The liver is a common site of metastatic disease for numerous cancers, most frequently gastrointestinal and haematolymphoid tumours.
Epidemiology
In Australia, most malignancies involving the liver are secondary deposits of cancer from other primaries (40:1 ratio). This is in contrast to Asia where the ratio is closer to 3:1 and in Africa where hepatocellular carcinoma is more common, in part due to endemic hepatitis B infection as well as shorter life expectancy.
Aetiology and Pathogenesis
The reason the liver is a common site of metastasis is thought to be a combination of:
- High blood supply
- In the case of gastrointestinal tumours, all draining blood passes through the liver through the portal system rather than the systemic circulation, perhaps accounting for the high rate of liver metastases in these tumours
- Tumour cell arrest by Kuppfer cells in the sinusoids of the liver parenchyma
- Ease of angiogenesis
Natural History
Liver metastases may occur as single deposits in several tumour types (colorectal carcinoma, neuroendocrine carcinoma and renal cell carcinoma) but in most other malignancies hepatic metastases develop in conjunction with metastases in other sites (eg. lung, bone, brain - eg: breast cancer). The most common site of origin are tumours of the upper gastrointestinal tract and colorectal cancer. About half of patients with metastatic breast and lung cancer develop liver metastases. A third of those with metastatic tumours of the bladder will develop liver lesions. Prostate and ovarian carcinomas spread to the liver uncommonly. Lymphoma involves the liver in about 20% of cases. Metastatic sarcoma rarely spreads to the liver (1/20 cases), preferring the lung.
Clinical Presentation
Patients may present with symptoms relating to enlargement of the liver (right upper quadrant pain, bloating), liver failure (jaundice, ascites) or general symptoms of metastatic disease (fatigue, anorexia, cachexia). There may be no symptoms in oligometastatic disease and no signs on examination either. Patients with extensive metastases may have massive hepatomegaly or other signs of liver failure (ascites, splenomegaly, jaundice).
Imaging with ultrasound or CT demonstrate the liver lesions over 5 mm in size if contrast is used. PET scanning is useful for detection of liver metastases in otherwise asymptomatic patients. MRI provides excellent detection of liver metastases but is usually unnecessary unless there is small oligometastatic disease. Bloods may return abnormalities of the liver function tests, with alterations in coagulation profile and albumin levels in cases of liver failure.
Tumour/Normal Tissue Features
Macroscopic
The macroscopic appearance of a liver lesion may give some clue as to its site of origin.
- Central necrosis is a common feature
- Mucinous adenocarcinomas may have a gelatinous surface
- Neuroendocrine carcinomas have a fish-flesh like texture
- Melanomas are usually pigmented
Microscopic
Microscopic features often allow classification into the appropriate site of origin. Differentiation from primary hepatocellular carcinoma is usually easy as it has well defined cytological and immunohistochemical features (eg. sinusoids, hepatocyte antigen positivity). Intrahepatic cholangiocarcinoma may mimic (or be mimicked by) adenocarcinomas from other sites and differentiation may be difficult if the classical features of each option are not present. Neuroendocrine, squamous cell carcinomas, lymphomas and sarcomas have typical appearances and this allows them to be easily distinguished from primary hepatic lesions.
Prognosis
Most patients die within one year unless they have oligometastatic disease that is resectable and they are fit for surgery.
