1. Tumours of the liver
John J O’Leary

2. TUMOURS AND TUMOUR-LIKE LESIONS
Benign epithelial tumours Liver cell adenoma Bile duct adenoma Bile duct cystadenoma Biliary papillomatosis
Focal nodular hyperplasia
Benign non-epithelial tumours Haemangioma Others are very rare

3. Ultrasound of
a benign liver
tumour

4. Liver cell adenoma: Women of childbearing age
Assoc. with use of the OCP
Risk of rupture and haemorrhage

5. Molecular genetics of liver cell adenoma
Transcription factor 1 (TCF1) mutations in liver cell adenoma tumorigenesis (Bluteau et al., 2002b).

6. Malignant epithelial tumours. Hepatocellular carcinoma. Hepatoblastoma
Malignant epithelial tumours Hepatocellular carcinoma Hepatoblastoma Cholangiocarcinoma Bile duct cystadenocarcinoma.
Malignant non-epithelial tumours Angiosarcoma Other sarcomas and other tumours are rare.
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.

7. HEPATOCELLULAR CARCINOMA
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).

11. 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

23. Hep B and hepatocellular carcinoma: ICC

24. 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)

25. Potential ethanol-related genes in Hepatocellular cancer

27. BILE DUCT CARCINOMA (CHOLANGIOCARCINOMA)
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.

30. ANGIOSARCOMA 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.

33. METASTATIC TUMOURS
Most common malignant liver tumour in the Western world.
Metastases are present in the liver at autopsy in 40% of all patients with malignant neoplasms.
The liver is an especially common site for secondary spread from the gastrointestinal tract, pancreaticobiliary tract, lung and breast.
Morphology - single to innumerable deposits possible Large deposits at the surface may show “umbilification.”

35. TUMOUR-LIKE LESIONS Focal nodular hyperplasia.
Nodular regenerative hyperplasia.
Cysts - solitary, polycystic disease, hydatid cyst, choledochal cyst.
Biliary hamartoma (von Meyenburg complex).
Other exist.

36. Hepatoblastoma

38. Hepatoblastoma