Current Opinion in Oncology:
ENDOCRINE TUMORS: Edited by Julie Ann Sosa
Ultrasound elastography in the evaluation of thyroid nodules for thyroid cancer
Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
Correspondence to Denise Carneiro-Pla, MD, FACS, Department of Surgery, Medical University of South Carolina, 25 Courtenay drive, Suite 7008, Charleston, SC 29425, USA. Tel: +1 843 876 0108; fax: +1 843 876 4705; e-mail: firstname.lastname@example.org
Purpose of review: High-resolution ultrasonography has become mandatory while evaluating patients with thyroid nodules. Although B-mode and Doppler ultrasonography are highly sensitive for diagnosis of thyroid lesions, they lack specificity in differentiating benign from malignant nodules. Ultrasound elastography has proven valuable in discriminating these lesions. This review discusses recent findings regarding the use of elastography as a tool in the evaluation of thyroid masses as well as the different methods and scoring systems used to determine tissue elasticity.
Recent findings: There are several methods and scores utilized to evaluate the stiffness of normal tissue and solid thyroid lesions, such as strain elastography, acoustic radiation force impulse, and shear wave elastography. Interpretation of data is usually qualitative and subjective obtained with operator-dependent techniques except for shear wave elastography, in which data acquisition is operator-independent with interpretation quantitative and objective in nature. Various software and scoring systems are applied to produce/interpret data resulting in widely variable sensitivity and specificity in differentiating malignant from benign lesions ranging from 73 to 98% and 71 to 100%, respectively.
Summary: Although elastography seems promising in identifying malignant thyroid nodules with acceptable accuracy, further studies are necessary to change the current management of thyroid lesions. Consequently, elastography should be used as an additional tool in the work-up of thyroid nodules instead of a single predictor of which lesions should be followed without fine-needle aspiration cytology. Therefore, this exciting methodology, so far, is inadequate to guide the management of thyroid lesions.
Presently, thyroid nodules are often diagnosed in asymptomatic patients with many of these nodules frequently presenting as nonpalpable lesions. More than 60% of the population will present with thyroid nodules if screened with cervical ultrasonography with 25% having thyroid cancer as shown by autopsy studies. Ultrasonography is essential for diagnosis of small thyroid lesions and is mandatory in the evaluation of any thyroid mass. B-mode and Doppler ultrasonography are highly sensitive in identifying malignant nodules when performed by experienced ultrasonographers. Suspicious features such as hypoechogenicity, microcalcifications, absence of halo, hypervascularity, irregular borders, and mass growth pattern anterior–posterior larger than medial–lateral (taller than wider on the transverse images of the thyroid lobe) are very sensitive in pointing out malignant nodules, especially when several of these features are present on a given thyroid lesion. Although very sensitive, high-resolution ultrasonography lacks specificity given that many benign thyroid nodules can present with one or more of the above-described malignant features.
Ultrasound elastography has been described as an accurate predictor of malignancy by determining tissue elasticity. This is a novel, exciting, and promising ultrasound methodology, which allows ‘virtual palpation’ of otherwise nonpalpable lesions. This technology was first described in 1991 and has been used in the evaluation of several organs and tissues ever since . There are several methods that utilize elastography to determine nodule stiffness in an attempt to differentiate benign from malignant thyroid lesions. Even though there are several studies on the subject, currently elastography is not a determinant part of thyroid nodule evaluation with questions remaining about its reliability when thyroid lesions are not highly selected [2▪]. The most recent studies describing these novel methods of obtaining additional data and imaging from thyroid nodules as well as various interpretations of this information are described below.
SONOELASTOGRAPHY OR STRAIN ELASTOGRAPHY
There are several reports describing the findings of elastography in the evaluation of thyroid nodules since 2005; however, these studies are often highly selective based on fine-needle aspiration cytology instead of surgical pathology, and frequently in a small group of patients. This method qualitatively determines tissue elasticity by operator external compression of the lesion causing tissue deformation; less displacement is seen on harder nodules (blue areas) than in softer lesions (red or green areas depending on the system). Nodule elasticity is expressed by a strain ratio or as elasticity scores performed by using real-time sonoelastography superimposed to B-mode images. The subjectively determined elasticity score ranges from elasticity score = 1 for softer lesions to elasticity score = 4 for harder nodules in comparison to surrounding normal thyroid tissue (Fig. 1) [3▪▪]. Some studies use the Ueno scoring system that classifies nodules in five categories instead. This method has proven to be highly operator dependent requiring a stable technique for reproducibility with interobserver agreement as low as 68% for unselected patients [4▪]. The reliability of elastography is questioned not only because of the scanning technique requiring standardization of external compression, but also because of the scoring systems which are based on the subjective classification of color patterns throughout the area of interest. Depending on the scoring system used and cutoff values applied, the sensitivity of this technique in pointing out thyroid cancers ranges from 74 to 98% with specificity 72 to 100%. Another limitation of this method is that even though benign nodules tend to be softer than malignant ones, not all thyroid cancers are hard lesions and not all benign nodules are soft to palpation, such as the case of cystic papillary, medullary and follicular carcinomas as well as thyroiditis. Furthermore, multinodular goiters can have limited volume of normal tissue for comparison, and cystic lesions as well as nodules with eggshell calcifications may produce inconsistent findings. Studies comparing elastography to gray-scale high-resolution ultrasonography are conflicting with a few reports showing no improvement in the differentiation between benign and malignant nodules, whereas others describing an increase on not only specificity but also sensitivity [5–7,8▪▪].
Most studies support elastography not as a substitute but as a useful complement to gray-scale ultrasonography in differentiating the histology of thyroid nodules. B-mode and Doppler ultrasonography still have the higher sensitivity, whereas elastography improves its specificity in pointing nodules suspicious for thyroid cancer [3▪▪,9–11].
