Preoperative Molecular Markers in Thyroid Nodules

Zeyad T Sahli, Philip W Smith, Christopher B Umbricht, Martha A Zeiger, Zeyad T Sahli, Philip W Smith, Christopher B Umbricht, Martha A Zeiger

Abstract

The need for distinguishing benign from malignant thyroid nodules has led to the pursuit of differentiating molecular markers. The most common molecular tests in clinical use are Afirma® Gene Expression Classifier (GEC) and Thyroseq® V2. Despite the rapidly developing field of molecular markers, several limitations exist. These challenges include the recent introduction of the histopathological diagnosis "Non-Invasive Follicular Thyroid neoplasm with Papillary-like nuclear features", the correlation of genetic mutations within both benign and malignant pathologic diagnoses, the lack of follow-up of molecular marker negative nodules, and the cost-effectiveness of molecular markers. In this manuscript, we review the current published literature surrounding the diagnostic value of Afirma® GEC and Thyroseq® V2. Among Afirma® GEC studies, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) ranged from 75 to 100%, 5 to 53%, 13 to 100%, and 20 to 100%, respectively. Among Thyroseq® V2 studies, Se, Sp, PPV, and NPV ranged from 40 to 100%, 56 to 93%, 13 to 90%, and 48 to 97%, respectively. We also discuss current challenges to Afirma® GEC and Thyroseq® V2 utility and clinical application, and preview the future directions of these rapidly developing technologies.

Keywords: Afirma; Thyroseq; molecular test; non-invasive follicular thyroid neoplasm with papillary-like nuclear features; thyroid cancer.

References

    1. Gharib H. Changing trends in thyroid practice: understanding nodular thyroid disease. Endocr Pract (2004) 10(1):31–9.10.4158/EP.10.1.31
    1. Guth S, Theune U, Aberle J, Galach A, Bamberger C. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest (2009) 39(8):699–706.10.1111/j.1365-2362.2009.02162.x
    1. Howlader N, Noone A, Krapcho M, Miller D, Bishop K, Altekruse S, et al. SEER Cancer Statistics Review, 1975–2013. Bethesda, MD: National Cancer Institute; (2016).
    1. Hahn SY, Shin JH, Lim HK, Jung SL, Oh YL, Choi IH, et al. Preoperative differentiation between noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and non-NIFTP. Clin Endocrinol (2017) 86(3):444–50.10.1111/cen.13263
    1. Brito JP, Yarur AJ, Prokop LJ, McIver B, Murad MH, Montori VM. Prevalence of thyroid cancer in multinodular goiter versus single nodule: a systematic review and meta-analysis. Thyroid (2013) 23(4):449–55.10.1089/thy.2012.0156
    1. Nguyen G-K, Lee MW, Ginsberg J, Wragg T, Bilodeau D. Fine-needle aspiration of the thyroid: an overview. Cytojournal (2005) 2(1):12.10.1186/1742-6413-2-12
    1. Werga P, Wallin G, Skoog L, Hamberger B. Expanding role of fine-needle aspiration cytology in thyroid diagnosis and management. World J Surg (2000) 24(8):907–12.10.1007/s002680010163
    1. Gharib H, Goellner J, Johnson D. Fine-needle aspiration cytology of the thyroid. A 12-year experience with 11,000 biopsies. Clin Lab Med (1993) 13(3):699–709.
