, Volume 49, Issue 1, pp 191–195 | Cite as

Differentiated thyroid cancer patients with a previous indeterminate (Thy 3) cytology have a better prognosis than those with suspicious or malignant FNAC reports

  • Pierpaolo Trimboli
  • Massimo Bongiovanni
  • Fabio Rossi
  • Leo Guidobaldi
  • Anna Crescenzi
  • Luca Ceriani
  • Giuseppe Nigri
  • Stefano Valabrega
  • Francesco Romanelli
  • Luca Giovanella
Original Article


The prognosis of differentiated thyroid cancers (DTC) read at cytology as indeterminate and classified as Thy 3 according to the British Thyroid Association has recently been suggested to be good. To obtain robust information about this potential novelty, in this study we retrospectively reviewed DTC with a prior fine-needle aspiration cytology (FNAC) of Thy 3, Thy 4 or Thy 5 presently followed up at two institutes. Patients with no FNAC before surgery were excluded and a series of 284 DTC was enrolled in the study. Of these, 53 had Thy 3, 108 Thy 4, and 123 had Thy 5 prior to surgery. At histology, 280 (98.6 %) papillary and 4 follicular (1.4 %) cancers were found. Overall, the less aggressive cancer forms were prevalent in all three groups. The lower TNM stages (I and II) were more frequent in the Thy 3 group (96.2 %) than in the other cases (76.6 %) (p < 0.001). Neck lymph node metastasis at diagnosis was found in 3.8 % of Thy 3, 18.5 % of Thy 4, and 26 % of Thy 5 cases. At follow-up, a 16.2 % recurrence rate was recorded, ranging from 1.9 % in Thy 3 group to 19.5 % for Thy 4 and Thy 5 (p < 0.001). According to the Kaplan–Meier curve, Thy 3 was thus a favorable prognostic factor compared with Thy 4 and Thy 5 (OR = 0.079, p < 0.001, 95 %CI 0.01–0.59). At multivariate analysis, Thy 3 was an independent predictor of good prognosis (OR = 0.06, p = 0.03, 95 %CI 0.01–0.80). In conclusion, DTC with a preoperative Thy 3 cytology have a better prognosis than those with Thy 4 and Thy 5 due to less aggressive tumor types and lower TNM stage at diagnosis.


Thyroid cancer Cytology FNAC Prognosis Thy 3 


Conflict of interest

The authors have no conflicts of interest to declare.

Supplementary material

12020_2014_453_MOESM1_ESM.tif (304 kb)
Supplementary material 1 (TIFF 303 kb)


