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Published in: Annals of Surgical Oncology 6/2014

01-06-2014 | Endocrine Tumors

The Impact of Molecular Testing on the Surgical Management of Patients with Thyroid Nodules

Authors: Patricia Aragon Han, MD, Matthew T. Olson, MD, Roghayeh Fazeli, MD, Jason D. Prescott, MD, PhD, Sara I. Pai, MD, PhD, Eric B. Schneider, PhD, Ralph P. Tufano, MD, MBA, Martha A. Zeiger, MD

Published in: Annals of Surgical Oncology | Issue 6/2014

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Abstract

Background

The use of molecular tests as an adjunct to FNA diagnosis of thyroid nodules has been increasing. However, the true impact of these tests on surgical practice has not been demonstrated. This study examines the usefulness of molecular testing on surgical management decisions in patients referred for thyroid surgery at a tertiary care center.

Methods

Clinical information was collected from patients who presented to Johns Hopkins Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between August 2009 and March 2013. Tests included an RNA-based gene expression classifier, a DNA-based somatic mutation panel, BRAF, NRAS, and/or RET/PTC translocation. A surgical management algorithm was created by consensus of four thyroid surgeons. Postsurgical pathology analysis in each case was then used to judge the appropriateness of the surgical decision-making and the usefulness of preoperative molecular testing, in guiding surgical planning.

Results

Of 114 patients assessed by preoperative molecular testing, 87 (72 %) underwent surgery. Surgical management was altered in nine (10 %) patients on the basis of molecular testing. Of these, surgical management change was appropriate, relative to the postoperative pathology analysis, for three patients and inappropriate for six patients.

