Molecular Testing of Thyroid Indeterminate Nodules for Clinical Management Decision

Hyeung Kyoo Kim; Euy Young Soh

doi:10.11106/ijt.2019.12.1.9

Journal List > Int J Thyroidol > v.12(1) > 1126572

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Kim and Soh: Molecular Testing of Thyroid Indeterminate Nodules for Clinical Management Decision

Review Article

International Journal of Thyroidology 2019; 12(1): 9-14.

Published online: 31 May 2019

DOI: https://doi.org/10.11106/ijt.2019.12.1.9

Molecular Testing of Thyroid Indeterminate Nodules for Clinical Management Decision

Hyeung Kyoo Kim, Euy Young Soh

Department of Surgery, Ajou University School of Medicine, Suwon, Korea.

Correspondence: Euy Young Soh, MD, PhD, Department of Surgery, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Korea. Tel: 82-31-219-5201, Fax: 82-31-219-5755, sohey@aumc.ac.kr

Received 31 January 2019 Revised 13 April 2019 Accepted 26 April 2019

The Korean Thyroid Association

(open-access):

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Thyroid nodules are the most common endocrine tumor. Ultrasonography and fine-needle aspiration (FNA) are currently accurate diagnostic tools for evaluating thyroid nodules. However, 10–30% of FNA specimens are cytologically indeterminate. Making an accurate diagnosis between benign and malignant nodules is important so that patients with malignant nodule receive proper treatment and patients with benign nodule can avoid unnecessary treatment. Several genetic changes such as point mutations of the BRAF or RAS and rearrangements of the RET/PTC1, RET/PTC3, PAX8/PPARY are used to adjust to indeterminate FNA. Such a mutational analysis has an excellent positive predictive value (PPV), but there is a weakness in the low negative predictive value (NPV). Gene-expression classifier (GEC) has been found helpful in identify nodules that are benign rather than malignant. GEC has an excellent NPV, but there is a weakness of low PPV. Multiplatform mutational and miRNA test (MPT) and next-generation sequencing assay (NGS) are being studied to compensate for these weaknesses. Molecular tests appear to be a good solution for improving the accuracy of indeterminate FNA cytology specimens and support the clinical management decisions in patients with indeterminate cytologic nodules, but further prospective multicenter trials are required for validation of reported findings and need evaluation of cost-effectiveness. This paper will review recently available molecular diagnostic tools of thyroid nodule.

Keywords: Thyroid cancer, Indeterminate thyroid nodules, Molecular testing

Figures and Tables

Table 1

Management option for indeterminate thyroid nodules on FNA

AUS: atypia of undetermined significance, FLUS: follicular lesion of undetermined significance, FNA: fine needle aspiration

Table 2

Molecular test in indeterminate cytology

AUS: atypia of undetermined significance, DNA: deoxyribonucleic acid, F/H: family history, FLUS: follicular lesion of undetermined significance, FN: fine needle aspiration, GEC: gene expression classifier, Hx.: history, mRNA: messenger ribonucleic acid, NPV: negative predictive value, PPV: positive predictive value, SM: suspicious for malignancy

Notes

This is a review article for 11th Bumsan Academic Awards.

References

1. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med. 1993; 328(8):553–559.

2. Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: An appraisal. Ann Intern Med. 1993; 118(4):282–289.

3. Cibas ES, Ali SZ. NCI Thyroid FNA State of the Science Conference. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol. 2009; 132(5):658–665.

4. Horne MJ, Chhieng DC, Theoharis C, Schofield K, Kowalski D, Prasad ML, et al. Thyroid follicular lesion of undetermined significance: Evaluation of the risk of malignancy using the two-tier sub-classification. Diagn Cytopathol. 2012; 40(5):410–415.

5. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, 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):1–133.

6. Yi KH, Lee EK, Kang HC, Koh Y, Kim SW, Kim IJ, et al. 2016 Revised Korean Thyroid Association management guidelines for patients with thyroid nodules and thyroid cancer. Int J Thyroidol. 2016; 9(2):59–126.

