Diagnostic Imaging Pathways - Focal Liver Lesion (Investigation)
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This pathway provides guidance on imaging in patients with focal liver lesions, dependent on whether the patient has risk factors for primary cancer or metastases or whether the lesion is ‘incidental’.
Date reviewed: September 2015
Date of next review: 2017/2018
Published: February 2016
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Move the mouse cursor over the PINK text boxes inside the flow chart to bring up a pop up box with salient points.
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The relative radiation level (RRL) of each imaging investigation is displayed in the pop up box.
| SYMBOL | RRL | EFFECTIVE DOSE RANGE |
 | None | 0 |
 | Minimal | < 1 millisieverts |
 | Low | 1-5 mSv |
 | Medium | 5-10 mSv |
 | High | >10 mSv |
Images
Image GalleryNote: These images open in a new page | ||
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| 1 |  |
Hepatic Haemangioma Image 1 (Computed Tomography): Post-contrast images demonstrating initial peripheral enhancement, followed by delayed filling of the lesion with contrast. These features are typical of a haemangioma. |
| 2a |  |
Hepatic Haemangioma Image 2a, 2b and 2c (Triphasic Computed Tomography): Non-contrast scan (Image 2a) demonstrates a subtle low attenuation lesion in segment 6 of the liver (arrow). There is globular peripheral enhancement of the lesion in the post contrast arterial phase scan (Image 2b) with delayed filling in of the lesion in the portal venous phase (Image 2c). |
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| 2d |  |
Image 2d (Ultrasound): Ultrasound scan demonstrating the liver lesion in same patient. |
| 3a |  |
Hepatic Haemangioma
Image 3a (H&E, x2.5): Histological section of a hepatic haemangioma showing variously sized, dilated and congested blood vessels set in a fibrous stroma with residual islands of liver parenchyma. |
| 4a |  |
Hepatic Adenoma Image 4a and 4b (Computed Tomography): Coronal and axial views demonstrating several enhancing liver lesions. |
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| 4c |  |
Image 4c (Ultrasound): Ultrasound scan demonstrating the liver lesions in same patient. |
| 5a |  |
Hepatic Focal Nodular Hyperplasia Image 5a and 5b (Triphasic Computed Tomography): The arterial phase scan (Image 5a) shows a hyperattenuating nodular lesion (narrow arrow) with the typical central scar (broad arrow) in segment 4 of the liver. On the delayed portal venous phase (Image 5b), the lesion becomes isoattenuating (arrow). |
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Hepatic Focal Nodular Hyperplasia Image 6a, 6b, 6c and 6d (Magnetic Resonance Imaging): Gadolinium-enhanced T1-weighted MRI (Image 6a) demonstrates an ill-defined low-signal intensity mass in segment 4 of the liver with intense enhancement in the arterial phase (Image 6b). Minor enhancement persists in the portal venous phase (Image 6c) and the lesion becomes isointense with enhancement of the central scar (arrow) on the delayed image (Image 6d). |
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| 7 |  |
Simple Hepatic Cyst Image 7 (Ultrasound): Simple-appearing cyst in the left lobe of liver. |
| 8a |  |
Hepatocellular Carcinoma Image 8a and 8b (Ultrasound): Within segment 6 of the liver, there is an approximately 2cm subcapsular hypoechoic lesion (arrow) which does not demonstrate any increased vascularity. |
| 8b | |
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| 8c |  |
Image 8c, 8d, 8e and 8f (Triphasic Computed Tomography): CT of the same patient shows a cirrhotic liver with patent hepatic and portal veins as well as ascites. Within segment 6, there is a nodular area which demonstrates slight enhancement corresponding to the lesion identified on ultrasound (arrow). This lesion could represent either a dysplastic cirrhotic nodule or an early hepatocellular carcinoma. |
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| 8g |  |
Image 8g, 8h, 8i and 8j (Magnetic Resonance Imaging): MRI of the same patient demonstrates a lesion measuring approximately 2.5 cm in diameter on the inferomedial aspect of segment 5 in a subcapsular location. This is bulging the capsule of the liver at the level of the upper pole of the right kidney. The lesion is essentially isointense to the rest of the liver on T1 weighted imaging (out of phase) but is slightly hyperintense on in-phase imaging suggesting that the rest of the liver has some fatty infiltration. The lesion is slightly hyperintense on first echo T2 but is not clearly visible on more heavily weighted T2 imaging. The lesion shows arterial enhancement but washes out in the portal venous phase, with the rim of the lesion remaining enhanced. The appearances are consistent with a hepatocellular carcinoma. |
| 8h |  |
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| 8i |  |