Conclusions

In this study, molecular testing of thyroid nodule did not alter the surgical management of the majority of patients with thyroid nodules. These results indicate that molecular testing may be overused in patients for whom the results would not change surgical management. Furthermore, our data question the usefulness of the molecular tests examined in guiding preoperative surgical decision-making.
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Literature
1.
go back to reference Brander A, Viikinkoski P, Tuuhea J, Voutilainen L, Kivisaari L. Clinical versus ultrasound examination of the thyroid gland in common clinical practice. J Clin Ultrasound. 1992;20(1):37–42.PubMedCrossRef Brander A, Viikinkoski P, Tuuhea J, Voutilainen L, Kivisaari L. Clinical versus ultrasound examination of the thyroid gland in common clinical practice. J Clin Ultrasound. 1992;20(1):37–42.PubMedCrossRef
2.
go back to reference Yassa L, Cibas ES, Benson CB, Frates MC, Doubilet PM, Gawande AA, et al. Long-term assessment of a multidisciplinary approach to thyroid nodule diagnostic evaluation. Cancer. 2007;111(6):508–16.PubMedCrossRef Yassa L, Cibas ES, Benson CB, Frates MC, Doubilet PM, Gawande AA, et al. Long-term assessment of a multidisciplinary approach to thyroid nodule diagnostic evaluation. Cancer. 2007;111(6):508–16.PubMedCrossRef
3.
go back to reference American Thyroid Association Guidelines Taskforce on Thyroid N, Differentiated Thyroid C, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, et al. Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11):1167–214.PubMedCrossRef American Thyroid Association Guidelines Taskforce on Thyroid N, Differentiated Thyroid C, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, et al. Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11):1167–214.PubMedCrossRef
4.
go back to reference Layfield LJ, Cibas ES, Gharib H, Mandel SJ. Thyroid aspiration cytology: current status. CA Cancer J Clin. 2009;59(2):99–110.PubMedCrossRef Layfield LJ, Cibas ES, Gharib H, Mandel SJ. Thyroid aspiration cytology: current status. CA Cancer J Clin. 2009;59(2):99–110.PubMedCrossRef
5.
go back to reference Olson MT, Clark DP, Erozan YS, Ali SZ. Spectrum of risk of malignancy in subcategories of ‘atypia of undetermined significance’. Acta Cytol. 2011;55(6):518–25.PubMedCrossRef Olson MT, Clark DP, Erozan YS, Ali SZ. Spectrum of risk of malignancy in subcategories of ‘atypia of undetermined significance’. Acta Cytol. 2011;55(6):518–25.PubMedCrossRef
6.
go back to reference 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):3390–7.PubMedCentralPubMedCrossRef 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):3390–7.PubMedCentralPubMedCrossRef
7.
go back to reference 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):705–15.PubMedCrossRef 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):705–15.PubMedCrossRef
8.
go back to reference Ferraz C, Eszlinger M, Paschke R. Current state and future perspective of molecular diagnosis of fine-needle aspiration biopsy of thyroid nodules. J Clin Endocrinol Metab. 2011;96(7):2016–26.PubMedCrossRef Ferraz C, Eszlinger M, Paschke R. Current state and future perspective of molecular diagnosis of fine-needle aspiration biopsy of thyroid nodules. J Clin Endocrinol Metab. 2011;96(7):2016–26.PubMedCrossRef
9.
go back to reference Tetzlaff MT, LiVolsi V, Baloch ZW. Assessing the utility of a mutational assay for B-RAF as an adjunct to conventional fine needle aspiration of the thyroid gland. Adv Anat Pathol. 2006;13(5):228–37.PubMedCrossRef Tetzlaff MT, LiVolsi V, Baloch ZW. Assessing the utility of a mutational assay for B-RAF as an adjunct to conventional fine needle aspiration of the thyroid gland. Adv Anat Pathol. 2006;13(5):228–37.PubMedCrossRef
10.
go back to reference 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 cytologica. 2011;55(6):570–5.PubMedCrossRef 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 cytologica. 2011;55(6):570–5.PubMedCrossRef
11.
go back to reference Canadas-Garre M, Becerra-Massare P, Lopez de la Torre-Casares M, Villar-del Moral J, Céspedes-Mas S, Vílchez-Joya R, et al. Reduction of false-negative papillary thyroid carcinomas by the routine analysis of BRAF(T1799A) mutation on fine-needle aspiration biopsy specimens: a prospective study of 814 thyroid FNAB patients. Ann Surg. 2012;255(5):986–992.PubMedCrossRef Canadas-Garre M, Becerra-Massare P, Lopez de la Torre-Casares M, Villar-del Moral J, Céspedes-Mas S, Vílchez-Joya R, et al. Reduction of false-negative papillary thyroid carcinomas by the routine analysis of BRAF(T1799A) mutation on fine-needle aspiration biopsy specimens: a prospective study of 814 thyroid FNAB patients. Ann Surg. 2012;255(5):986–992.PubMedCrossRef
12.
go back to reference Marchetti I, Lessi F, Mazzanti CM, Bertacca G, Elisei R, Coscio GD, et al. A morpho-molecular diagnosis of papillary thyroid carcinoma: BRAF V600E detection as an important tool in preoperative evaluation of fine-needle aspirates. Thyroid. 2009;19(8):837–42.PubMedCrossRef Marchetti I, Lessi F, Mazzanti CM, Bertacca G, Elisei R, Coscio GD, et al. A morpho-molecular diagnosis of papillary thyroid carcinoma: BRAF V600E detection as an important tool in preoperative evaluation of fine-needle aspirates. Thyroid. 2009;19(8):837–42.PubMedCrossRef
13.