    1. Gharib H, Papini E, Garber J, Duick D, Harrell R, Hegedüs L, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi Medical guidelines for clinical practice for the diagnosis and management of thyroid nodules—2016 update. Endocr Pract (2016) 22(5):622–39.10.4158/
    1. Cibas ES, Ali SZ. The 2017 Bethesda system for reporting thyroid cytopathology. J Am Soc Cytopathol (2017) 6(6):217–22.10.1016/j.jasc.2017.09.002
    1. Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda system for reporting thyroid cytopathology: a meta-analysis. Acta Cytol (2012) 56(4):333–9.10.1159/000339959
    1. Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol (2009) 132(5):658–65.10.1309/AJCPPHLWMI3JV4LA
    1. Baloch ZW, LiVolsi VA, Asa SL, Rosai J, Merino MJ, Randolph G, et al. Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute thyroid fine-needle aspiration state of the science conference. Diagn Cytopathol (2008) 36(6):425–37.10.1002/dc.20830
    1. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med (1993) 328(8):553–9.10.1056/NEJM199302253280807
    1. Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell (2014) 159(3):676–90.10.1016/j.cell.2014.09.050
    1. 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):625–7.10.1093/jnci/95.8.625
    1. Pusztaszeri MP, Krane JF, Faquin WC. BRAF testing and thyroid FNA. Cancer Cytopathol (2015) 123(12):689–95.10.1002/cncy.21614
    1. Cohen Y, Rosenbaum E, Clark DP, Zeiger MA, Umbricht CB, Tufano RP, et al. Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid: a potential application for the preoperative assessment of thyroid nodules. Clin Cancer Res (2004) 10(8):2761–5.10.1158/1078-0432.CCR-03-0273
    1. Xing M, Alzahrani AS, Carson KA, Viola D, Elisei R, Bendlova B, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA (2013) 309(14):1493–501.10.1001/jama.2013.3190
    1. Kebebew E, Weng J, Bauer J, Ranvier G, Clark OH, Duh Q-Y, et al. The prevalence and prognostic value of BRAF mutation in thyroid cancer. Ann Surg (2007) 246(3):466.10.1097/SLA.0b013e318148563d
    1. Xing M, Westra WH, Tufano RP, Cohen Y, Rosenbaum E, Rhoden KJ, et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab (2005) 90(12):6373–9.10.1210/jc.2005-0987
    1. Fugazzola L, Puxeddu E, Avenia N, Romei C, Cirello V, Cavaliere A, et al. Correlation between B-RAFV600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature. Endocr Relat Cancer (2006) 13(2):455–64.10.1677/erc.1.01086
    1. Liu R, Bishop J, Zhu G, Zhang T, Ladenson PW, Xing M. Mortality risk stratification by combining BRAF V600E and TERT promoter mutations in papillary thyroid cancer: genetic duet of BRAF and TERT promoter mutations in thyroid cancer mortality. JAMA Oncol (2017) 3(2):202–8.10.1001/jamaoncol.2016.3288
    1. Liu X, Qu S, Liu R, Sheng C, Shi X, Zhu G, et al. TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. J Clin Endocrinol Metab (2014) 99(6):E1130–6.10.1210/jc.2013-4048
    1. Kim KB, Cabanillas ME, Lazar AJ, Williams MD, Sanders DL, Ilagan JL, et al. Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAFV600E mutation. Thyroid (2013) 23(10):1277–83.10.1089/thy.2013.0057
    1. Falchook GS, Millward M, Hong D, Naing A, Piha-Paul S, Waguespack SG, et al. BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid (2015) 25(1):71–7.10.1089/thy.2014.0123
    1. Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet (2014) 384(9940):319–28.10.1016/S0140-6736(14)60421-9
    1. Zhang M, Lin O. Molecular testing of thyroid nodules: a review of current available tests for fine-needle aspiration specimens. Arch Pathol Lab Med (2016) 140(12):1338–44.10.5858/arpa.2016-0100-RA
