Shear wave elastography combined with fine-needle aspiration biopsy in the diagnosis of China Thyroid Imaging Reporting and Data System category 4 thyroid nodules

Introduction

Shear wave elastography (SWE) provides quantitative indexes such as the maximum, minimum, mean, and standard deviation of the Young modulus, which can reflect the stiffness of the target thyroid nodule (1). Meanwhile, fine-needle aspiration biopsy (FNAB) is a reliable and safe method for diagnosing thyroid nodules; however, its diagnostic ability varies, with some FNA results being indeterminate (2). The Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) is used to evaluate the malignant risk of thyroid nodules and was proposed by the Ultrasound Medical Branch of the Chinese Medical Association in 2020 specifically for the modern Chinese context. As the risk of malignancy in thyroid nodules classified as C-TIRADS category 4 ranges from 2% to 90% (3-5), combining different methods to differentiate and diagnose these nodules is needed. Our study retrospectively analyzed the conventional ultrasound images, SWE images, and FNAB results of 209 C-TIRADS category 4 nodules which were confirmed by postoperative pathological results to assess the diagnostic efficiency of SWE combined with FNAB in diagnosing these nodules. We present this article in accordance with the STARD reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-aw-521/rc).

Methods

Patients

The cases in this study were from the Affiliated Hospital of Yangzhou University and Jiangsu Provincial Corps Hospital, Chinese People’s Armed Police Forces. From July 2021 to July 2024, 220 patients with thyroid nodules met the following inclusion criteria: (I) maximum nodule diameter of ≥5 mm; (II) C-TIRADS category 4 classification; (III) completion of SWE and FNAB, and (IV) confirmation via postoperative pathological result. There were two exclusion criteria: (I) a patient age ≤14 or ≥80 years (n=5); and (II) lack of complete SWE images (n=6). For multiple nodules, the one with the greatest possibility of malignancy was preferred, followed by the one with the largest diameter. Finally, 209 nodules in 209 patients were included for analysis. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, and was approved by the Ethics Committee of Affiliated Hospital of Yangzhou University (approval No. 2021-YKL4-28-004) and Jiangsu Provincial Corps Hospital, Chinese People’s Armed Police Forces (approval No. 2021-JS003). The Committee waived the requirement for individual consent due to the retrospective nature of the analysis.

Conventional ultrasound and SWE

The instruments used for conventional ultrasonic examination were an iU22 device (Philips, Amsterdam, the Netherlands) with a 5- to 12-MHz probe and a LOGIQ E9 device (GE HealthCare, Chicago, IL, USA) with 6- to 15-MHz probe. The operating radiologists had more than 8 years’ experience in thyroid examination. During the examination, the patient was supine, with full exposure of the anterior cervical region. The radiologists carefully examined the patient’s thyroid nodules and cervical lymph nodes. According to the C-TIRADS standard, all thyroid nodules were classified (6).

The instrument used for SWE was the Aixplorer (Supersonic Imagine, Aix-en-Provence, France) with a 4- to 15-MHz probe. The operating radiologists had more than 15 years’ experience in thyroid nodule ultrasound diagnosis. The target nodule was scanned and measured five times in the longitudinal section and the transverse section, respectively. The Young maximum elastic modulus (Emax; in kPa), an SWE indicator, was recorded (as the mean of 10 measurements).

FNAB operation and classification

The condition and the target nodule were assessed before puncture. Patients signed informed consent form before puncture biopsy. During the operation, the patient was in a supine position without a pillow. The neck skin was disinfected, and local anesthesia was administered. Under ultrasound guidance, an appropriate puncture path was selected. A 5-mL empty syringe needle (22 G and 32 mm) was used to puncture the target nodule and was gently inserted 5–10 times. The syringe needle was then removed, and the puncture fluid was applied to coat a glass slide and quickly fixed with 95% ethanol. The above-described operation was repeated twice for other parts of the target nodule. FNAB cytology reports were classified on the basis of the 2017 Bethesda system (7). The indeterminate nodules in our study included Bethesda categories III, IV, and V (7).

Statistical analysis

SPSS 22.0 software (IBM Corp., Armonk, NY, USA) was used for statistical processing. Quantitative data with a normal distribution and quantitative data with a nonnormal distribution are expressed as the mean ± standard deviation and the median with first and third quartiles, respectively, and were compared with the t-test and nonparametric Mann-Whitney test, respectively. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff value for the Emax of SWE. When SWE was combined with FNAB, benign nodules according to FNAB were classified as negative, while nodules designated as malignant according to FNAB were classified as positive. For nodules with indeterminate FNAB results, those with an SWE Emax ≤ the cutoff value were considered negative; otherwise, they were considered positive. The Chi-squared test was used to compare the sex ratio and the diagnostic efficiency. P<0.05 was considered statistically significant.