  1. 1.
    S.I. Sherman, Thyroid carcinoma. Lancet 36, 501–511 (2003)CrossRefGoogle Scholar
  2. 2.
    B.K. Kinder, Well differentiated thyroid cancer. Curr. Opin. Oncol. 15, 71–77 (2003)CrossRefPubMedGoogle Scholar
  3. 3.
    J.L. Pasieka, Anaplastic thyroid cancer. Curr. Opin. Oncol. 15, 78–83 (2003)CrossRefPubMedGoogle Scholar
  4. 4.
    S.B. Edge, D.R. Byrd, C.C. Compton, A.G. Fritz, F.L. Greene, A. Trotti, Thyroid. AJCC Cancer Staging Manual, 7th edn. (Springer, NY, 2010), pp. 87–96Google Scholar
  5. 5.
    T. Rago, M. Scutari, F. Latrofa, V. Loiacono, P. Piaggi, I. Marchetti, R. Romani, F. Basolo, P. Miccoli, M. Tonacchera, P. Vitti, The large majority of 1520 patients with indeterminate thyroid nodule at cytology have a favorable outcome and a clinical risk score has a high negative predictive value for a more cumbersome cancer disease. J. Clin. Endocrinol. Metab. 9(10), 3700–3707 (2014)CrossRefGoogle Scholar
  6. 6.
    Royal College of Physicians of London, Guidelines for the management of thyroid cancer, 2nd edn. (The Lavenham Press, Suffolk, 2007)Google Scholar
  7. 7.
    R.A. De Lellis, Pathology and genetics of tumours of endocrine organs, World Health Organization, 3rd edn. (IARC Press, Lyon, 2004)Google Scholar
  8. 8.
    L. Giovanella, G. Treglia, R. Sadeghi, P. Trimboli, L. Ceriani, F.A. Verburg, Unstimulated highly sensitive thyroglobulin in follow-up of differentiated thyroid cancer patients: a meta-analysis. J. Clin. Endocrinol. Metab. 99, 440–447 (2014)CrossRefPubMedGoogle Scholar
  9. 9.
    P. Trimboli, D. La Torre, L. Ceriani, E. Condorelli, O. Laurenti, F. Romanelli, C. Ventura, A. Signore, S. Valabrega, L. Giovanella, High sensitive thyroglobulin assay on thyroxine therapy: can it avoid stimulation test in low and high risk differentiated thyroid carcinoma patients? Horm. Metab. Res. 45, 664–668 (2013)CrossRefPubMedGoogle Scholar
  10. 10.
    S.Z. Ali, E.S. Cibas, The Bethesda system for reporting thyroid cytopathology. Thyroid 19, 1159–1165 (2009)CrossRefPubMedGoogle Scholar
  11. 11.
    P. Trimboli, G. Treglia, L. Guidobaldi, E. Saggiorato, G. Nigri, A. Crescenzi, F. Romanelli, F. Orlandi, S. Valabrega, R. Sadeghi, L. Giovanella, Clinical characteristics as predictors of malignancy in patients with indeterminate thyroid cytology: a meta-analysis. Endocrine 46, 52–59 (2014)CrossRefPubMedGoogle Scholar
  12. 12.
    M. Bongiovanni, A. Spitale, W.C. Faquin, L. Mazzucchelli, Z.W. Baloch, The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytol. 56, 333–339 (2012)CrossRefPubMedGoogle Scholar
  13. 13.
    A. Bartolazzi, F. Orlandi, E. Saggiorato, M. Volante, F. Arecco, R. Rossetto, N. Palestini, E. Ghigo, M. Papotti, G. Bussolati, M.P. Martegani, F. Pantellini, A. Carpi, M.R. Giovagnoli, S. Monti, V. Toscano, S. Sciacchitano, G.M. Pennelli, C. Mian, M.R. Pelizzo, M. Rugge, G. Troncone, L. Palombini, G. Chiappetta, G. Botti, A. Vecchione, R. Bellocco, Italian Thyroid Cancer Study Group (ITCSG): Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study. Lancet Oncol. 9, 543–549 (2008)CrossRefPubMedGoogle Scholar
  14. 14.
    P. Trimboli, E. Condorelli, A. Catania, S. Sorrenti, Clinical and ultrasound parameters in the approach to thyroid nodules cytologically classified as indeterminate neoplasm. Diagn. Cytopathol. 37, 783–785 (2009)CrossRefPubMedGoogle Scholar
  15. 15.
    N. Nasrollah, P. Trimboli, L. Guidobaldi, D.D. Cicciarella Modica, C. Ventura, G. Ramacciato, S. Taccogna, F. Romanelli, S. Valabrega, A. Crescenzi, Thin core biopsy should help to discriminate thyroid nodules cytologically classified as indeterminate. A new sampling technique. Endocrine 43, 659–665 (2013)CrossRefPubMedGoogle Scholar
  16. 16.
    A. Heinzel, D. Müller, F.F. Behrendt, L. Giovanella, F.M. Mottaghy, F.A. Verburg, Thyroid nodules with indeterminate cytology: molecular imaging with 99mTc-methoxyisobutylisonitrile (MIBI) is more cost-effective than the Afirma® gene expression classifier. Eur. J. Nucl. Med. Mol. Imaging 41, 1497–1500 (2014)CrossRefPubMedGoogle Scholar
  17. 17.
    L. Davies, H.G. Welch, Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA 295, 2164–2167 (2006)CrossRefPubMedGoogle Scholar
  18. 18.
    P. Trimboli, S. Ulisse, F.M. Graziano, A. Marzullo, M. Ruggieri, A. Calvanese, F. Piccirilli, R. Cavaliere, A. Fumarola, M. D’Armiento, Trend in thyroid carcinoma size, age at diagnosis, and histology in a retrospective study of 500 cases diagnosed over 20 years. Thyroid 16, 1151–1155 (2006)CrossRefPubMedGoogle Scholar
  19. 19.
    V.A. LiVolsi, S.L. Asa, The demise of follicular carcinoma of the thyroid gland. Thyroid 4, 233–236 (1994)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Pierpaolo Trimboli
    • 1
    • 2
  • Massimo Bongiovanni
    • 3
  • Fabio Rossi
    • 1
  • Leo Guidobaldi
    • 4
  • Anna Crescenzi
    • 5
  • Luca Ceriani
    • 2
  • Giuseppe Nigri
    • 6
  • Stefano Valabrega
    • 6
  • Francesco Romanelli
    • 7
  • Luca Giovanella
    • 2
  1. 1.Section of Endocrinology and DiabetologyOspedale IsraeliticoRomeItaly
  2. 2.Department of Nuclear Medicine and Thyroid CentreOncology Institute of Southern SwitzerlandBellinzonaSwitzerland
  3. 3.Institute of PathologyUniversity HospitalLausanneSwitzerland
  4. 4.Section of PathologyOspedale IsraeliticoRomeItaly
  5. 5.Section of PathologyUniversity Hospital Campus Bio MedicoRomeItaly
  6. 6.Department of Medical and Surgical Sciences, Ospedale S. AndreaSapienza UniversityRomeItaly
  7. 7.Department of Experimental MedicineSapienza UniversityRomeItaly

Personalised recommendations