    1. Nishino M. Molecular cytopathology for thyroid nodules: a review of methodology and test performance. Cancer Cytopathol (2016) 124(1):14–27.10.1002/cncy.21612
    1. 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):705–15.10.1056/NEJMoa1203208
    1. Hang J-F, Westra WH, Cooper DS, Ali SZ. The impact of noninvasive follicular 1 thyroid neoplasm with papillary-like nuclear features on the performance of Afirma gene expression classifier. Cancer Cytopathol (2017) 125(9):683–91.10.1002/cncy.21879
    1. Harrison G, Sosa JA, Jiang X. Evaluation of the Afirma gene expression classifier in repeat indeterminate thyroid nodules. Arch Pathol Lab Med (2017) 141(7):985–9.10.5858/arpa.2016-0328-OA
    1. Kay-Rivest E, Tibbo J, Bouhabel S, Tamilia M, Leboeuf R, Forest V-I, et al. The first Canadian experience with the Afirma® gene expression classifier test. J Otolaryngol Head Neck Surg (2017) 46(1):25.10.1186/s40463-017-0201-7
    1. Samulski TD, LiVolsi VA, Wong LQ, Baloch Z. Usage trends and performance characteristics of a “gene expression classifier” in the management of thyroid nodules: an institutional experience. Diagn Cytopathol (2016) 44(11):867–73.10.1002/dc.23559
    1. Wu JX, Young S, Hung ML, Li N, Yang SE, Cheung DS, et al. Clinical factors influencing the performance of gene expression classifier testing in indeterminate thyroid nodules. Thyroid (2016) 26(7):916–22.10.1089/thy.2015.0505
    1. Yang SE, Sullivan PS, Zhang J, Govind R, Levin MR, Rao JY, et al. Has Afirma gene expression classifier testing refined the indeterminate thyroid category in cytology? Cancer Cytopathol (2016) 124(2):100–9.10.1002/cncy.21624
    1. Chaudhary S, Hou Y, Shen R, Hooda S, Li Z. Impact of the Afirma gene expression classifier result on the surgical management of thyroid nodules with category III/IV cytology and its correlation with surgical outcome. Acta Cytol (2016) 60(3):205–10.10.1159/000446797
    1. Abeykoon JP, Mueller L, Dong F, Chintakuntlawar AV, Paludo J, Mortada R. The effect of implementing gene expression classifier on outcomes of thyroid nodules with indeterminate cytology. Horm Cancer (2016) 7(4):272–8.10.1007/s12672-016-0263-4
    1. Noureldine SI, Najafian A, Han PA, Olson MT, Genther DJ, Schneider EB, et al. Evaluation of the effect of diagnostic molecular testing on the surgical decision-making process for patients with thyroid nodules. JAMA Otolaryngol Head Neck Surg (2016) 142(7):676–82.10.1001/jamaoto.2016.0850
    1. Al-Qurayshi Z, Deniwar A, Thethi T, Mallik T, Srivastav S, Murad F, et al. Association of malignancy prevalence with test properties and performance of the gene expression classifier in indeterminate thyroid nodules. JAMA Otolaryngol Head Neck Surg (2016) 143(4):403–8.10.1001/jamaoto.2016.3526
    1. Witt RL. Outcome of thyroid gene expression classifier testing in clinical practice. Laryngoscope (2016) 126(2):524–7.10.1002/lary.25607
    1. Wong KS, Angell TE, Strickland KC, Alexander EK, Cibas ES, Krane JF, et al. Noninvasive follicular variant of papillary thyroid carcinoma and the Afirma gene-expression classifier. Thyroid (2016) 26(7):911–5.10.1089/thy.2015.0644
    1. Zhu Q-L, Faquin WC, Samir AE. Relationship between sonographic characteristics and Afirma gene expression classifier results in thyroid nodules with indeterminate fine-needle aspiration cytopathology. AJR Am J Roentgenol (2015) 205(4):861–5.10.2214/AJR.14.13984
