Ultrasound of focal liver lesions - RAD Magazine 2010...Ultrasound of focal liver lesions RAD...
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Ultrasound of focal liver lesions RAD Magazine, 36, 424, 33-34 By J Harding MRCP, FRCR and M Callaway MRCP, FRCR Department of Radiology, University Hospitals Bristol NHS Foundation Trust Introduction Ultrasound is the most common initial investi- gation when imaging the liver. It is available, non-invasive, safe and does not use ionising radi- ation. Ultrasound is often the first line investi- gation for potential liver disease and frequently identifies asymptomatic focal liver lesions. The majority of single asymptomatic focal liver lesions are benign, but an accurate non-invasive diagno- sis is important for risk stratification and patient management. We review the ultrasound features of focal hepatic lesions. Simple hepatic cysts Simple cysts in the liver are common, the prevalence increasing with age. Up to 18 per cent prevalence in the general population has been reported from imaging stud- ies 1,2 and they tend to be found in the fifth to eighth decade of life, more common in women (4:1). The cause of hepatic cysts is unknown. Cysts are lined by biliary-type epithelium and may result from progressive dilatation of biliary microhamartomas. Cysts are easily identified on ultrasound with classic diagnostic features; well defined, rounded, hypoechoic lesions of varying sizes with posterior acoustic enhancement. No further management is necessary unless the patient becomes symptomatic. If the cyst wall is irregular or thickened, colour Doppler can help differentiate cystic metastases from abscesses and simple cysts. The presence of colour signals in any solid component of cystic lesions carries a high diagnostic value in differentiating hepatic cystic malignancies from abscesses and simple cysts (sensitivity/specificity; 85%/96% 1 ). Haemangioma Cavernous haemangioma is the most common primary liver tumour, occurring in 0.4-20% of the general population in autopsy series. 2 Haemangiomas are most common in mid- dle aged women (5:1), occur more frequently in the right lobe of the liver, are usually single and rarely greater than 5cm. Haemangiomas arise from the endothelial cells that line blood vessels and consist of multiple, large, vascular chan- nels lined by a single layer of endothelial cells and sup- ported by collagenous walls. They are almost always asymptomatic, incidentally discovered and are uncommon in cirrhosis (the fibrotic process in cirrhotic liver may pro- hibit their development). At ultrasound, the most common appearance is of a well- circumscribed, uniformly hyperechoic lesion. This is caused by multiple interfaces between walls of the cavernous spaces and blood within them. 3 This classic appearance occurs in up to 70 per cent. In the remaining 30 per cent, definite diag- nosis with ultrasound can be difficult and haemangiomas are a great mimic. In large haemangiomas, heterogeneous areas are inter- spersed within the hyperechoic mass and they can also develop a central scar. Haemangiomas can be iso-echoic or even hypoechoic, mimicking the appearance of a metasta- sis. Other atypical features include hypoechoic lesions with a thin hyperechoic rim and scalloped borders. 4 Haemangiomas can appear hypoechoic in echogenic, fatty livers 5 (figure 1) and may become fibrotic and shrink in patients with progressive cirrhosis leading to difficulty with radiological and pathological diagnosis. 6 Colour Doppler/contrast enhanced ultrasound (CEUS) has a limited role in the specific diagnosis of haemangioma (the classic centripetal fill-in pattern is seen in only a minority 7 ). If there is a classic appearance on ultrasound, no additional imaging is required. If there is diagnostic doubt, MRI is usu- ally sufficient to make an accurate diagnosis. Focal nodular hyperplasia Focal nodular hyperplasia (FNH) is the second most com- mon primary hepatic tumour, seen in autopsy series as eight per cent of primary hepatic tumours 8 but probably occur- ring in the general population with a much greater fre- quency than previously reported. FNH is most common in women (80-95%) in their third or fourth decade. 9 FNH is often discovered incidentally during imaging, usu- ally as a solitary lesion (80-95%). 