the underlying cirrhosis as well as removing all tumours. Most tumours can
metastasize to the liver and the detection of liver metastases is generally
associated with a poor prognosis. However, colorectal liver metastases are
curable with liver resection and therefore screening following resection of a
primary colon cancer is essential. Both gall bladder cancer and hilar cholangiocarcinoma have a poor prognosis because they are often advanced at
presentation, with invasion of local vital structures as well as perineural
and lymphatic spread. Radical resection can potentially be curative, but
often only palliative treatment to relieve biliary obstruction is possible.

Hepatobiliary tumour classification
Cell type

Benign

Malignant

Hepatocyte

Liver cell adenoma

Hepatocellular
carcinoma
Fibrolamellar carcinoma

Hepatocellular
hyperplasia
Focal nodular
hyperplasia
Nodular regenerative
hyperplasia
Macroregenerative
nodules
Cholangioepithelial

Cholangiocarcinoma

Polycystic liver disease

Carcinoma of the gall
bladder
Ampullary cancer

Hepatobiliary
cystadenoma
Bile duct adenoma
Papillomatosis

Keywords benign; cholangiocarcinoma; focal nodular hyperplasia; gall
bladder carcinoma; haemangioma; hepatocellular carcinoma; liver cell
adenoma; metastasis; peri-ampullary tumour
Mesenchymal

Angiosarcoma

Mesenchymal
hamartoma
Haemangioma

Epithelioid
hemangioendothelioma

Infantile
haemangioendothelioma
Lipoma/angiomyolipoma
Leiomyoma
Fibroma
Focal fatty change

Charlie Imber FRCS is a specialist registrar in HPB and Liver Transplant
Surgery at the Royal Free Hospital in London. He carried out general
surgical training in London prior to clinical and research training in the
HPB and Liver Transplant field in Oxford and Birmingham. Competing
interests: none declared.
Others
Brian Davidson FRCPS (Glas) FRCS (Eng) is Professor of HPB and Liver
Transplant Surgery at the Royal Free Hospital and Royal Free and
University College School of Medicine, UCL. Major research interests
are liver tissue engineering including liver ischaemia–reperfusion injury
and organ preservation and the molecular biology of HPB cancer.
Competing interests: none declared.

MEDICINE 35:2

Simple hepatic cyst

Inflammatory
pseudotumour
Myxoma
Epidermoid cyst
Benign teratoma

Myxoma

Table 1

121

© 2006 Elsevier Ltd. All rights reserved.

carcinoid syndrome Local pain bleeding Macroregenerative nodules HCA/FNH metastases Diagnosis Management CT/MRI − well demarcated hypodense lesion (pre contrast) peripheral nodular enhancement (early phase) + centripetal filling (late phase) CT − hypodense with peripheral contrast enhancement + centripetal filling to become hypervascular in the arterial phase Sulphur colloid scintigraphy (Tc-99) – cold spot Colour doppler US – spokewheel vascularity radiating from a central scar CT/ MRI – central scar (60%) Sulphur colloid scintigraphy (Tc-99) – hot spot Alpha-fetoprotein Conservative unless symptoms or complications Resection Conservative Resection Transplantation CT/MRI – arterial phase Locoregional hypervascularity chemotherapy Percutaneous ablative techniques Tumour markers Resection Systemic chemotherapy CT/MRI – typically Local ablative hypodense lesion techniques with some arterial rim enhancement CT. MEDICINE 35:2 122 © 2006 Elsevier Ltd. The majority remain stable over time although they can enlarge and require resection to improve the ­symptoms. but can cause symptoms by mass effect. US. weight loss. Etoh.2 Haemangioma The most common benign tumour of the liver. HCC fever. liver failure. can occur as solitary or multiple tumours (40%). Acute rupture with intra-abdominal bleeding is extremely rare. . with an incidence ranging from 0. ethyl alcohol. breast and stomach primary Depending on primary Benign tumours Often asymptomatic Pain. anorexia. 1:1 bronchus. They can be capillary or cavernous and are probably congenital in origin. They have no potential for malignant transformation. MRI. All rights reserved. oral contraceptive pill. pancreas. It is commoner in women (3:1) and occurs most frequently between the ages of 30–70 years. ultrasound. There is some evidence to suggest that growth is hormone dependent and associated with the oral contraceptive pill (OCP) or pregnancy. OCP.4–20% in published ultrasound and autopsy series. haemorrhage or ­thrombosis. computed tomography. Table 2 In the majority of cases they are entirely asymptomatic.Tumours Common liver tumours Liver tumour Aetiology Female: Histology male Symptoms/ complications Haemangioma Nil 3:1 Large blood filled spaces lined by endothelium Adenoma Mass effect Bleeding/ HCC thrombosis Kasabach-Merritt Metastases syndrome Adenoma (HCA) OCP Endocrine disorders 11:1 Uniform mass Mass effect of hepatocytes Malignant transformation without ducts or portal triads Kleinfelters syndrome Focal nodular hyperplasia (FNH) Nil 9:1 Regenerating nodules + connective tissue septae Major differential FNH Rupture HCC Mass effect HCA HCC Hepatocellular carcinoma (HCC) Liver cirrhosis – 2:1 especially viral + metabolic Promoters: Etoh aflatoxin Varying degrees of differentiation Metastasize Hepatic metastases Colon/rectum. magnetic resonance imaging.

