Imaging features of metastatic liver cancer

Background

US has been used since the 1970s, and conventional US has unique advantages, such as low cost, lack of radiation, and widespread availability. However, US is less sensitive than other imaging modalities for liver metastases. Experience and technique of the doctor or technician acquiring US images may also vary significantly. Some studies report sensitivity of US in detection of liver metastases to be as low as 38%. Although US contrast agents were introduced and used worldwide since the 1990s, United States Food and Drug Administration (FDA) approval of the first contrast agent for liver lesions in children and adults took place in 2015. CEUS uses microbubbles that enable the demonstration of tissue perfusion similar to contrast enhancement in CT and MRI, but with subtle differences. Numerous studies demonstrate increased sensitivity and specificity of CEUS compared with conventional US, with sensitivities ranging between 72% and 96% and specificities between 93% and 98%. For example, in a prospective study that evaluated detection of hepatic metastases with US, CEUS, and contrast-enhanced CT (CECT) in 253 patients with suspected hepatic metastases from various primary malignancies, CEUS improved sensitivity from approximately 40% to 83% and specificity from 63% to 84%. The sensitivity and specificity of CECT in the same study was demonstrated to be 89% and 89%, respectively.

According to the latest guidelines and good clinical practice recommendations for CEUS in the liver from 2012 that involved collaboration of multiple leading ultrasound societies worldwide, the indications for liver CEUS are the following :

• Incidental findings on conventional US

• Lesion(s) or suspected lesion(s) detected with US in patients with a known history of a cancer, as an alternative to CT or MRI

• Patients with contraindications to CT and MRI contrast administration

• Inconclusive MRI/CT findings

• Inconclusive biopsy results

US contrast agents are not nephrotoxic and are safe for use in patients with renal failure and even dialysis. These contrast agents are also safe in patients with iodine contrast allergies. The overall rate of severe allergic reactions is lower compared with iodinated CT contrast and is comparable to magnetic resonance (MR) contrast agents. ^,

Imaging findings

Although most metastases are hypoechoic (darker) with respect to the underlying liver parenchyma ( Fig. 15.1 A–B), some metastases can also be isoechoic (similar to) and hyperechoic (brighter) to adjacent liver ( Fig. 15.2 A–B). Echogenicity of liver metastases can vary, based on primary tumor and based on the composition of underlying liver parenchyma that can be affected by hepatic steatosis, prior chemotherapy treatments, and other forms of liver disease. Thus primary (benign or malignant neoplasms) and metastatic liver lesions may have similar US characteristics (Compare Fig. 15.2 B with Fig. 15.3 ); for example, metastases and hemangiomas (see Chapter 88A ) may both demonstrate hyperechoic appearance with respect to adjacent liver.

A hypoechoic halo sign (bull’s eye sign) is a helpful way to distinguish benign from malignant lesions. This is a sign of difference in acoustic impedance along the periphery compared with the center of the lesion, which reflects parenchymal compression and active growth on pathologic correlation. Therefore the halo sign is usually indicative of an expansile, malignant mass, such as a metastasis or a primary hepatic neoplasm ( Fig. 15.4 ).

Liver metastases demonstrate variable enhancement when evaluated with the CEUS technique. The arterial phase imaging characteristics vary between no enhancement, rim enhancement, and diffuse hyperenhancement. There is rapid, complete washout on the portal venous phase ( Fig. 15.5 ). In contrast, hepatocellular carcinoma (HCC) demonstrates a later washout, and benign lesions demonstrate minimal or absent washout. Cholangiocarcinoma (see Chapter 50 ) demonstrates rapid washout on CEUS (unlike on CT and MRI where it demonstrates progressive delayed enhancement) and, therefore, cannot be reliably distinguished from a metastasis.

Limitations and pitfalls

The quality of images is highly dependent on the operator’s skill and patient’s body habitus, with both traditional US and CEUS. Small lesions, particularly less than 0.5 cm, are usually not adequately visualized and characterized. Liver lesions subjacent to interposed bowel may be completely obscured by the shadowing artifact from air contained within bowel loops. Specific anatomic location also plays a role. For example, lesions adjacent to the diaphragm (particularly in segments VII and VIII) or near the heart are technically challenging to image because of motion and may be missed. Deep lesions in a setting of fatty liver are poorly visualized secondary to decreased acoustic penetration.

Peribiliary metastases are particularly challenging to diagnose, even with CEUS. One study demonstrated that in a group of 35 patients with proven peribiliary metastases, only one was visualized with CEUS. In the same study, all peribiliary lesions were detected on MRI.

Occasionally benign entities can mimic metastases on traditional US and CEUS. In the setting of hepatic steatosis, benign lesions, such as focal nodular hyperplasia (FNH), which is usually isoechoic to normal liver parenchyma, will appear hypoechoic (dark) relative to the liver (see Chapter 88A ). A hypoechoic lesion is often interpreted as metastatic disease ( Fig. 15.6 ). Focal fatty sparing or focal fat can mimic a mass lesion, particularly if it demonstrates an unusual shape or occurs in an atypical location. One study that looked at detection of metastases occult on conventional US with CEUS and MRI in cancer patients with hepatic steatosis demonstrated that in 1 out of 37 patients, CEUS misinterpreted geographic hepatic steatosis as metastases, which was correctly diagnosed with MRI.

Abscesses can be isoechoic, hypoechoic, or hyperechoic relative to the hepatic parenchyma and can present as a solid, partially cystic, or a predominantly cystic lesion (see Chapter 70 ). Acoustic through transmission and lack of internal flow on Doppler interrogation favors an abscess rather than a neoplastic process. However, necrotic or cystic metastases may contain substantial cystic components and may not demonstrate appreciable internal vascularity, which makes it difficult to differentiate them from an abscess. Other benign entities, such as tuberculosis (TB), sarcoidosis, and inflammatory pseudotumors, may present as mass lesions and can mimic metastatic disease. ^,