Nikiforov, Yuri E.1; Hoda, Rana2; Nikiforova, Marina N.1; Urmacher, Carlos2; Yip, Linwah3; Ferris, Robert L.4; Carty, Sally E.3
1 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2 CBLPATH, Inc., Rye Brooke, New York, NY, USA
3 Division of Endocrine Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4 Division of Head and Neck Surgery, Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Background /Purpose: Mutation-based molecular panels can be used to improve cancer diagnosis in thyroid nodules. Recent studies have reported the association between specific mutations and risk of cancer recurrence. The goal of this study was to evaluate a possibility of thyroid cancer risk stratification using pre-operative FNA samples.
Methods: We evaluated 4,770 consecutive FNA samples with indeterminate cytology (Bethesda III, IV, V) submitted for ThyroSeq v2 testing in 2015-2016. The proportion of samples positive for low-risk mutations (RAS and RAS-like mutations), intermediate-risk mutations (BRAF V600E and other BRAF V600E-like mutations), and high-risk mutations (multiple driver mutations including TERT and TP53) was calculated. Surgical outcome was available on 55 patients with high-risk molecular signature.
Results: Out of all FNA tested samples, 65.3% were negative for all mutations and 4.6% were negative for cancer-associated mutations, whereas 30.1% were test-positive. Among those, 20.1% were positive for low-risk mutations, 5.9% for intermediate-risk mutations, and 4.0% for high-risk mutations. Among patients in the high-risk group with available surgical follow-up, 91% of cancers were found to have one or several pathological features associated with aggressive clinical course. Thyroid FNA cytology in these nodules was Bethesda III in 31% of cases and Bethesda IV in 25% of cases.
Discussion & Conclusion: The results of this study demonstrate that cancer risk stratification can be performed pre-operatively in FNA samples from indeterminate cytology nodules. Molecular testing allows caregivers to identify pre-operatively a small subset of thyroid cancers with high-risk disease, even in nodules with Bethesda III-IV FNA cytology.