Preoperative Malignancy Risk Stratification in Bethesda IV Thyroid Nodules Using Integrated Clinical, Ultrasonographic, and Biochemical Parameters in Surgical Oncology Practice.
5 affiliations
- 1Department of General Surgery, Division of Surgical Oncology, Kastamonu Training and Research Hospital, Kastamonu 37150, Türkiye.
- 2Department of Radiology, Sakarya University Faculty of Medicine, Sakarya 54290, Türkiye.
- 3Department of Medical Education, Sakarya University Faculty of Medicine, Sakarya 54290, Türkiye.
- 4Department of Gastroenterological Surgery, Sakarya University Training and Research Hospital, Sakarya 54100, Türkiye.
- 5Department of Surgical Oncology, Sakarya Training and Research Hospital, Sakarya 54100, Türkiye.
Abstract
Background and Objectives: Bethesda Category IV thyroid nodules present a diagnostic challenge due to their variable risk of malignancy and uncertain cytological features. Therefore, determining the risk of malignancy before surgery is important. This study aims to identify clinical, biochemical, and ultrasonographic factors associated with malignancy and to explore the performance of a multivariable analysis based on routinely available preoperative features in thyroid nodules. Methods: This retrospective, single-center study included 105 patients who underwent thyroidectomy for Bethesda Category IV cytology. The mean age was 50.13 ± 11.78 years. 87 patients (82.9%) were female, and 18 (17.1%) were male. Patients were classified into benign/borderline (n = 79) and malignant (n = 26) groups based on their postoperative histopathological findings. Demographic characteristics, serum thyroid function tests, thyroid autoantibody levels, and ultrasonographic findings were compared. Variables significantly associated with malignancy were included in a Firth bias-reduced penalized multivariable logistic regression analysis. The discriminative performance of the multivariable analysis was evaluated using ROC curve analysis, and internal validation was performed using bootstrap resampling. The AUC was compared with that of ACR TI-RADS using DeLong's test. Results: The malignant group showed a significantly higher prevalence of male sex, irregular margins, a taller-than-wide shape, and microcalcification (all p < 0.05). In the multivariable logistic regression analysis, only irregular margins (OR = 9.46, 95% CI: 1.88-47.59; p = 0.006) were independently associated with malignancy. The model demonstrated acceptable discrimination in this study population (n = 105), with an AUC of 0.717. The AUC of the multivariable analysis was 0.717, compared with 0.704 for ACR TI-RADS, and the difference was not statistically significant (ΔAUC = 0.013; DeLong p = 0.803). Conclusions: In Bethesda Category IV thyroid nodules, irregular margins remained independently associated with malignancy. The multivariable analysis did not demonstrate significantly better discrimination than ACR TI-RADS. These findings should be considered exploratory and require external validation in larger cohorts.
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BibTeX
@article{kahraman2026preoperative,
title = {{Preoperative Malignancy Risk Stratification in Bethesda IV Thyroid Nodules Using Integrated Clinical, Ultrasonographic, and Biochemical Parameters in Surgical Oncology Practice.}},
author = {Yavuz Selim Kahraman and İsmail Özer and Muhammet Raşit Aydın and Emre Gönüllü and Fuldem Mutlu and Adem Şentürk},
journal = {Diagnostics (Basel, Switzerland)},
year = {2026},
month = sep,
doi = {10.3390/diagnostics16193136},
url = {https://europepmc.org/article/MED/42882293},
note = {CC BY},
}
RIS
TY - JOUR
TI - Preoperative Malignancy Risk Stratification in Bethesda IV Thyroid Nodules Using Integrated Clinical, Ultrasonographic, and Biochemical Parameters in Surgical Oncology Practice.
AU - Yavuz Selim Kahraman
AU - İsmail Özer
AU - Muhammet Raşit Aydın
AU - Emre Gönüllü
AU - Fuldem Mutlu
AU - Adem Şentürk
PY - 2026
DA - 2026/09/27
JO - Diagnostics (Basel, Switzerland)
DO - 10.3390/diagnostics16193136
UR - https://europepmc.org/article/MED/42882293
AB - Background and Objectives: Bethesda Category IV thyroid nodules present a diagnostic challenge due to their variable risk of malignancy and uncertain cytological features. Therefore, determining the risk of malignancy before surgery is important. This study aims to identify clinical, biochemical, and ultrasonographic factors associated with malignancy and to explore the performance of a multivariable analysis based on routinely available preoperative features in thyroid nodules. Methods: This retrospective, single-center study included 105 patients who underwent thyroidectomy for Bethesda Category IV cytology. The mean age was 50.13 ± 11.78 years. 87 patients (82.9%) were female, and 18 (17.1%) were male. Patients were classified into benign/borderline (n = 79) and malignant (n = 26) groups based on their postoperative histopathological findings. Demographic characteristics, serum thyroid function tests, thyroid autoantibody levels, and ultrasonographic findings were compared. Variables significantly associated with malignancy were included in a Firth bias-reduced penalized multivariable logistic regression analysis. The discriminative performance of the multivariable analysis was evaluated using ROC curve analysis, and internal validation was performed using bootstrap resampling. The AUC was compared with that of ACR TI-RADS using DeLong's test. Results: The malignant group showed a significantly higher prevalence of male sex, irregular margins, a taller-than-wide shape, and microcalcification (all p < 0.05). In the multivariable logistic regression analysis, only irregular margins (OR = 9.46, 95% CI: 1.88-47.59; p = 0.006) were independently associated with malignancy. The model demonstrated acceptable discrimination in this study population (n = 105), with an AUC of 0.717. The AUC of the multivariable analysis was 0.717, compared with 0.704 for ACR TI-RADS, and the difference was not statistically significant (ΔAUC = 0.013; DeLong p = 0.803). Conclusions: In Bethesda Category IV thyroid nodules, irregular margins remained independently associated with malignancy. The multivariable analysis did not demonstrate significantly better discrimination than ACR TI-RADS. These findings should be considered exploratory and require external validation in larger cohorts.
SN - 2075-4418
ER -