Results

Clinical data and pathological results

This study included 55 males (26.3%) and 154 females (73.7%), with an age range from 20 to 78 years and an average age of 45.3±14.3 years. The maximum diameters of the nodules ranged from 5 to 28 mm. Among the 209 nodules, the numbers of nodules in C-TIRADS categories 4A, 4B, and 4C were 56 (26.8%), 74 (35.4%), and 79 (37.8%), respectively.

Of the 209 nodules, 153 (73.2%) were identified as malignant and 56 (26.8%) as benign by postoperative pathology. There were 149 thyroid papillary carcinomas (71.3%), 4 follicular thyroid carcinomas (1.9%), 29 nodular goiters (13.9%), 18 follicular adenomas (8.6%), 2 cases of subacute thyroiditis (1.0%), 3 cases of chronic lymphocytic thyroiditis (1.4%), 2 adenomatous goiters (1.0%), and 2 Hashimoto nodules (1.0%). There was no significant difference in the maximum diameter of nodules between the benign and malignant types (P>0.05); however, there were significant differences in the male-female ratio and the age of patients (all P values <0.05) (Table 1).

Diagnostic efficiency of SWE and FNAB

Postoperative pathology was the gold standard used for diagnosis. The ROC curve indicated that the optimal cutoff value of Emax was 42.65 kPa, and the area under the ROC curve (AUC) for Emax was 0.823 [95% confidence interval (CI) 0.765–0.880] (Figure 1). SWE identified 82 negative nodules and 127 positive ones and had a sensitivity, specificity, and accuracy of 75.2% (115/153), 78.6% (44/56), and 76.1% (159/209), respectively (Table 2 and Figures 2,3). FNAB identified 42 benign nodules, 59 indeterminate nodules, and 108 malignant nodules, which was consistent with the histology results. Of the 42 nodules classified as benign by FNAB, 2 nodules were inconsistent with histology. The sensitivity, specificity, and accuracy of FNAB were 70.6% (108/153), 71.4% (40/56), and 70.8% (148/209), respectively.

Figure 1 The ROC curve of SWE Emax. The area under the ROC curve (AUC, 95% CI) of SWE Emax was 0.823 (95% CI: 0.765–0.880). AUC, area under the receiver operating characteristic curve; CI, confidence interval; Emax, Young maximum elastic modulus; ROC, receiver operating characteristic; SWE, shear wave elastography.

Figure 2 The SWE image of a benign thyroid nodule. Thyroid follicular adenoma in a 38-year-old woman. The SWE Emax of the nodule was 26.1 kPa. Emax, Young maximum elastic modulus; SWE, shear wave elastography.

Figure 3 The SWE image of a malignant thyroid nodule. Thyroid papillary carcinoma in a 55-year-old woman. The SWE Emax of the nodule was 46.0 kPa. Emax, Young maximum elastic modulus; SWE, shear wave elastography.

Diagnostic efficiency of the combination of SWE and FNAB

After SWE was combined with FNAB, 68 and 141 nodules were identified as negative and positive respectively, and the sensitivity, specificity, and accuracy were 92.2% (141/153), 100.0% (56/56), and 94.3% (197/209), respectively (Table 2). The combination of SWE and FNAB significantly improved the sensitivity, specificity, and accuracy (all P values <0.001) (Table 3).