10 Although FNH generally has no clinical significance, recognition of the radiologic char- acteristics of FNH is important to avoid unnecessary biopsy or follow-up. Malignant transformation of this lesion has not been reported. FNH occurs due to a localised hepatocyte response to an underlying congenital arterio-venous malformation. All the normal constituents of liver are present in an abnormally organised pattern within an otherwise normal liver. FNH is composed of aggregates of hepatocytes held together in a fibrous meshwork with a dominant scar. FNH has no cap- sule but tends to be well delineated. Kupffer cells are usu- ally present but can have variable functional capacity. Calcification is rare but described. 11 Ultrasound findings are variable. The lesion often appears as a homogeneous mass that is iso- or slightly hyperechoic compared with the liver and can be difficult to detect as it contains the same components as the back- ground liver. A central scar is only seen on US in around 20 per cent. 12 The scar represents the central feeding vessel and this can be clearly identified using colour Doppler. Doppler may also demonstrate centrifugal pattern to the periphery (where large draining veins may be seen; figures 2a, 2b) in a spoke like manner. Dynamic CEUS is increasingly used in the diagnosis which depicts the hypervascularity of FNH in the arterial phase of enhancement more clearly than colour Doppler alone. 13 A characteristic feature is centrifugal filling to the periphery in the arterial phase and a uniform or lobulated dense stain at the capillary phase. This may be the final diagnostic method for lesions that are larger than 3cm which have a typical spoke-wheel structure. Overall, the specificity of US is low but increased with Doppler and CEUS. If diag- nostic doubt remains, MRI is indicated. Adenoma Hepatic adenoma is a rare, benign tumour of the liver with an incidence of around one in 1,000,000 14 though this rises to four per 100,000 in women taking the oral contraceptive pill with an overall female ratio of 9:1 15 and presents in young adults. Incidence is increased in patients with glycogen stor- age disease, diabetes, haemochromatosis or acromegaly as well as in males using anabolic steroids. Hepatic steatosis may be a risk factor. 16 Adenomas include sheets of well-differentiated hepato- cytes that contain fat and glycogen and can produce bile but no bile ducts are present. There is a characteristic lack of portal vein tracts and terminal hepatic veins. Approximately eighty per cent of adenomas are solitary. Most hepatic ade- nomas do not contain Kupffer cells. Hepatic adenomas demonstrate variable echogenicity at ultrasound and are a diagnostic challenge. Differentiating hepatic adenomas from other liver lesions such as FNH or HCC is usually not possible based on either grey scale or Doppler characteristics (figure 3). CEUS has been shown to increase sensitivity in benign lesions to around 83% 17 but adenoma formed only 3% of this sample. MRI interpreta- tion is often challenging. Adenomas can rupture and bleed, causing right upper
Transcript of Ultrasound of focal liver lesions - RAD Magazine 2010...Ultrasound of focal liver lesions RAD...
Ultrasound of focal liver lesionsRAD Magazine, 36, 424, 33-34
By J Harding MRCP, FRCRand M Callaway MRCP, FRCR
Department of Radiology, University HospitalsBristol NHS Foundation Trust
IntroductionUltrasound is the most common initial investi-gation when imaging the liver. It is available,non-invasive, safe and does not use ionising radi-ation. Ultrasound is often the first line investi-gation for potential liver disease and frequentlyidentifies asymptomatic focal liver lesions. Themajority of single asymptomatic focal liver lesionsare benign, but an accurate non-invasive diagno-sis is important for risk stratification and patientmanagement. We review the ultrasound featuresof focal hepatic lesions. Simple hepatic cystsSimple cysts in the liver are common, the prevalenceincreasing with age. Up to 18 per cent prevalence in thegeneral population has been reported from imaging stud-ies1,2 and they tend to be found in the fifth to eighth decadeof life, more common in women (4:1).
The cause of hepatic cysts is unknown. Cysts are lined bybiliary-type epithelium and may result from progressivedilatation of biliary microhamartomas.
Cysts are easily identified on ultrasound with classicdiagnostic features; well defined, rounded, hypoechoic lesionsof varying sizes with posterior acoustic enhancement. Nofurther management is necessary unless the patient becomessymptomatic.
