The Association between Subcategorization, Cytomorphological Features, and Ultrasonographic Characteristics with Surgical Outcomes of Atypia of Undetermined Significance Thyroid Nodules

Introduction: Thyroid nodule is commonly detected while performing an ultrasound of the neck. American College of Radiology, Thyroid imaging reporting and data system (ACR-TIRADS) is a classification used to characterize thyroid nodules based on ultrasound findings. The objective of this study is to evaluate the role of ACR-TIRADS classification in differentiating benign and malignant thyroid nodules. Methods: This is a prospective study conducted at Manipal Teaching Hospital. A total of 70 patients presenting to our radiology department for fine needle aspiration cytology (FNAC) of thyroid nodule were enrolled in the study. Thyroid nodules were grouped as 1- 5 according to the ACR-TIRADS. The ACR-TIRADS findings were correlated with FNAC and or biopsy findings as available. Subsequently; sensitivity, specificity, accuracy, positive predictive value and negative predictive value of ACR-TIRADS in differentiating benign from malignant nodules were assessed. Results: Mean age of patients in our study was 52.16 years (18-89 years). Male patients were 11 (15.7 %) and female were 59 (84.30 %). According to Ultrasonography; 1.4% of thyroid nodules were labelled as ACR-TIRADS 1; 21.4% as ACR-TIRADS 2; 32.85% as ACR- TIRADS 3; 28.6 % as ACR-TIRADS 4 and 15.7 % as ACR-TIRADS 5. ROC curve analysis showed AUC of 0.78 (95% CI). ACR-TRIADS had sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy of 87.5%, 68.5 %, 45.16 %, 94.87 %, 72.86 % respectively. Conclusion: ACR- TIRADS has high sensitivity and accuracy in differentiating benign and malignant thyroid nodules.

This study aimed to evaluate a new risk stratification system, the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS), published in 2017. From January 2015 to December 2016, 1033 thyroid nodules in 1013 patients who had undergone sonography and thyroid surgery or fine-needle aspiration (FNA) in our hospital were included. The sonographic features were described in a standard manner and analyzed according to the white paper of the ACR TI-RADS Committee. Nodules were assigned points for each feature, and the points were totaled to determine the final TI-RADS levels. Of the 1033 nodules, 725 were benign and 308 were malignant proven by operation or FNA. The malignant risk was associated with the composition, echogenicity, shape, margins, and echogenic foci of the nodules (P < 0.001). The calculated risk of malignancy was higher in nodules with macrocalcifications than those with peripheral calcifications, which is different from the ACR TI-RADS. The calculated malignancy rates of nodules with TR5, TR4, TR3, and TR2 were 67.1%, 13.0%, 1.1%, and 0%, respectively, which showed a higher malignant risk than the suggested threshold of TR5 in the ACR TI-RADS. Six nodules with TR4 recommended for no follow-up and 55 nodules with TR5 recommended for follow-up were malignant with cervical lymph node metastasis. The ACR TI-RADS provides effective malignancy risk stratification for thyroid nodules and was useful for the decision for FNA. However, the points assigned for echogenic foci, the set of the TI-RADS risk thresholds, and FNA thresholds may need more consideration and prospective validation.

The Diagnostic Performance and Interobserver Consistency of Contrast-enhanced Ultrasound Thyroid Imaging Reporting and Data System for Assessing Thyroid Nodules: A Retrospective and Multicenter Study.

We evaluated the frequency, risk factors and the follow-up outcomes of thyroid nodules, and genetic alterations in thyroid cancer, in youth with childhood-onset Hashimoto thyroiditis (HT) residing in an iodine-sufficient country. A retrospective cohort study. A total of 213 patients (194 females, mean age 10.6years at the time of HT diagnosis) were ultrasonographically evaluated. Thyroid nodules were categorized using the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TI-RADS). Thyroid nodules were detected in 40 (18.8%) patients over a median follow-up period of 3.4years, usually after the onset of puberty. A family history of thyroid disease (hazard ratio 2.1, p=.031) was predictive of thyroid nodule detection. Papillary thyroid carcinoma (PTC) was diagnosed in 9 (4.2% of all and 22.5% of nodule-positive patients). The malignant nodules had a higher K-TIRADS or ACR-TI-RADS risk level compared with benign nodules (p<.01 for both). Genetic alterations were revealed in 7 (BRAFV600E in 6 and RET-ERC1 fusion in 1) of the eight available tumour tissue samples. None showed evidence of disease over a median follow-up period of 3.4years. The nodule detection rate was 18.8%, with a 22.5% risk of malignancy among the detected nodules in childhood-onset HT patients, showing increased risk in those with a family history. Additional large-scale studies are required to evaluate the usefulness of K-TIRADS or ACR-TI-RADS risk level for the differentiation of paediatric thyroid nodules.

