Investigating focal liver lesionsBMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e657 (Published 08 February 2012) Cite this as: BMJ 2012;344:e657
- Dhruv V Patel, specialist registrar, clinical radiology,
- Victoria Scott, foundation year 2 doctor,
- James Pilcher, consultant radiologist
- Correspondence to: D Patel
Incidental liver lesions on medical imaging are relatively common and the vast majority are benign
Fatty infiltration is increasing in prevalence and can make the detection and characterisation of focal liver lesions difficult
The choice of and need for further investigation when a focal liver lesion is identified depends on several patient factors and ideally should be recommended by the reporting radiologist
Contrast enhanced ultrasonography, computed tomography, and magnetic resonance imaging of focal liver lesions rely on the recognition of characteristic enhancement patterns
Biopsy may be needed where imaging fails to characterise a lesion adequately
A 31 year old Anglo-Indian man presented to his general practitioner for a discussion of cardiovascular risk factors because of a strong family history of ischaemic heart disease. He had no medical history of note. The patient denied excessive consumption of alcohol, although he admitted to a relatively unhealthy, high fat diet. Routine liver function tests showed raised alanine aminotransferase and aspartate aminotransferase. The patient was subsequently referred for abdominal ultrasonography, which showed moderate fatty change throughout the liver and an incidental 2.4 cm focal mass of mixed reflectivity in segment VII (fig 1⇓).
What is the next investigation?
Various imaging methods incidentally show focal liver lesions. The primary function of investigating a focal liver lesion is to characterise it with confidence as either needing no or only routine follow-up, or needing further, more rigorous exploration (including biopsy). The exclusion of malignancy is paramount, and most benign lesions can be characterised on non-invasive imaging grounds alone.
Conventional ultrasonography is often used as the first line imaging investigation for assessment of the liver and focal liver lesions as it is non-invasive, readily available, safe, and inexpensive. Conventional ultrasonography, however, is limited in that many focal lesions display overlapping and similar morphological features such as reflectivity, size, and shape. Further imaging of these focal lesions with computed tomography or magnetic resonance is common and is based predominantly on the administration of intravenous contrast agents. As different liver lesions vary in their blood supply, administration of a contrast agent allows evaluation and characterisation of the enhancement pattern of the lesion with respect to the background liver. In the diagnosis of the focal liver lesion, magnetic resonance imaging has higher sensitivity and specificity (82.1% and 93.4% respectively)1 than computed tomography (71.0% and 64.5%).
Contrast enhanced ultrasonography, which has been used increasingly in recent years, has been shown to perform as effectively as contrast enhanced computed tomography or magnetic resonance imaging.2 3
In this patient, non-alcoholic fatty liver disease is likely to account for the diffuse background changes seen in the liver and the derangement of the liver function enzymes. However, the underlying nature of the incidental focal hepatic lesion needs to be established.
The differential diagnosis for a focal liver lesion includes simple hepatic cyst, haemangioma, focal nodular hyperplasia, focal fatty infiltration or sparing, and hepatic adenoma and malignancy, either primary or secondary. The table⇓ summarises the common features of these lesions.
It is good standard radiological practice when reporting any notable incidental lesion for the radiologist to recommend or arrange any further necessary imaging. Figure 2⇓ shows a simplified protocol that our centre uses for investigating an incidental liver lesion. We emphasise the need always to consider further investigation in conjunction with other general factors, such as the patient’s age, preferred investigation, and comorbidity and the local availability of imaging methods and expertise.
Computed tomography allows for the assessment of the internal composition of focal hepatic lesions. When combined with contrast enhancement, computed tomography can show the enhancement characteristics of a lesion via a triple phase technique. The liver is initially imaged before the administration of intravenous contrast, (that is, unenhanced). The next series of images (the arterial phase) is obtained about 20 to 30 seconds after the injection of the contrast agent, as it enters the liver via the hepatic artery. The next series (the portal venous phase) is done 60 to 70 seconds later, with the images showing contrast returning from the mesenteric veins via the portal vein to the liver. Delayed images may be optionally obtained at 10-15 minutes after injection of the contrast agent (equilibrium phase). The observed features can then be examined and correlated with the typical features of several lesions, both benign and malignant.
Unfortunately the triple phase technique has the drawback of a substantial radiation dose (10-20 mSv12) and requires the use of iodinated contrast. The use of contrast material in patients with impaired renal function is contraindicated as there is an increased risk that the contrast will induce nephropathy. The exact threshold of serum creatinine concentration or of estimated glomerular filtration rate that precludes the administration of contrast agent varies between institutions, but typically the agent would not be administered if the creatinine concentration was >150-200 μmol/L or the estimated glomerular filtration rate <30 mL/min/1.73 m213; in this situation, alternative imaging modalities should be considered.
In addition, for small lesions (typically <1 cm in diameter), computed tomography may not have the capacity to produce images with optimal resolution as it cannot resolve or visualise objects below a certain size (“partial volume” artefact).