If the cyst wall is irregular or thickened, colour Dopplercan help differentiate cystic metastases from abscesses andsimple cysts. The presence of colour signals in any solidcomponent of cystic lesions carries a high diagnostic value indifferentiating hepatic cystic malignancies from abscessesand simple cysts (sensitivity/specificity; 85%/96%1).HaemangiomaCavernous haemangioma is the most common primary livertumour, occurring in 0.4-20% of the general population inautopsy series.2 Haemangiomas are most common in mid-dle aged women (5:1), occur more frequently in the rightlobe of the liver, are usually single and rarely greater than5cm.
Haemangiomas arise from the endothelial cells that lineblood vessels and consist of multiple, large, vascular chan-nels lined by a single layer of endothelial cells and sup-ported by collagenous walls. They are almost alwaysasymptomatic, incidentally discovered and are uncommonin cirrhosis (the fibrotic process in cirrhotic liver may pro-hibit their development).
At ultrasound, the most common appearance is of a well-circumscribed, uniformly hyperechoic lesion. This is causedby multiple interfaces between walls of the cavernous spacesand blood within them.3 This classic appearance occurs in upto 70 per cent. In the remaining 30 per cent, definite diag-nosis with ultrasound can be difficult and haemangiomasare a great mimic.
In large haemangiomas, heterogeneous areas are inter-spersed within the hyperechoic mass and they can alsodevelop a central scar. Haemangiomas can be iso-echoic oreven hypoechoic, mimicking the appearance of a metasta-sis. Other atypical features include hypoechoic lesions witha thin hyperechoic rim and scalloped borders.4
Haemangiomas can appear hypoechoic in echogenic, fattylivers5 (figure 1) and may become fibrotic and shrink inpatients with progressive cirrhosis leading to difficulty withradiological and pathological diagnosis.6
Colour Doppler/contrast enhanced ultrasound (CEUS) hasa limited role in the specific diagnosis of haemangioma (theclassic centripetal fill-in pattern is seen in only a minority7).If there is a classic appearance on ultrasound, no additionalimaging is required. If there is diagnostic doubt, MRI is usu-ally sufficient to make an accurate diagnosis.Focal nodular hyperplasiaFocal nodular hyperplasia (FNH) is the second most com-mon primary hepatic tumour, seen in autopsy series as eightper cent of primary hepatic tumours8 but probably occur-ring in the general population with a much greater fre-quency than previously reported. FNH is most common inwomen (80-95%) in their third or fourth decade.9
FNH is often discovered incidentally during imaging, usu-ally as a solitary lesion (80-95%).10 Although FNH generallyhas no clinical significance, recognition of the radiologic char-acteristics of FNH is important to avoid unnecessary biopsyor follow-up. Malignant transformation of this lesion hasnot been reported.
FNH occurs due to a localised hepatocyte response to anunderlying congenital arterio-venous malformation. All thenormal constituents of liver are present in an abnormallyorganised pattern within an otherwise normal liver. FNHis composed of aggregates of hepatocytes held together in afibrous meshwork with a dominant scar. FNH has no cap-sule but tends to be well delineated. Kupffer cells are usu-ally present but can have variable functional capacity.Calcification is rare but described.11
Ultrasound findings are variable. The lesion oftenappears as a homogeneous mass that is iso- or slightlyhyperechoic compared with the liver and can be difficult todetect as it contains the same components as the back-ground liver. A central scar is only seen on US in around 20per cent.12 The scar represents the central feeding vesseland this can be clearly identified using colour Doppler.Doppler may also demonstrate centrifugal pattern to theperiphery (where large draining veins may be seen; figures2a, 2b) in a spoke like manner.