go back to reference Kim SW, Lee JI, Kim JW, Ki CS, Oh YL, Choi YL, et al. BRAFV600E mutation analysis in fine-needle aspiration cytology specimens for evaluation of thyroid nodule: a large series in a BRAFV600E-prevalent population. J Clin Endocrinol Metab. 2010;95(8):3693–700.PubMedCrossRef Kim SW, Lee JI, Kim JW, Ki CS, Oh YL, Choi YL, et al. BRAFV600E mutation analysis in fine-needle aspiration cytology specimens for evaluation of thyroid nodule: a large series in a BRAFV600E-prevalent population. J Clin Endocrinol Metab. 2010;95(8):3693–700.PubMedCrossRef
14.
go back to reference 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):2092–8.PubMedCrossRef 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):2092–8.PubMedCrossRef
15.
go back to reference Cantara S, Capezzone M, Marchisotta S, Capuano S, Busonero G, Toti P, et al. Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology. J Clin Endocrinol Metab. 2010;95(3):1365–9.PubMedCrossRef Cantara S, Capezzone M, Marchisotta S, Capuano S, Busonero G, Toti P, et al. Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology. J Clin Endocrinol Metab. 2010;95(3):1365–9.PubMedCrossRef
16.
go back to reference Jin L, Sebo TJ, Nakamura N, Qian X, Oliveira A, Majerus JA, et al. BRAF mutation analysis in fine needle aspiration (FNA) cytology of the thyroid. Diagn Mol Pathol B. 2006;15(3):136–43.CrossRef Jin L, Sebo TJ, Nakamura N, Qian X, Oliveira A, Majerus JA, et al. BRAF mutation analysis in fine needle aspiration (FNA) cytology of the thyroid. Diagn Mol Pathol B. 2006;15(3):136–43.CrossRef
17.
go back to reference Ward LS, Kloos RT. Molecular markers in the diagnosis of thyroid nodules. Arquivos Brasileiros Endocrinol Metab. 2013;57(2):89–97.CrossRef Ward LS, Kloos RT. Molecular markers in the diagnosis of thyroid nodules. Arquivos Brasileiros Endocrinol Metab. 2013;57(2):89–97.CrossRef
18.
go back to reference Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, et al. BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 2003;95(8):625–7.PubMedCrossRef Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, et al. BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 2003;95(8):625–7.PubMedCrossRef
19.
go back to reference Kleiman DA, Sporn MJ, Beninato T, Crowley MJ, Nguyen A, Uccelli A, et al. Preoperative BRAF(V600E) mutation screening is unlikely to alter initial surgical treatment of patients with indeterminate thyroid nodules: a prospective case series of 960 patients. Cancer. 2013;119(8):1495–502.PubMedCrossRef Kleiman DA, Sporn MJ, Beninato T, Crowley MJ, Nguyen A, Uccelli A, et al. Preoperative BRAF(V600E) mutation screening is unlikely to alter initial surgical treatment of patients with indeterminate thyroid nodules: a prospective case series of 960 patients. Cancer. 2013;119(8):1495–502.PubMedCrossRef
20.
go back to reference Pacini F, Castagna MG, Brilli L, Pentheroudakis G, Group EGW. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl 5):v214–9.PubMedCrossRef Pacini F, Castagna MG, Brilli L, Pentheroudakis G, Group EGW. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl 5):v214–9.PubMedCrossRef
21.
go back to reference Pacini F, Castagna MG, Brilli L, Pentheroudakis G, Group EGW. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):110–119.CrossRef Pacini F, Castagna MG, Brilli L, Pentheroudakis G, Group EGW. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):110–119.CrossRef
22.
go back to reference Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006;16(2):109–42.PubMedCrossRef Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006;16(2):109–42.PubMedCrossRef
23.
go back to reference Olson MT, Boonyaarunnate T, Aragon Han P, Umbricht CB, Ali SZ, Zeiger MA. A tertiary center’s experience with second review of 3885 thyroid cytopathology specimens. J Clin Endocrinol Metab. 2013;98(4):1450–7.PubMedCrossRef Olson MT, Boonyaarunnate T, Aragon Han P, Umbricht CB, Ali SZ, Zeiger MA. A tertiary center’s experience with second review of 3885 thyroid cytopathology specimens. J Clin Endocrinol Metab. 2013;98(4):1450–7.PubMedCrossRef
24.
go back to reference Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Thyroid. 2009;19(11):1159–65.PubMedCrossRef Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Thyroid. 2009;19(11):1159–65.PubMedCrossRef
25.
go back to reference Fisher RA. The logic of inductive inference. J R Stat Soc. 1935;98(1):39–82.CrossRef Fisher RA. The logic of inductive inference. J R Stat Soc. 1935;98(1):39–82.CrossRef
27.
go back to reference Guyatt GH, Sackett D, Haynes RB. Evaluating diagnostic tests. In: Haynes RB, Sackett DL, Guyatt GH, Tugwell P, eds. Clinical epidemiology: how to do clinical practice research. 3rd edn. Philadelphia: Lippincott Williams & Wilkins; 2006:273-322. Guyatt GH, Sackett D, Haynes RB. Evaluating diagnostic tests. In: Haynes RB, Sackett DL, Guyatt GH, Tugwell P, eds. Clinical epidemiology: how to do clinical practice research. 3rd edn. Philadelphia: Lippincott Williams & Wilkins; 2006:273-322.
Metadata
Title
The Impact of Molecular Testing on the Surgical Management of Patients with Thyroid Nodules
Authors
Patricia Aragon Han, MD
Matthew T. Olson, MD
Roghayeh Fazeli, MD
Jason D. Prescott, MD, PhD
Sara I. Pai, MD, PhD
Eric B. Schneider, PhD
Ralph P. Tufano, MD, MBA
Martha A. Zeiger, MD
Publication date
01-06-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 6/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-3508-x

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