The role of fine-needle aspiration biopsy and post-operative histology in the evaluation of thyroid nodules




thyroid nodules, fine-needle aspiration biopsy, post-operative cytology, Bethesda classification, review


Thyroid nodules present a serious problem, and mostly they do not carry neoplastic characteristics. Thus, they do not need to be surgically treated. The risk of malignancy varies from 5 to 15 %. Steps to diagnose malignancy should include a careful clinical evaluation, laboratory tests, a thyroid ultrasound exam and a fine-needle aspiration biopsy. Fine-needle aspiration biopsy (FNAB) is the most important diagnostic tool in the assessment of thyroid nodules. Today it is considered the gold standard for malignancy diagnosis in thyroid cancer. In this review we evaluate the role of FNAB and post-operative cytology in the evaluation of thyroid nodules. FNA results are classified as diagnostic (satisfactory) or nondiagnostic (unsatisfactory). Unsatisfactory smears (5–10 %) result from hypocellular specimens usually caused by cystic fluid, bloody smears, or suboptimal preparation. Diagnostic smears are conventionally subclassified into benign, indeterminate, or malignant categories. Benign cytology (60–70 %) is negative for malignancy, and includes cysts, colloid nodule, or Hashimoto thyroiditis. Malignant cytology (5 %) is almost always positive for malignancy, and includes primary thyroid tumors or nonthyroid metastatic cancers. Indeterminate or suspicious specimens (10–20 %) include atypical changes, Hurthle cells or follicular neoplasms. The new Bethesda Cytologic Classification has a 6-category classification, subdividing indeterminate further by risk factors. Considering the increasing worldwide incidence of thyroid microadenomas, recently it is recommended to undergo FNAB under ultrasound guidance even in small (< 1cm) nodules if they are correlated with suspicious ultrasonographic features or suspicious neck lymph nodes. FNAB is a cheap and reliable diagnostic tool that can be used in the selection candidates for surgery and pre-operative diagnosis of thyroid carcinomas. It was concluded that FNAB is the gold standard in the evaluation of thyroid nodules and can prevent many unnecessary surgeries. False-negative FNA cytology remains a concern for clinicians treating patients with thyroid nodules. Post-operative histology give the definitive diagnosis and studies confirm that it has a significant discordance between pre-operative cytology and post-operative histology in patients with thyroid nodule. Cytopathologists should strengthen their criteria for the identification of adenomatous hyperplasia, thyroiditis, cystic lesions or suspicious thyroid nodules to avoid misdiagnoses.


Download data is not yet available.


Kavanagh J, McVeigh N, McCarthy E, Bennett K, Beddy P. Ultrasound-guided fine needle aspiration of thyroid nodules: factors affecting diagnostic outcomes and confounding variables. Acta Radiol. 2017;58(3):301-306. doi: 10.1177/0284185116654331.

Varshney R, Forest VI, Zawawi F, Rochon L, Hier MP, Mlynarek A, et al. Ultrasound-guided fine-needle aspiration of thyroid nodules: does size matter? Am J Otolaryngol. 2014;35(3):373-6. doi: 10.1016/j.amjoto.2013.12.005.

Wong R, Farrell SG, Grossmann M. Thyroid nodules: diagnosis and management. Med J Aust. 2018;209(2):92-98. doi: 10.5694/mja17.01204.

Durante C, Grani G, Lamartina L, Filetti S, Mandel SJ, Cooper DS. The Diagnosis and Management of Thyroid Nodules: A Review. JAMA. 2018;319(9):914-924. doi: 10.1001/jama.2018.0898.

Singh Ospina N, Iñiguez-Ariza NM, Castro MR. Thyroid nodules: diagnostic evaluation based on thyroid cancer risk assessment. BMJ. 2020;368:I6670. doi: 10.1136/bmj.l6670.

Cordes M, Schmidkonz C, Horstrup K, Weppler M, Kuwert T. Fine-needle aspiration biopsies of thyroid nodules. Nuklearmedizin. 2018;57(6):211-215. doi: 10.3413/Nukmed-0981-18-06.