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| 9a |  |
Hepatocellular Carcinoma
Image 9a and 9b : Hepatectomy specimens showing a multifocal hepatocellular carcinoma with areas of necrosis and haemorrhage arising in a cirrhotic liver. |
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| 9c |  |
Image 9c (H&E, x2.5) and 9d (H&E, x10): Histological sections of a hepatocellular carcinoma arising on a background of cirrhosis. The usual lobular architecture is replaced by irregular and thickened trabeculae of malignant hepatocytes. There is mild nuclear pleomorphism. |
| 9d |  |
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Teaching Points
Teaching Points
- Ultrasound is widely available, involves no exposure to radiation and often effective at determining the aetiology of liver nodules. Contrast enhanced ultrasound (CEUS) is a useful tool for lesion characterization when available
- For the evaluation of focal liver lesions, the sensitivites of CEUS, CT and MRI are similar. MRI has a higher per lesion sensitivity than CT. MRI should be the preferred imaging modality for the diagnosis of hepatocellular carcinoma (HCC) in patients with chronic liver disease
- PET-CT is especially useful for problem-solving in selected patients and detection of extra-hepatic metastases
- Image guided biopsy is usually only required when the radiological appearances are non-diagnostic and can distinguish benign versus malignant with high accuracy
HS1
Focal Liver Lesion (Investigation)
Risk factors for non-cystic focal liver lesions
- For hepatocellular carcinoma
- Positive hepatitis B or C serology
- Cirrhosis / chronic hepatitis / primary biliary cirrhosis / autoimmune hepatitis
- Ethnicity (South East Asians: males >40; females >50; Africans >20)
- Family history of hepatocellular carcinoma
- Genetic haemochromatosis
- Non-alcoholic steatohepatitis
- Excess alcohol consumption
- For metastatic disease
- Current or previous extra-hepatic malignancy
- For adenomas
- Females on oral contraceptive agents or hormonal replacement therapy
- Males on androgenic steroids
- Glycogen storage disease (rare)
HS2
Liver Lesion (Incidental)
- The great majority of incidentally-detected liver nodules are benign
- Even in patients with known extrahepatic primary malignancy, small liver lesions, if single or very few in number, are more likely to be benign than malignant
- The problem of incidental lesions, in the liver and elsewhere, is an important component of the burgeoning issue of over diagnosis and the potential harming of healthy people
- It is important to distinguish hepatic adenomas (HA) from focal nodular hyperplasia (FNH) as the former can present acutely due to rupture and consequent haemoperitoneum in addition to the risk of malignant transformation up to 10% of these tumours
HS3
Hepatocellular Cancer (Surveillance)
- In patients with cirrhosis, the risk of developing hepatocellular carcinoma (HCC) is highest with HCV, in Asians and in more advanced stages of cirrhosis
- Ultrasonography (US) 6 monthly is recommended as the primary surveillance modality
- Survival was significantly better in patients who underwent surveillance
- The earliest identifiable HCCs often show atypical radiological features and these are the very lesions that need to be diagnosed to enable a higher likelihood of cure
- Sensitivity for detecting hepatocellular carcinoma on US varies with the size of the lesion
- The use of serum alpha-fetoprotein (AFP) alone as a surveillance tool is not recommended
- The use of AFP to complement US surveillance is controversial
HS4
Hepatocellular Cancer (Suspected)
- In patients at risk of HCC
- Liver lesions <1cm are usually subject to follow-up imaging
- Lesions >1cm should undergo further imaging, preferably with MRI with a liver-specific contrast agent
- Lesions in patients at high risk for HCC showing typical features of HCC on imaging (arterial enhancement and then wash-out) can be treated as HCC without biopsy
- Biopsy should be reserved for lesions with non-diagnostic appearances on imaging
HS5
Focal Liver Lesion (History of Malignancy)
- Even in patients with known extra-hepatic primary malignancy, small liver lesions, if single or very few in number, are more likely to be benign than malignant
- In patients with known or suspected extra-hepatic primary malignancy, imaging is usually a combination of ultrasound and CT, dependent on which modality the lesion was initially discovered
- Simple cysts can be confidently diagnosed on US. May detect or characterize other lesions. If US were the patient’s primary imaging modality, contrast-enhanced US (CEUS) is a valuable adjunct performed at the same attendance, if available. Otherwise the next step is usually CT scan
HS6
Ultrasound (US) ± Contrast-Enhanced Ultrasound (CEUS)
