Advertisement

Endocrine

, Volume 52, Issue 1, pp 39–45 | Cite as

Galectin-3 and HBME-1 improve the accuracy of core biopsy in indeterminate thyroid nodules

  • Pierpaolo Trimboli
  • Leo Guidobaldi
  • Stefano Amendola
  • Naim Nasrollah
  • Francesco Romanelli
  • Daniela Attanasio
  • Giovanni Ramacciato
  • Enrico Saggiorato
  • Stefano Valabrega
  • Anna Crescenzi
Endocrine Methods and Techniques

Abstract

Core needle biopsy (CNB) has been recently described as an accurate second-line test in thyroid inconclusive cytology (FNA). Here we retrospectively investigated the potential improvement given by Galectin-3, Cytokeratin-19, and HBME-1 on the accuracy of CNB in thyroid nodules with prior indeterminate FNA report. The study included 74 nodules. At CNB diagnosis, 15 were cancers, 40 were benign, and 19 had uncertain/non-diagnostic CNB report. The above immunohistochemical (IHC) panel was analyzed in all cases. After surgery, 19 malignant and 55 benign lesions were found. All 15 cancers and all 40 benign nodules diagnosed at CNB were confirmed at final histology. Regarding the uncertain CNB group, 4 (21 %) were malignant and 15 (79 %) benign. When we considered all the series, the most accurate IHC combination was Galectin-3 plus HBME-1, while HBME-1 was the most sensitive marker in those nodules with uncertain CNB report. The combination of CNB plus IHC could indentify 19/19 cancers and 53/55 benign lesions. Sensitivity and specificity of CNB increased from 79 to 100 % and from 73 to 96 %, respectively, by adding IHC. CNB can diagnose the majority of thyroid nodules with previous indeterminate FNA cytology, while the accuracy of CNB is increased by adding Galectin-3, Cytokeratin-19, and HBME-1 panel. We suggest to adopt CNB as a second-line approach to indeterminate thyroid FNA, and apply IHC in those lesions with uncertain/non-diagnostic CNB report. This approach should improve the pre-surgical diagnosis of patients. These results should be confirmed in larger prospective series.

