Preoperative Systemic Inflammatory Indices as Adjunctive Biomarkers for Malignancy Prediction in Bethesda III (AUS) Thyroid Nodules
In brief
A blood inflammation score lifts thyroid cancer prediction AUC from 0.695 to 0.761
In 352 patients who had surgery for indeterminate thyroid nodules, adding the systemic immune-inflammation index to clinical and ultrasound findings improved prediction of malignancy; 56% had cancer on pathology. The gain was modest, and the index was not useful as a stand-alone test. Results need prospective external validation before clinical use.
- Journal
- Cancers (Q1)
- Published
- 1 October 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Gökhan Rıza Baykal, Müge Keskin, Kübra Katipoğlu, Ersin Gürkan Dumlu, Didem Özdemir, Oya Topaloğlu, et al.
- PMID
- 42882864
- DOI
- 10.3390/cancers18193170
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (top studies of the week, 18 October 2026): Systemic inflammatory indices predict malignancy in Bethesda III thyroid nodules
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.
Abstract as published, via PubMed.
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