- Ultrasound (US) contrast agents (‘microbubbles’) comprise an albumen or phospholipid shell containing a stable perfluorocarbon or sulfur hexafluoride gas. They are predominantly blood-pool agents, the encapsulated microbubbles being small enough to pass through pulmonary and systemic circulations after intravenous injection and durable enough to re-circulate for several minutes
- Examination with US contrast is based on the dynamic assessment of macro- and microvasculature of organs and their pathologies. They are, in principle, comparable to the use of contrast agents for CT and MRI with the added advantage of the capability for imaging continuously during the passage of the contrast agent, thereby obtaining what is effectively a dynamic real-time ultrasound angiogram with greater temporal resolution than contrast-enhanced CT or MRI. In addition, quantitative assessment of contrast uptake can be measured by generating Time-Intensity Curves
- CEUS improves diagnostic performance in differentiating HCCs from non-neoplastic nodules in cirrhotic patients compared with baseline ultrasound (16) and, if available, can be recommended as the first diagnostic step when liver lesions are detected on ultrasound surveillance, especially as the procedure can be performed immediately without the need for further attendance or preparation and may therefore avoid further and more expensive examinations
- Advantages of CEUS
- Ability to assess the contrast enhancement patterns in real time
- Higher temporal resolution when compared with other imaging modalities
- Enhancement dynamics of the lesions can be studied quantitatively and qualitatively
- No predefined scan time points or need to perform bolus tracking
- Excellent tolerance and safety profiles of ultrasound contrast agents allow for their repeated administrations in the same session when needed
- Can be given in the presence of renal impairment
- The imaging can be performed at the same attendance as the ultrasound at which the lesion was discovered, with resultant early reassurance of the patient and his / her doctors in the majority of cases
- Disadvantages of CEUS
- Operator and body habitus dependent
- Specificity and sensitivity are reduced in moderately or markedly fatty livers and with deeply positioned lesions
- Very small focal liver lesions (<3 mm) may be overlooked
- If the baseline ultrasound is suboptimal, CEUS may be unreliable
- Indications for CEUS for lesion characterization in the following clinical situations
- Incidental findings on routine ultrasound
- Lesion(s) or suspected lesion(s) detected with ultrasound in patients with a known history of a malignancy, as an alternative to CT or MRI
- Need for a contrast study when CT and MRI contrast are contraindicated
- Inconclusive cytology / histology results
- Inconclusive MRI / CT
HS7
Computed Tomography (CT)
- CT with the administration of intravenous iodinated contrast is used to characterise liver lesions. Images are commonly taken during the
- Pre-contrast phase
- Arterial phase (20-30 seconds after administration of contrast) - useful for identifying hypervascular lesions
- Portal venous phase (70-80 seconds after administration of contrast) - often sufficient for hypovascular metastases
- CT scan is the usual first line investigation of metastatic disease, being of high sensitivity and able to perform widespread extra-hepatic imaging of the abdomen, pelvis and thorax
- Dependent on the primary tumour, hepatic metastases may be hypervascular (higher attenuation) or hypovascular (lower attenuation) relative to the surrounding liver. The latter are more common and are seen, for example, in colorectal cancer, most lung cancers and most breast cancers. Hypervascular metastases may be seen in malignant carcinoid, neuroendocrine cancers, melanoma, renal cell cancer, thyroid cancer, hepatocellular cancer
HS8
Magnetic Resonance Imaging (MRI)
- MRI is more likely to provide a definitive diagnosis than CT and has an important role in characterizing benign lesions
- Usually breath hold T1 and fast spin-echo T2 weighted images are used for the evaluation of a liver nodule
- Gadolinium-enhanced dynamic MRI imaging improves the characterisation of liver lesions
- Images are commonly taken during the
- Arterial phase (20-30 seconds after administration of contrast) – useful for identifying hyper-vascular lesions
- Portal venous phase (70-80 seconds after administration of contrast)
- The patterns of enhancement with gadolinium at MRI of various types of liver lesion are similar to those seen with iodinated contrast at CT
- Hepatobiliary (liver-specific) gadolinium contrast agents (gadoxetic acid ) are increasingly used, which are taken up by normal liver and by lesions containing hepatocytes (such as focal nodular hyperplasia) on delayed phase imaging. The use of the delayed phase of these agents has been shown to increase sensitivity compared to dynamic phases alone. Thus, MRI with these agents is useful for differentiation of FNH and HA
