Approximately 25% of thyroid nodules are cytologically indeterminate with variable cancer risk. Many of these patients undergo surgery that could have been avoided in cases where nodules are benign. The objective of this study is to assess correlations between pre-operative ThyroSeq v3 molecular testing and post-operative histopathology.
A retrospective analysis of cytologically indeterminate nodules tested with ThyroSeq v3 between January 2018 and August 2019 at the McGill University affiliated tertiary care hospital was conducted. Patients aged 18 years and older with cytologically indeterminate nodules (Bethesda III, IV, or V) who underwent ThyroSeq v3 testing and who underwent surgery were included. Chi-square analysis was performed to compare post-surgical histopathology and pre-operative ThyroSeq v3 results.
Sixty-three patients with 64 nodules met inclusion criteria; 54 nodules from females. Average age was 53.1 for females (16-88, SD=14.8), and 61.4 for males (39-79, SD=14.2). Average nodule size was 2.3cm (0.8-6.7, SD=1.16). From 64 nodules, 56 were malignant (88%) including 1 (2%) non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and 8 were benign (12%). Tumors with one type of molecular alteration were less likely to be malignant than tumors with multiple coexisting molecular alterations (RR=0.8, 95%CI 0.68-0.93, P=0.015). Tumors with gene mutation (GM) alone were less likely to be solid variant of papillary thyroid carcinoma (SVPTC) (OR=0.09 95%CI 0.01-0.75 P=0.009) and tumors with Pax8/PPARG rearrangement were more likely to be SVPTC than tumors without (100% vs 16% P=0.03). Tumors with any gene expression alteration (GEA) were more likely to be oncocytic variant of papillary thyroid carcinoma (OVPTC) (OR=9.1 95%CI 0.95-87.3 P=0.04) and tumors with GM + GEA were more likely to be OVPTC (OR=13.2 95%CI 1.8-95.8 P=0.01). Tumors with EIF1AX mutation were more likely to be poorly differentiated thyroid carcinoma (PDTC) or Hürthle cell carcinoma (HCC) (OR=18.3, 95%CI 1.44-233.4, P=0.03).
In this study, 88% of cytologically indeterminate nodules that underwent ThyroSeq v3 testing followed by surgery were malignant or NIFTP. Furthermore, specific molecular profiles increased the likelihood of SVPTC, OVPTC, PDTC and HCC. These findings may help guide the decision to operate, the extent of the operation, and the timing of surgery.