Diagnostic Performance of European and American College of Radiology Thyroid Imaging Reporting and Data System Classification Systems in Thyroid Nodules Over 20 mm in Diameter

Background: One major drawback of using ultrasound for diagnosing thyroid nodules is its limited ability to distinguish between benign and malignant nodules. In China, the common methods for risk stratification and guiding fine needle aspiration (FNA) in diagnosing thyroid nodules are the Chinese Thyroid Imaging Reports and Data Systems (C-TIRADS) and American College of Radiology-Thyroid Imaging Reporting and Data System (ACR-TIRADS). Objectives: This review seeks to assess the effectiveness of C-TIRADS and ACR-TIRADS in accurately identifying the risk of malignancy in Chinese patients suspected of thyroid cancer. Methods: A detailed search was conducted in PubMed, Google Scholar, Medline, Embase, Web of Science, Cochrane, and China National Knowledge Infrastructure (CNKI) databases from January 2018 to December 2022. The analysis only considered original articles from China reporting the use of C-TIRADS and ACR-TIRADS confirmed by histology and FNA. Results: This review analyzed 26 studies with a total of 23,064 thyroid nodules from 19,114 patients to compare the diagnostic performance of C-TIRADS and ACR-TIRADS in predicting malignancy risk in thyroid nodules. Although the malignancy rates in each risk category were similar between the two systems, the TIRADS showed better diagnostic performance than C-TIRADS in terms of pooled specificity (95.0 % vs. 66.8 % of C-TIRADS). However, the pooled analysis showed that C-TIRADS had a better pooled sensitivity (94.6 % vs. 76.5% of ACR-TIRADS). The diagnostic odds ratio was 1.37 (95 % CI: 0.75-2.51) for ACR-TIRADS and 0.89 (95 % CI: 0.36-2.16) for C-TIRADS. Conclusion: Based on the results, both C-TIRADS and ACR-TIRADS are effective in predicting the risk of malignancy in thyroid nodules with similar overall diagnostic accuracy. The combination of both systems can be beneficial in enhancing accuracy in suspicious or uncertain cases. The long-term experience of the trained radiologists can readily help in concluding the diagnosis. As no single system or combination of systems can provide a 100% accurate prediction of the malignancy of thyroid nodules, the ultimate diagnosis relies on the concluding assessment of experienced radiologists and the medical team.

BackgroundSmall thyroid nodules (≤ 10 mm) are common findings in thyroid ultrasonography. The first purpose of this study was to compare the performance of three guidelines in the diagnosis of malignancy for small thyroid nodules. The second aim was to find the ultrasonographic characteristics potentially associated with the risk of malignancy. This prospective cross-sectional study was performed on the patients with a diagnosis of small thyroid nodules (≤ 10 mm), who were rereferred to the radiologists for sonography and FNA. Sonographic features were recorded and scored according to the American College of Radiology-Thyroid Imaging Reporting and Data System (ACR-TIRADS), American Thyroid Association (ATA-2015), and Korean-TIRADS (K-TIRADS). Finally, FNA was conducted and cytological findings were reported.ResultsIn total, 287 thyroid nodules from 256 subjects (64 men and 192 women) were finally included in the study. The accuracy of ACR-TIRADS categories TR5 and TR4/5 was 88.9% and 72.1%, respectively. This rate for ATA-2015 classes high suspicion and intermediate suspicion/high suspicion was 88.9% and 82.6%, respectively. For K-TIRADS classes 5 and 4/5, the diagnostic accuracy was 89.6% and 82.9%, respectively. Significant direct associations were found between malignancy and punctate echogenic foci (odds ratio [OR] = 6.46), hypoechogenicity (OR = 6.39), ill-defined margin (OR = 4.38), and irregular margin (OR = 7.33).ConclusionThe differences in the strength of the three guidelines in the prediction of the malignancy should be considered by clinicians and radiologists in the management of thyroid nodules smaller than 10 mm.

