Combined use of fine-needle aspiration biopsy, MIBI scans and frozen section biopsy offers the best diagnostic accuracy in the assessment of the hypofunctioning solitary thyroid nodule

  • Luis Mauricio Hurtado-López
  • Sara Arellano-Montaño
  • Evelyn Migdalia Torres-Acosta
  • Felipe Rafael Zaldivar-Ramirez
  • Reyna Margarita Duarte-Torres
  • Patricia Alonso-de-Ruiz
  • Iván Martínez-Duncker
  • Carlos Martínez-DunckerEmail author



The probability of malignancy is increased in hypofunctioning solitary thyroid nodules (HFNs). Fine-needle aspiration biopsy (FNA), 99mTc-methoxyisobutylisonitrile (MIBI) and frozen section biopsy (FS) have limited independent diagnostic accuracy for the differential diagnosis of HFNs. The goal of this study was to assess the accuracy of the three independent diagnostic methods in distinguishing between benign and malignant disease.


A total of 130 patients with an HFN on the 99mTc-pertechnetate scan were included in this study. FNA, MIBI scans, FS, thyroidectomy and histological analysis of surgical specimens for final diagnosis were performed in all patients.


Of the 130 patients, 80 (61.54%) had benign lesions and 50 (38.46%), malignant lesions. FNA was diagnostic in 78/130 (60%) patients and non-diagnostic in 52/130 (40%) patients. None of the patients with a negative MIBI scan had a final histological diagnosis of malignancy, and MIBI scans were negative in 38.46% of patients with non-diagnostic FNA results. FS was diagnostic in 104/130 (80%) patients and non-diagnostic in 26/130 (20%) patients. Sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios were 81.3%, 97.8%, 96%, 88%, 36.95 and 0.19 respectively for FNA; 100%, 61.3%, 61.7%, 100%, 2.58 and 0 respectively for MIBI; and 80.5%, 100%, 100%, 89%, 0 and 0.2 respectively for FS. Use of both MIBI scans and FS in patients with non-diagnostic FNA rendered a specificity and sensitivity of 100%.


MIBI scans exclude malignancy in a significant proportion of patients with non-diagnostic FNAs (38% in this study). Cystic nodules with a positive MIBI scan should be further investigated even when the FNA result indicates a benign lesion. Combined use of FNA, MIBI and FS offers the best diagnostic accuracy.


