Hepatic metastases are 18-40 times more common than primary liver tumors 6. Ultrasound, CT, and MRI are all useful for detection of hepatic metastases and evaluation across multiple post-contrast CT series, or MRI pulse sequences are necessary.
The demographics of patients with liver metastases will mirror that of the underlying primaries. Incidence, therefore, increases with age.
Liver metastases are usually asymptomatic and found during workup of a malignancy which has presented in other ways. 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
- low-grade fever 2
The most common sites of primary malignancy that metastasize to the liver are 2:
- gastrointestinal tract (via portal circulation)
- breast cancer
- lung cancer
- genitourinary system
- adrenocortical carcinomas 13
- essentially all metastatic solid malignancies
- testicular cancer 15
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 patients 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.
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
See also: ultrasound appearance of hepatic metastases.
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.
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.
Most frequent appearances are 5:
- T1: moderately hypointense
- T2: mildly to moderately hyperintense
T1 C+ (Gd): enhancement may be lesional or perilesional 7 (enhancement outside the confines of the T1 delineated lesion)
- small lesions (<1.5 cm) tend to uniformly enhance.
- larger lesions (>1.5 cm) tend to show transient rim enhancement (i.e. with wash-out); 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):
- Eovist is often useful for detection and confirmation of metastatic disease
- on the delayed phase, metastatic lesion do not retain any Eovist and essentially appear as "holes" in the liver
Fluid-fluid levels are considered a specific finding for neuroendocrine tumor metastases 9.
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 (Clinical risk score (CRS), "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 treatment for hepatic metastases.
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
- 1. Vogl TJ, Lencioni R, Hammerstingl RM et-al. Magnetic Resonance Imaging in Liver Disease, Technical Approach, Diagnostic Imaging of Liver Neoplasms, Focus on a New Superparamagnetic Contrast Agent. Thieme. (2003) ISBN:1588902366. Read it at Google Books - Find it at Amazon
- 2. Doherty GM, Way LW. Current surgical diagnosis & treatment. McGraw-Hill Medical. (2006) ISBN:007142315X. Read it at Google Books - Find it at Amazon
- 3. Lencioni R, Cioni D, Bartolozzi C. Focal liver lesions, detection, characterization, ablation. Springer Verlag. (2005) ISBN:3540644644. Read it at Google Books - Find it at Amazon
- 4. Lin E, Garg K, Escott E et-al. Practical differential diagnosis for CT and MRI. Thieme Medical Pub. (2008) ISBN:1588906558. Read it at Google Books - Find it at Amazon
- 5. Semelka RC. Abdominal-pelvic MRI. Wiley. (2006) ISBN:0471692735. Read it at Google Books - Find it at Amazon
- 6. Namasivayam S, Martin DR, Saini S. Imaging of liver metastases: MRI. Cancer Imaging. 2007;7 : 2-9. doi:10.1102/1470-7330.2007.0002 - Free text at pubmed - Pubmed citation
- 7. Danet IM, Semelka RC, Leonardou P et-al. Spectrum of MRI appearances of untreated metastases of the liver. AJR Am J Roentgenol. 2003;181 (3): 809-17. AJR Am J Roentgenol (full text) - Pubmed citation
- 8. Wernecke K, Vassallo P, Bick U et-al. The distinction between benign and malignant liver tumors on sonography: value of a hypoechoic halo. AJR Am J Roentgenol. 1992;159 (5): 1005-9. AJR Am J Roentgenol (abstract) - Pubmed citation
- 9. Sommer WH, Zech CJ, Bamberg F et-al. Fluid-fluid level in hepatic metastases: a characteristic sign of metastases of neuroendocrine origin. Eur J Radiol. 2012;81 (9): 2127-32. doi:10.1016/j.ejrad.2011.09.012 - Pubmed citation
- 10. Pulitanò C, Castillo F, Aldrighetti L et-al. What defines 'cure' after liver resection for colorectal metastases? Results after 10 years of follow-up. HPB (Oxford). 2010;12 (4): 244-9. Free text at pubmed - Pubmed citation
- 11. Fong Y, Fortner J, Sun RL et-al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann. Surg. 1999;230 (3): 309-18. Free text at pubmed - Pubmed citation
- 12. Paschalidis N, Kalaitzis J, Voultsos M, Marinis A, Rizos S. Primary non-hodgkin lymphoma of the liver mimicking metastases. (2016) Hellenic Journal of Surgery. 83 (2): 98. doi:10.1007/s13126-011-0018-1 - Pubmed
- 13. Toro A, Di Carlo I. Liver Metastases from Adrenocortical Carcinomas. (2018) International urogynecology journal. 27 (3): 1. doi:10.1007/978-3-319-09293-5_1 - Pubmed
- 14. Tatokoro M, Kihara K. Liver Metastases from Ureteral and Bladder Cancer. (2018) International urogynecology journal. 27 (3): 175. doi:10.1007/978-3-319-09293-5_14 - Pubmed
- 15. Kimakura M, Abe T, Nagahara A, et al. Metastatic testicular cancer presenting with liver and kidney dysfunction treated with modified BEP chemotherapy combined with continuous hemodiafiltration and rasburicase. (2016) Anti-cancer drugs. 27 (4): 364-8. doi:10.1097/CAD.0000000000000334 - Pubmed