Ultrasound is widely used for detecting thyroid nodules in clinical practice. This retrospective study aimed to assess the diagnostic efficacy of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS), S-Detect, and elastography of the carotid artery for suspicious thyroid nodules and to determine the complementary value of artificial intelligence and elastography. Between January 2021 and November 2021, 101 consecutive patients with 138 thyroid nodules were enrolled in The First Hospital of China Medical University. All nodules were evaluated using ACR-TIRADS categories (TR), S-Detect, and elastography, and then the diagnostic performance of the different methods and the combined assessment were compared. The inclusion criteria were the following: (I) TR3, TR4, and TR5 nodules, which were defined as "suspicious nodules"; (II) patients who had surgical or cytopathological results after ultrasound examination; and (III) voluntary enrollment in this study. Meanwhile, the exclusion criteria were the following: (I) TR1 and TR2 nodules, (II) patients who had undergone fine-needle aspiration before ultrasound examination, and (III) inconclusive cytologic findings. A total of 71 patients (12 men and 59 women) with 94 suspicious thyroid nodules (42 benign nodules and 52 malignant nodules) were finally included in this study. S-Detect had a significantly better sensitivity than did ACR-TIRADS [S-Detect: 98.1%, 95% confidence interval (CI): 89.7-100.0%; ACR-TIRADS: 84.6%, 95% CI: 71.9-93.1%; P=0.036], but its specificity was much lower (S-Detect: 19.0%; 95% CI: 8.6-34.1%; ACR-TIRADS: 40.5%, 95% CI: 25.6-56.7%; P=0.032). The accuracy was not significantly different between S-Detect (62.8%; 95% CI: 52.2-72.5%) and ACR-TIRADS (64.9%; 95% CI: 54.4-74.5%) (P=0.761). The elasticity contrast index (ECI) was not definitively useful in identifying suspicious thyroid nodules (P=0.592). Compared with the use of ACR-TIRADS and S-Detect alone, the specificity (45.2%; 95% CI: 29.8-61.3%), positive predictive value (65.2%; 95% CI: 52.4-76.5%), accuracy (66.0%; 95% CI: 55.5-75.4%), and the area under the receiver operating characteristic curve (0.640; 95% CI: 0.534-0.736) of their combination were higher but not significantly so. At present, S-Detect cannot replace manual diagnosis, and the value of elastography of the carotid artery in diagnosing suspected thyroid nodules remains unclear.

To evaluate the malignancy risk and characteristics of thyroid nodules with two "Atypia of Undetermined Significance" or "Follicular Lesion of Undetermined Significance" (AUS/FLUS) results, and compare characteristics of malignancies with two AUS/FLUS results to those with one AUS/FLUS result. Of 441 thyroid nodules with initial AUS/FLUS results, 236 underwent repeat fine-needle-aspiration (FNA), with 58 obtaining repeated AUS/FLUS results. Thyroid Imaging Reporting and Data System (TIRADS) categories were assigned, and clinico-pathological characteristics were compared between benign and malignant nodules and between malignancies with two consecutive AUS/FLUS results and those with one AUS/FLUS result. Thirty-one percent (18/58) of nodules with two AUS/FLUS results and 58.1% (18/31) of confirmed nodules were malignant. Age, gender, nodule size, ultrasound features and TIRADS categories did not differ between benign and malignant nodules or between malignancies with one and two AUS/FLUS results. Malignancies with two AUS/FLUS results had a higher proportion of a follicular variant of papillary thyroid carcinoma (PTC) (46.7% vs. 13.6%, P = 0.009). Thyroid nodules with two AUS/FLUS results had a high malignancy risk of at least 31.0% and a higher proportion of a follicular variant of PTC. Surgery should be considered regardless of ultrasound features. • Thyroid nodules with two consecutive AUS/FLUS results had a high malignancy risk. • Ultrasound features are less useful in nodules with two AUS/FLUS results. • The follicular variant of PTC is more frequent in malignancies with two AUS/FLUS results.

Objectives:This study aimed to investigate ultrasound (US) features of thyroid nodules categorized as nondiagnostic (ND) and atypia of undetermined significance (AUS) according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and their potential implications for clinical management.Materials and Methods:A retrospective study was conducted on patients who underwent thyroid nodules FNAC between 2019 and 2023. Nodules falling into the ND and AUS categories were analyzed for US features, nodule size, composition, echogenicity, shape, margin, echogenic foci, the distribution of the American College of Radiology’s Thyroid Imaging Reporting and Data System (ACR TI-RADS) categories, and other parameters. The study included a total of 1,199 patients and 1,252 nodules (ND: 1110; AUS: 142).Results:No significant differences in age, gender, nodule features, echogenicity, shape, margin, echogenic foci, TI-RADS scores, localization, number of nodules, or thyroid parenchymal disease presence were found between the ND and AUS categories (p > 0.05). Also, no statistically significant difference in nodule size (<10 mm vs. ≥10 mm) existed between the ND and AUS categories (p = 0.475). Both showed predominantly solid composition and hyperechoic/isoechoic echogenicity. High proportions of TI-RADS 4 nodules were observed in both groups, with 727 (65.5%) in ND and 95 (66.9%) in AUS.Conclusion:This study found no statistically significant differences in US characteristics between the ND and AUS categories, indicating potential similarities in their radiological appearances. Also, no significant difference in nodule size (<10 mm and ≥10 mm) was observed between these categories. Clinical management should consider further investigations, including repeat FNAC, due to the diagnostic challenges and malignancy risk in both categories.

