Size-dependent heterogeneity in the associations of C-TIRADS ultrasound features with malignancy in thyroid nodules.
5 affiliations
- 1Department of Interventional Ultrasound, Cancer Hospital of Shantou University Medical College, Shantou, China.
- 2Department of Interventional Ultrasound, Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
- 3Department of Ultrasound, Cancer Hospital of Shantou University Medical College, Shantou, China.
- 4Department of Ultrasound, Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
- 5Department of Thoracic Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Abstract
Aim
To investigate whether the associations between Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) ultrasound features and malignancy vary according to thyroid nodule size.Methods
This two-center retrospective cohort study included 3726 thyroid nodules, which were categorized according to maximum diameter as ≤1 cm or >1 cm. Extreme gradient boosting models and SHapley Additive exPlanations (SHAP) were used for exploratory visualization of the contributions of individual ultrasound features to malignancy prediction in the overall cohort and the two size subgroups. Multivariable Firth logistic regression was used to estimate the adjusted associations between the C-TIRADS features and malignancy. Single-feature interaction models were constructed to assess whether nodule size modified these associations. The discriminative performance of the original C-TIRADS model and the interaction model was compared using the area under the receiver operating characteristic curve (AUC). Center-adjusted sensitivity analyses were also performed.Results
Vertical orientation and solid composition showed greater contributions to malignancy prediction and stronger associations with malignancy in nodules ≤1 cm, whereas microcalcification and ill-defined/irregular margin or extrathyroidal extension showed stronger associations with malignancy in nodules >1 cm. Significant feature-by-size interactions were identified for vertical orientation, solid composition, microcalcification, and ill-defined/irregular margin or extrathyroidal extension, whereas no significant interactions were observed for markedly hypoechoic or comet-tail artifact. The interaction model showed a modest but statistically significant improvement in discriminative performance compared with the original C-TIRADS model (AUC 0.918 vs. 0.911, P < 0.001). The center-adjusted sensitivity analyses yielded consistent findings.Conclusion
The associations between C-TIRADS ultrasound features and malignancy exhibit significant size-dependent heterogeneity. In nodules ≤1 cm, vertical orientation and solid composition may indicate a substantially higher likelihood of malignancy and therefore warrant particularly careful clinical evaluation, whereas microcalcification and ill-defined/irregular margin or extrathyroidal extension may be more informative for malignancy assessment in nodules >1 cm. Considering nodule size when interpreting individual C-TIRADS features may improve diagnostic discrimination.
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BibTeX
@article{guo2026sizedependent,
title = {{Size-dependent heterogeneity in the associations of C-TIRADS ultrasound features with malignancy in thyroid nodules.}},
author = {Dongming Guo and Yonghua Xu and Xianying Liao and Haiqing Huang and Yuxia Zhai and Haitao Li and Zhihui Lin and Jiajia Wang and Zhe Chen},
journal = {Frontiers in endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1844286},
url = {https://europepmc.org/article/MED/42908584},
note = {CC BY},
}
RIS
TY - JOUR
TI - Size-dependent heterogeneity in the associations of C-TIRADS ultrasound features with malignancy in thyroid nodules.
AU - Dongming Guo
AU - Yonghua Xu
AU - Xianying Liao
AU - Haiqing Huang
AU - Yuxia Zhai
AU - Haitao Li
AU - Zhihui Lin
AU - Jiajia Wang
AU - Zhe Chen
PY - 2026
DA - 2026/10/07
JO - Frontiers in endocrinology
DO - 10.3389/fendo.2026.1844286
UR - https://europepmc.org/article/MED/42908584
AB - Aim To investigate whether the associations between Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) ultrasound features and malignancy vary according to thyroid nodule size.Methods This two-center retrospective cohort study included 3726 thyroid nodules, which were categorized according to maximum diameter as ≤1 cm or >1 cm. Extreme gradient boosting models and SHapley Additive exPlanations (SHAP) were used for exploratory visualization of the contributions of individual ultrasound features to malignancy prediction in the overall cohort and the two size subgroups. Multivariable Firth logistic regression was used to estimate the adjusted associations between the C-TIRADS features and malignancy. Single-feature interaction models were constructed to assess whether nodule size modified these associations. The discriminative performance of the original C-TIRADS model and the interaction model was compared using the area under the receiver operating characteristic curve (AUC). Center-adjusted sensitivity analyses were also performed.Results Vertical orientation and solid composition showed greater contributions to malignancy prediction and stronger associations with malignancy in nodules ≤1 cm, whereas microcalcification and ill-defined/irregular margin or extrathyroidal extension showed stronger associations with malignancy in nodules >1 cm. Significant feature-by-size interactions were identified for vertical orientation, solid composition, microcalcification, and ill-defined/irregular margin or extrathyroidal extension, whereas no significant interactions were observed for markedly hypoechoic or comet-tail artifact. The interaction model showed a modest but statistically significant improvement in discriminative performance compared with the original C-TIRADS model (AUC 0.918 vs. 0.911, P < 0.001). The center-adjusted sensitivity analyses yielded consistent findings.Conclusion The associations between C-TIRADS ultrasound features and malignancy exhibit significant size-dependent heterogeneity. In nodules ≤1 cm, vertical orientation and solid composition may indicate a substantially higher likelihood of malignancy and therefore warrant particularly careful clinical evaluation, whereas microcalcification and ill-defined/irregular margin or extrathyroidal extension may be more informative for malignancy assessment in nodules >1 cm. Considering nodule size when interpreting individual C-TIRADS features may improve diagnostic discrimination.
SN - 1664-2392
ER -