Copy number variations identified in thyroid FNA specimens are associated with Hurthle cell cytomorphology

Background The fine-needle aspiration (FNA) diagnosis of thyroid Hurthle cell neoplasms (HCNs) remains challenging. This study explored a possible association of copy number variations (CNVs) with Hurthle cell lesions of the thyroid. Methods Thyroid FNA cases that were diagnosed as follicular lesion of undetermined significance (FLUS) or follicular neoplasm (FN)/HCN for which the ThyroSeq version 3 genomic classifier test was performed were retrieved. Results A total of 324 thyroid FNA cases (228 FLUS cases, 46 HCN cases, and 50 FN cases) were included in the study. FLUS cases were further classified as Hurthle cell type (follicular lesion of undetermined significance-Hurthle cell type [FLUS-HCT]; 20 cases) or non-Hurthle cell type (follicular lesion of undetermined significance-non-Hurthle cell type [FLUS-NHCT]; 208 cases). HCN and FLUS-HCT cases showed a higher prevalence of CNVs (23 of 66 [35%]) in comparison with those classified as FN or FLUS-NHCT (14 of 258 [5%]; P < .001). A total of 105 patients had histopathologic follow-up. Cases with CNVs were more likely to be neoplastic (18 of 26 [69%]) and associated with Hurthle cell changes (14 of 26 [54%]) in comparison with cases without any molecular alterations (neoplastic, 8 of 24 [33%]; Hurthle cell changes, 2 of 24 [8%]; P < .05). In HCN/FLUS-HCT cases with CNVs (n = 14), Hurthle cell changes (13 of 14 [93%]) and neoplasms (9 of 14 [64%]) were more likely to be seen on surgical follow-up in comparison with the 17 cases without CNVs (Hurthle cell changes, 6 of 17 [35%]; neoplastic, 3 of 17 [18%]; P < .05). Conclusions CNVs identified in thyroid FNA cases are associated with Hurthle cell morphology and are suggestive of a neoplasm with Hurthle cell features in thyroid FNAs classified as FLUS-HCT/HCN. This finding may be helpful in triaging patients who would benefit from surgical management.