Advertisement

Application of Molecular Tests in Indeterminate Thyroid FNA

  • Theresa Scognamiglio
  • Rana S. HodaEmail author
  • Christina M. Narick
  • Yuri E. Nikiforov
Chapter

Abstract

Indeterminate diagnoses on FNA is the major limitation of thyroid cytology. The problem results from cytological features overlapping between non-neoplastic and neoplastic follicular lesions, which are reflected by the low concordance among pathologists in the indeterminate category. (See Chaps. 5, 6, and 7).

Keywords

Molecular tests Indeterminate thyroid FNA Afirma ThyGeNEXT - ThyraMIR ThyroSeq Papillary thyroid carcinoma Medullary thyroid carcinoma 

References

Introduction

  1. 1.
    Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159:676–90.  https://doi.org/10.1016/j.cell.2014.09.050.CrossRefGoogle Scholar
  2. 2.
    Patel KN, Angell TE, Babiarz J, Barth NM, Blevins T, Duh QY, et al. Performance of a genomic sequencing classifier for the preoperative diagnosis of cytologically indeterminate thyroid nodules. JAMA Surg. 2018a;153:817–24.  https://doi.org/10.1001/jamasurg.2018.1153.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Haugen BR, Sawka AM, Alexander EK, Bible KC, Caturegli P, Doherty GM, et al. American Thyroid Association guidelines on the management of thyroid nodules and Differentiated Thyroid Cancer Task Force review and recommendation on the proposed renaming of encapsulated follicular variant papillary thyroid carcinoma without invasion to noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Thyroid. 2017;27:481–3.  https://doi.org/10.1089/thy.2016.0628.CrossRefPubMedGoogle Scholar
  4. 4.
    Krane JF, Cibas ES, Alexander EK, Paschke R, Eszlinger M. Molecular analysis of residual ThinPrep material from thyroid FNAs increases diagnostic sensitivity. Cancer Cytopathol. 2015;123:356–61.  https://doi.org/10.1002/cncy.21546.CrossRefPubMedGoogle Scholar

Afirma

  1. 5.
    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;367:705–15.  https://doi.org/10.1056/NEJMoa1203208.CrossRefPubMedGoogle Scholar
  2. 6.
    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;99:119–25.  https://doi.org/10.1210/jc.2013-2482.CrossRefPubMedGoogle Scholar
  3. 7.
    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;122:737–44.  https://doi.org/10.1002/cncy.21455.CrossRefPubMedGoogle Scholar
  4. 8.
    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;25:789–96.  https://doi.org/10.1089/thy.2015.0049.CrossRefPubMedGoogle Scholar
  5. 9.
    Harrell RM, Bimston DN. Surgical utility of Afirma: effects of high cancer prevalence and oncocytic cell types in patients with indeterminate thyroid cytology. Endocr Pract. 2014;20:364–9.  https://doi.org/10.4158/EP13330.OR.CrossRefPubMedGoogle Scholar
  6. 10.
    Angell TE, Heller HT, Cibas ES, Barletta JA, Kim MI, Krane JF, Marqusee E. Independent comparison of the Afirma genomic sequencing classifier and gene expression classifier for cytologically indeterminate thyroid nodules. Thyroid. 2019;29:650–6.  https://doi.org/10.1089/thy.2018.0726.. [Epub ahead of print]CrossRefPubMedGoogle Scholar
  7. 11.
    Patel KN, Angell TE, Babiarz J, Barth NM, Blevins T, Duh QY, et al. Performance of a genomic sequencing classifier for the preoperative diagnosis of cytologically indeterminate thyroid nodules. JAMA Surg. 2018b;153:817–24.  https://doi.org/10.1001/jamasurg.2018.1153.CrossRefPubMedPubMedCentralGoogle Scholar