Discussion

Our study demonstrated that SWE has a high diagnostic efficiency for C-TIRADS category 4 thyroid nodules. For C-TIRADS category 4 nodules, a combination of methods or technologies is necessary to improve diagnostic accuracy (8). SWE reflects the elasticity of tissues by generating shear waves through the transmission of acoustic radiation pulses without external force (9,10). The study by Li et al. showed that the combination of SWE and C-TIRADS could significantly improve the diagnostic efficiency for category 4a and 4b thyroid nodules (11). Kosar Tunc et al. reported that the combination of SWE, superb microvascular imaging (SMI), and TI-RADS could improve the diagnostic efficiency for thyroid nodules (12). Chen et al. demonstrated that SMI and SWE provide additional predictive values of risk stratification in TI-RADS category 4 thyroid nodules (13). In Polat et al.’s study, combining SWE with TI-RADS for diagnosing thyroid nodules provided greater diagnostic specificity than did TI-RADS alone (14). Latia et al. proposed that using elasticity imaging hardness as an adjunct to characteristics of high suspicion observed by routine ultrasound could improve the detection rate of malignant nodules in patients with FNAB results indicating Bethesda category IV (15). Latia et al. confirmed that two-dimensional SWE could accurately distinguish malignant thyroid nodules in cases with chronic autoimmune thyroiditis and supported it as a supplementary tool for routine ultrasound (16). Additionally, Mehanna et al., using data from the ElaTION trial, concluded that difficulties remain in differentiating thyroid nodules via SWE and that further research on the value of SWE in the diagnosis of thyroid nodules may be futile unless the technology is improved (17). Certain factors may influence the quality of the elastography: size, depth, location, composition, and calcification of the nodule; background thyroid parenchyma; patient anatomy; stability of the acquisition; and region of interest (ROI) placement strategy. Very small nodules (<5 mm) present a technical challenge to consistent ROI placement and reliable wave generation. Deeply located nodules may yield unreliable measurements due to shear wave attenuation. Predominantly cystic or spongiform nodules lack sufficient solid tissue for valid SWE measurement. The technique is most reliable in solid or predominantly solid nodules. Macrocalcifications (>2 mm) are a prominent confounder. The calcification itself is extremely stiff, producing artifactual peak values, and their posterior acoustic shadow creates a signal void, preventing measurement in the region behind it. Microcalcifications have a less pronounced effect. Diffuse pathologies such as Hashimoto thyroiditis or Graves disease can increase the overall stiffness of glands, potentially reducing the contrast between a malignant nodule and its background and lowering the specificity of SWE. A short neck, prominent sternocleidomastoid muscles, or excessive subcutaneous adipose tissue can hinder optimal probe placement and wave propagation. This was verified in negative cases of elastography with malignant histology in our study. Elastography enhances conventional ultrasound by providing valuable information on tissue stiffness, improving the differentiation of benign and malignant thyroid nodules by incorporating stiffness as an indicator of malignancy. However, elastographic evaluation of medullary thyroid carcinoma presents different challenges, as these tumors often appear soft or heterogeneous on both strain elastography and SWE, frequently leading to false-negative results (18).

FNAB under ultrasound guidance is widely performed in many hospitals and has become a reliable and safe method for the diagnosis of thyroid nodules. However, repeated FNAB or core needle biopsy (CNB) is required when the puncture specimen is unsatisfactory or the diagnosis is unclear. Sbeit et al.’ s study highlighted the importance of preoperative FNAB in planning the thyroidectomy for cases with a goiter, with FNAB results allowing patients and physicians to make more informed decisions (19). Fallahi et al. identified false positive and negative rates in FNAB as critical concerns, posing challenges in the diagnosis of malignancy in cases of smaller nodules and multinodular goiter (2). Research in the field has begun to focus on reducing unnecessary FNAB. For instance, Chen et al. found that visual evaluation of microvascular morphological patterns could aid in differentiating thyroid nodules and possibly decrease the risk of unnecessary FNAB of benign thyroid nodules (20). Ni et al. proposed that artificial intelligence (AI) could serve as a better “gatekeeper” against unnecessary FNAB than could radiologists by distinguishing benign nodules that radiologists initially evaluated as malignant (21). In our study, the sensitivity, specificity, and accuracy of FNAB were 70.6% (108/153), 71.4% (40/56), and 70.8% (148/209), respectively; meanwhile, the combination of SWE with FNAB yielded values of 92.2% (141/153), 100.0% (56/56), and 94.3% (197/209), respectively. Therefore, combination of SWE with FNAB provides greater sensitivity, specificity, and accuracy of diagnosis (all P values <0.001).

FNAB plays a key role in detecting or excluding malignancy. However, up to 30% of cases are cytologically indeterminate and carry a malignancy risk ranging from 10% to 40%. Diagnostic surgery is traditionally performed in such cases but is unnecessary in approximately 75% of cases. Accordingly, more accurate diagnostic strategies are warranted (22). Bailey et al. suggested that CNB is particularly useful for repeated non-diagnostic FNA, atypical cells, or when tissue is needed for diagnostic, prognostic, or molecular profiling of malignancies such as anaplastic thyroid carcinoma (23). Future prospective studies, including cost-benefit analyses, are warranted to further define the indications for CNB (24).

This study involved certain limitations which should be discussed. First, only the Emax was considered, and statistical analysis of other indicators of SWE was lacking. Second, as indicated by Cheng et al., the selection of ROI size may critically impact the diagnostic results derived from SWE (25), but this was not accounted for in our study. Third, the sample size was relatively small, and validation in large samples is needed. Fourth, selection bias might have arisen due to the retrospective nature of the analysis.

Conclusions

SWE and FNAB demonstrated reliable diagnostic efficiency for C-TIRADS category 4 thyroid nodules. Their combination improved the sensitivity, specificity, and accuracy and thus should be more broadly applied in a clinical practice.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-aw-521/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-aw-521/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-aw-521/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-aw-521/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, and was approved by the Ethics Committee of Affiliated Hospital of Yangzhou University (approval No. 2021-YKL4-28-004) and Jiangsu Provincial Corps Hospital, Chinese People’s Armed Police Forces (approval No. 2021-JS003). The Committee waived the requirement for individual consent due to the retrospective nature of the analysis.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: J. Gray)