Importance of cytological subclassification of thyroid nodules with Bethesda category III cytology (AUS/FLUS) into architectural atypia only and nuclear atypia: A prospective study

Background: The objective of this study was to compare two cytological subcategories of thyroid nodules with Bethesda category III initial cytology. Methods: This was a prospective study. All patients with thyroid nodules>1 cm were eligible and 98 patients with category III cytology were selected. Cytology was subcategorized into architectural atypia only (AA, n=45) and nuclear atypia (NA, n=53). All patients underwent a second fine-needle aspiration (FNA). Only patients whose second cytology was benign and ultrasonography was non-suspicious were not referred for surgery. In these patients, the nodules were considered benign. Results: The second FNA more frequently revealed benign cytology in the AA subcategory (44.4% vs. 24.5% in the NA subcategory). The second cytology suggested follicular neoplasm or was suspicious for follicular neoplasm (category IV) in 5 patients (11.1%) of subcategory AA and was suspicious for malignancy (category V) in 13 (24.5%) of subcategory NA. Finally, malignancy was diagnosed in 15.5% of cases of subcategory AA and in 41.5% of subcategory NA. Follicular carcinoma was more frequent in subcategory AA, while classical papillary carcinoma was more frequent in subcategory NA. Excluding cases of the noninvasive encapsulated follicular variant of papillary carcinoma, malignancy was diagnosed in 11.1% of patients of subcategory AA and in 35.8% of subcategory NA. Conclusions: The results showed that subclassification of the Bethesda category III improves cancer risk prediction, with potential repercussions for clinical practice.