Malignant Liver Tumours 14621

Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma is the commonest primary hepatic malignancy (80%-90%) representing over 5% of all cancers . There are 500,000 to one million new cases each year worldwide (Bruix et al. 2001). It is commoner in developing countries but its incidence is rising in the West. It is commonly associated with liver cirrhosis particularly secondary to high alcohol consumption. HCC develops from dysplastic nodules and there are three steps in development; regenerative nodule; dysplastic nodule (low grade; high grade with focus of HCC) and small HCC (Wanless 1996). The lesions have been classified as expanding, spreading or multifocal and can be classified from grade I to IV based on histological criteria (Edmondson and Steiner 1954). Normal contrast enhanced MRI shows non-specific variable signal intensity changes although most (80%) are hyperin-tense on T2 weighted images. Signal intensity on T1 weighted images correlates with histological grade with high signal intensity seen more commonly in well-differentiated disease. A low intensity rim may be seen on T1 weighted images due to the presence of a well-defined capsule surrounding the tumour (Grazioli et al. 1999). Where this is present it is associated with improved prognosis and allows differentiation from metastatic deposits and cholangiocarci-noma. The vascular supply of the tumour is typically from the systemic arterial supply and HCC typically shows a peak of contrast enhancement during the arterial phase of multiphasic contrast enhanced studies. Multiphasic imaging is of utmost importance for the detection of small HCCs since they are often isointense on other pulse sequences and on portal and late phase images. A relationship between tumour grade and peak contrast enhancement has been demonstrated with a lower peak enhancement relating to smaller and better differentiated lesions (Yamashita et al. 1994). Poorly differentiated lesions may not show this early peak enhancement and can be difficult to distinguish from other tumour types.

HCC typically spreads by vascular invasion along the hepatic portal vein and dynamic contrast enhanced MR studies allow identification of such embolic growth due to the early arterial phase of enhancement of the intravenous tumour mass.

Hepatocellular carcinomas contain Kupffer cells and functioning hepatocytes so that liver specific contrast agents will produce enhancement (Tanaka et al. 1996). All HCCs demonstrate enhancement with Mn-DPDP and enhancement is greater in patients with well-differentiated tumours (Rofsky and Earls 1996). Hepatocytic uptake has also been demonstrated with the Gd-BOPTA and has again been shown to be greater in well-differentiated lesions (Manfredi et al. 1999). Signal characteristics of HCCs following administration of RES-specific contrast agents vary depending on the number of Kupffer cells within the lesion (Lim et al. 2001), although most tumours do not show a significant decrease in signal intensity. The signal intensity of normal liver does of course decrease improving the contrast noise ratio and improving lesion identification. There have been many studies addressing the sensitivity and specificity of different imaging approaches for the identification of HCC. Contrast enhanced multiphasic imaging certainly appears to be of significant value in the detection of small tumours whilst the use of ferru-moxides alone, or in combination with conventional multiphasic imaging with a gadolinium chelate provide significant improvements in diagnostic accuracy for larger tumours (Asahina et al. 2003).

Cholangiocellular Carcinoma

Cholangiocarcinoma is the second most common primary liver tumour after HCC representing 10% of all primary hepatic malignancies. MRI demonstrates peripheral high signal on T2 weighted images with a central hypointense area due to scar tissue. Multi-phasic contrast enhanced studies showed progressive moderate enhancement in the peripheral part of the tumour. Although the morphological pattern of enhancement is similar to that seen in haemangio-mas the rate of enhancement is far slower.

Metastatic Disease

Metastatic deposits are by far the most common malignant lesions seen in the liver and metastatic spread to the liver is one of the most important disease patterns in clinical oncology. As many as 50% of patients dying from malignancy will have meta-static disease in the liver at autopsy and the presence and extent of liver metastasis are a major prognostic feature in a broad range of tumour types. The role of radiological investigations is to identify the presence of metastatic lesions, to distinguish them from less sinister benign abnormalities that may also be present and to identify their location to determine whether or not the disease is treatable by resection or partial hepatectomy.

MRI is extremely efficient at differentiating between metastasis and benign lesions such as hae-mangiomas or cysts (Mitchell, Saini, Weinreb et al. 1994). Most liver metastatic deposits will appear hypointense on T1 weighted images and hyperin-tense on T2. Although the signal intensity on T2 weighted images is usually less than typically seen in haemangiomas and benign cystic lesions there may be confusion particularly where metastatic deposits have areas of central necrosis or cyst formation (Bartolozzi et al. 1999). Some endocrine tumour deposits may also demonstrate extremely high signal on T2 weighted images (these include carcinoid, islet cell tumour, renal carcinoma, thyroid carcinoma and phaeochromocytoma) (Morana et al. 2002). Meta-static disease from malignant melanoma will show different signal characteristics due to the presence of paramagnetic melanin within the tumour cells. This produces deposits which may be hyperintense on T1 weighted images and hypointense on T2.

Metastatic deposits may demonstrate heterogeneous signal intensity due to central areas of liquefac-tive necrosis or haemorrhage. These areas will show high signal on T2 weighted images often associated with a decrease in signal intensity on T1. This appearance, described as a target lesion, is highly indicative of malignancy and therefore of metastatic disease.

Multiphasic contrast enhanced imaging provides valuable additional information concerning the characterisation and extent of metastatic disease (see Fig. 14.6). Most metastatic lesions are hypovascular and show little or no enhancement during the arterial phase. Enhancement occurs predominantly in the peripheral component of the tumour with no enhancement being seen in central necrotic areas, even on late phase images. These typical enhancement patterns are not however seen in all metastatic liver deposits and a significant number will be hypervascular (these include carcinoid, islet cell tumour, renal carcinoma, thyroid carcinoma, phaeochromocytoma, melanoma and the breast carcinoma) with rapid enhancement during the arterial phase often associated with apparent hypointensity on later phases due to rapid washout of the contrast media from the hypervascular, high flow peripheral component of the tumour.

Metastatic lesions typically have a very variable vascular supply and are capable of parasitising arterial input from both the systemic arterial and hepatic portal systems. The vascular supply may therefore represent any admixture of these two sources, which can give rise to difficulties in the interpretation of enhancement patterns from multiphasic studies. Despite this there is considerable evidence that multiphasic contrast enhanced imaging does enhance the detection of focal liver lesions when compared with unenhanced studies. However, hepatic biliary and RES-targeted agents provide a more reliable method for enhancing the contrast between pathological areas and normal liver and significantly improve the detection of liver metastasis and the accuracy of surgical planning.

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