    1. Celik B, Whetsell CR, Nassar A. Afirma GEC and thyroid lesions: an institutional experience. Diagn Cytopathol (2015) 43(12):966–70.10.1002/dc.23378
    1. Marti JL, Avadhani V, Donatelli LA, Niyogi S, Wang B, Wong RJ, et al. Wide inter-institutional variation in performance of a molecular classifier for indeterminate thyroid nodules. Ann Surg Oncol (2015) 22(12):3996–4001.10.1245/s10434-015-4486-3
    1. Brauner E, Holmes BJ, Krane JF, Nishino M, Zurakowski D, Hennessey JV, et al. Performance of the Afirma gene expression classifier in Hürthle cell thyroid nodules differs from other indeterminate thyroid nodules. Thyroid (2015) 25(7):789–96.10.1089/thy.2015.0049
    1. McIver B, Castro MR, Morris JC, Bernet V, Smallridge R, Henry M, et al. An independent study of a gene expression classifier (Afirma) in the evaluation of cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab (2014) 99(11):4069–77.10.1210/jc.2013-3584
    1. Lastra RR, Pramick MR, Crammer CJ, LiVolsi VA, Baloch ZW. Implications of a suspicious Afirma test result in thyroid fine-needle aspiration cytology: an institutional experience. Cancer Cytopathol (2014) 122(10):737–44.10.1002/cncy.21455
    1. Han PA, Olson MT, Fazeli R, Prescott JD, Pai SI, Schneider EB, et al. The impact of molecular testing on the surgical management of patients with thyroid nodules. Ann Surg Oncol (2014) 21(6):1862–9.10.1245/s10434-014-3508-x
    1. 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 (2013) 99(1):119–25.10.1210/jc.2013-2482
    1. Harrell R, Bimston D. Surgical utility of Afirma: effects of high cancer prevalence and oncocytic cell types in patients with indeterminate thyroid cytology. Endocr Pract (2013) 20(4):364–9.10.4158/EP13330.OR
    1. 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):3627–34.10.1002/cncr.29038
    1. Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, Ferris RL, et al. Impact of the multi-gene ThyroSeq next-generation sequencing assay on cancer diagnosis in thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance cytology. Thyroid (2015) 25(11):1217–23.10.1089/thy.2015.0305
    1. Taye A, Gurciullo D, Miles BA, Gupta A, Owen RP, Inabnet WB, et al. Clinical performance of a next-generation sequencing assay (ThyroSeq v2) in the evaluation of indeterminate thyroid nodules. Surgery (2018) 163(1):97–103.10.1016/j.surg.2017.07.032
    1. Valderrabano P, Khazai L, Leon ME, Thompson ZJ, Ma Z, Chung CH, et al. Evaluation of ThyroSeq v2 performance in thyroid nodules with indeterminate cytology. Endocr Relat Cancer (2017) 24(3):127–36.10.1530/ERC-16-0512
    1. Shrestha RT, Evasovich MR, Amin K, Radulescu A, Sanghvi TS, Nelson AC, et al. Correlation between histological diagnosis and mutational panel testing of thyroid nodules: a two-year institutional experience. Thyroid (2016) 26(8):1068–76.10.1089/thy.2016.0048
    1. Khatami R, Heimann A, Hwang S, Shroyer K, Wu M. ThyroSeq V2 application study for indeterminate thyroid FNAs with surgical follow-up; experience at a university hospital. Am J Clin Pathol (2016) 5(5):S80–1.10.1093/ajcp/aqw165.018
    1. Tolerado G, Godley FA, Cerda SR, Mcaneny D, Doherty GM, Braverman L, et al. Large Independent Prospective Study to Evaluate the Performance of ThyroSeq2 Multigene Next Generation Sequencing Panel Analysis on Cancer Diagnosis in Thyroid Nodules with Indeterminate Cytopathology ThyroSeq Press Release: ThyroSeq (2016). Report No.: 1050–7256.
    1. Shrestha RT, Evasovich MR, Shahi M, Radulescu AI, Amin K, Burmeister L. Surgical outcomes of Thyroseq® markers at the university of Minnesota. Endocrine Society. Boston: (2016).
