Molecular alterations in Hürthle cell neoplasms of thyroid: A fine needle aspiration cytology study with cytology‐histology correlation

Background Hürthle cell features are frequently observed on the fine‐needle aspiration (FNA) cytology of thyroid nodules and often pose a diagnostic challenge because of a significant overlap between cytomorphologic features seen in benign and malignant lesions. Molecular alterations (MAs) associated with these lesions are not well described. The objective of the current study was to evaluate the molecular profile of Hürthle cell lesions classified as Hürthle cell neoplasm (HCN) on cytologic evaluation. Methods The authors retrospectively reviewed their electronic database for cytologic diagnoses of HCN from January 1, 2017 to March 31, 2020. Results In total, 279 cases from 275 patients who had a diagnosis of HCN were included in the study. Molecular testing results were available in 85 cases (51 with MAs and 34 without MAs) and, of those, 42 had histologic follow‐up available. Eight of 10 malignant cases had MAs, whereas the remaining 2 cases were negative for MAs. The most frequently encountered predominant genetic alterations or classifier findings were chromosome copy number alterations (n = 15), followed by NRAS (n = 8), KRAS (n = 7), suspicious (n = 6), EIF1AX (n = 4), TSHR (n = 3), gene overexpression (n = 3), positive microRNA classifier (n = 2), and 1 each of BRAF K601E, TERT, and HRAS mutations. One hundred thirty‐seven cases had histologic follow‐up available; of those, 28 were classified as malignant, and 109 were classified as benign (neoplastic and nonneoplastic). The overall risk of malignancy associated with HCN was 20%, and the risk of HCN with MAs was 25%. Conclusions The cytologic diagnosis of HCN includes various MAs without any obvious trend, and most malignant cases (80%) have some type of MA. Cases with a cytologic diagnosis of Hürthle cell neoplasm exhibit various molecular alterations, but no consistent association is observed in histologically benign or malignant cases. Because molecular data pertinent to Hürthle cell neoplasms are evolving, identifying additional molecular findings along with the fine‐needle aspiration results may direct future larger cohort studies to discover any association.