Thyroid carcinoma has been in a rising trend worldwide within the last few years [1]. This increase appears to be due, at least in part, to the advancement in the diagnosis of small thyroid cancers with the growing application of high-resolution imaging. However, many of the thyroid cancers are identified at an early stage and can be treated successfully, resulting in a relatively low death rate, despite the rise in incidence over the years [2]. The detection of thyroid nodules is a common outcome of neck ultrasound examination, and their initial classification as benign or malignant is typically determined on the basis of the grey scale ultrasound examination characteristics, with confirmation of the diagnosis achieved by fine needle aspiration cytology (FNA) [3]. Some ultrasonographic characteristics of malignancy are a solid component, hypoechogenicity, taller than wide shape, irregular margins, absence of a halo, microcalcifications, and intranodular vascularity on color Doppler ultrasonography [4].

Biological property of tissue stiffness is important and may be associated with structural changes, related to neoplasia, fibrosis and inflammation. As an addition to the traditional thyroid ultrasound, ultrasound elastography is a newer modality to measure tissue stiffness [5]. Based on the World Federation for Ultrasound in Medicine and Biology guidelines, the thyroid elastography can be primarily divided into two categories: strain elastography, based on external compression, and shear wave elastography [3]. Strain elastography has several drawbacks since it is operator dependent and it gives little quantitative information [6]. Shear wave elastography, on the other hand, is a quantitative method that uses the shear wave properties of the tissue to measure its stiffness in kilopascals and could potentially be used to distinguish malignant thyroid nodules from benign ones by assessing increased stiffness [7-10].

Fine needle aspiration cytology of thyroid nodules is still a valuable, inexpensive, and precise procedure for evaluation of suspicious thyroid nodules and is widely used [11]. The Bethesda System for Reporting Thyroid Cytopathology is a system which has standardized thyroid cytologic reporting and enhanced clinical decision-making [12]. But fine needle aspiration cytology is an invasive test and sometimes the results can be inconclusive or indeterminate. Thus, non-invasive imaging modalities can have a clinical utility to help refine the pre-cytology risk stratification. Shear wave elastography is a technique used to measure the speed of shear waves, which can then be used to calculate Young's modulus, a measure of tissue stiffness in kilopascals [13].

The aim of this study was to assess the feasibility of non-invasive shear wave elastography as a pre-FNA biopsy discriminatory tool between benign and malignant thyroid nodules [14]. There have been a number of reports that quantitative elastography values are distinct for benign and malignant thyroid nodules. In France, a study was carried out to assess thyroid nodules based on ultrasound characteristics (vascularity, hypoechogenicity, and microcalcifications) and to compare with an artificial combined score of ultrasound and shear wave elastography. Among 146 nodules, 29 (19.9%) were malignant. The mean elasticity index was significantly higher in the malignant nodules (150 ± 95 kPa) than in the benign nodules (36 ± 30 kPa). For tissue elasticity, the sensitivity and specificity were 85.2% and 93.9% respectively at a cutoff value of 65 kPa. The ultrasound score alone had a lower sensitivity, and combining the ultrasound score with the shear wave elastography score enhanced diagnostic performance [6]. For this reason, shear wave elastography could be valuable in the assessment of thyroid nodules, in order to better distinguish benign and malignant thyroid diseases. The use of FNA may benefit in selecting patients for fine needle aspiration, decrease the number of patients undergoing unnecessary invasive procedures and facilitate earlier diagnosis and management of thyroid malignancy when used as an adjunct to gray-scale ultrasound. The aim of the present study was to evaluate the diagnostic accuracy of SWE to diagnose benign and malignant thyroid nodules using the gold standard of fine needle aspiration cytology.

Objective

To determine the diagnostic accuracy of shear wave elastography in diagnosis of benign and malignant thyroid nodules, considering the FNAC as gold standard in suspected thyroid nodules.