but some of the commonest include colon/rectum (35% at time of presentation). Histologically. size and number of tumours. Both the dose of hormones and the length of usage increase the risk. potential for malignant change. but its association with the OCP is more tenuous than adenoma. They can also invade the biliary tract leading to obstructive jaundice and haemobilia. Small tumours are asymptomatic. Histological confirmation can be sought if diagnostic uncertainty remains on radiological grounds. and the poor results achieved with large HCC. Liver cell adenoma This is a benign proliferation of hepatocytes in an otherwise normal liver. guidelines exist in the UK based on the ‘Milan Criteria’ for the use of transplantation in patients with HCC. location or number does not reliably correlate with risk. Other aetiological risk factors include cirrhosis due to metabolic liver disease such as haemochromatosis. especially hepatitis B and C cirrhosis. bronchus. on biopsy. surgical packing or liver resection. It occurs predominantly in women (11:1) aged 20–40 years and has a strong association with the oral contraceptive pill. or has a giant lesion (>4 cm). The combination of biliary obstruction and melaena can lead to silvery stools. pancreas. depending on the extent of liver resection required and the position. other pathology should be sought with upper gastrointestinal (GI) endoscopy and biliary ultrasound. Bulky adenomata causing symptoms by mass effect should be removed and. Pregnancy increases the risk of complications and some other form of contraception should therefore be advised. Alcohol can cause cirrhosis as well as acting as a co-factor increasing the rate of HCC development in the presence of hepatitis B and C. clomiphene. Ultrasound combined with serial alpha-fetoprotein (AFP) measurement is used as a surveillance tool in high risk patients. Liver resection can be required if no other cause of persisting pain is demonstrated. as well as the characteristic obstructive picture on liver function tests associated with a 123 © 2006 Elsevier Ltd. Focal nodular hyperplasia (FNH) This is truly a benign lesion without risk of malignant transformation. In one series. Due to limited organ availability.5 Palliative treatment options include transarterial chemoembolization (TACE). exogenous testosterone use/abuse. It is the second commonest liver lesion after haemangioma. HCC can also develop in a normal liver. It usually occurs on a background of chronic liver disease. bleeding or rupture require emergency intervention. although female hormones are thought to have a potential trophic effect and increase the risk of symptoms. The management in an asymptomatic patient is more difficult. Colorectal metastases can be cured by liver resection and therefore follow up of patients after removal of a primary colorectal cancer with serial carcinoembyonic antigen (CEA) blood measurements and annual imaging of the liver with CT is recommended. hepatotoxins and tobacco. Fibrolamellar carcinoma is a form of hepatocellular carcinoma which occurs at a younger age (20–35 years) and in a normal liver. weight loss and general malaise.Tumours As a result of their benign nature. breast and stomach tumours. It therefore has strong geographical variations in incidence. Metastatic spread occurs principally to the lung. but advanced disease can lead to liver decompensation. being most common in Eastern Asia and sub-Saharan Africa where endemic viral cirrhosis rates are MEDICINE 35:2 Biliary tract tumours Ampullary tumours Tumours arising at the ampulla of Vater usually present with obstructive jaundice. and is preferentially dealt with by liver resection. This predilection for GI cancer is as a result of portal vein drainage where tumour cells can embolize via the mesenteric veins. HCC exhibit varying degrees of differentiation and in tumours over 2 cm in diameter 60% have evidence of microscopic vascular invasion. in the emergency setting.3% in adult livers. Other endocrine associations include pregnancy. particularly cirrhotics of viral origin. Unfortunately.g. Liver transplantation offers a potentially attractive therapeutic option by treating the underlying liver cirrhosis as well as removing the cancer. There continues to be debate about the risk of malignant transformation of liver cell adenoma. the adrenal and bone. to be malignant. The link with the OCP is too weak to justify a recommendation of cessation unless the patient is symptomatic. and the possibility of misdiagnosis. Patients should be advised to stop the OCP. . Liver metastases Most tumours can metastasize to the liver. Prognosis is poor in the majority but can be improved dramatically to approximately 40% patient survival at 5 years if surgical resection is possible. weight loss. Primary malignant liver tumours (Table 2) Hepatocellular carcinoma (HCC) This accounts for 90% of all primary liver malignancy and is the fourth most common malignant tumour in the world. Up to 30% are multiple. Avoidance of the OCP is preferable but not mandatory. danazol therapy and Kleinfelter syndrome. by transarterial embolization (TAE). Most clinicians would advise resection because of the unpredictable risk of rupture. particularly the portal and hepatic veins. Surgical resection may be possible in cirrhotic patients with good liver function. anorexia. It has a better prognosis than HCC. All rights reserved. with incidence in one large autopsy study of 0. the vast majority of patients can be reassured and need no follow up. asthenia.4 If symptomatic. abdominal fullness and pain. In asymptomatic patients with unequivocal radiological findings no further investigation or treatment is required. Liver cell adenomas are usually solitary fleshy nodules with a white macroscopic appearance. radiofrequency ablation) used either in a neoadjuvant or adjuvant setting may provide additional benefit. About 90% of cases occur in women. percutaneous alcohol injection and thermal ablation. once diagnosed. They spread mainly by direct invasion of blood vessels. tumour size. Chemotherapy and percutaneous ablative techniques (e. 6% of lesions presumed benign on a radiological basis were found.3 Patients with large adenomata may be at greatest risk of developing complications. very high. Most patients with colorectal liver metastases are asymptomatic when diagnosed due to imaging follow up but patients can present with upper abdominal discomfort.

