Skip to main content

Advertisement

SpringerLink
Log in

Testing for Afirma in Thyroid Nodules with High-Risk Indeterminate Cytology (TIR3B): First Italian Experience

  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

A percentage of 15 to 30% of thyroid fine-needle aspiration (FNA) is indeterminate, i.e., TIR3A and TIR3B according to the Italian consensus for thyroid cytology. Afirma, a molecular analysis of thyroid FNA specimens, has recently gained popularity as an adjunct to microscopic cytological evaluation, in order to avoid diagnostic surgery in patients with indeterminate thyroid cytology. We described the first Italian experience with Afirma tests in a single Italian institution and assessed the performance of the Afirma test in TIR3B. Moreover, this is a preliminary study to assess the patient response to the offer of Afirma testing. The Afirma test was proposed to 67 patients with thyroid nodules that had yielded TIR3B cytology. Fifty-one patients (76.1%) chose the Afirma test, 25/51 underwent the test but the remaining 26 did not because of cost. A total of 41/67 (61.2%) patients underwent surgery, and 22/41 (53.7%) nodules were carcinomas. Of the 25 tested by Afirma, 9 (36%) were classified as Afirma-suspicious (Afirma-S); seven of them underwent surgery, and in 6/7 (85.7%), a cancer was proven at histology. Afirma is the procedure that many Italian patients with TIR3B lesions would choose. However, its routine clinical application in Italy is currently limited by high costs for the patient. When Afirma is performed in this setting of patients, the cancer risk of suspicious result is higher than that expected in all the series of TIR3B. Therefore, testing for Afirma in these nodules may be useful for managing patients and tailoring their surgical approach.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Yang J, Schnadig V, Logrono R, Wasserman PG (2009) Fine-needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations. Cancer 111:306–315

    Article  Google Scholar 

  2. Chudova D, Wilde JI, Wang E, Wang H, Rabbee N, Egidio CM, Reynolds J, Tom E, Pagan M, Rigl CT, Friedman L, Wang CC, Lanman RB, Zeiger M, Kebebew E, Rosai J, Fellegara G, LiVolsi V, Kennedy GC (2010) Molecular classification of thyroid nodules using high-dimensionality genomic data. J Clin Endocrinol Metab 95:5296–5304

    Article  CAS  Google Scholar 

  3. Baloch ZW, Fleisher S, LiVolsi VA, Gupata PK (2002) Diagnosis of “follicular neoplasm”: a gray zone in thyroid fine-needle aspiration cytology. Diagn Cytopathol 26:41–44

    Article  Google Scholar 

  4. Nardi F, Basolo F, Crescenzi A, Fadda G, Frasoldati A, Orlandi F, Palombini L, Papini E, Zini M, Pontecorvi A, Vitti P (2014) Italian consensus for the classification and reporting of thyroid cytology. J Endocrinol Invest 37:593–599

    Article  Google Scholar 

  5. Perros P, Boelaert K, Colley S, Evans C, Evans RM, Gerrard Ba D et al (2014) Guidelines for the management of thyroid cancer. Clin. Endocrinol (Oxf.) 81:1–122

    Article  CAS  Google Scholar 

  6. Cibas ES, Syed AZ (2009) NCI Thyroid FNA state of the science conference. The Bethesda System for reporting thyroid cytopathology. Am J Clin Pathol 132:658–665

    Article  Google Scholar 

  7. Trimboli P, Crescenzi A, Castellana M, Giorgino F, Giovanella L, Bongiovanni M (2018) Italian consensus for the classification and reporting of thyroid cytology: the risk of malignancy between indeterminate lesions at low or high risk. A systematic review and meta-analysis. Endocrine 63:430–438

    PubMed  Google Scholar 

  8. Trimboli P, Palermo A, Deandrea M, Piccardo A, Campennì A, Valabrega S (2019) Prognosis of patients with differentiated thyroid carcinomas having a preoperative cytological report of indeterminate at low or high risk. A multicenter study. Endocrine https://doi.org/10.1007/s12020-019-02013-9, 66, 557, 562

    Article  CAS  PubMed  Google Scholar 

  9. Straccia P, Rossi ED, Bizzarro T, Brunelli C, Cianfrini F, Damiani D, Fadda G (2015) A meta-analytic review of the Bethesda system for reporting thyroid cytopathology: has the rate of malignancy in indeterminate lesions been underestimated? Cancer Cytopathol 123:713–722

