Figures 1 and 2: Axial T1-weighted in-phase images demonstrate a large mass in the right hepatic lobe with slight T1 hyperintensity lesion. The liver is cirrhotic.

Figure 3: Axial T2-weighted fast spin echo image, demonstrates T2 hyperintense satellite lesions.

Figure 4: Arterial phase VIBE image demonstrates heterogeneous peripheral enhancement of the large mass in the right hepatic lobe. There are also multiple areas of enhancement in the periphery of the liver consistent with a diffusely infiltrative process.

Figure 5: Portal venous phase VIBE image demonstrates that the large mass in the right hepatic lobe becomes hypointense and the peripheral infiltrating lesions become isointense to the rest of the liver parenchyma.

Figure 6: Portal venous phase VIBE image demonstrates a filling defect (arrow) in the main portal vein which enhances, and is thus consistent with tumor thrombus.

Diffuse infiltrative hepatocellular carcinoma with invasion into the main portal vein.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy, accounting for 82% of malignant epithelial neoplasms of the liver. It is the fifth most common cancer worldwide. Hepatitis B and C confer a 20-fold increased risk for developing HCC. In North America, HCC tends to arise in patients with cirrhosis from alcohol, viral hepatitis, chronic active hepatitis, and hemochromotosis. Serum alpha-fetoprotein is a reliable marker that is elevated in 70-80% of cases.

Hepatocellular carcinoma is considered to arise from dysplastic nodules and to progress in a stepwise fashion from early HCC to advanced HCC. Although HCC is commonly associated with cirrhosis, HCC may occur in its absence. Cirrhosis is present in 67-96% of patients with HCC in Asia and in 38-50% of patients in the West. On gross pathology, in the normal liver, HCC typically presents as a solitary, well-defined mass. HCC in a cirrhotic liver can demonstrate three major morphologic patterns: single or massive HCC, multifocal or nodular HCC that mimics metastasis, or diffuse HCC. HCC is solitary in approximately 50%, multifocal in approximately 40%, and diffuse in less than 10% of cases. The massive (solitary) form consists of a large solitary and infiltrating tumor, and in most cases there is no underlying cirrhosis. The nodular form is characterized by the presence of one or more encapsulated or non-encapsulated nodules and is seen predominantly in the cirrhotic liver. The diffuse form, is characterized by miliary infiltration of the liver parenchyma. An external fibrous pseudocapsule is present in 30-67% of cases and, occasionally, tumors may be pedunculated. The massive and nodular types of HCC are typically hypervascular, with blood supply predominantly derived from the hepatic artery. HCC may exhibit intratumoral necrosis, hemorrhage, and fatty change, which progress as the tumor grows in size. Calcification occurs in 2-12% of tumors. HCC is distinguished from secondary liver cancers by its propensity to invade into and grow within the portal vein (62% of autopsy cases), hepatic vein (26%), and bile duct (10%).

Radiological imaging plays a crucial role in the clinical management of this disease, with respect to diagnosis and patient follow-up. The underlying cirrhosis that occurs in most patients with HCC complicates the detection of HCC with computed tomography (CT) and magnetic resonance (MR) imaging.

The MR imaging features of hepatocellular carcinoma vary with the size of the tumor, the histologic pattern, the degree of tumor differentiation, the amount of fibrosis, the presence of hemorrhage, the degree of tumor vascularity, and the intracellular content of glycogen, fat or metal ions. The nodular type HCC is often well defined and possibly encapsulated. The diffuse form of HCC is poorly marginated and shows an infiltrative pattern, with a high tendency to invade the portal vein branches. The signal intensity of HCC may be inhomogeneous and vary greatly. HCC typically appears isointense to hyperintense on T2-weighted images and has variable signal intensity on T1-weighted images. High signal intensity within a HCC lesion on T1-weighted images may reflect the presence of a copper-binding protein. In early advanced hepatocellular carcinoma the appearance of a low signal intensity nodule within a high intensity nodule (“nodule within nodule”) has been described on T1-weighted images. The majority of HCC tumors are hypervascular, but some are very hypovascular. On chemical shift MR imaging, HCC tumors usually do not demonstrate signal drop-out on the in and out of phase images because fatty change occurs in no more than 10% of HCC lesions.

On dynamic gadolinium-enhanced MR imaging, HCC lesions will enhance in the arterial phase because of the abundant neovascularity. In the portal phase, HCC lesions are usually isointense. In the delayed phase, HCC lesions appear hypointense because of wash-out of contrast. Some HCC tumors, however, demonstrate progressive enhancement, or minimal/slight enhancement during dynamic imaging. Small HCC, measuring < 1.5 cm are frequently isointense on both T1- and T2-weighted images and can be detected only on immediate gadolinium-enhanced images as diffuse, homogeneously enhancing lesions. Therefore, the most sensitive sequence for detecting small HCCs is hepatic arterial dominant phase images. Diffuse infiltration with HCC may be subtle or simulate the appearance of acute or chronic hepatitis or recent onset scarring on imaging studies.

In the normal liver, HCC must be differentiated from benign entities such as hepatocellular adenoma and FNH, as well as other primary hepatic malignancies and metastatic disease. Features such as the presence of a central scar is characteristic of FNH, while intra-tumoral hemorrhage and the presence of fat is indicative of hepatic adenoma. Tissue specific contrast agents such as mangafodipin trisodium (Mn-DPDP) and superparamagnetic iron oxides (SPIO) particles cannot differentiate between well-differentiated HCC, regenerative or dysplastic nodules, adenoma or focal nodular hyperplasia. These agents are taken functioning hepatocytes (Mn-DPDP) and Kupffer's cells (SPIO), which can be found in all these entities. HCC can be differentiated from metastatic disease based on the lesion's appearance on hepatic arterial dominant phase gadolinium-enhanced images. HCC typically demonstrates enhancing stroma throughout the entire tumor, whereas, metastases have peripheral enhancement. Detecting hepatocellular carcinoma in a cirrhotic liver continues to be an imaging challenge despite recent advances in imaging technology. A study by Krinsky et al demonstrated that MR imaging, when correlated with explant pathology, is insensitive for detection of small (<2 cm) HCCs and dysplastic nodules in cirrhotic livers, but it may be useful in detecting HCCs larger than 2 cm.

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