Preoperative Systemic Inflammatory Indices as Adjunctive Biomarkers for Malignancy Prediction in Bethesda III (AUS) Thyroid Nodules.
5 affiliations
- 1Department of Endocrinology and Metabolism, Ankara Bilkent City Hospital, Ankara 06800, Türkiye.
- 2Department of Endocrinology and Metabolism, Ankara Bilkent City Hospital, Health Sciences University, Ankara 06800, Türkiye.
- 3Department of Pathology, Ankara Bilkent City Hospital, Ankara 06800, Türkiye.
- 4Department of General Surgery, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara 06800, Türkiye.
- 5Department of Endocrinology and Metabolism, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara 06800, Türkiye.
Abstract
Background/Objectives: Atypia of undetermined significance (AUS; Bethesda category III) remains a challenging thyroid cytological diagnosis because of its heterogeneous malignancy risk and limited preoperative certainty. Molecular testing can improve risk stratification but is not universally available. This study evaluated the diagnostic and incremental predictive value of preoperative complete blood count-derived systemic inflammatory indices in surgically treated Bethesda III thyroid nodules. Methods: This retrospective cohort included 352 patients who underwent thyroidectomy for Bethesda III thyroid nodules. Preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were evaluated. Postoperative histopathology served as the reference standard. Receiver operating characteristic analysis and multivariable logistic regression were performed, followed by incremental model assessment, bootstrap internal validation, Hashimoto thyroiditis interaction analysis, and exploratory molecular subgroup analysis. Results: Among 352 patients, 197 (56.0%) had malignant histopathology. Malignant nodules showed higher NLR, PLR, SII, SIRI, and AISI and lower LMR. All six indices remained independently associated with malignancy after multivariable adjustment, with the strongest positive associations observed for SII (adjusted OR, 2.09; 95% CI, 1.60-2.72) and NLR (adjusted OR, 1.96; 95% CI, 1.51-2.54). SII demonstrated the numerically highest individual discrimination (AUC 0.687; 95% CI, 0.631-0.740), followed by NLR (AUC 0.661) and AISI (AUC 0.659); SII and NLR did not differ significantly (DeLong p = 0.182). Addition of SII increased the AUC of the clinico-ultrasonographic model from 0.695 to 0.761, with an optimism-corrected AUC of 0.721. Hashimoto thyroiditis did not significantly modify these associations. In the molecular subgroup, mutation status increased model discrimination from 0.765 to 0.824, whereas no statistically significant additional improvement with SII was detected in the exploratory molecular subgroup. Conclusions: Preoperative systemic inflammatory indices, particularly SII, provide modest but incremental predictive information beyond conventional clinical and ultrasonographic variables in surgically treated Bethesda III thyroid nodules. Their role appears complementary rather than diagnostic when used in isolation, particularly when comprehensive molecular testing is unavailable. Prospective external validation is required before clinical implementation.
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BibTeX
@article{baykal2026preoperative,
title = {{Preoperative Systemic Inflammatory Indices as Adjunctive Biomarkers for Malignancy Prediction in Bethesda III (AUS) Thyroid Nodules.}},
author = {Gökhan Rıza Baykal and Müge Keskin and Kübra Katipoğlu and Ersin Gürkan Dumlu and Didem Özdemir and Oya Topaloğlu and Reyhan Ersoy and Bekir Çakır},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18193170},
url = {https://europepmc.org/article/MED/42882864},
note = {CC BY},
}
RIS
TY - JOUR
TI - Preoperative Systemic Inflammatory Indices as Adjunctive Biomarkers for Malignancy Prediction in Bethesda III (AUS) Thyroid Nodules.
AU - Gökhan Rıza Baykal
AU - Müge Keskin
AU - Kübra Katipoğlu
AU - Ersin Gürkan Dumlu
AU - Didem Özdemir
AU - Oya Topaloğlu
AU - Reyhan Ersoy
AU - Bekir Çakır
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18193170
UR - https://europepmc.org/article/MED/42882864
AB - Background/Objectives: Atypia of undetermined significance (AUS; Bethesda category III) remains a challenging thyroid cytological diagnosis because of its heterogeneous malignancy risk and limited preoperative certainty. Molecular testing can improve risk stratification but is not universally available. This study evaluated the diagnostic and incremental predictive value of preoperative complete blood count-derived systemic inflammatory indices in surgically treated Bethesda III thyroid nodules. Methods: This retrospective cohort included 352 patients who underwent thyroidectomy for Bethesda III thyroid nodules. Preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were evaluated. Postoperative histopathology served as the reference standard. Receiver operating characteristic analysis and multivariable logistic regression were performed, followed by incremental model assessment, bootstrap internal validation, Hashimoto thyroiditis interaction analysis, and exploratory molecular subgroup analysis. Results: Among 352 patients, 197 (56.0%) had malignant histopathology. Malignant nodules showed higher NLR, PLR, SII, SIRI, and AISI and lower LMR. All six indices remained independently associated with malignancy after multivariable adjustment, with the strongest positive associations observed for SII (adjusted OR, 2.09; 95% CI, 1.60-2.72) and NLR (adjusted OR, 1.96; 95% CI, 1.51-2.54). SII demonstrated the numerically highest individual discrimination (AUC 0.687; 95% CI, 0.631-0.740), followed by NLR (AUC 0.661) and AISI (AUC 0.659); SII and NLR did not differ significantly (DeLong p = 0.182). Addition of SII increased the AUC of the clinico-ultrasonographic model from 0.695 to 0.761, with an optimism-corrected AUC of 0.721. Hashimoto thyroiditis did not significantly modify these associations. In the molecular subgroup, mutation status increased model discrimination from 0.765 to 0.824, whereas no statistically significant additional improvement with SII was detected in the exploratory molecular subgroup. Conclusions: Preoperative systemic inflammatory indices, particularly SII, provide modest but incremental predictive information beyond conventional clinical and ultrasonographic variables in surgically treated Bethesda III thyroid nodules. Their role appears complementary rather than diagnostic when used in isolation, particularly when comprehensive molecular testing is unavailable. Prospective external validation is required before clinical implementation.
SN - 2072-6694
ER -