    Article  Google Scholar 

  10. Ahn SH, Kim SD, Jeong Wj (2017) Comparison of risk of malignancy in a subgroup with atypia of undetermined significance/follicular lesion of undetermined significance: a meta-analysis. Head Neck 39:1699–1610

    Article  Google Scholar 

  11. Valderrabano P, Khazai L, Thompson ZJ, Sharpe SC, Tarasova VD, Otto KJ (2018) Cancer risk associated with nuclear atypia in cytologically indeterminate thyroid nodules: a systematic review and meta-analysis. Thyroid 28:210–219

    Article  Google Scholar 

  12. Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi V, Mandel SJ, Raab SS, Rosai J, Steward DL, Walsh PS, Wilde JI, Zeiger MA, Lanman RB, Haugen BR (2012) Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med 367:705–715

    Article  CAS  Google Scholar 

  13. Alexander EK, Schorr M, Klopper J, Kim C, Sipos J, Nabhan F, Parker C, Steward DL, Mandel SJ, Haugen BR (2014) Multi Center clinical experience with the Afirma Gene Expression Classifier. J Clin Endocrinol Metab 99:119–125

    Article  CAS  Google Scholar 

  14. Angell TE, Heller HT, Cibas E, Barletta J, Kim MI, Krane JF et al (2019) Independent comparison of the Afirma genomic sequencing classifier (GSC) and gene expression classifier (GEC) for cytologically indeterminate thyroid nodules. Thyroid 29:650–656

    Article  CAS  Google Scholar 

  15. Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedüs L, Paschke R, Valcavi R, Vitti P, AACE/ACE/AME Task Force on Thyroid Nodules (2016) AACE/ACE/AME Task Force on Thyroid Nodules. AACE/ACE/AME Medical Guidelines for Clinical practice for the diagnosis and management of thyroid nodules-2016 Update. Endocr Pract 22:622–639

  16. Nikiforov YE, Steward DL, Robinson-Smith TM, Haugen BR, Klopper JP, Zhu Z, Fagin JA, Falciglia M, Weber K, Nikiforova MN (2009) Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab 94:2092–2098

    Article  CAS  Google Scholar 

  17. Nikiforov YE, Ohori NP, Hodak SP, Carty SE, LeBeau SO, Ferris RL, Yip L, Seethala RR, Tublin ME, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforova MN (2011) 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 96:3390–3397

    Article  CAS  Google Scholar 

  18. Moses W, Weng J, Sansano I, Peng M, Khanafshar E, Ljung BM, Duh QY, Clark OH, Kebebew E (2010) Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy. World J Surg 34:2589–2594

    Article  Google Scholar 

  19. Nikiforova MN, Mercurio S, Wald AI, Barbi de Moura M, Callenberg K, Santana-Santos L et al (2018) Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules. Cancer 124:1682–1690

    Article  CAS  Google Scholar 

  20. Partyka KL, Randolph ML, Lawrence KA, Cramer H, Wu HH (2018) Utilization of direct smears of thyroid fine-needle aspirates for ancillary molecular testing: A comparison of two proprietary testing platforms. Diagn Cytopathol 46:320–325

    Article  Google Scholar 

  21. Santos MTD, Buzolin AL, Gama RR, Silva ECAD, Dufloth RM, Figueiredo DLA et al (2018) Molecular Classification of Thyroid Nodules with Indeterminate Cytology: Development and Validation of a Highly Sensitive and Specific New miRNA-Based Classifier Test Using Fine-Needle Aspiration Smear Slides. Thyroid https://doi.org/10.1089/thy.2018.0254

    Book  Google Scholar 

  22. Nishino M, Nikiforova M (2018) Update on Molecular Testing for Cytologically Indeterminate Thyroid Nodules. Arch Pathol Lab Med 142:446–457

    Article  CAS  Google Scholar 

  23. Walsh PS, Wilde JI, Tom EY, Reynolds JD, Chen DC, Chudova DI, Pagan M, Pankratz DG, Wong M, Veitch J, Friedman L, Monroe R, Steward DL, Lupo MA, Lanman RB, Kennedy GC (2012) Analytical performance verification of a molecular diagnostic for cytology-indeterminate thyroid nodules. J Clin Endocrinol Metab 97:E2297–E2306

    Article  CAS  Google Scholar 

  24. Li H, Robinson KA, Anton B, Saldanha IJ, Ladenson PW (2011) Cost-effectiveness of a novel molecular test for cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab 96:E1719-E1726