This was a cross-sectional study conducted in the Department of Radiology, Dr. Ziauddin University Hospital, Karachi from 1st June 2021 to 5th October 2021. The estimated sample size was 131 patients. The sample size was calculated using an expected sensitivity of 84.0%, expected specificity of 84.7%, expected prevalence of thyroid nodules of 40%, confidence level of 95%, and desired precision of 10%. Non-probability consecutive sampling technique was used. Patients with already diagnosed thyroid nodules on gray-scale ultrasound were included. Patients aged 25 to 80 years, of either gender, who were already scheduled for thyroid nodule fine needle aspiration cytology and had not received any previous treatment for thyroid nodules were included in the study. Non-consenting patients, patients with known malignancy, patients with cystic thyroid nodules, and patients with previously treated thyroid pathology were excluded from the study. Data Collection All patients with thyroid nodules who presented with clinical suspicion of malignancy or suspicious gray-scale ultrasound features and were referred to Dr. Ziauddin University Hospital, Karachi, for fine needle aspiration cytology were enrolled after obtaining informed consent. The purpose and procedure of the study were explained to all participants. Ultrasound evaluation of the thyroid nodule was performed before fine needle aspiration cytology using a Toshiba Aplio i800 ultrasound machine. Gray-scale ultrasound, color Doppler ultrasound, and shear wave elastography were performed by a senior radiologist with at least three years of experience using a high-frequency linear probe. Gray-scale features, Doppler findings, and shear wave elastography values in kilopascals were recorded for each thyroid nodule. Based on ultrasound and elastography findings, nodules were categorized as benign or malignant. After ultrasound evaluation, all patients underwent fine needle aspiration cytology. The final diagnosis was recorded as benign, malignant, or inconclusive according to cytology results. Fine needle aspiration cytology was taken as the gold standard for determining the diagnostic accuracy of shear wave elastography. Relevant information, including patient name, age, registration number, date of examination, gray-scale ultrasound findings, color Doppler findings, shear wave elastography values, and cytology results, was recorded on a predesigned proforma by the researcher. Data Analysis Data were entered and analyzed using SPSS version 22.0. Descriptive statistics were calculated for all study variables. Qualitative variables such as gender, gray-scale ultrasound findings, color Doppler findings, shear wave elastography interpretation, and fine needle aspiration cytology results were presented as frequencies and percentages. Quantitative variables such as age, nodule size, number of nodules, and shear wave elastography value in kilopascals were presented as mean ± standard deviation. A 2 × 2 diagnostic table was constructed by comparing shear wave elastography findings with fine needle aspiration cytology results. Sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy of shear wave elastography were calculated by taking fine needle aspiration cytology as the gold standard. Stratification was performed with respect to age and gender to control effect modifiers, and post-stratification diagnostic accuracy was calculated. A p-value of ≤0.05 was considered statistically significant where applicable.

A total of 131 patients with diagnosed thyroid nodules on gray scale ultrasound were included in this study. The mean age of the patients was 43.79 ± 12.19 years, with a median age of 39 years and an IQR of 19 years. The mean nodule size was 7.06 ± 3.31 mm, with a median size of 7 mm and an IQR of 3 mm. The mean number of nodules was 1.11 ± 0.31, indicating that most patients had a single thyroid nodule. The mean shear wave elastography measurement was 53.83 ± 13.56 kPa, with a median value of 55 kPa and an IQR of 25 kPa. \

Table 1. Descriptive Statistics of Patient and Nodule Characteristics

Among all 131 patients, there were 22 true positive, 10 false positive, 5 false negative, and 94 true negative cases. The overall sensitivity was 81.5%, specificity was 90.4%, positive predictive value was 68.8%, negative predictive value was 94.9%, and diagnostic accuracy was 88.4%. In patients aged 50 years or below, diagnostic accuracy was higher at 92.7%, with sensitivity of 80.0% and specificity of 95.1%. In patients older than 50 years, sensitivity was 83.3%, but specificity and accuracy were lower at 72.7% and 76.4%, respectively.

Table 2. Diagnostic Accuracy of Gray-Scale Ultrasound Plus SWE Compared With FNAC

TP = true positive; FP = false positive; FN = false negative; TN = true negative; PPV = positive predictive value; NPV = negative predictive value; SWE = shear wave elastography; FNAC = fine needle aspiration cytology.

The overall 2×2 diagnostic table showed that, out of 27 malignant nodules on fine needle aspiration cytology, gray-scale ultrasound plus shear wave elastography correctly identified 22 as malignant, while 5 were incorrectly categorized as benign. Among 104 benign nodules on fine needle aspiration cytology, 94 were correctly identified as benign, while 10 were incorrectly labeled as malignant.

