The prevalence of thyroid nodules has necessitated the differentiation between benign and malignant ones. As the clinical examination cannot provide a definitive diagnosis, thus, ultrasonography and radioisotope scanning were employed for sorting out the nodules that should be further assessed by histopathology [9].
The sonographic appearance of suspicious nodules can predict the need for histopathological evaluation of them. The US elastography can provide an objective assessment of tissue stiffness [6].
In this context, our results had outlined the most predictive US feature of malignancy by B-mode, as hypo or marked hypo-echogenicity, with the highest sum of the sensitivity and specificity (66.6 and 90.9%, respectively), and this was incongruent with Zhao et al. [13] who had described the micro-calcification as being the most predictive US feature of malignancy (85% sensitivity and 75.6% specificity); this difference is explained by the different sample sizes, where they had a larger sample (313 patients) and a relatively larger number of malignant nodules (194).
From the above and in concordance with Sibos study [14], there is no single US criterion that carries sufficiently high accuracy measures in distinguishing the nodules, but the combination of multiple criteria could increase the sensitivity and specificity.
Horvath et al. [15] had introduced the TI-RADS for risk stratification of thyroid malignancy. Their tested sensitivity was 88%, and NPV was 88%; Russ et al. [16] had also reported high sensitivity (95.7%) and NPV (99.7%) for diagnosing thyroid malignancy by TI-RADS, then Tessler et al. [10] had updated the TI-RADS scoring; the latter was used in our study with the pooled sensitivity and NPV of TI-RADS (in our study) of 84.8 and 91.6%, respectively.
The ROC curves—in our study—had indicated that the cutoff value of ACR TI-RADS was TR4, and the AUC was 0.84 (95%CI 0.754–0.907) with the diagnostic sensitivity and specificity of ACR TI-RADS of 84.8% and 83.3%, respectively; this was concordant with Zhang et al. [17], where their cutoff value for the ACR TI-RADS was TR5, and AUC was 0.864 (95%CI 0.879–0.934) (81.4% sensitivity and 84.8% specificity); Xu et al. [18] also had reported an approximate cutoff point for malignancy by ACR TI-RADS, which was more than TR4 (80.6% sensitivity, 78.4% specificity, and 79.6% accuracy of the average value).
By using the color Doppler, we had noticed that the presence of intra-nodular vascularity (Type 1b) was close to the possibility of malignancy, but simultaneously, the presence of the peri-nodular vascularity or avascular nodules cannot exclude it, so the color Doppler solely had a limited role in the differentiation between the thyroid nodules; however, in congruence with Manoj et al. [19], we found that (1b) pattern was the cutoff value for the suggestion of malignancy with 54.5% sensitivity, 100% specificity, and 81.4% NPV.
Shear wave elastography is one of the elastography techniques that had gained a high sensitivity and specificity for evaluation of the thyroid nodules and can decrease the unnecessary invasive procedures [9, 20].
We had found that EIs were significantly higher in malignant thyroid nodules than in benign ones (p < 0.0001), this was stated in the meta-analysis study done by Peiliang et al. (84.3% sensitivity and 88.4% specificity) [21].
Hye et al. [22] had reported higher EIs in thyroid carcinoma relative to the benign nodules with Emean with diagnostic specificity of 86.4% and PLR of 4.2; this is nearly compatible to our study, where, the Emean had a diagnostic specificity of 83.3% and PLR of 5.09.
Among the tested SWE EIs, we had selected the elasticity ratio (ER) as the best cutoff value because it has the highest sensitivity and specificity values in the differentiation between the malignant and the benign thyroid nodules. The ER cutoff value of 2.6 had the highest AUC value (96.3%; 95% CI 93.3–99.4%); it had a sensitivity, specificity, PLR, PPV, and NPV of 90.9, 89.4, 8.5, 81, and 85.1%, respectively.