Dynamic CEUS is increasingly used in the diagnosiswhich depicts the hypervascularity of FNH in the arterialphase of enhancement more clearly than colour Doppleralone.13 A characteristic feature is centrifugal filling to theperiphery in the arterial phase and a uniform or lobulateddense stain at the capillary phase. This may be the finaldiagnostic method for lesions that are larger than 3cm whichhave a typical spoke-wheel structure. Overall, the specificityof US is low but increased with Doppler and CEUS. If diag-nostic doubt remains, MRI is indicated.AdenomaHepatic adenoma is a rare, benign tumour of the liver withan incidence of around one in 1,000,00014 though this rises tofour per 100,000 in women taking the oral contraceptive pillwith an overall female ratio of 9:115 and presents in youngadults. Incidence is increased in patients with glycogen stor-age disease, diabetes, haemochromatosis or acromegaly aswell as in males using anabolic steroids. Hepatic steatosismay be a risk factor.16
Adenomas include sheets of well-differentiated hepato-cytes that contain fat and glycogen and can produce bile butno bile ducts are present. There is a characteristic lack ofportal vein tracts and terminal hepatic veins. Approximatelyeighty per cent of adenomas are solitary. Most hepatic ade-nomas do not contain Kupffer cells.
Hepatic adenomas demonstrate variable echogenicity atultrasound and are a diagnostic challenge. Differentiatinghepatic adenomas from other liver lesions such as FNH orHCC is usually not possible based on either grey scale orDoppler characteristics (figure 3). CEUS has been shown toincrease sensitivity in benign lesions to around 83%17 butadenoma formed only 3% of this sample. MRI interpreta-tion is often challenging.
Adenomas can rupture and bleed, causing right upper
quadrant pain.18 Hepatic adenomas can undergo malignanttransformation to hepatocellular carcinoma.19 Malignanttransformation is rare but for this reason, surgical resec-tion is advocated20 although the primary reason for resec-tion is the risk of haemorrhage which increases withincreasing tumour size and hormone use.21
MetastasesThe liver is a very common site for metastatic disease.Metastases are far more common than primary tumours(20:1). Ninety per cent of hepatic metastases are multiple,often varying in size. Growing metastases compress adja-cent liver parenchyma causing atrophy and forming a con-nective tissue rim. Large metastases often outgrow theirblood supply causing hypoxia and necrosis at the centre ofthe lesion.
Most metastases are hypovascular but some primarytumours characteristically have hypervascular metastases,eg renal and thyroid carcinoma. Metastases vary because ofdifferences in blood supply, haemorrhage, cellular differen-tiation, fibrosis and necrosis.
Ultrasound is widely used but specificity is poor. This isimproved with the addition of colour Doppler imaging andcontrast ultrasound which aids in the localisation of lesions,differentiation between ducts and blood vessels, vascularinvasion and degree of vascularity of liver metastases. In asample of 209 patients with hepatic malignancy (final diag-nosis established by histopathology, CT, MRI or HIDA-scintigraphy), CEUS had a reported sensitivity 90% andspecificity 99% in the diagnosis of malignant lesions22 andrecent reports show no statistically significant differencebetween CEUS and MDCT.23,24
Iso-echoic and infiltrating metastases are ill defined anddifficult to identify. Hyperechoic metastases are often hyper-vascular; their echogenicity is most probably related to thenumber of blood-tissue interfaces rather than the blood ves-sel walls themselves. Hypoechoic metastases are often hypo-vascular comprising uniform tissue cellularity.
Cystic metastases display complexity with mural nod-ules, thickened walls/septae and can contain fluid/debris. Ifcalcified, metastases are densely echogenic and can shadow.The calcification and echogenicity result from intratumoralmucin or necrosis and this pattern is particularly commonwith carcinoma of the colon of the mucin secreting type,adenocarcinoma of the breast and melanoma. Hepatocellular carcinomaHepatocellular carcinoma (HCC) is the most common pri-mary hepatic tumour and one of the most common cancersworldwide though rare in the western hemisphere withprevalence of four per 100,000, two per cent of all malig-nancies. It is much more prevalent in Asia and Africa, high-est prevalence in Japan (4-5%). However, incidence is risingin the West, thought to be related to increased Hepatitis Cinfection and cirrhosis. In low prevalence areas, HCC tendsto present aged 70-80 (male predominance 2:1) although inhigh prevalence areas, patients are much younger withincreased male majority. Patients with cirrhosis generallypresent earlier.