BackgroundIt is challenging to identify Papillary Thyroid Cancer (PTC) which shows atypia of undetermined significance (AUS) by Fine-needle Aspiration (FNA). This study aims to seek the meaningful quantitative biomarkers of the microvasculature and construct a classification model for PTC with AUS based on these new biomarkers and Thyroid Imaging Reporting and Data System (TI-RADS).MethodsThis prospective study enrolled 281 patients with 300 thyroid nodules showing AUS. These cases were divided into two groups with the largest dimension (LD) of 10 mm, A (< 10 mm) and B (≥ 10 mm). Firstly, an open-source artifact suppression algorithm, which combined a multi-scale Frangi filter and TOPHAT operation, was proposed for the segmentation of micro-vessels in Ultra Micro-Angiography (UMA) images. Then, 18 quantitative biomarkers were calculated and analyzed through Mann-Whitney test (U-test), while LASSO regression was utilized to remove collinear features. Finally, two different classification models were built using logistic regression through the selected biomarkers combined with Chinese TI-RADS (C TI-RADS) or American College of Radiology TI-RADS (ACR TI-RADS). The performances were evaluated using the mean Area Under the Curve (AUC) value and the DeLong test, through a 5-fold cross-validation experiment.ResultsGroup A comprised 58 benign nodules and 104 PTCs, while Group B consisted of 60 benign nodules and 78 PTCs. Four biomarkers were selected in Group A. The 5-fold cross-validation experiment showed that the mean Area Under Curve (AUC) improved from 0.725 with ACR TI-RADS to 0.851 (P < 0.05), while the mean AUC improved from 0.809 with C TI-RADS to 0.882 (P < 0.05). In Group B, four different biomarkers were selected, and the classification models showed improvements from 0.841 with ACR TI-RADS to 0.874 and from 0.894 with C TI-RADS to 0.936.ConclusionsThis study demonstrated the potential value of microvasculature in the prediction of PTC in AUS Cases and improved the performance of ultrasound examination. Moreover, the morphology of microvasculature showed different changes at different LD groups.

The optimal management of thyroid nodules that undergo fine-needle aspiration (FNA) with findings of atypia of undetermined significance (AUS) is unclear. Categorizing nodules by AUS subtype and ultrasound characteristics may improve risk stratification. Therefore, the purpose of this study is to evaluate the association between AUS subtype and ultrasound features on risk of malignancy (ROM). We performed a review of all patients with a thyroid nodule who underwent an FNA at our institution between January 2010 and November 2015. Patients with AUS were divided into groups with (1) nuclear atypia, (2) architectural atypia, or (3) Hurthle cell atypia. Their ultrasound features were assessed using the American Thyroid Association (ATA) thyroid nodule sonographic patterns. We conducted a univariate and multivariable analysis to determine the association between AUS subtype and other variables of interest with ROM. Of the 3428 thyroid nodules that underwent FNA, 237 (6.9%) had AUS. Of the 97 surgically resected nodules, 67 (69%) were benign and 30 (31%) were malignant. On univariate analysis nuclear atypia (p < 0.01) was associated with a thyroid malignancy. On multivariable analysis, both ATA high-risk ultrasound features (p = 0.04, odds ratio [OR] 3.68) and nuclear atypia (p < 0.01, OR 11.8) were independently associated with a final diagnosis of thyroid carcinoma. Nuclear atypia and ATA high-risk ultrasound features are useful in identifying patients with AUS that are at a higher risk of thyroid malignancy. Surgeons should take these factors into consideration when evaluating patients with AUS.