Jack GA, Sternberg SB, Aronson MD, Mukamal KJ, Oshin A, Hennessey JV. Nondiagnostic Fine-Needle Aspiration Biopsy of Thyroid Nodules: Outcomes and Determinants. Thyroid. 2020;30(7):992-998. doi: 10.1089/thy.2019.0140.

Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133. doi: 10.1089/thy.2015.0020.

Choe J, Baek JH, Park HS, Choi YJ, Lee JH. Core needle biopsy of thyroid nodules: outcomes and safety from a large single-center single-operator study. Acta Radiol. 2018;59(8):924-931. doi: 10.1177/0284185117741916.

Mais DD, Crothers BA, Davey DD, et al. Trends in Thyroid Fine-Needle Aspiration Cytology Practices: Results From a College of American Pathologists 2016 Practice Survey. Arch Pathol Lab Med. 2019;143(11):1364-1372. doi: 10.5858/arpa.2018-0429-CP.

Alvarado-Santiago M, Alvarez-Valentin D, Ruiz-Bermudez O, et al. Fine-Needle Thyroid Aspiration Biopsy: Clinical Experience at the Endocrinology Clinics of the University Hospital of Puerto Rico. P R Health Sci J. 2017;36(1):5-10.

Crothers BA, Darragh TM, Tambouret RH, et al. Trends in Cervical Cytology Screening and Reporting Practices: Results From the College of American Pathologists 2011 PAP Education Supplemental Questionnaire. Arch Pathol Lab Med. 2016;140(1):13-21. doi: 10.5858/arpa.2015-0004-CP.

Padmanabhan V, Barkan GA, Tabatabai L, Souers R, Nayar R, Crothers BA. Touch imprint (TI) cytology of needle core biopsies (NCB) in pathology laboratories: A practice survey of participants in the College of American Pathologists (CAP) Non Gynecologic Cytopathology (NGC) Education Program. Diagn Cytopathol. 2019;47(3):149-155. doi: 10.1002/dc.24023.

Gürkan Dumlu E, Kiyak G, et al. Correlation of thyroid fine-needle aspiration with final histopathology: a case series. Minerva Chir. 2013;68(2):191-7.

Ha SM, Kim JK, Baek JH. Detection of Malignancy Among Suspicious Thyroid Nodules <1 cm on Ultrasound with Various Thyroid Image Reporting and Data Systems. Thyroid. 2017;27(10):1307-1315. doi: 10.1089/thy.2017.0034.

Jackson BS. Controversy regarding when clinically suspicious thyroid nodules should be subjected to surgery: Review of current guidelines. Medicine (Baltimore). 2018;97(50):e13634. doi: 10.1097/MD.0000000000013634.

Cesur M, Corapcioglu D, Bulut S, et al. Comparison of palpation-guided fine-needle aspiration biopsy to ultrasound-guided fine-needle aspiration biopsy in the evaluation of thyroid nodules. Thyroid. 2006;16(6):555-61. doi: 10.1089/thy.2006.16.555.

Robitschek J, Straub M, Wirtz E, Klem C, Sniezek J. Diagnostic efficacy of surgeon-performed ultrasound-guided fine needle aspiration: a randomized controlled trial. Otolaryngol Head Neck Surg. 2010;142(3):306-9. doi: 10.1016/j.otohns.2009.11.011.

Giuffrida D, Gharib H. Controversies in the management of cold, hot, and occult thyroid nodules. Am J Med. 1995;99(6):642-50. doi: 10.1016/s0002-9343(99)80252-6.

Bakhos R, Selvaggi SM, DeJong S, et al. Fine-needle aspiration of the thyroid: rate and causes of cytohistopathologic discordance. Diagn Cytopathol. 2000;23(4):233-7. doi: 10.1002/1097-0339(200010)23:4<233::aid-dc3>;2-l.

Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytol. 2012;56(4):333-9. doi: 10.1159/000339959.

Gul K, Ersoy R, Dirikoc A, et al. Ultrasonographic evaluation of thyroid nodules: comparison of ultrasonographic, cytological, and histopathological findings. Endocrine. 2009;36(3):464-72. doi: 10.1007/s12020-009-9262-3.

Mekel M, Gilshtein H, Al-Kurd A, et al. Negative Fine-Needle Aspiration in Patients with Goiter: Should We Doubt It? World J Surg. 2016;40(1):124-8. doi: 10.1007/s00268-015-3216-0.

Wu HH, Jones JN, Osman J. Fine-needle aspiration cytology of the thyroid: ten years experience in a community teaching hospital. Diagn Cytopathol. 2006 Feb;34(2):93-6. doi: 10.1002/dc.20389.

Lee YH, Lee NJ, Kim JH, Suh SI, Kim TK, Song JJ. Sonographically guided fine needle aspiration of thyroid nodule: discrepancies between cytologic and histopathologic findings. J Clin Ultrasound. 2008 Jan;36(1):6-11. doi: 10.1002/jcu.20412.

Deng D, Chen X, Wang H, Wu H. Typical manifestations of Hürthle cell adenoma of the thyroid on contrast-enhanced CT: A case report. Medicine (Baltimore). 2019;98(22):e15866. doi: 10.1097/MD.0000000000015866.

Bohacek L, Milas M, Mitchell J, Siperstein A, Berber E. Diagnostic accuracy of surgeon-performed ultrasound-guided fine-needle aspiration of thyroid nodules. Ann Surg Oncol. 2012;19(1):45-51. doi: 10.1245/s10434-011-1807-z.

Lew JI, Snyder RA, Sanchez YM, Solorzano CC. Fine needle aspiration of the thyroid: correlation with final histopathology in a surgical series of 797 patients. J Am Coll Surg. 2011;213(1):188-94; discussion 194-5. doi: 10.1016/j.jamcollsurg.2011.04.029.

Richmond BK, Judhan R, Chong B, et al. False-negative results with the Bethesda System of reporting thyroid cytopathology: predictors of malignancy in thyroid nodules classified as benign by cytopathologic evaluation. Am Surg. 2014;80(8):811-6.

Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedüs L, Vitti P; AACE/AME/ETA Task Force on Thyroid Nodules. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: executive summary of recommendations. J Endocrinol Invest. 2010;33(5 Suppl):51-6.

Zhu Y, Song Y, Xu G, Fan Z, Ren W. Causes of misdiagnoses by thyroid fine-needle aspiration cytology (FNAC): our experience and a systematic review. Diagn Pathol. 2020 Jan 3;15(1):1. doi: 10.1186/s13000-019-0924-z.

McCoy KL, Jabbour N, Ogilvie JB, Ohori NP, Carty SE, Yim JM. The incidence of cancer and rate of false-negative cytology in thyroid nodules greater than or equal to 4 cm in size. Surgery. 2007;142(6):837–844.

Porterfield JR Jr, Grant CS, Dean DS, et al. Reliability of benign fine needle aspiration cytology of large thyroid nodules. Surgery. 2008;144(6):963-8; discussion 968-9. doi: 10.1016/j.surg.2008.09.006.

Agcaoglu O, Aksakal N, Ozcinar B, et al. Factors that affect the false-negative outcomes of fine-needle aspiration biopsy in thyroid nodules. Int J Endocrinol. 2013;2013:126084. doi: 10.1155/2013/126084.

Malheiros DC, Canberk S, Poller DN, Schmitt F. Thyroid FNAC: Causes of false-positive results. Cytopathology. 2018;29(5):407-417. doi: 10.1111/cyt.12575.

Erkinuresin T, Demirci H. Diagnostic accuracy of fine needle aspiration cytology of thyroid nodules. Diagnosis (Berl). 2020;7(1):61-66. doi: 10.1515/dx-2019-0039.

