Thyroid Nodules with Atypia or Follicular Lesions of Undetermined Significance (Bethesda Category III): Importance of Ultrasonography and Cytological Subcategory

Background: One possible result of fine-needle aspiration (FNA) in patients with thyroid nodules is "follicular lesion of undetermined significance" (FLUS) or "atypia of undetermined significance" (AUS). The risk of malignancy is relevant information to define appropriate management, and knowledge of predictors of malignancy in these nodules is therefore important. The objective of this prospective study was to evaluate clinical, laboratory, ultrasonographic, and cytological predictors of malignancy in patients with thyroid nodules and FLUS/AUS cytology. Methods: The sample consisted of 150 patients with thyroid nodules and an indication for FNA whose cytology was classified as FLUS/AUS according to the Bethesda classification criteria. Results: In the second FNA, cytology was nondiagnostic in 2 (1.3%) nodules and benign in 54 (36%), FLUS/AUS cytology persisted in 73 (48.6%), and cytology was suspicious for follicular neoplasm in 11 (7.3%) and for malignancy in 10 (6.6%). The rate of malignancy was 22.6%. Clinical and laboratory data or nodule size were not predictors of malignancy. The rate of malignancy was lower in nodules initially classified as FLUS (10.8% versus 41.3% with AUS). Ultrasonography (US) was also useful for predicting malignancy, with sensitivity, specificity, and positive and negative predictive values of 79.4%, 90.5%, 71%, and 93.75%, respectively. Different malignancy rates were obtained when the two parameters, cytological subcategory and US, were combined: (i) 3.9% for nodules nonsuspicious on US and FLUS, (ii) 11.4% for nonsuspicious nodules with AUS, (iii) 46.6% for suspicious nodules with FLUS, and (iv) 87% for suspicious nodules with AUS. Conclusions: The combination of cytological subcategory (FLUS or AUS) and US provides different risks of malignancy for nodules initially classified as Bethesda category III.