Predictors of malignancy in high-risk indeterminate (TIR3B) cytopathology thyroid nodules

Purpose: The classification of indeterminate cytopathology at thyroid fine-needle-aspiration (FNA) has been updated to reduce the number of unnecessary surgery; the 2014 Italian classification introduced the low-risk (TIR3A) and high-risk (TIR3B) subcategories. Aim of this study was to identify the ultrasonographic (US), clinical and cytological predictors of malignancy among TIR3B nodules from a single institution. Methods: A prospective observational study including 1844 patients who underwent thyroid FNA from June 2014 to January 2019. Ultrasonographic, clinical and cytological features were recorded. All TIR3B diagnoses were referred to surgery. According to final histology, patients were divided into thyroid cancer (TC) or benign nodules. Chi-square test, or Fisher exact test when appropriate, were used to compare groups and logistic regression analyses were used to determine independent predictors of malignancy. Results: Of 1844 FNAs, 96 (5.2%) were TIR3B. Histology report was available in 65. Among them, 25 (38.5%) were TC. Predictors of TC were nodule size < 20 mm [Odds Ratio (OR) = 5.88, 95% CI 1.91–18.11, p = 0.002], absence or weak intralesional flow [OR = 0.3, 95% CI 0.09–0.77, p = 0.015], microcalcifications [OR = 6.5, 95% CI 1.90–21.93, p = 0.003] at US; nuclear inclusions [OR = 25.3, 95% CI 1.34–476.07, p = 0.031] and chromatin clearing [OR = 3.7, 95% CI 1.27–10.99, p = 0.017] at cytopathology. Patients aged < 55 years had a significantly higher risk of TC [OR = 9.7, 95% CI 2.79–34.07, p < 0.001]. In multivariate analysis, age < 55 and nodule size < 20 mm resulted as independent risk factors. Conclusions: Patients < 55 years receiving a diagnosis TIR3B on nodules < 20 mm, with microcalcifications, showing specific nuclear atypia at cytopathology are more likely to have TC. Combining US, cytological and clinical features could help determining which patients with a TIR3B diagnosis should be referred to surgery.