Interpace

  1. 12.
    Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res. 2003;63:1454–7.PubMedGoogle Scholar
  2. 13.
    Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003;88:5399–404.CrossRefGoogle Scholar
  3. 14.
    Nikiforov Y. Thyroid carcinoma: Molecular pathways and therapeutic targets. Mod Pathol. 2008;21:S37–43.CrossRefGoogle Scholar
  4. 15.
    Zhao L, Dias-Santagata D, Sadow PM, Faquin WC. Cytological, molecular, and clinical features of non invasive follicular thyroid neoplasm with papillary-like nuclear features versus invasive forms of follicular variant of papillary thyroid carcinoma. Cancer Cytopathol. 2017;125:323–31.  https://doi.org/10.1002/cncy.21839.CrossRefPubMedGoogle Scholar
  5. 16.
    Howell GM, Hodak SP, Yip L. RAS mutations in thyroid cancer. Oncologist. 2013;18:926–32.  https://doi.org/10.1634/theoncologist.2013-0072.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 17.
    Placzkowski KA, Reddi HV, Grebe SK, Eberhardt NL, McIver B. The role of the PAX8/PPARgamma fusion oncogene in thyroid cancer. PPAR Res. 2008;2008:672829.  https://doi.org/10.1155/2008/672829.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 18.
    Xing M, Liu R, Liu X, Murugan AK, Zhu G, Zeiger MA, et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol. 2014;32:2718–26.  https://doi.org/10.1200/JCO.2014.55.5094.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 19.
    Liu R, Xing M. Diagnostic and prognostic TERT promoter mutations in thyroid fine needle aspiration biopsy. Endocr Relat Cancer. 2014;21:825–30.  https://doi.org/10.1530/ERC-14-0359.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 20.
    National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology Thyroid (version1.2018). 2018 May 22. https://www.nccn.org/professionals/physician_gls/default.aspx.
  10. 21.
    Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, 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(Suppl 1):1–60.  https://doi.org/10.4158/EP161208.GL.CrossRefGoogle Scholar
  11. 22.
    Nikiforov Y, 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;2:1023–9.  https://doi.org/10.1001/jamaoncol.2016.0386.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 23.
    Johnson DN, Furtado LV, Long BC, Zhen CJ, Wurst M, Mujacic I, et al. Noninvasive follicular thyroid neoplasms with papillary-like nuclear features are genetically and biologically similar to adenomatous nodules and distinct from papillary thyroid carcinomas with extensive follicular growth. Arch Pathol Lab Med. 2018;142:838–50.  https://doi.org/10.5858/arpa.2017-0118-OA.CrossRefPubMedGoogle Scholar
  13. 24.
    Oczko-Wojciechowska M, Pfeifer A, Rusinek D, Pawlaczek A, Zebracka-Gala J, Kowalska M, et al. The prevalence of somatic RAS mutations in medullary thyroid cancer – a Polish population study. Endocrinol Pol. 2015;66:121–5.  https://doi.org/10.5603/EP.2015.0018.CrossRefGoogle Scholar
  14. 25.
    Wylie D, Beaudenon-Huibregtse S, Haynes BC, Giordano TJ, Labourier E. Molecular classification of thyroid lesions by combined testing for miRNA gene expression and somatic gene alteration. J Pathol Clin Res. 2016;2:93–103.  https://doi.org/10.1002/cjp2.38.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 26.
    Tan W, Liu B, Qu S, Liang G, Luo W, Gong C. MicroRNAs and cancer: key paradigms in molecular therapy. Oncol Lett. 2018;15:2735–42.  https://doi.org/10.3892/ol.2017.7638.CrossRefPubMedGoogle Scholar
  16. 27.
    Banizs A, Silverman J. The utility of combined mutation analysis and microRNA classification in reclassifying cancer risk of cytologically indeterminant thyroid nodules. Diagn Cytopathol. 2019;47:268–74.  https://doi.org/10.1002/dc.24087.CrossRefPubMedGoogle Scholar
  17. 28.
    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;100:2743–50.  https://doi.org/10.1210/jc.2015-1158.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 29.
    Kumar G, Ablordeppey K, Timmaraju VA, , Song-Yang JW, Yaqoob S, Repko B, et al. Comprehensive genotyping for somatic variation and microRNA expression accurately predicts malignancy risk of thyroid nodules (Poster). American Thyroid Association Annual Meeting, 2017.Google Scholar
  19. 30.
    Ablordeppey K, Timmaraju VA, Song-Yang JW, Yaqoob S, Mireskandari A, Narick C, et al. Overcoming challenges in expanding NGS based mutation panels to analyze indeterminate thyroid nodule aspirates. Thyroid. 2018;28(S1):A–23.  https://doi.org/10.1089/thy.2018.29065.abstracts.CrossRefGoogle Scholar
  20. 31.
    Kumar G, et al. The majority of non-diagnostic (insufficient) thyroid nodule cytology samples can effectively undergo molecular (combined mutational and microRNA classifier) analysis using a needle aspiration approach (Poster). American Thyroid Association Annual Meeting, Denver. 2016.Google Scholar
  21. 32.
    Kumar G, Timmaraju VA, Song-Yang JW, Repko B, Narick C, Mireskandari A, Finkelstein S. Utility of microdissected cytology smears for molecular analysis of thyroid malignancy. Diagn Cytopathol. 2019;47:289–96.  https://doi.org/10.1002/dc.24100.CrossRefPubMedGoogle Scholar