Elastography sensitivity in identifying malignant nodules varies widely among studies because each study uses either a different scoring system or a distinct cutoff value as a predictor of cancer. Although elasticity scores 2 or lower have a sensitivity of 74% and specificity of 76%, higher elasticity scores are more specific in differentiating benign from malignant lesions with a sensitivity and specificity of elasticity score = 4 ranging from 75 to 91% and 98 to 100%, respectively [2▪,12–14]. Data from reports using elasticity score greater than 3 as a predictor of malignancy showed a sensitivity and specificity ranging from 85 to 89% and 84 to 91%, respectively [3▪▪,11,15]. In another study, elasticity scores greater than 3.5 reached 82% sensitivity and 72% specificity in identifying thyroid cancers .
Tissue elasticity can also be measured based on semiquantitative data reported as strain ratio or strain index values. A strain index greater than 2.31 predicted malignancy with a sensitivity of 86% and a specificity of 82%, whereas in another study a strain ratio greater than 2 had a sensitivity of 97% and specificity of 92% [6,16]. Xing et al. described that a strain ratio greater than 3.79 had 98% sensitivity and 86% specificity in predicting which nodules were malignant. Ning et al. reported that a strain ratio cutoff of 4.2 achieved 81% sensitivity and 83% specificity.
Another method of measuring tissue elasticity is by calculating the elasticity contrast index, which does not require external compression. Tissue elasticity is measured by displacement of the nodule caused by carotid pulsation. With this method, authors have described an adequate intraobserver and interobserver agreement, increasing the reliability of the study .
ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY
Although this methodology has been described in the evaluation of diffuse thyroid disease, it has been infrequently reported in the differentiation between benign and malignant thyroid nodules [18,19]. Acoustic radiation force impulse (ARFI) evaluates tissue elasticity by stimulation of lesions using short-duration acoustic pulses to generate localized displacements in tissues. The shear wave velocities of the region of interest are displayed on the monitor. Friedrich-Rust et al. indicated that the shear wave velocity of malignant nodules is significantly higher than of benign lesions. When a cutoff of 3.3 m/s was used to differentiate benign versus malignant thyroid nodules, the specificity was 95%. In another study, the cutoff of 2.55 m/s reached a sensitivity of 83% and specificity 93% in differentiating thyroid nodules . Tissue elasticity data obtained from ARFI is not translated in color-coded images as in other elastography methods. This method seems to be a transition technology from strain elastography to shear wave elastography.
SHEAR WAVE ELASTOGRAPHY
Shear wave elastography is not widely available in all ultrasound systems at the present time; however, it has shown encouraging results in a few studies. One of the promising features of this methodology is that it is user independent with no compressive maneuvers necessary. Shear wave methodology captures the waves which propagate from the stimulated tissue in question with an ultrafast ultrasound tracking method, which displays real-time information in terms of velocity or estimated tissue stiffness expressed in kilopascals. In this method, the information is color coded with harder areas shown in red and softer in blue, which is the opposite of the color patterns of strain elastography (Fig. 2) [21▪].
Using the 34.5 kPa cutoff, sensitivity in identifying papillary cancer was 77% with specificity of 71%, whereas the cutoff greater than 42.1 kPa achieved 53% sensitivity and 78% specificity. These results are much lower than a previous study by Sebag et al., suggesting that possibly shear wave elastography is not as operator-independent as once thought [21▪]. Although some preliminary data has shown that shear wave elastography is more accurate than sonoelastography, further studies are necessary .
Sonoelastography is an exciting and promising methodology, which can improve the specificity of gray-scale ultrasonography; however, by itself it is not sensitive enough to dictate the current management of thyroid nodules. Because of its high specificity in predicting malignancy, elastography in addition to B-mode and Doppler ultrasonography can be helpful in determining which nodules should be biopsied or excised. On the contrary, it is not sensitive enough to determine which nodules can only be followed with imaging without fine-needle aspiration cytology.
The studies described in this review are based on imaging of mainly papillary thyroid cancers, which are characteristically harder with more calcifications than follicular and medullary carcinomas. Currently, there are limited data on follicular and medullary carcinoma as well as cystic papillary thyroid cancers, which either can present with benign features on ultrasonography and on palpation, leaving elastography as valuable additional information to gray-scale ultrasonography on the evaluation of thyroid nodules rather than an essential tool. Fine-needle aspiration cytology remains the most accurate method of differentiating benign from malignant nodules. Hopefully, with increased availability of the shear wave elastography software and further studies, especially based on surgical pathology instead of cytology, this ultrasound tool can become a routine adjunct to gray-scale ultrasonography during evaluation of thyroid masses.
Conflicts of interest
The author has no conflict of interest to disclose.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
▪ of special interest
▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 99).
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This study discusses the decreased specificity of elastography in differentiating malignant lesions when patients are not highly selected, such as patients with cystic lesions.
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This is a large study showing the benefits and limitations of elastography in thyroid evaluation. It demonstrates that conventional ultrasonography has the highest sensitivity and elastography has the highest specificity suggesting that both complement each other on thyroid nodule evaluation.
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This report describes the reasons for decreased reliability of elastography as well as the interobserver and intraobserver agreement on elastography interpretation.
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This study reports the limitations and inaccuracy of elastography in differentiating benign from malignant nodules in patients with undetermined thyroid cytology.
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This is the largest recent study on shear wave elastography. Authors report poorer results than initial studies on shear wave elastography on evaluation of thyroid nodule. It successfully discusses that this method might not be completely operator-independent.
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Minerva Chirurgica, 68(2):
acoustic radiation force impulse; elastography; shear wave elastography; sonoelastography; thyroid cancer; thyroid nodules; thyroid ultrasonography
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