Correlation of Cytologic Features With Molecular Testing of Indeterminate Oncocytic (Hürthle Cell) Thyroid Lesions

ABSTRACT Introduction Indeterminate oncocytic/Hürthle cell lesions on thyroid cytology are reflexed to molecular testing. This study aims to examine the cytologic characteristics of thyroid fine‐needle aspiration (FNA) smears with oncocytes classified as atypia of undetermined significance (AUS) with particular molecular patterns that can aid in determining a more conclusive Bethesda category upfront thus decreasing unnecessary testing and associated costs. Materials and Methods Our pathology database was searched for thyroid FNAs with AUS for oncocyte predominance from 2019 to 2022. Sixty six cases that underwent ThyroSeq testing (33 positive and 33 negative) were selected. Two cytopathologists reviewed the smears for cellularity, colloid: cell ratio, artifacts, lymphocytes, microfollicles, and oncocytic nuclear atypia. Molecular results and surgical follow‐up were obtained through chart review. Statistical analysis was done using STATA16.1 (StataCorp LLC College Station, TX). Results Among the 33 ThyroSeq‐positive cases, 20 had surgical follow‐up. Only 1 case was malignant. Hypercellularity, microfollicular architecture, and oncocytic atypia were associated with a higher incidence of molecular alterations. Five of 66 cases demonstrated microfollicles. Four of these had positive molecular findings, and one was negative. Twenty of 33 (61%) cases with positive molecular findings had no oncocytic nuclear atypia. Of the molecular positive cases with oncocytic atypia that underwent resection, seven of nine (78%) were neoplastic. RAS mutations were the most common finding detected in non‐neoplastic and neoplastic lesions. Conclusions Microfollicles were infrequently seen in nodules with oncocytic predominance; however, those that had microfollicles had high incidence of positive molecular findings. Oncocytic nuclear atypia was present in all the resected neoplastic cases. NRAS and KRAS mutations were the most common molecular abnormalities detected.