Transcript Tumours-of-the

Tumours of the liver
John J O’Leary
TUMOURS AND TUMOUR-LIKE LESIONS
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Benign epithelial tumours
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Focal nodular hyperplasia
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Benign non-epithelial tumours Haemangioma
Others are very rare
Liver cell adenoma
Bile duct adenoma
Bile duct cystadenoma
Biliary papillomatosis
Ultrasound of
a benign liver
tumour
Liver cell adenoma:
Women of childbearing age
Assoc. with use of the OCP
Risk of rupture and haemorrhage
Molecular genetics of liver cell adenoma
Transcription factor 1 (TCF1) mutations in liver cell adenoma tumorigenesis (Bluteau et al., 2002b).
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Malignant epithelial tumours.
Hepatocellular carcinoma.
Hepatoblastoma.
Cholangiocarcinoma.
Bile duct cystadenocarcinoma.
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Malignant non-epithelial tumours.
Angiosarcoma.
Other sarcomas and other tumours are rare.
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Metastatic tumours.
• Comments:
Haemangioma is the most common benign tumour.
Metastatic carcinomas are the most common of the malignant tumours.
Hepatocellular carcinoma is the most common of the primary ones.
Hepatoblastoma is the most common liver tumour in young children.
HEPATOCELLULAR CARCINOMA
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5% of all cancers in the world. The most common cancer in some areas.
Marked geographical distribution: 85% occur where HBV is endemic.
Constant risk factors are male gender, age, cirrhosis which pre-exists in 85% in
Western world;absent in 50% in areas of high HBV incidence where it occurs in
younger age group (20-40).
Enviromental factors are HBV, HCV, aflatoxin (Aspergillus flavus) and other
naturally occuring carcinogens.
Inherited conditions, haemochromatosis, tyrosinemia.
Morphology - soft tumour - multiple nodules, solitary mass or diffuse. Propensity
for vascular invasion. Forms trabeculae of malignant hepatocytes but many
patterns possible. May produce bile if well differentiated.
Spread to regional lymph nodes, lungs and less often elsewhere.
Alpha-fetoprotein - raised plasma levels a useful but non-specific marker.
Extremely poor prognosis. (Better in sub-type fibrolamellar carcinoma).
HBV and cancer of the liver
• Repeated cycles of cell death and regeneration are
important
• Accumulated genetic mutations during continuous
cycles of regeneration
• Genomic instability more likely in the presence of
HBV
• HBV is clonal in all tumours [HBV integrated]
• HBV-X protein [regulatory element]: is a
transcriptional transacting regulator of many genes
• HBV-X protein disrupts normal growth by activation of
host cell proto-oncogenes
• Some HBV proteins mat bind and inactivate p53
Hep B and hepatocellular carcinoma: ICC
Figure 1. Diagram depicting some of the major features of the insulin/IGF-1 signal transduction cascade involved in hepatocyte and human hepatocellular
carcinoma cell growth.
insulin receptor substrate-1 (IRS-1)
Potential ethanol-related genes in
Hepatocellular cancer
BILE DUCT CARCINOMA (CHOLANGIOCARCINOMA)
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Less common than HCC but more evenly distributed worldwide.
A disease of older individuals; males and females affected equally.
Not associated with cirrhosis.
Highest incidence in S.E.Asia, associated with liver fluke infestation Clonorchis sinensis and Opisthorchis viverrini.
Other risk conditions include primary sclerosing cholangitis and
congenital anomalies of the biliary tree, eg Caoli’s disease and
choledochal cysts. In most cases the cause is unknown.
Morphology - firm white tumour - an adenocarcinoma, mucin production
detectable.
Spread to regional lymph nodes, lungs and elsewhere, and to
peritoneum.
Extremely poor prognosis.
ANGIOSARCOMA
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Rare, but the commonest liver sarcoma.
More common in males than in females.
Aetiological agents include thorium dioxide (Thorotrast), vinyl chloride,
arsenic, copper sulphate, anabolic and other steroids.
Morphology - spongy haemorrhagic nodules throughout the liver.
- characteristically, malignant endothelial cells grow on the
surface of liver cell plates using them like a scaffold
(tectorial growth).
Spread to regional lymph nodes, spleen, lungs, bone, adrenals, brain.
Extremely poor prognosis.
METASTATIC TUMOURS
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Most common malignant liver tumour in the Western world.
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Metastases are present in the liver at autopsy in 40% of all patients
with malignant neoplasms.
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The liver is an especially common site for secondary spread from the
gastrointestinal tract, pancreaticobiliary tract, lung and breast.
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Morphology - single to innumerable deposits possible.
Large deposits at the surface may show “umbilification.”
TUMOUR-LIKE LESIONS
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Focal nodular hyperplasia.
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Nodular regenerative hyperplasia.
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Cysts - solitary, polycystic disease, hydatid cyst, choledochal cyst.
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Biliary hamartoma (von Meyenburg complex).
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Other exist.
Hepatoblastoma
Hepatoblastoma