    1. 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):1–133.10.1089/thy.2015.0020
    1. Dedhia PH, Rubio GA, Cohen MS, Miller BS, Gauger PG, Hughes DT. Potential effects of molecular testing of indeterminate thyroid nodule fine needle aspiration biopsy on thyroidectomy volume. World J Surg (2014) 38(3):634–8.10.1007/s00268-013-2430-x
    1. Noureldine SI, Olson MT, Agrawal N, Prescott JD, Zeiger MA, Tufano RP. Effect of gene expression classifier molecular testing on the surgical decision-making process for patients with thyroid nodules. JAMA Otolaryngol Head Neck Surg (2015) 141(12):1082–8.10.1001/jamaoto.2015.2708
    1. Ferris RL, Baloch Z, Bernet V, Chen A, Fahey TJ, III, Ganly I, et al. American thyroid association statement on surgical application of molecular profiling for thyroid nodules: current impact on perioperative decision making. Thyroid (2015) 25(7):760–8.10.1089/thy.2014.0502
    1. Francis GL, Waguespack SG, Bauer AJ, Angelos P, Benvenga S, Cerutti JM, et al. Management guidelines for children with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on pediatric thyroid cancer. Thyroid (2015) 25(7):716–59.10.1089/thy.2014.0460
    1. Valderrabano P, Leon ME, Centeno BA, Otto KJ, Khazai L, McCaffrey JC, et al. Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests. Eur J Endocrinol (2016) 174(5):621–9.10.1530/EJE-15-1163
    1. Parajuli S, Jug R, Ahmadi S, Jiang X. Hurthle cell predominance impacts results of GEC and molecular panel performance in indeterminate thyroid nodules. J Am Soc Cytopathol (2017) 6(5):S70–1.10.1016/j.jasc.2017.06.175
    1. Pankratz DG, Hu Z, Kim SY, Monroe RJ, Wong MG, Traweek ST, et al. Analytical performance of a gene expression classifier for medullary thyroid carcinoma. Thyroid (2016) 26(11):1573–80.10.1089/thy.2016.0262
    1. Kloos RT, Monroe RJ, Traweek ST, Lanman RB, Kennedy GC. A genomic alternative to identify medullary thyroid cancer preoperatively in thyroid nodules with indeterminate cytology. Thyroid (2016) 26(6):785–93.10.1089/thy.2016.0001
    1. Chudova D, Wilde JI, Wang ET, Wang H, Rabbee N, Egidio CM, et al. Molecular classification of thyroid nodules using high-dimensionality genomic data. J Clin Endocrinol Metab (2010) 95(12):5296–304.10.1210/jc.2010-1087
    1. Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol (2016) 2(8):1023–9.10.1001/jamaoncol.2016.0386
    1. Maletta F, Massa F, Torregrossa L, Duregon E, Casadei GP, Basolo F, et al. Cytological features of “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” and their correlation with tumor histology. Hum Pathol (2016) 54:134–42.10.1016/j.humpath.2016.03.014
    1. Strickland KC, Howitt BE, Marqusee E, Alexander EK, Cibas ES, Krane JF, et al. The impact of noninvasive follicular variant of papillary thyroid carcinoma on rates of malignancy for fine-needle aspiration diagnostic categories. Thyroid (2015) 25(9):987–92.10.1089/thy.2014.0612
    1. Faquin WC, Wong LQ, Afrogheh AH, Ali SZ, Bishop JA, Bongiovanni M, et al. Impact of reclassifying noninvasive follicular variant of papillary thyroid carcinoma on the risk of malignancy in the Bethesda System for Reporting Thyroid Cytopathology. Cancer Cytopathol (2015) 124(3):181–7.10.1002/cncy.21631
    1. Piana S, Frasoldati A, Di Felice E, Gardini G, Tallini G, Rosai J. Encapsulated well-differentiated follicular-patterned thyroid carcinomas do not play a significant role in the fatality rates from thyroid carcinoma. Am J Surg Pathol (2010) 34(6):868–72.10.1097/PAS.0b013e3181dbee07
    1. Vivero M, Kraft S, Barletta JA. Risk stratification of follicular variant of papillary thyroid carcinoma. Thyroid (2013) 23(3):273–9.10.1089/thy.2012.0369
    1. Ganly I, Wang L, Tuttle RM, Katabi N, Ceballos GA, Harach HR, et al. Invasion rather than nuclear features correlates with outcome in encapsulated follicular tumors: further evidence for the reclassification of the encapsulated papillary thyroid carcinoma follicular variant. Hum Pathol (2015) 46(5):657–64.10.1016/j.humpath.2015.01.010