If unresectable. Epidemiology of hepatocellular adenoma. 4 Belghiti J. Pereira S P et al. . Davidson B R. includes a hepatectomy and hilar lymphadenectomy. Ishak K G et al. Natural history of hepatic haemangiomas: clinical and ultrasound study. Gut 2002. Jenkins R L. Radical resection offers the best prognosis. 32: 677–80. Khan S A. Lancet Oncol 2004. 2 Gandolfi L. Fusai K. Doci R et al. N Engl J Med 1996. The majority of patients (70%) have gallstones. Strategies to increase the resectability of liver metastases from colorectal cancer. metastatic spread or significant medical co-morbidity are ­contra-indications to surgical resection. Dig Surg 2003. ◆ References 1 Gedaly R. Gall bladder cancer This is the commonest of all biliary tract cancers but still only represents 2% of all cancers. All rights reserved. Pomposelli J J. Goldin R. Management of colorectal liver metastases. Lewis W D. Davidson B R. Vitelli E. Khan S A. 51(Suppl 6): VI1–9. Thomas H C. 3 Rooks J B. Major vessel ­invasion. possibly along with excision of the biliary tree with internal drainage. Perineural and lymphatic spread is common with these tumours. Resection of presumed benign liver tumours. the relief of jaundice by endoscopic insertion of a biliary endoprosthesis can provide palliation. Verros G. Gut 1991. The role of oral contraceptive use. Systemic treatment and liver transplantation for hepatocellular carcinoma: two ends of the therapeutic spectrum. Meyer T. Further reading Burroughs A. Cholangiocarcinoma. and therefore local resection is rarely curative. Pateron D. Arch Surg 1999. 5: 409–18. Carcinogens including the chemical methylene chloride and aflatoxin exposure have also been implicated. 366: 1303–14. with or without adjuvant chemotherapy. The disease usually presents in patients over the age of 70 and can be found incidentally following ­cholecystectomymaking histological examination of all explant gallbladders mandatory. Panis Y et al. Aetiological factors include inflammatory bowel disease and primary sclerosing cholangitis (PSC). Radical resection therefore MEDICINE 35:2 124 © 2006 Elsevier Ltd. Resection of these tumours by m pylorus preserving pancreatoduodenectomy is associated with a good prognosis (40–50% survival at 5 years). These tumours are adenocarcinomas that are generally papillary in the periampullary area. 20: 481–96. Spread of these tumours is primarily into liver ­parenchyma and hilar lymphatics. Colorectal Dis 2003. Hochhauser D. enucleation. Br J Surg 1993. Cholangiocarcinoma This is an uncommon tumour with marked geographical variation. 80: 380–3. 5: 2–23. nodular in the mid-duct and stenosing at the hepatic duct confluence (Klatskin tumour). Davidson B R. Pomfret E A. Palliative treatment involves relief of biliary obstruction by stenting. systemic chemotherapy and/or photo­ dynamic therapy. Distal tumours are resected along with a pancreatoduodenectomy and hilar tumours with a partial hepatectomy.Tumours ­ icrocytic hypochromic anaemia. Guidelines for the diagnosis and treatment of cholangiocarcinoma – a consensus document. Colecchia A. Taylor Robinson S D. 242: 644–8. Davidson B R. 334: 693–9. Solmi L. Cavernous hemangioma of the liver: anatomic resection vs. Fusai G. 134: 407–11. Ory H W. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. Lancet 2005. Regalia E. 5 Mazzaferro V. Leo P. JAMA 1979.