ThyroSeq v2 Provides Highly Accurate Diagnosis of Cytologically Indeterminate Thyroid Nodules
Introduction: Fine-needle aspiration (FNA) for the evaluation of thyroid nodules results in indeterminate cytology in 20% to 30% cases. This study examined whether the ThyroSeq v2 next-generation sequencing panel could improve cancer diagnosis in nodules with cytology diagnosis of follicular (or oncocytic) neoplasm/suspicious for a follicular (or oncocytic) neoplasm (FN/SFN). ThyroSeq v2 tests for point mutations in 13 genes and for 42 types of gene fusions that occur in thyroid cancer.
Method: Thyroid biopsy samples from 143 thyroid nodules with a diagnosis of FN/SFN were evaluated using ThyroSeq v2. Ninety-one (91) samples were tested after surgery was already completed (retrospective samples), and 52 samples were tested prior to surgery (prospective samples).
Results: Surgical excision of the nodules showed that 104 were benign and 39 were malignant. When performed preoperatively, findings from the ThyroSeq v2 had 90% sensitivity, 93% specificity, a positive predictive value of 83%, a negative predictive value of 96%, and 92% accuracy.
Conclusion: The ThyroSeq v2 next-generation molecular marker significantly improves the diagnosis of cancer in thyroid nodules found to be FN/SFN on thyroid biopsy. The method appears to be highly accurate (92%) in classifying these thyroid nodules as malignant or benign.
Dr. Priyathama Vellanki is an Assistant Professor, Division of Endocrinology, Metabolism and Lipids at Emory University School of Medicine in Atlanta, GA.
The diagnosis of follicular neoplasm comprises about 10% of thyroid fine-needle aspirations (FNA) and carries a malignancy risk of 26.1%.1 The 2009 American Thyroid Association (ATA) guidelines recommend a diagnostic lobectomy in these patients. However, since the malignancy risk is approximately 30%, it is likely that surgery could be avoided in a large percentage of these patients.2
This current study by Nikifirov and colleagues validates a commercially available molecular test. This test employs next-generation sequencing, which allows for a larger number of genes to be identified with a smaller amount of DNA. The current test, Thyroseq v2 has been shown to identify most of the mutations that occur in different thyroid cancers.3 This study validated Thyroseq v2 in both a prospective and retrospective cohort of patients. Overall, this study showed a high negative and positive predictive value, therefore, showing that a negative test correctly identifies thyroid cancer and a positive test correctly identifies most patients who have thyroid cancer.
The overall strength of this study is it was validated by a large cohort in a prospective and retrospective manner. Unlike other tests, Thyroseq v2 also offered both high positive and negative predictive values. Even though this test was validated in a large cohort, most of the patients were part of the retrospective cohort and only 36% comprised the prospective cohort. Therefore, it would be helpful to validate this test in a larger prospective cohort.
Furthermore, this test was not studied in other types of indeterminate nodules such as atypia of uncertain significance and follicular lesion of uncertain significance. Nevertheless, Thyroseq v2 tests multiple genes in order to maximize detection of or rule out thyroid cancer in indeterminate nodules, which in turn may avoid unnecessary surgeries.
1. Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytologica. 2012;56:333-339.
2. Gharib H, Papini E, Paschke R, Duick D, et al. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules: Executive Summary of Recommendations. Endocrine Practice. May 2010;16(3):468-475.
3. Nikiforova MN, Wald AI, Roy S, Durso MB, Nikiforov YE. Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations in thyroid cancer. JCEM. 2013;98:E1852-1860.