Dean DS, Gharib H. Fine-Needle Aspiration Biopsy of the Thyroid Gland. 2015 Apr 26. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA):, Inc.; 2000. PMID: 25905400.

Ogilvie JB, Piatigorsky EJ, Clark OH. Current status of fine needle aspiration for thyroid nodules. Adv Surg. 2006;40:223-38. doi: 10.1016/j.yasu.2006.06.003.

Banks ND, Kowalski J, Tsai HL, et al. A diagnostic predictor model for indeterminate or suspicious thyroid FNA samples. Thyroid. 2008;18(9):933-41. doi: 10.1089/thy.2008.0108.

Cibas ES, Ali SZ; NCI Thyroid FNA State of the Science Conference. The Bethesda System For Reporting Thyroid Cytopathology. Am J Clin Pathol. 2009 Nov;132(5):658-65. doi: 10.1309/AJCPPHLWMI3JV4LA.

Cibas ES, Sanchez MA. The National Cancer Institute thyroid fine-needle aspiration state-of-the-science conference: inspiration for a uniform terminology linked to management guidelines. Cancer. 2008;114(2):71-3. doi: 10.1002/cncr.23343.

Baloch ZW, Cibas ES, Clark DP, Layfield LJ, Ljung BM, Pitman MB, Abati A. The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation. Cytojournal. 2008;5:6. doi: 10.1186/1742-6413-5-6.

Hambleton C, Kandil E. Appropriate and accurate diagnosis of thyroid nodules: a review of thyroid fine-needle aspiration. Int J Clin Exp Med. 2013;6(6):413-22.

Elisei R, Molinaro E, Agate L, et al. Are the clinical and pathological features of differentiated thyroid carcinoma really changed over the last 35 years? Study on 4187 patients from a single Italian institution to answer this question. J Clin Endocrinol Metab. 2010;95(4):1516-27. doi: 10.1210/jc.2009-1536.

Ito Y, Miyauchi A, Inoue H, et al. An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg. 2010 Jan;34(1):28-35. doi: 10.1007/s00268-009-0303-0.

Mehanna R, Murphy M, McCarthy J, O'Leary G, Tuthill A, Murphy MS, Sheahan P. False negatives in thyroid cytology: impact of large nodule size and follicular variant of papillary carcinoma. Laryngoscope. 2013;123(5):1305-9. doi: 10.1002/lary.23861.

Pinchot SN, Al-Wagih H, Schaefer S, Sippel R, Chen H. Accuracy of fine-needle aspiration biopsy for predicting neoplasm or carcinoma in thyroid nodules 4 cm or larger. Arch Surg. 2009;144(7):649-55. doi: 10.1001/archsurg.2009.116.

Rosen JE, Stone MD. Contemporary diagnostic approach to the thyroid nodule. J Surg Oncol. 2006 Dec 15;94(8):649-61. doi: 10.1002/jso.20701.

Bilimoria KY, Bentrem DJ, Ko CY, et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg. 2007;246(3):375-81; doi: 10.1097/SLA.0b013e31814697d9.

Wang CC, Friedman L, Kennedy GC, et al. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid. 2011 Mar;21(3):243-51. doi: 10.1089/thy.2010.0243.

Bongiovanni M, Crippa S, Baloch Z, et al. Comparison of 5-tiered and 6-tiered diagnostic systems for the reporting of thyroid cytopathology: a multi-institutional study. Cancer Cytopathol. 2012;120(2):117-25. doi: 10.1002/cncy.20195.

Mufti ST, Molah R. The bethesda system for reporting thyroid cytopathology: a five-year retrospective review of one center experience. Int J Health Sci (Qassim). 2012 Jun;6(2):159-73. doi: 10.12816/0005991.




How to Cite

Xhardo, E., Xhemalaj, D., Agaçi, F., & Kapisyzi, P. (2022). The role of fine-needle aspiration biopsy and post-operative histology in the evaluation of thyroid nodules. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), 17(4), 315–321.



Literature Review