- These agents also have excellent sensitivities for metastases, show a better performance than triple-phase MDCT for the detection of hepatic metastasis, especially for small (≤1 cm) lesions
- In the context of suspected metastatic disease MRI is usually reserved for: problem solving / lesion characterization; further liver imaging to detect additional hepatic metastases if surgical intervention is contemplated
- On a per lesion and per patient basis, MRI is the most accurate modality for evaluating colorectal liver metastases, being more sensitive than CT and having a slightly higher sensitivity to PET / CT
- Diffusion-weighted imaging (DWI) at MRI is particularly sensitive for the detection of metastases on a per-lesion basis. However, on its own, without other MRI sequences, it is controversial whether DWI is reliable in distinguishing benign from malignant lesions. In general, DWI should be combined with other MRI sequences for lesion characterization
HS9
18F-fluorodeoxyglucose (FDG) Positron Emission Tomography-Computed Tomography (PET-CT)
- Malignant cells characteristically have increased metabolism compared to normal cells, and may be reflected by areas of increased activity on PET-CT scanning
- However, the 18F-PET-avidity of metastatic disease tends to parallel the avidity of the primary tumour, which in turns varies among cancer-type and even within the same cancer type
- The roles of PET-CT in hepatic metastases are as follows
- Occasional problem solving when diagnosis on other modalities remains uncertain
- To determine the presence of extra-hepatic metastases in order to avoid hepatic resection in those patients in whom it is otherwise contemplated
- To monitor disease activity and disease recurrence following treatment
- In recent years it has become possible to perform PET-CT with Somatostatin Receptors labeled with 68-gallium for the detection of neuroendocrine tumours, including carcinoid tumours. This has been shown to be highly accurate
- A further study in patients with neuroendocrine primary tumours also found PET-CT and MRI to be highly accurate
HS10
Technetium-99m-labelled Red Blood Cell Scan (99mTc-RBC scan)
- Technetium-99m-labelled red blood cell scan has a high specificity and positive predictive value for hepatic haemangiomas but a negative test result does not indicate a diagnosis and therefore further imaging investigation is then required
- Hepatic haemangiomas occur in up to 7% of the population and are the most common benign tumour of the liver
- Some of these do not demonstrate the characteristic CT and ultrasound appearance and can be difficult to distinguish from other causes of a focal liver lesion
- An increase in delayed blood pool activity is typical of a haemangioma and this appearance is rarely seen with other causes of liver nodules
- The test has a limited sensitivity for the detection of small lesions and those located adjacent to the heart or major vessels
- The use of the test is decreasing as a negative scan excludes haemangioma but does not otherwise aid diagnosis
HS11
Image-guided Biopsy
- In the absence of risk factors, the role for biopsy in the diagnosis of hepatic incidentalomas is limited as the advances in dynamic imaging techniques are sensitive for diagnosing hepatocellular carcinoma (HCC) in most liver nodules
- The accuracy of percutaneous needle biopsy is around 90% but the risk of needle track tumour implantation following a biopsy of a hepatocellular carcinoma is 2.7% overall
- Thus needle tract seeding of tumour is a justifiable concern especially if such seeding could impact patient survival and also management options. There has been a more liberal approach for liver lesion biopsies in recent years unless transplantation is considered
- Other complications include intraperitoneal haemorrhage, haemobilia, pneumothorax, infection, bile leak, parenchymal bleeding and pericardial tamponade
- This underlines the importance of performing percutaneous needle biopsy only when absolutely necessary or when the information gained is likely to alter the management
- However, in individuals with risk factors for hepatocellular carcinoma
- Lesions <1cm are usually followed up by serial imaging
- Management should be for HCC, if the lesion(s) show characteristic intense arterial enhancement with contrast washout in delayed venous phase, on
- One imaging modality (for lesions >2 cm) or,
- Two imaging modalities (for lesions 1-2 cm) and / or,
- Alpha-fetoprotein is raised, otherwise biopsy is recommended
- Image-guided fine needle aspiration (FNA) is able to distinguish benign from malignant lesion with high accuracy , but less accurate in providing a specific malignant diagnosis
References
References
Date of literature search: September 2015
The search methodology is available on request. Email
References are graded from Level I to V according to the Oxford Centre for Evidence-Based Medicine, Levels of Evidence. Download the document
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