    Article  CAS  Google Scholar 

  25. Haymart MR, Banerjee M, Yang D, Stewart AK, Sisson JC, Koenig RJ et al (2013) Variation in the Management of Thyroid Cancer. J Clin Endo Metabol 98:2001–2008

    Article  CAS  Google Scholar 

  26. Duick DS, Klopper JP, Diggans J, Friedman L, Kennedy GC, Lanman RB, McIver B (2012) The impact of benign gene expression classifier test results on the Endocrinologist-patient operate in patient with thyroid nodules with indeterminate FNA cytology. Thyroid 22:996–1001

    Article  CAS  Google Scholar 

  27. Alexander EK, Schorr M, Klopper J, Kim C, Sipos J, Nabhan F et al (2013) Multicentre clinical experience with the Afirma gene expression classifier. J Clin Endocrinol Metab 99:119–125

    Article  Google Scholar 

  28. Marti JL, Avadhani V, Donatelli LA, Niyogi S, Wang B, Wong RJ, Shaha AR, Ghossein RA, Lin O, Morris LG, Ho AS (2015) Wide Inter-institutional Variation in Performance of a Molecular Classifier for Indeterminate. Thyroid Nodules Ann Surg Oncol 22:3996–4001

    Article  Google Scholar 

  29. Harrell RM, Bimston DN (2014) Surgical utility of Afirma: effects of high cancer prevalence and oncocytic cell types in patients with indeterminate thyroid cytology. Endocr Pract 20:364–369

    Article  Google Scholar 

  30. McIver B, Castro MR, Morris JC, Bernet V, Smallridge R, Henry M et al (2014) An independent study of a gene expression classifier (Afirma) in the evaluation of cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab 99:4069–4077

    Article  CAS  Google Scholar 

  31. Kay-Rivest E, Tibbo J, Bouhabel S, Tamilia M, Leboeuf R, Forest VI et al (2017) The first Canadian experience with the Afirma® gene expression classifier test Journal of Otolaryngology - Head and Neck Surgery 46:25 https://doi.org/10.1186/s40463-017-0201-7

  32. Endo M, Nabhan F, Porter K, Roll K, Shirley LA, Azaryan I, Tonkovich D, Perlick J, Ryan LE, Khawaja R, Meng S, Phay JE, Ringel MD, Sipos JA (2019) Afirma Gene Sequencing Classifier Compared with Gene Expression Classifier in Indeterminate Thyroid Nodules. Thyroid 29:1115–1124

    Article  CAS  Google Scholar 

  33. Hao Y, Choi Y, Babiarz JE, Kloos RT, Kennedy GC, Huang J, Walsh PS (2019) Analytical Verification Performance of Afirma Genomic Sequencing Classifier in the Diagnosis of Cytologically Indeterminate Thyroid Nodules. Front Endocrinol (Lausanne) 10:438 https://doi.org/10.3389/fendo.2019.00438

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. EndocrinologiaOggi, Rome, Italy

    Massimiliano Andrioli, Silvia Carocci, Stefania Alessandrini, Mostafa Amini & Dominique Van Doorne

  2. Endocrinology, Valmontone Hospital, Valmontone (RM), Roma, Italy

    Daniela Pace

  3. Area di Medicina Interna, Policlinico Universitario Campus Bio-medico, Rome, Italy

    Angelo Lauria

  4. U.O.C. Chirurgia Endocrina e Metabolica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Marco Raffaelli

  5. Clinic for Nuclear Medicine and Competence Center for Thyroid Diseases, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland

    Pierpaolo Trimboli

Authors
  1. Massimiliano Andrioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Silvia Carocci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefania Alessandrini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mostafa Amini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dominique Van Doorne
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniela Pace
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Angelo Lauria
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marco Raffaelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pierpaolo Trimboli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Massimiliano Andrioli.

Ethics declarations

All procedures performed in studies were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of Interest

The authors declare that they have no conflict of interest.

Statement of Ethics

All study participants provided a written informed consent.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Andrioli, M., Carocci, S., Alessandrini, S. et al. Testing for Afirma in Thyroid Nodules with High-Risk Indeterminate Cytology (TIR3B): First Italian Experience. Endocr Pathol 31, 46–51 (2020). https://doi.org/10.1007/s12022-020-09604-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12022-020-09604-7

Keywords

Search

Navigation