Magnetic resonance imaging
Magnetic resonance imaging can evaluate the internal chemical composition of a lesion and is especially useful for evaluating cystic hepatic abnormalities. It does not use ionising radiation but is time consuming and relatively expensive and requires the patient to lie extremely still. In combination with contrast agents, magnetic resonance imaging (like computed tomography) can examine the enhancement features of a lesion but again may suffer from partial volume artefact when dealing with smaller abnormalities.
Claustrophobic patients are unsuitable for magnetic resonance imaging, and gadolinium based contrast is contraindicated in patients with renal impairment owing to the risks of systemic nephrogenic fibrosis associated with that contrast.14 Liver specific contrast media can be used, often as second line “problem solving” agents to distinguish between focal liver lesions of hepatocellular origin and those of non-hepatocellular origin.
Biopsy of a focal lesion under image guidance, either computed tomography or more commonly ultrasonography, enables histological analysis and in the vast majority of patients is a safe and accurate procedure.15 However, this is typically considered only when imaging has failed to characterise an abnormality with certainty. It carries the inherent risks of percutaneous biopsy; a recent study of 539 image guided liver biopsies recorded a complication rate of 2%,15 predominantly relating to post-procedural pain and symptomatic haemorrhage. Biopsy of a focal lesion under image guidance is also time consuming, with the patient requiring preprocedural coagulation testing and most centres advocating a period of bed rest after the biopsy.16
Isotope radiolabelled scanning is perhaps most useful in those patients for whom pre-existing renal dysfunction precludes contrast enhancement in computed tomography or magnetic resonance imaging. It can allow for lesion characterisation by displaying uptake by differing cell type. For example, Kupffer cell activity seen in cases of focal nodular hyperplasia and less often within hepatic adenomas can result in focal increased and persistent tracer uptake on technetium sulfur colloid scans. Radiolabelled red cell scanning is also useful in diagnosing haemangiomas. In cases of known or suspected malignancy, positron emission tomography-computed tomography (PET-CT) may also be of value. Such examinations, however, carry an inherent radiation dose and have relatively poor spatial resolution. In addition, many causes of false positive results for uptake exist, and availability of radiotracer can be a problem.
Contrast enhanced ultrasonography
Contrast enhanced ultrasonography is a fairly recent tool in the detection and characterisation of focal liver lesions, including those <1 cm in diameter. It can often obviate the need for further cross sectional imaging in investigating focal liver lesions,17 18 with the potential for substantial cost savings.19 20 A recent multicentre study found that for diagnosing focal liver lesions, contrast enhanced ultrasonography was more sensitive and specific (95.5% and 70.5% respectively) than contrast enhanced magnetic resonance imaging (81.8% and 42.9%) or contrast enhanced computed tomography (72.2% and 37.5%).17
The microbubble contrast agents used with ultrasonography consist of an inert gas or air surrounded by a protein or phospolipid shell; unlike other contrast agents, they act as pure blood-pool enhancement agents. Contrast enhanced ultrasonography is a relatively rapid procedure requiring placement of an intravenous cannula. It does not use radiation and is a suitable technique in patients with renal dysfunction, no matter how severe. Its use is limited, however, in those with end stage cardiac failure, and its safety and efficacy is untested in pregnant patients and children. Its availability is currently limited by local expertise but is expected to expand as experience and confidence in the technique increase. Its use also requires additional software on ultrasound scanners.
Our patient initially had gadolinium enhanced magnetic resonance imaging, as recommended by the radiologist’s report on the initial ultrasound scan. The gadolinium enhanced magnetic resonance scan confirmed the segment VII abnormality (fig 3⇓). The lesion showed isointensity to the liver on standard T1 and T2 weighted images but was hyperintense on fat saturated images, reflecting the diffuse background fatty change of the liver. After contrast injection, persistent hyperenhancement of the lesion was visible. The differential diagnosis as a result of magnetic resonance imaging was between focal nodular hyperplasia and hepatic adenoma. Contrast enhanced ultrasonography was then recommended, and this showed a well defined mass with enhancement of a central feeding vessel and spoke-wheel radial branches, consistent with focal nodular hyperplasia (fig 4⇓). Repeat contrast enhanced ultrasonography six months later was entirely stable (fig 5⇓), although the fatty infiltration had improved slightly after dietary modification. In this case, after the initial conventional ultrasound scan, either contrast enhanced ultrasonography or magnetic resonance imaging would have been an appropriate next investigation.
Cite this as: BMJ 2012;344:e657
This series provides an update on the best use of different imaging methods for common or important clinical presentations. The series advisers are Fergus Gleeson, consultant radiologist, Churchill Hospital, Oxford, and Kamini Patel, consultant radiologist, Homerton University Hospital, London. To suggest a topic for this series, please email us at.
Contributors: DVP prepared the manuscript and selected the patient and images; VS and JP contributed to the editing. DVP is the guarantor.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned; externally peer reviewed.
Patient consent obtained.