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BACKGROUND: Although The Bethesda System for Reporting Thyroid Cytopathology has provided clinicians with a standardized classification scheme for the diagnosis of thyroid fine-needle aspiration cytology (FNAC) specimens, the indeterminate categories of Bethesda III (B3)-atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)-and Bethesda IV (B4)-follicular neoplasm/suspicious for follicular neoplasm (FN/SFN)-continue to pose challenges with regards to ideal diagnostic and therapeutic management. Having previously demonstrated the presence of nuclear atypia as a high-risk subgroup in B3, the objective of this study was to evaluate the malignancy rates in the B4 subgroup with nuclear atypia. METHODS: A retrospective review of all thyroid FNACs diagnosed as B4 (FN/SFN) between 2008 and 2015 was conducted at a tertiary referral center in Singapore. Data on patient demographics, sonographic features, and final histological diagnosis were collected. This was compared to data from a previous analysis on all nodules diagnosed as B3 (AUS/FLUS) over a similar period. RESULTS: A total of 137/309 (44.3%) and 88/111 (79.3%) FNACs diagnosed as B3 and B4, respectively, underwent surgical excision yielding final histopathological diagnoses. The malignancy rate of B4 was 31/88 (35.2%) compared to B3, which was 37/137 (27.0%). Subclassification based on the presence of architectural versus nuclear atypia showed significantly higher malignancy rates in B4 nodules with nuclear atypia (21.8% vs. 57.6%; p 

Original publication




Journal article



Publication Date





511 - 521


Bethesda classification, atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), fine-needle aspiration cytology, follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN), malignancy risk, thyroid, Adenocarcinoma, Follicular, Adult, Biopsy, Fine-Needle, Carcinoma, Medullary, Carcinoma, Papillary, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Assessment, Thyroid Gland, Thyroid Neoplasms