Hepatic metastases are 18-40 times more common than primary liver tumors ⁶. Ultrasound, CT, and MRI are helpful in detecting hepatic metastases and evaluation across multiple post-contrast CT series, or MRI pulse sequences are necessary. 

Epidemiology

The demographics of patients with liver metastases will mirror that of the underlying primaries. Incidence, therefore, increases with age.

Clinical presentation

Liver metastases are usually asymptomatic and found during the workup of a malignancy. If the hepatic metastatic burden is large, then the presentation or symptoms related to the liver disease may include:

• localized pain and tenderness due to capsular stretching

• disordered liver metabolic function

• ascites

• low-grade fever ²

Pathology

The most common sites of primary malignancy that metastasize to the liver are ²:

• gastrointestinal tract (via portal circulation)

  • colorectal carcinoma (termed colorectal liver metastases, CRLMs)

  • pancreatic ductal adenocarcinoma

  • esophageal cancer

  • gastric carcinoma

  • gastrointestinal stromal tumor

  • neuroendocrine tumors

• breast cancer

• lung cancer

• genitourinary system

  • ovarian cancer

  • endometrial cancer

  • renal cell carcinoma

  • ureteral and bladder cancer ¹⁴

• melanoma

  • uveal melanoma

• sarcomas

• adrenocortical carcinomas ¹³

• essentially all metastatic solid malignancies

• testicular cancer ¹⁵

Radiographic features

One of the main difficulties in liver imaging for metastatic disease is the high prevalence of benign liver lesions that can be misinterpreted as evidence of metastatic disease, thus dramatically changing a patient's stage, and therefore treatment options. Liver hemangiomas, and to a lesser degree focal nodular hyperplasia (FNH), are the main sources of confusion ³. Additionally, pseudolesions (e.g. transient hepatic attenuation differences (THADs), focal fatty sparing / focal fatty change) may further muddy the waters. Therefore, an understanding of the various appearances of metastatic disease is crucial.

Ultrasound

Routine greyscale ultrasound, contrast-enhanced ultrasound, and intra-operative ultrasound all have roles to play.

Unfortunately, not only do metastases have a wide range of appearances, but background echogenicity changes of the liver due to fatty change make absolute statements difficult to make. In general, however, metastases may appear as ³:

• rounded and well-defined

• positive mass effect with distortion of adjacent vessels

• hypoechoic: most common ~65% and is a concerning feature ⁸

• hypoechoic halo due to compressed and fat-spared liver

• cystic, calcified, infiltrative and echogenic appearances are all possible: see liver metastases ultrasound appearances

Contrast-enhanced ultrasound has similar characteristics to CT, able to distinguish between hypovascular liver lesions, and hypervascular liver lesions.

See also: ultrasound appearance of hepatic metastases.

CT

Liver metastases are typically hypoattenuating on unenhanced CT, enhancing less than surrounding liver following contrast ¹. If there is concomitant hepatic steatosis, then the lesions may be iso- or even slightly hyperattenuating. Enhancement is typically peripheral, and although there may be central filling in on portal venous phase, the delayed phase will show washout; helpful in distinguishing a metastasis from a hemangioma ¹.

Some primaries have a tendency to produce hyper-enhancing metastases, including renal cell carcinoma, thyroid carcinoma, neuroendocrine tumors, etc. (see hypervascular liver lesions).

MRI

The appearance of liver metastases on MRI is also variable, but MRI is more sensitive than CT for the detection of liver metastases ⁵. MRI examination of the liver may involve numerous sequences (see liver MRI protocol), and choice of the gadolinium contrast agent (extracellular contrast agent or Eovist) is an important consideration.

The most frequent appearances are ⁵:

• T1: moderately hypointense

• T2: mildly to moderately hyperintense

• T1 C+ (Gd): enhancement may be lesional or perilesional (enhancement outside the confines of the T1 delineated lesion) ⁷

  • small lesions (<1.5 cm) tend to uniformly enhance

  • larger lesions (>1.5 cm) tend to show transient rim enhancement (i.e. with washout); helpful feature in distinguishing a metastasis from a liver hemangioma

  • perilesional enhancement is most commonly seen in colorectal and pancreatic adenocarcinoma metastases ⁵

• T1 C+ (Eovist/Primovist):

  • Eovist/Primovist is often useful for detection and confirmation of metastatic disease

  • on the delayed phase, metastatic lesions do not retain any Eovist/Primovist and essentially appear as "holes" in the liver

• DWI/ADC b600-800: restricted diffusion with ADC values lower than those of the surrounding parenchyma¹⁸

Fluid-fluid levels are considered a specific finding for neuroendocrine tumor metastases ⁹.

Radiology report

The following should be included in the radiology report ¹⁷:

• number, size and location (using the Couinaud classification) of tumor(s)

• relationship to the main portal pedicles and hepatic veins

• portal vein patency

• radiological signs of portal hypertension

• extrahepatic metastatic disease

Treatment and prognosis

Hepatic metastases from colorectal adenocarcinoma can potentially be treated with hepatic metastasectomy, since they may be the only site of metastatic disease. Up to 20% of patients undergoing metastasectomy for this indication remain disease-free ¹⁰. Multiple staging systems for disease-free survival after metastasectomy have been proposed and are being refined. One of the more frequently used systems (e.g. "Fong" score) includes variables such as ¹¹:

• node-negative primary

• single hepatic metastasis

• hepatic metastasis size <5 cm

• CEA <200 ng/mL

• disease-free interval >1 year

These variables suggest a better metastasectomy disease-free survival.

Transarterial chemotherapy and radioembolization are other options for the treatment of hepatic metastases. MRI-guided adaptive radiation therapy is a new and unique method of liver tumor treatment for both primary and metastatic disease ¹⁶.

Differential diagnosis

General differential imaging considerations include:

• hepatic hemangioma: usually hyperechoic, geographic, no mass effect, discontinuous peripheral nodular enhancement and 'filling in' ¹

• multiple hepatic cysts: no enhancement or mural nodules; can be hyper-dense/intense due to blood or infection

• hepatocellular carcinoma (HCC): hypervascular, more often solitary, possible hypoechoic US halo, cirrhotic liver, vascular invasion

• focal nodular hyperplasia (FNH)

  • often younger patients

  • central scar, with persistent delayed enhancement

• hepatic adenoma

• transient hepatic attenuation differences (THAD): often in cirrhosis

• multifocal fatty infiltration/focal fatty sparing: periligamentous, perivascular distribution; MRI in-out phase signal changes, vessels course through "lesions"; no mass effect

• ​multiple biliary hamartomas

• cholangiocarcinoma: delayed enhancement, capsular retraction 

• multiple liver abscesses: possible CT cluster sign and right pleural effusion

• hepatic peliosis

• primary non-Hodgkin lymphoma ¹²