7. Nikiforova MN, Nikiforov YE. Molecular diagnostics and predictors in thyroid cancer. Thyroid. 2009; 19(12):1351–1361.

8. Adeniran AJ, Hui P, Chhieng DC, Prasad ML, Schofield K, Theoharis C. BRAF mutation testing of thyroid fine-needle aspiration specimens enhances the predictability of malignancy in thyroid follicular lesions of undetermined significance. Acta Cytol. 2011; 55(6):570–575.

9. Mekel M, Nucera C, Hodin RA, Parangi S. Surgical implications of B-RafV600E mutation in fine-needle aspiration of thyroid nodules. Am J Surg. 2010; 200(1):136–143.

10. Kim SK, Hwang TS, Yoo YB, Han HS, Kim DL, Song KH, et al. Surgical results of thyroid nodules according to a management guideline based on the BRAF(V600E) mutation status. J Clin Endocrinol Metab. 2011; 96(3):658–664.

11. Liu X, Bishop J, Shan Y, Pai S, Liu D, Murugan AK, et al. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer. 2013; 20(4):603–610.

12. Liu R, Xing M. Diagnostic and prognostic TERT promoter mutations in thyroid fine-needle aspiration biopsy. Endocr Relat Cancer. 2014; 21(5):825–830.

13. Patel SG, Carty SE, McCoy KL, Ohori NP, LeBeau SO, Seethala RR, et al. Preoperative detection of RAS mutation may guide extent of thyroidectomy. Surgery. 2017; 161(1):168–175.

14. Paulson VA, Shivdasani P, Angell TE, Cibas ES, Krane JF, Lindeman NI, et al. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features accounts for more than half of “carcinomas” harboring RAS mutations. Thyroid. 2017; 27(4):506–511.

15. Nikiforov YE, Ohori NP, Hodak SP, Carty SE, LeBeau SO, Ferris RL, et al. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab. 2011; 96(11):3390–3397.

16. Nikiforov YE, Steward DL, Robinson-Smith TM, Haugen BR, Klopper JP, Zhu Z, et al. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab. 2009; 94(6):2092–2098.

17. Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012; 367(8):705–715.

18. Duick DS, Klopper JP, Diggans JC, Friedman L, Kennedy GC, Lanman RB, et al. The impact of benign gene expression classifier test results on the endocrinologist-patient decision to operate on patients with thyroid nodules with indeterminate fine-needle aspiration cytopathology. Thyroid. 2012; 22(10):996–1001.

19. Alexander EK, Schorr M, Klopper J, Kim C, Sipos J, Nabhan F, et al. Multicenter clinical experience with the Afirma gene expression classifier. J Clin Endocrinol Metab. 2014; 99(1):119–125.

20. Labourier E, Shifrin A, Busseniers AE, Lupo MA, Manganelli ML, Andruss B, et al. Molecular testing for miRNA, mRNA, and DNA on fine-needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology. J Clin Endocrinol Metab. 2015; 100(7):2743–2750.

21. Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, Ferris RL, et al. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer. 2014; 120(23):3627–3634.

22. Gupta N, Dasyam AK, Carty SE, Nikiforova MN, Ohori NP, Armstrong M, et al. RAS mutations in thyroid FNA specimens are highly predictive of predominantly low-risk follicular-pattern cancers. J Clin Endocrinol Metab. 2013; 98(5):E914–E922.

23. Lee L, How J, Tabah RJ, Mitmaker EJ. Cost-effectiveness of molecular testing for thyroid nodules with atypia of undetermined significance cytology. J Clin Endocrinol Metab. 2014; 99(8):2674–2682.

24. Wu JX, Lam R, Levin M, Rao J, Sullivan PS, Yeh MW. Effect of malignancy rates on cost-effectiveness of routine gene expression classifier testing for indeterminate thyroid nodules. Surgery. 2016; 159(1):118–126.

TOOLS

Similar articles