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. 2021 Feb;129(2):164-170.
doi: 10.1002/cncy.22362. Epub 2020 Oct 8.

ThyroSeq v3 for Bethesda III and IV: An institutional experience

Dimpi Desai  1 , Marcos Lepe  2 , Zubair Wahid Baloch  2 , Susan J Mandel  1
Affiliations

ThyroSeq v3 for Bethesda III and IV: An institutional experience

Dimpi Desai et al. Cancer Cytopathol. 2021 Feb.

Abstract

Background: The ThyroSeq v3 genomic classifier is a commercial molecular test that examines a wide spectrum of genomic alterations in a thyroid fine-needle aspiration (FNA) sample and reports test results as either negative or positive. The authors report their institutional experience with ThyroSeq v3.

Methods: Thyroid FNA specimens diagnosed as either atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) (Bethesda category III [Bethesda III] according to The Bethesda System for Reporting Thyroid Cytopathology) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) (Bethesda IV) that had ThyroSeq v3 results available from December 2017 through October 2019 were retrieved for analysis. FNA diagnoses were correlated with ThyroSeq v3 results and follow-up histopathology.

Results: In total, 415 cases (AUS/FLUS, n = 251; FN/SFN, n = 164) were retrieved: 294 (71%) were reported as ThyroSeq v3-negative, and 121 (29%) were reported as ThyroSeq v3-positive. The benign call rate (BCR) of ThyroSeq v3 for AUS/FLUS (82%; 206 of 251 cases) was significantly higher (P < .001) than that for FN/SFN (BCR, 54%; 88 of 164 cases). Histopathologic follow-up was available for 127 cases (ThyroSeq v3-positive, 96; ThyroSeq v3-negative, 31), of which 57 were benign and 70 were malignant (including noninvasive follicular thyroid neoplasm with papillary-like nuclear features). The negative predictive value of ThyroSeq v3 was significantly higher for AUS/FLUS (99.5%) than for FN/SFN (95.4%; P < .0294), given malignancy rates of 10% for AUS/FLUS and 30% for FN/SFN. Forty-five unique combinations of genetic alterations were detected in the operated ThyroSeq-positive cases, and there were only 5 false-negative cases, comprised of 4 low-risk neoplasms.

Conclusions: The high BCR of ThyroSeq v3 for AUS/FLUS prevents surgery in a majority of patients. The ThyroSeq v3 genomic classifier reveals the complexity of the genetic signature of indeterminate nodules.

Keywords: RAS; THADA/IGF2BP3; ThyroSeq v3; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); benign call rate; follicular or oncocytic (Hurthle cell) neoplasm/suspicious for a follicular or oncocytic (Hurthle cell) neoplasm (FN/SFN); indeterminate cytology; rate of malignancy; thyroid carcinoma; thyroid nodule.

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References

    1. Gharib H. Changing trends in thyroid practice: understanding nodular thyroid disease. Endocr Pract. 2004;10:31-39.
    1. Nikiforov YE, Baloch ZW. Clinical validation of the ThyroSeq v3 genomic classifier in thyroid nodules with indeterminate FNA cytology. Cancer Cytopathol. 2019;127:225-230.
    1. Mayson SE, Haugen BR. Molecular diagnostic evaluation of thyroid nodules. Endocrinol Metab Clin North Am. 2019;48:85-97.
    1. Steward DL, Carty SE, Sippel RS, et al. Performance of a multigene genomic classifier in thyroid nodules with indeterminate cytology: a prospective blinded multicenter study. JAMA Oncol. 2019;5:204-212.
    1. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26:1-133.

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