Table 3. Overall 2×2 Diagnostic Table of Gray-Scale Ultrasound Plus SWE

The nodules in the thyroid gland are very common lesions in clinical practice. The reported estimate of frequency is 10% in women and 2% in men and less than 10% are malignant. On ultrasound (US), incidental thyroid nodules may be detected as high as 68% and only 5-15% of these will be malignant. Thyroid nodules are frequently seen in radiological practice and differentiating the benign from malignant nodules is critical to proper clinical management. While conventional gray-scale ultrasound can be used to detect suspicious characteristics including hypoechogenicity, irregular margins, microcalcifications, taller-than-wide shape, and increased vascularity, these findings can be seen in both benign and malignant lesions [15]. The definitive method of diagnosis is fine-needle aspiration cytology but is invasive and sometimes gives inconclusive results. Shear wave elastography, in this context, gives extra quantitative data regarding the stiffness of tissue which in a malignant nodule is usually stiffer due to increased cellularity, fibrosis, and stromal reaction. The present study reports the results of 131 patients who had thyroid nodules evaluated with gray-scale ultrasound and shear wave elastography and were correlated with fine needle aspiration cytology. The mean age of the patients was 43.79 ± 12.19 years, while the mean nodule size was 7.06 ± 3.31 mm. The mean shear wave elastography measurement was 53.83 ± 13.56 kPa, which shows that the evaluation of tissue stiffness was an important part of the diagnostic workup. The majority of patients had only one thyroid nodule, and the average number of nodules was 1.11 ± 0.31 [16] Overall, gray scale sonography combined with shear-wave elastography had a good diagnostic value for malignant thyroid nodules. The sensitivity was 81.5%, specificity was 90.4%, positive predictive value was 68.8%, negative predictive value was 94.9%, and overall diagnostic accuracy was 88.4%. The results indicate that conventional ultrasound and shear wave elastography may be helpful in determining the difference between benign and malignant thyroid nodules [17]. The high negative predictive value is especially significant as it suggests that nodules marked as benign by this combined strategy are highly likely to be benign in selected patients, potentially decreasing the need for unnecessary invasive procedures. The stiffness values seen in this study are similar to previous studies that showed malignant thyroid nodules had significantly higher stiffness values than benign nodules [18]. Shear wave elastography has been shown in previous studies to increase the diagnostic confidence and could potentially increase sensitivity with a moderate reduction in specificity. The sensitivity of 81.5% in the present study implies that most malignant lesions could be detected before cytological diagnosis, whereas the specificity of 90.4% suggests the test was effective in correctly identifying benign lesions. Diagnostic accuracy was greater for diagnostic age group ≤ 50 years than in the group > 50 years. The sensitivity, specificity, negative predictive value, and accuracy were 80.0%, 95.1%, 96.3%, and 92.7%, respectively, in patients under 50 years of age. However, there were significant differences among those older than 50 years, with sensitivity of 83.3%, specificity of 72.7%, negative predictive value of 88.9% and accuracy of 76.4%. This decrease in specificity and accuracy in older patients may be associated with age-related changes like fibrosis, calcification, degenerative changes and chronic inflammation, which may lead to the development of false-positive elastography results. There was gender variation in diagnostic performance in both cases of gender-stratified analysis. Sensitivity and negative predictive value were 100.0% for male patients, indicating that there were no patients with malignant nodules who were missed. However, specificity was 68.0%, and was therefore lower, indicating a higher false-positive rate in males. Specificity was excellent at 97.5% and the accuracy was 92.2% for female patients, while sensitivity was 54.5% which means that there were some misdiagnosed malignant nodules. The difference could be attributed to disease distribution, nodule characteristics, differences in sample size between males and females or biological difference in thyroid disease. The results of the subgroups should, however, be viewed with caution since the groups were small [20]. The results of this study confirm that SWE can be used as an adjunct, rather than a substitute for FNA cytology. The overall diagnostic accuracy was good for shear wave elastography with high negative predictive value, but false-positive and false-negative results still occurred. Overall, there were 10 'benign' nodules that were wrongly identified as malignant and 5 'malignant' nodules that were wrongly identified as benign. Thus, shear wave elastography should be evaluated in conjunction with gray scale ultrasound characteristics, Doppler features, clinical risk factors and cytology when indicated. There are a number of limitations to this present study. It was performed in a single tertiary care center and the number of patients included in the study (n=131) may limit the generalizability of the findings. The study was done using fine needle aspiration cytology as the gold standard – however, in cases of malignancy or suspicion, surgical histopathology will be more definitive. Shear wave elastography measurements can also be affected by operator experience, nodule size, depth, calcification, cystic change and technical factors. Conclusive FNAC results may also be influenced if the result is not interpreted separately, as inconclusive results may have an impact.

Gray-scale ultrasound combined with shear wave elastography showed good diagnostic accuracy in differentiating benign and malignant thyroid nodules, using fine needle aspiration cytology as the gold standard. The technique demonstrated sensitivity of 81.5%, specificity of 90.4%, positive predictive value of 68.8%, negative predictive value of 94.9%, and overall accuracy of 88.4%. The high specificity and negative predictive value suggest that shear wave elastography is particularly useful in identifying benign nodules and may help reduce unnecessary invasive procedures when used along with conventional ultrasound findings.

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