Keywords

Thyroid Nodule Core needle biopsy (CNB) Galectin-3 

Notes

Acknowledgments

The authors of this paper thank Rachele Conte MD PhD and Agnese Di Fiore MD PhD, who significantly contribute to mind the entire casuistry.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    H. Gharib, E. Papini, R. Paschke, D.S. Duick, R. Valcavi, L. Hegedüs, P. Vitti, AACE/AME/ETA Task Force on Thyroid Nodules, American association of clinical endocrinologists, associazione medici endocrinologi, and europeanthyroid association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr. Pract. 1, 1–43 (2010)CrossRefGoogle Scholar
  2. 2.
    American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, D.S. Cooper, G.M. Doherty, B.R. Haugen, R.T. Kloos, S.L. Lee, S.J. Mandel, E.L. Mazzaferri, B. McIver, F. Pacini, M. Schlumberger, S.I. Sherman, D.L. Steward, R.M. Tuttle, Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19, 1167–1214 (2009)CrossRefGoogle Scholar
  3. 3.
    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
  4. 4.
    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
  5. 5.
    E.K. Alexander, G.C. Kennedy, Z.W. Baloch, E.S. Cibas, D. Chudova, J. Diggans, L. Friedman, R.T. Kloos, V.A. LiVolsi, S.J. Mandel, S.S. Raab, J. Rosai, D.L. Steward, P.S. Walsh, J.I. Wilde, M.A. Zeiger, R.B. Lanman, B.R. Haugen, Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N. Engl. J. Med. 367, 705–715 (2012)CrossRefPubMedGoogle Scholar
  6. 6.
    E. Saggiorato, Pompa R. De, M. Volante, S. Cappia, F. Arecco, A.P. Dei Tos, F. Orlandi, M. Papotti, Characterization of thyroid ‘follicular neoplasms’ in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application. Endocr. Relat. Cancer 12, 305–317 (2005)CrossRefPubMedGoogle Scholar
  7. 7.
    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
  8. 8.
    G. Fadda, E.D. Rossi, M. Raffaelli, A. Pontecorvi, S. Sioletic, F. Morassi, C.P. Lombardi, G.F. Zannoni, G. Rindi, Follicular thyroid neoplasms can be classified as low- and high-risk according to HBME-1 and Galectin-3 expression on liquid-based fine-needle cytology. Eur. J. Endocrinol. 165, 447–453 (2011)CrossRefPubMedGoogle Scholar
  9. 9.
    P. Trimboli, A. Crescenzi, Thyroid core needle biopsy: taking stoke of the situation. Endocrine 48, 779–785 (2015)CrossRefPubMedGoogle Scholar
  10. 10.
    K.T. Park, S.H. Ahn, J.H. Mo, Y.J. Park, J. Park, S.I. Choi, S.Y. Park, Role of core needle biopsy and ultrasonographic finding in management of indeterminate thyroid nodules. Head Neck 33, 160–165 (2011)CrossRefPubMedGoogle Scholar
  11. 11.
    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
  12. 12.
    N. Nasrollah, P. Trimboli, F. Rossi, S. Amendola, L. Guidobaldi, C. Ventura, R. Maglio, G. Nigri, F. Romanelli, S. Valabrega, A. Crescenzi, Patient’s comfort with and tolerability of thyroid core needle biopsy. Endocrine 45, 79–83 (2014)CrossRefPubMedGoogle Scholar
  13. 13.
    D.G. Na, J.H. Kim, J.Y. Sung, J.H. Baek, K.C. Jung, H. Lee, H. Yoo, Core-needle biopsy is more useful than repeat fine-needle aspiration in thyroid nodules read as nondiagnostic or atypia of undetermined significance by the bethesda system for reporting thyroid cytopathology. Thyroid 22, 468–475 (2012)CrossRefPubMedGoogle Scholar
  14. 14.
    Y.J. Choi, J.H. Baek, E.J. Ha, H.K. Lim, J.H. Lee, J.K. Kim, D.E. Song, Y. Shong, S.J. Hong, Different risk of malignancy and management recommendations in subcategories of thyroid nodules with atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS): the role of US-guided core-needle biopsy (CNB). Thyroid 24, 494–501 (2014)CrossRefPubMedGoogle Scholar
  15. 15.
    G. Fadda, F. Basolo, A. Bondi, G. Bussolati, A. Crescenzi, O. Nappi, F. Nardi, M. Papotti, G. Taddei, L. Palombini, Cytological classification of thyroid nodules. Proposal of the SIAPEC-IAP Italian Consensus Working Group. Pathologica 102, 405–408 (2010)PubMedGoogle Scholar
  16. 16.
    R. De Lellis, R. Lloyd, P. Heitz, C. Eng, Pathology and genetics of tumour of endocrine organs, in World Health Organization classification of tumours, ed. by P. Kleihues, L. Sobin (IARC, Lyon, 2004), pp. 49–133Google Scholar
  17. 17.