ThyroSeq

  1. 33.
    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;94:2092–8.  https://doi.org/10.1210/jc.2009-0247.CrossRefPubMedGoogle Scholar
  2. 34.
    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;95:1365–9.  https://doi.org/10.1210/jc.2009-2103.CrossRefPubMedGoogle Scholar
  3. 35.
    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 1,056 FNA samples. J Clin Endocrinol Metab. 2011;96:3390–7.  https://doi.org/10.1210/jc.2011-1469.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 36.
    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;120:3627–34.  https://doi.org/10.1002/cncr.29038.CrossRefPubMedGoogle Scholar
  5. 37.
    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;25:1217–23.  https://doi.org/10.1089/thy.2015.0305.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 38.
    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;26:1068–76.  https://doi.org/10.1089/thy.2016.0048.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 39.
    Taye A, Gurciullo D, Miles BA, Gupta A, Owen RP, Inabnet WB 3rd, et al. Clinical performance of a next-generation sequencing assay (ThyroSeq v2) in the evaluation of indeterminate thyroid nodules. Surgery. 2018;163:97–103.  https://doi.org/10.1016/j.surg.2017.07.032.CrossRefPubMedGoogle Scholar
  8. 40.
    Nikiforova MN, Mercurio S, Wald AI, Barbi de Moura M, Callenberg K, Santana-Santos L, et al. Analytical performance of the ThyroSeq v3 Genomic Classifier for cancer diagnosis in thyroid nodules. Cancer. 2018;124:1682–90.  https://doi.org/10.1002/cncr.31245.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 41.
    Steward DL, Carty SE, Sippel RS, Yang SP, Sosa JA, Sipos JA, et al. Performance of a multigene genomic classifier in thyroid nodules with indeterminate cytology: a prospective blinded multicenter study. JAMA Oncol. 2018;5:204.  https://doi.org/10.1001/jamaoncol.2018.4616. [Epub ahead of print].CrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Theresa Scognamiglio
    • 1
  • Rana S. Hoda
    • 2
    Email author
  • Christina M. Narick
    • 3
  • Yuri E. Nikiforov
    • 4
  1. 1.Department of Pathology and Laboratory MedicineNew York Presbyterian Hospital, Weill Cornell Medical CollegeNew YorkUSA
  2. 2.CBLPathRye BrookUSA
  3. 3.Interpace DiagnosticsPittsburghUSA
  4. 4.Department of Pathology, Division of Molecular and Genomic PathologyUniversity of PittsburghPittsburghUSA

Personalised recommendations