MIBI Scintigraphy Fine-needle aspiration Frozen section Thyroid nodule 


  1. 1.
    McCaffrey TV. Thyroid cancer in the new millennium. Cancer Control 2000; 7:209–210.PubMedGoogle Scholar
  2. 2.
    Jossart GH, Clark OH. Well-differentiated thyroid cancer. Curr Prob Surg 1994; 31:935–1011.Google Scholar
  3. 3.
    Brooks AD, Shaha AR, DuMornay W, Huvos AG, Zakowski M, Brennan MF, Shah J. Role of fine-needle aspiration biopsy and frozen section analysis in the surgical management of thyroid tumors. Ann Surg Onc 2001; 8:92–100.CrossRefGoogle Scholar
  4. 4.
    Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med 1993; 328:553–559.Google Scholar
  5. 5.
    Burguera B, Gharib H. Thyroid incidentalomas: prevalence, diagnosis, significance, and management. Endocrinol Metab Clin North Am 2000; 29:187–203.Google Scholar
  6. 6.
    Tyler DS. Evaluation of solitary thyroid nodules. Ann Surg Oncol 2000; 7:376–378.PubMedGoogle Scholar
  7. 7.
    Charkes ND. Thyroid and whole-body imaging. In: Ingbar SH, Braverman LE, eds. The thyroid, 5th edn. Philadelphia: Lippincott; 1986:458–478.Google Scholar
  8. 8.
    Messaris G, Evangelou GN, Tountas C. Incidence of carcinoma in cold nodules of the thyroid gland. Surgery 1973; 74:447–448.PubMedGoogle Scholar
  9. 9.
    American Association of Clinical Endocrinologists and the American College of Endocrinology. Clinical practice guidelines for the diagnosis and management of thyroid nodules. Scholar
  10. 10.
    Shulkin BL, Shapiro B. The role of imaging tests in the diagnosis of thyroid carcinoma. Endocrinol Metab Clin North Am 1990; 19:523–541.PubMedGoogle Scholar
  11. 11.
    Boigon M, Moyer D. Solitary thyroid nodules. Separating benign from malignant conditions. Postgrad Med 1995; 98:73–74, 77–80.PubMedGoogle Scholar
  12. 12.
    Veith FJ, Brooks JR, Grigsby WP, Selenkow HA. The nodular thyroid gland and cancer. A practical approach to the problem. N Engl J Med 1964; 270:431–436.PubMedGoogle Scholar
  13. 13.
    Hurtado-López LM, Zaldivar-Ramirez FR, Pulido-Cejudo A, Muñoz-Solis O, Basurto Kuba E. Criterios clínicos de malignidad en el nódulo tiroideo. ¿Estan vigentes? Cir Gen 2001; 23:25–28.–1/im-cg011c.htm.Google Scholar
  14. 14.
    Bennedbaek FN, Hegedus L. Management of the solitary thyroid nodule: result of a North American survey. J Clin Endocrinol Metab 2000; 85:2493–2494.PubMedGoogle Scholar
  15. 15.
    Bennedbaek FN, Perrild H, Hegedus L. Diagnosis and treatment of the solitary thyroid nodule: result of a European survey. Clin Endocrinol (Oxf) 1999; 50:357–363.Google Scholar
  16. 16.
    Walsh RM, Watkinson JC, Franklyn J. The management of the solitary thyroid nodule: a review. Clin Otolaryngol 1999; 24:388–397.CrossRefPubMedGoogle Scholar
  17. 17.
    Harada T, Ito Y, Shimaoka K, Taniguchi T, Matsudo O, Senoo T. Clinical evaluation of thallium-201 chloride scan for thyroid nodule. Eur J Nucl Med 1980; 5:125–130.PubMedGoogle Scholar
  18. 18.
    Klain M, Maurea S, Cuocolo A, et al. Technetium-99m tetrofosmin imaging in thyroid diseases: comparison with Tc-99m pertechnetate, thallium-201 and Tc-99m-methoxyisobutylisonitrile scans. Eur J Nucl Med 1996; 23:1568–1574.PubMedGoogle Scholar
  19. 19.
    Kresnik E, Gallowitsch H-J, Mikosch P, Stettner H, Igere I, Gomez I, Kumming G, Lind P. Fluorine-18-fluorodeoxyglucose positron emission tomography in the preoperative assessment of thyroid nodules in an endemic goiter area. Surgery 2003; 133:294–299.CrossRefPubMedGoogle Scholar
  20. 20.
    Okumura Y, Takeda Y, Sato S, Komatsu M, Nakagawa T, Akaki S, Kuroda M, Joja I, Hiraki Y. Comparison of differential diagnostic capabilities of201Tl scintigraphy and fine-needle aspiration of thyroid nodules. J Nucl Med 1999; 40:1971–1977.Google Scholar
  21. 21.
    Schomacker K, Schicha H. Use of myocardial imaging agents for tumour diagnosis: a success story? Eur J Nucl Med 2000; 27:1845–1863.CrossRefPubMedGoogle Scholar
  22. 22.
    Sinha PS, Beeby DI, Ryan P. An evaluation of thallium imaging for detection of carcinoma in clinically palpable solitary, nonfunctioning thyroid nodules. Thyroid 2001; 11:85–89.CrossRefPubMedGoogle Scholar
  23. 23.
    Mandell DL, Genden EM, Mechanick JI, Berman DA, Biller HF, Urken ML. Diagnostic accuracy of fine-needle aspiration and frozen section in nodular thyroid disease. Otolaryngol Head Neck Surg 2001; 124:531–536.CrossRefPubMedGoogle Scholar
  24. 24.
    Burch HB, Burman KD, Reed HL, Buckner L, Raber T, Ownbey JL. Fine needle aspiration of thyroid nodules. Determinants of insufficiency rate and malignancy yield at thyroidectomy. Acta Cytol 1996; 40:1176–1183.PubMedGoogle Scholar
  25. 25.
    Shaha A. Controversies in the management of thyroid nodule. Laryngoscope 2000; 110:183.PubMedGoogle Scholar
  26. 26.