Although matching Veyrieres et al. [23], Bhatia et al. [24], Sebag et al. [25], and Kim et al. [26] studies, up to our knowledge, the most accurate cutoff value of SWE has not yet been unified. This difference between the studies may be attributed to the choice of different standards. We had selected the best cutoff value in ER ( which was 2.6), whereas they had used the best parameter that gave a NPV or a PPV of at least 80%.
Consistent with this rule in the selection of the best cut-off value, many published studies over the past years are concordant with us, including Liu et al. [27], Park et al. [28], Zhao et al. [13], and Zhang et al. [17], where they had also considered that the EIs are significantly higher in malignant nodules with high accuracy measures.
Adding to our knowledge, two important salient findings—in our study—were demonstrated where the combination of SWE and TI-RADS as well as color Doppler and TI-RADS to a certain extent had increased the diagnostic performance in differentiating thyroid nodules. Moreover, when we used the SWE (ER) and TI-RADS, we had obtained higher accuracy measures compared with the TI-RADS alone; therefore, such a combination of TI-RADS and EIs can minimize the need for unnecessary surgery or biopsy in suspicious thyroid nodules; this was concordant with Park et al. [28], Zhao et al. [13], and Xu et al.’s [18] studies, where the combined use of the TI-RADS findings and the EIs had increased the accuracy measures.
However, it had been shown that the rise in the sensitivity was from 84.8% of TI-RADS alone to 90.9% with the combination of TI-RADS and SWE in “parallel” but the specificity was lower (74.2%) as compared with TI-RADS alone (83.3%); this was explained by the statistical way in which we chose the positive cases of possible malignancy as we use the parallel method when one or both methods had resulted in positivity, and the results were considered negative when only both methods had resulted in negativity; this relationship between both methods is termed “parallel”; and it can explain why the sensitivity is higher while the specificity is lower in the combined method than in TI-RADS alone.
Finally, from our results, we had found that the SWE and TI-RADS can form a complementary relationship in terms of the advantages. Where the TI-RADS can compensate for the limitations of SWE (that may be disturbed by macro-calcifications and the carotid artery pulsations) and vice versa, the SWE can compensate for TI-RADS, which can be influenced by the operator dependence and the interobserver variability. Thus, we suggest using SWE for the thyroid nodules with TI-RADS score greater than or equal to 4 as a complementary tool, other than doing the diagnosis separately to avoid unnecessary invasive diagnostic procedures in suspicious nodules.
Some limitations had been met in this work including the following:
First, all malignant nodules (24/33) were papillary carcinomas, while only three nodules were medullary carcinomas, and most of the benign nodules were nodular goiters; thus, other pathological types were not included, such as Hurthle cell thyroid carcinoma and primary thyroid lymphoma; thus, their tested parameters were not examined in this study.
Second, it is a one-center experience, so the data need to be tested by prospective multicenter and nonspecialized members to eliminate this selection bias.
Third is the isthmic lesions, where the relatively small size of the isthmus compared with the thyroid lobes and the ROI should cover the whole nodule with sufficient surrounding parenchyma are needed; however, isthmic lesions were seen in 10 of our cases, most of them were “isthmi-lobar” in location, thus surrounding thyroid parenchyma served to avoid this limitation; however, in pure isthmic lesions, breath-holding and cessation of swallowing as well as the application of a copious amount of gel is considered of paramount importance, moreover, repeating the process, where at least 3 successive measurements were taken for each nodule to choose the best SWE image.
Forth, is the inter\intra-observer variability and the operator dependency, this was much lessened by conducting the examinations using the same US machine at the same setting of the conventional US examination, and by the same operator under the direct supervision of an experienced senior.
Last, selection bias may exist because patients included in our study were scheduled for US-guided FNAC for suspicious thyroid nodules with US features (TR ≥ 3), this may decrease the diagnostic performance on TI-RADS, causing false-negative cytologic results.
Finally, it would be interesting to see any solid and conclusive results that can lead to a change in practice as the researches about the SWE are there and giving promising results for a long time, but it is not included in any known thyroid scoring systems so far.