Younger age and suspicious thyroid ultrasound findings may be independently associated with postoperative malignancy among surgically treated patients with benign thyroid cytology.
Investigators retrospectively evaluated 355 patients who underwent fine-needle aspiration biopsy and subsequent thyroid surgery at a single center between January 2020 and December 2024. The analysis included 176 patients with preoperative Bethesda II benign cytology and available postoperative histopathologic findings. Demographic, clinical, laboratory, and ultrasonographic data were obtained from hospital electronic records, radiology archives, and pathology reports. Surgical indications included suspicious ultrasound findings, progressive nodule growth, compressive symptoms, cosmetic concerns, patient preference, and other clinical factors.
The primary outcome was malignancy identified on postoperative histopathologic examination despite benign preoperative cytology. The investigators examined associations between malignancy and age, sex, nodule size, thyroid function, Thyroid Imaging Reporting and Data System (TIRADS) classification, and systemic inflammatory markers. TIRADS classifications were categorized as below 4 or 4 and greater, and multivariable logistic regression was used to evaluate independent associations with postoperative malignancy.
Postoperative histopathologic examination identified malignancy in 11% (n = 20) of patients, while 89% (n = 156) had benign findings. Malignancy was detected in 32% of patients with TIRADS classifications of 4 or greater vs. 7% with classifications below 4. In multivariable analysis, patients with TIRADS classifications of 4 or greater had about 5.7 times the odds of postoperative malignancy compared with those in the lower-risk group.
Younger age was independently associated with malignancy. Patients with malignant postoperative findings had a median age of 29 years vs. 41 years among those with benign findings. In adjusted analyses, each additional year of age was associated with about 8% lower odds of malignancy.
Although nodules tended to be larger among those with malignant findings, the difference was not statistically significant. Median nodule diameter was 38 mm in the malignant group vs. 32 mm in the benign group. Sex, body mass index, and thyroid function tests showed no statistically significant differences between groups.
Systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, and C-reactive protein were not significantly associated with postoperative malignancy. Lactate dehydrogenase and albumin levels showed no independent associations. The absence of statistically significant associations did not exclude the potential biological relevance of these markers, particularly given the limited number of malignant cases.
The study had several limitations, including its retrospective, single-center design and restriction to surgically treated patients with Bethesda II cytology. Because surgery was performed for additional clinical or radiologic indications, the observed 11% malignancy rate should not be generalized to all patients with benign thyroid cytology or interpreted as the false-negative rate in an unselected population. The relatively small cohort limited statistical power and raised concerns about overfitting in multivariable analyses. The absence of independent pathology review and external validation further limited interpretation.
"These findings reflect a selected surgical population and should not be generalized to all patients with Bethesda II thyroid nodules or used alone to guide clinical management," wrote lead study author Adem Aslan, of the Department of General Surgery at AğrıİbrahimÇeçen University in Türkiye, and colleagues.
The study authors reported no conflicts of interest.
Source: Diagnostic Pathology