    Cochand-Priollet B, Guillausseau PJ, Chagnon S, et al. The diagnostic value of fine-needle aspiration biopsy under ultrasonography in nonfunctional thyroid nodules: a prospective study comparing cytologic and histologic findings. Am J Med 1994; 97:152–157.PubMedGoogle Scholar
  27. 27.
    Chang HY, Lin JD, Chen JF, et al. Correlation of fine needle aspiration cytology and frozen section biopsies in the diagnosis of thyroid nodules. J Clin Pathol 1997; 50:1005–1009.PubMedGoogle Scholar
  28. 28.
    Lee TI, Yang HJ, Lin SY, Lee MT, Braverman LE, Tang KT. The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer. Thyroid 2002; 12:619–626.CrossRefPubMedGoogle Scholar
  29. 29.
    Taneri F, Poyraz A, Salman B, et al. Using imprint and frozen sections in determining the surgical strategies for thyroid pathologies. Endocr Regul. 2001; 35:71–74.Google Scholar
  30. 30.
    Richards M, Chisholm R, Bruder JM, Strodel WE. Is thyroid frozen section too much for too little? Am J Surg 2002; 184:510–514.CrossRefPubMedGoogle Scholar
  31. 31.
    Lin HS, Komisr A, Opher E, Blaugrund SM. Surgical management of thyroid masses: assessing the need for frozen section evaluation. Laryngoscope 1999; 109:868–873.CrossRefPubMedGoogle Scholar
  32. 32.
    Castro MR, Gharib H. Thyroid nodules and cancer. Postgrad Med 2000; 107(1). Scholar
  33. 33.
    Tanju YE, Kutlan O, Levent K, et al. Correlation of technetium-99 MIBI and thallium-201 retention in solitary cold thyroid nodules with postoperative histopathology. Eur J Nucl Med 2000; 27:713–721.CrossRefPubMedGoogle Scholar
  34. 34.
    Sathekge MM, Mageza RB, Muthupei MN, Modiba MCM, Clauss RC. Evaluation of thyroid nodules with technetium-99m MIBI and technetium-99m pertechnetate. Head Neck 2001; 23:305–310.CrossRefPubMedGoogle Scholar
  35. 35.
    Kresnik E, Gallowitsch H-J, Mikosch P, Gomez I, Lind P. Technetium-99m-MIBI scintigraphy of thyroid nodules in an endemic goiter area. J Nucl Med 1997; 38:62–65.PubMedGoogle Scholar
  36. 36.
    Hirschowitz SL, Mandell D, Nieberg R, Carson K. The alcohol-fixed Diff-Quick stain. A novel rapid stain for the immediate interpretation of fine needle aspiration specimens. Acta Cytol 1994; 38:499–501.PubMedGoogle Scholar
  37. 37.
    Mair S, Lash RH, Suskin D, Mendelsohn G. Intraoperative surgical specimen evaluation: frozen section analysis, cytologic examination, or both? Am J Clin Pathol 1991; 96:8–14.PubMedGoogle Scholar
  38. 38.
    Brooks AD, Shaha AR, DuMornay W, et al. Role of fine-needle aspiration biopsy and frozen section analysis in surgical management of thyroid tumors. Ann Surg Oncol 2001; 8:92–100.CrossRefPubMedGoogle Scholar
  39. 39.
    Passler C, Prager M, Scheuba C, Kaserer K, Flores JA, Vierhapper H, Niederle B. The value of fine-needle aspiration biopsy (FNAB) in the differential diagnosis of the “cold” thyroid nodule. Wien Klin Wochenschr 1999; 111:240–245.PubMedGoogle Scholar
  40. 40.
    Boyd LA, Earnhardt RC, Dunn JT, Frierson HF, Hanks JB. Preoperative evaluation and predictive value of fine-needle aspiration and frozen section of thyroid nodules. J Am Coll Surg 1998; 187:494-502.CrossRefPubMedGoogle Scholar
  41. 41.
    Giuffrida D, Gharib H. Controversies in the management of cold, hot, and occult thyroid nodules. Am J Med 1995; 99:642–650.CrossRefPubMedGoogle Scholar
  42. 42.
    Koray D, Özlem K, Cem Y, Hakan Ö, Göksun A, Ferit T. A comparison of radionuclide thyroid angiography,99mTc-MIBI scintigraphy and power Doppler ultrasonography in the differential diagnosis of solitary cold thyroid nodules. Eur J Nucl Med 2003; 30:642–650.Google Scholar
  43. 43.
    McHenry CR, Walfish PG, Rosen IB. Non-diagnostic fine needle aspiration biopsy: a dilemma in management of nodular thyroid disease. Am Surg 1995; 59:415–419.Google Scholar
  44. 44.
    Chow LS, Gharib H, Goellner JR, Van Heerden JA. Nondiagnostic thyroid fine-needle aspiration cytology: management dilemmas. Thyroid 2001; 11:1147–1151.CrossRefPubMedGoogle Scholar
  45. 45.
    Abbas G, Heller KS, Khoynezhad A, Dubner S, Sznyter LA. The incidence of carcinoma in cytologically benign thyroid cysts. Surgery 2001; 130:1035–1038.CrossRefPubMedGoogle Scholar
  46. 46.
    Zaldivar-Ramírez FR, López-López JA, Hurtado-López LM. Nódulo tiroideo: Frecuencia de malignidad. Cir Gen 2001; 23:92–94.Google Scholar
  47. 47.
    Nódulo tiroideo. Consenso 2001. Cir Gen 2002; 24:76–83.–1/im-cg021m.htm.Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Luis Mauricio Hurtado-López
    • 1
  • Sara Arellano-Montaño
    • 1
  • Evelyn Migdalia Torres-Acosta
    • 1
  • Felipe Rafael Zaldivar-Ramirez
    • 1
  • Reyna Margarita Duarte-Torres
    • 1
  • Patricia Alonso-de-Ruiz
    • 1
  • Iván Martínez-Duncker
    • 1
  • Carlos Martínez-Duncker
    • 1
    • 2
    Email author
  1. 1.Thyroid ClinicGeneral Hospital of MexicoMéxico CityMéxico
  2. 2.Molecular Nuclear MedicineHospital Infantil de México “Federico Gómez”México México

Personalised recommendations