    P. Trimboli, N. Nasrollah, L. Guidobaldi, S. Taccogna, D.D. Cicciarella Modica, S. Amendola, F. Romanelli, A. Lenzi, G. Nigri, M. Centanni, L. Giovanella, S. Valabrega, A. Crescenzi, The use of core needle biopsy as first-line in diagnosis of thyroid nodules reduces false negative and inconclusive data reported by fine-needle aspiration. World J. Surg. Oncol. 12, 61 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    M.R. Nasr, S. Mukhopadhyay, S. Zhang, A.L. Katzenstein, Immunohistochemical markers in diagnosis of papillary thyroid carcinoma: utility of HBME 1 combined with CK-19 immunostaining. Mod. Pathol. 19, 1631–1637 (2006)CrossRefPubMedGoogle Scholar
  19. 19.
    M. Papotti, J. Rodriguez, R. De Pompa, A. Bartolazzi, J. Rosai, Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. Mod. Pathol. 18, 541–546 (2005)CrossRefPubMedGoogle Scholar
  20. 20.
    A. Bartolazzi, A. Gasbarri, M. Papotti, G. Bussolati, T. Lucante, A. Khan, H. Inohara, F. Marandino, F. Orlandi, F. Nardi, A. Vecchione, R. Tecce, O. Larsson, Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357, 1644–1650 (2001)CrossRefPubMedGoogle Scholar
  21. 21.
    C.G. Chiu, S.S. Strugnell, O.L. Griffith, S.J. Jones, A.M. Gown, B. Walker, I.R. Nabi, S.M. Wiseman, Diagnostic utility of galectin-3 in thyroid cancer. Am. J. Pathol. 176, 2067–2081 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    O.L. Griffith, C.G. Chiu, A.M. Gown, S.J.M. Jones, S.M. Wiseman, Biomarker panel diagnosis of thyroid cancer: a critical review. Expert Rev. Anticancer Ther. 8, 1399–1413 (2008)CrossRefPubMedGoogle Scholar
  23. 23.
    A.A. Renshaw, N. Pinnar, Comparison of thyroid fine-needle aspiration and core needle biopsy. Am. J. Clin. Pathol. 128, 370–374 (2007)CrossRefPubMedGoogle Scholar
  24. 24.
    D. Capper, M. Preusser, A. Habel, F. Sahm, U. Ackermann, G. Schindler, S. Pusch, G. Mechtersheimer, H. Zentgraf, A. von Deimling, Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol. 122, 11–19 (2011)CrossRefPubMedGoogle Scholar
  25. 25.
    A. Crescenzi, L. Guidobaldi, N. Nasrollah, S. Taccogna, D.D. Cicciarella Modica, L. Turrini, G. Nigri, F. Romanelli, S. Valabrega, L. Giovanella, A. Onetti Muda, P. Trimboli, Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers. Horm. Metab. Res. 46, 370–374 (2014)CrossRefPubMedGoogle Scholar
  26. 26.
    T.J. Sebo, What are the keys to successful thyroid FNA interpretation? Clin. Endocrinol. 77, 13–17 (2012)CrossRefGoogle Scholar
  27. 27.
    P. Trimboli, M. Bongiovanni, F. Rossi, L. Guidobaldi, A. Crescenzi, L. Ceriani, G. Nigri, S. Valabrega, F. Romanelli, L. Giovanella, Differentiated thyroid cancer patients with a previous indeterminate (Thy 3) cytology have a better prognosis than those with suspicious or malignant FNAC reports. Endocrine 49, 191–195 (2015)CrossRefPubMedGoogle Scholar
  28. 28.
    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. 99, 3700–3707 (2014)CrossRefPubMedGoogle Scholar
  29. 29.
    F. Nardi, F. Basolo, A. Crescenzi, G. Fadda, A. Frasoldati, F. Orlandi, L. Palombini, E. Papini, M. Zini, A. Pontecorvi, P. Vitti, Italian consensus for the classification and reporting of thyroid cytology. J. Endocrinol. Invest. 37, 593–599 (2014)CrossRefPubMedGoogle Scholar
  30. 30.
    E.S. Cibas, S.Z. Ali, The Bethesda system for reporting thyroid cytopathology. Thyroid 19, 1159–1165 (2009)CrossRefPubMedGoogle Scholar
  31. 31.
    A. Carpi, A.G. Naccarato, G. Iervasi, A. Nicolini, G. Bevilacqua, P. Viacava, P. Collecchi, L. Lavra, C. Marchetti, S. Sciacchitano, A. Bartolazzi, Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology. Br. J. Cancer 95, 204–209 (2006)CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    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 2015

Authors and Affiliations

  • Pierpaolo Trimboli
    • 1
  • Leo Guidobaldi
    • 2
  • Stefano Amendola
    • 1
  • Naim Nasrollah
    • 3
  • Francesco Romanelli
    • 4
  • Daniela Attanasio
    • 5
  • Giovanni Ramacciato
    • 6
  • Enrico Saggiorato
    • 7
  • Stefano Valabrega
    • 6
  • Anna Crescenzi
    • 8
  1. 1.Section of Endocrinology and DiabetologyOspedale IsraeliticoRomeItaly
  2. 2.Section of PathologyOspedale IsraeliticoRomeItaly
  3. 3.Section of SurgeryOspedale IsraeliticoRomeItaly
  4. 4.Department of Experimental MedicineSapienza UniversityRomeItaly
  5. 5.EndocrinologyAzienda Sanitaria LocaleViterboItaly
  6. 6.Department of Surgical and Medical Science, Sapienza UniversityOspedale S. AndreaRomeItaly
  7. 7.Service d’Endocrinologie, Pôle de MédecineCentre Hospitalier des EscartonsBriançonFrance
  8. 8.Section of PathologyUniversity Hospital Campus Bio MedicoRomeItaly

Personalised recommendations