    1. Rosario PW, Penna GC, Calsolari MR. Noninvasive encapsulated follicular variant of papillary thyroid carcinoma: is lobectomy sufficient for tumours ≥1 cm? Clin Endocrinol (2014) 81(4):630–2.10.1111/cen.12387
    1. Baloch ZW, LiVolsi VA. Encapsulated follicular variant of papillary thyroid carcinoma with bone metastases. Mod Pathol (2000) 13(8):861–5.10.1038/modpathol.3880153
    1. Howitt BE, Paulson VA, Barletta JA. Absence of BRAF V600E in non-infiltrative, non-invasive follicular variant of papillary thyroid carcinoma. Histopathology (2015) 67(4):579–82.10.1111/his.12680
    1. Liu Z, Zhou G, Nakamura M, Koike E, Li Y, Ozaki T, et al. Encapsulated follicular thyroid tumor with equivocal nuclear changes, so-called well-differentiated tumor of uncertain malignant potential: a morphological, immunohistochemical, and molecular appraisal. Cancer Sci (2011) 102(1):288–94.10.1111/j.1349-7006.2010.01769.x
    1. Sahli ZT, Umbricht CB, Schneider EB, Zeiger MA. Thyroid nodule diagnostic markers in the face of the new diagnosis, NIFT-P: time for a reset? Thyroid (2017) 27(11):1393–9.10.1089/thy.2017.0238
    1. Jiang X, Harrison GP, Datto MB. Young investigator challenge: molecular testing in noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Cancer Cytopathol (2016) 124(12):893–900.10.1002/cncy.21802
    1. 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):3390–7.10.1210/jc.2011-1469
    1. Najafian A, Noureldine S, Azar F, Atallah C, Trinh G, Schneider EB, et al. RAS mutations, and RET/PTC and PAX8/PPAR-gamma chromosomal rearrangements are also prevalent in benign thyroid lesions: implications thereof and a systematic review. Thyroid (2017) 27(1):39–48.10.1089/thy.2016.0348
    1. Duh Q-Y, Busaidy NL, Rahilly-Tierney C, Gharib H, Randolph G. A systematic review of the methods of diagnostic accuracy studies of the Afirma gene expression classifier. Thyroid (2017) 27(10):1215–22.10.1089/thy.2016.0656
    1. Angell TE, Frates MC, Medici M, Liu X, Kwong N, Cibas ES, et al. Afirma benign thyroid nodules show similar growth to cytologically benign nodules during follow-up. J Clin Endocrinol Metab (2015) 100(11):E1477–83.10.1210/jc.2015-2658
    1. Durante C, Costante G, Lucisano G, Bruno R, Meringolo D, Paciaroni A, et al. The natural history of benign thyroid nodules. JAMA (2015) 313(9):926–35.10.1001/jama.2015.0956
    1. Alexander EK, Hurwitz S, Heering JP, Benson CB, Frates MC, Doubilet PM, et al. Natural history of benign solid and cystic thyroid nodules. Ann Intern Med (2003) 138(4):315–8.10.7326/0003-4819-138-4-200302180-00010
    1. Kloos RT, Hanna JW, Haroldson J, Barth N. Systematic review of clinical utility and longer term follow up of Afirma GEC testing. Endocr Soc (2016).10.1210/endo-meetings.2016.THPTA.14.SAT-284
    1. Labourier E. Utility and cost-effectiveness of molecular testing in thyroid nodules with indeterminate cytology. Clin Endocrinol (2016) 85(4):624–31.10.1111/cen.13096
    1. Li H, Robinson KA, Anton B, Saldanha IJ, Ladenson PW. Cost-effectiveness of a novel molecular test for cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab (2011) 96(11):E1719–26.10.1210/jc.2011-0459
    1. Yip L, Apfel A, Singh A, Yoo J, McCoy K, Stang MT, et al. Comprehensive cost analysis of available molecular tests for thyroid nodules with follicular neoplasm cytology. International Thyroid Congress and American Thyroid Association. Lake Buena Vista, FL: (2015).
    1. Steward D, Carty S, Sippel R, Yang P, Sosa J, Sipos J, et al. Clinical validation of ThyroSeq V3® performance in thyroid nodules with indeterminate cytology: a prospective blinded multi-institutional validation study. American Thyroid Association. Victoria, Canada: (2017).

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