HCC develops predominantly in cirrhotic livers and cir-rhosis is a pre-malignant condition. Therefore, the risk fac-tors for HCC are those of cirrhosis such as alcohol abuse,viral hepatitis and metabolic liver disease. It very rarelyoccurs in patients with normal liver parenchyma.
HCC can undergo haemorrhage and necrosis because of alack of fibrous stroma. Vascular invasion is common, par-ticularly of the portal system. Invasion of the biliary sys-tem is less common. Aggressive HCC can cause hepaticrupture and haemoperitoneum.
The ultrasound appearance of HCC is variable and par-ticular care is needed to evaluate the liver completelybecause it is easy to overlook a small hepatic mass.25 This isvitally important because the only potentially curative treat-ment is liver transplant which itself requires the HCC tobe smaller than 3cm if lesions are multiple. Small HCCscan be homogeneously hyperechoic and can mimic haeman-gioma (figure 4). This may result from a large proportion offat in the tumour. Small HCCs can also appear hypoechoicwith larger HCCs frequently of mixed echogenicity.
Good quality ultrasound with careful evaluation of the
entire liver can be a screening examination for HCC inpatients at risk in combination with serum alpha-fetopro-tein evaluation; however, sensitivity of ultrasound for thedetection of lesions in a cirrhotic liver is limited. CEUSimproves sensitivity to around 85% in HCC26 though not inlesions less than 1cm.27 Diminishing of contrast agent in thelate phase compared with the arterial phase with respectto the surrounding liver tissue is a helpful sign in CEUS todiagnose malignancy with sensitivity of up to 98%.28
Vascular invasion can be adequately evaluated usingcolour Doppler imaging and conventional grey-scale ultra-sound. Tumour thrombus in hepatic veins, portal veins andinferior vena cava should be actively investigated. Portalvenous invasion is common in HCC but hepatic vein inva-sion is more specific. ConclusionUltrasound has a major role in the detection of focal liverlesions and in their primary characterisation. All lesionsneed careful ultrasound assessment, with particular atten-tion to vascularity, the presence of a central scar and localinvasion of other anatomical structures. Colour Doppler andcontrast enhanced ultrasound increases the sensitivity andspecificity of grey scale ultrasound.
The great majority of asymptomatic, single lesions arebenign. Hepatic cysts and haemangiomas with a classicappearance can be safely diagnosed with ultrasound alonebut atypical haemangioma is a great mimic. FNH is morecommon than previously appreciated and increasingly anincidental imaging finding. Metastases can be variable inappearance while the incidence of HCC is increasing relatedto the increasing prevalence of cirrhosis and can also havevariable appearances. Identifying small HCCs in high riskpatients is particularly important in order to meet livertransplant criteria and offer potentially curative treatment.Adenoma is a rare lesion and diagnostically challenging.
Whenever diagnostic doubt exists following ultrasoundfor focal hepatic lesions, further cross sectional imaging isindicated. MRI with or without hepatocyte specific contrastusually gives the most useful information for full imagingcharacterisation and avoids ionising radiation. CT permitsbetter evaluation of the extrahepatic tissues including thebones, bowel, lymph nodes and other abdominal viscera andis more helpful in the setting of malignant disease.
The final diagnosis of focal hepatic lesions is achievedusing several complementary imaging techniques. If defini-tive diagnosis is not established with imaging, ultrasoundguided biopsy or surgical resection may be needed to ensurea histological diagnosis.
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FIGURE 1Large left lobehypoechoic/hetero-geneous lesion in afatty liver. Atypicalappearances butconfirmed as hae-mangioma withMRI.
FIGURE 2aFocal NodularHyperplasia (FNH)in the posteriorleft lobe of liver.
FIGURE 2bFNH; ColourDoppler showingthe peripheraldraining vein(arrow).
FIGURE 4Example of anhyperechoic HCC(arrow) in a cir-rhotic liver withascites.
FIGURE 3Echogenic lesion in the anterior left lobe of liver laterconfirmed as adenoma at MRI. It is not possible tomake the diagnosis with ultrasound alone.
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