Recent advancements in diagnostic techniques have resulted in a higher detection rate of thyroid cancers within existing thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) 2023 and the American College of Radiology-Thyroid Imaging Reporting and Data System (ACR-TIRADS) are first-line investigations for thyroid nodules, aiding in diagnosis and management decisions. To evaluate the concordance between TBSRTC 2023 and ACR-TIRADS in reporting thyroid lesions and assess their accuracy in diagnosing malignancies. This retrospective, laboratory data-based study included patients presenting with thyroid nodules, who underwent ultrasonography and fine needle aspiration cytology (FNAC), followed by thyroidectomy. Overall concordance between TBSRTC, ACR-TIRADS, and histopathologic diagnosis was evaluated, along with their diagnostic accuracy. Risk of malignancy (ROM) was calculated for both systems using the final HPE diagnosis. 115 patient records were analyzed. Interobserver agreement between TBSRTC and ACR-TIRADS was moderate (kappa = 0.493 ± 0.093 [±SE]). ROM across extremes of TBSRTC and TIRADS categories were found to be similar. Higher TBSRTC grades correlated with higher ACR-TIRADS grades (Spearman's rank correlation coefficient = 0.594, P = 4.5 × 10 -16 ). The accuracy of FNAC findings and TIRADS to predict malignancy was 84.35% versus 80.87%, with no statistically significant difference ( P = 0.644). Our findings suggest a good concordance between both reporting systems for thyroid nodules, with moderate interrater agreement. Both systems are equally useful for surgical decision-making and avoiding unnecessary surgeries.

Comparison of the diagnostic performance for thyroid cancer on ultrasound between a convolutional neural network and visual assessment by radiologists has been inconsistent. Thus, we aimed to evaluate the diagnostic performance of the convolutional neural network compared with the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) for the diagnosis of thyroid cancer using ultrasound images. From March 2019 to September 2019, seven hundred sixty thyroid nodules (≥10 mm) in 757 patients were diagnosed as benign or malignant through fine-needle aspiration, core needle biopsy, or an operation. Experienced radiologists assessed the sonographic descriptors of the nodules, and 1 of 5 American College of Radiology TI-RADS categories was assigned. The convolutional neural network provided malignancy risk percentages for nodules based on sonographic images. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated with cutoff values using the Youden index and compared between the convolutional neural network and the American College of Radiology TI-RADS. Areas under the receiver operating characteristic curve were also compared. Of 760 nodules, 176 (23.2%) were malignant. At an optimal threshold derived from the Youden index, sensitivity and negative predictive values were higher with the convolutional neural network than with the American College of Radiology TI-RADS (81.8% versus 73.9%, P = .009; 94.0% versus 92.2%, P = .046). Specificity, accuracy, and positive predictive values were lower with the convolutional neural network than with the American College of Radiology TI-RADS (86.1% versus 93.7%, P < .001; 85.1% versus 89.1%, P = .003; and 64.0% versus 77.8%, P < .001). The area under the curve of the convolutional neural network was higher than that of the American College of Radiology TI-RADS (0.917 versus 0.891, P = .017). The convolutional neural network provided diagnostic performance comparable with that of the American College of Radiology TI-RADS categories assigned by experienced radiologists.

In the present study, the first aim was to compare the accuracy of three guidelines in the diagnosis of thyroid nodule malignancy. The second purpose was to find sonographic features potentially associated with the risk of malignancy. In this cross-sectional study, we prospectively recruited patients referred with a diagnosis of thyroid nodule (≥ 1cm) for fine-needle aspiration (FNA). Sonographic features were recorded and scored according to the American Thyroid Association (ATA-2015), the American College of Radiology-Thyroid Imaging Reporting and Data System (ACR-TIRADS), and the Korean TIRADS (K-TIRADS). FNA was conducted and cytological findings were reported. A total of 984 thyroid nodules were ultimately included, of which 144 (14.6%) were malignant and 840 (85.4%) were benign. The accuracy of ACR-TIRADS categories TR5 and TR4/5 was 88.3% and 69.3%, respectively. This rate for ATA-2015 classes High suspicion and Intermediate suspicion/High suspicion was 87.9% and 80.4%, respectively. For K-TIRADS classes 5 and 4/5, the diagnostic accuracy was 88.0% and 80.6%, respectively. The rate of unnecessary FNA was highest with ATA-2015 and K-TIRADS guidelines (53.9% and 53.7%, respectively), followed by ACR-TIRADS (32.0%). Significant direct associations were observed between malignancy and hypoechogenicity (odds ratio [OR] 5.78), fine calcification (OR = 6.7), rim calcification (OR = 2.56), ill-defined margin (OR = 3.31), and irregular margin (OR = 6.95). There are different strengths of ACR-TIRADS, K-TIRADS, and ATA-2015 guidelines in the prediction of malignant thyroid nodules, and clinicians and radiologists should consider these differences in the management of thyroid nodules.