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Malignancy Rate of Thyroid Nodules Defined as Follicular Lesion of Undetermined Significance and Atypia of Undetermined Significance in Thyroid Cytopathology and Its Relation with Ultrasonographic Features

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Abstract

Fine-needle aspiration biopsy (FNAB) has been widely accepted as the most accurate, safe, and cost-effective method for evaluation of thyroid nodules. The most challenging category in FNAB is atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS). The Bethesda system (BS) recommends repeat FNAB in that category due to its low risk of malignancy. In our study, we aimed to investigate the malignancy rate of thyroid nodules of AUS and FLUS and whether there were different malignancy rates among the different patterns in this category, and to evaluate the presence of biochemical, clinical, and echographic features possibly predictive of malignancy related to AUS and FLUS. Data of 268 patients operated for AUS and FLUS cytology were screened retrospectively. Ultrasonographic features and thyroid function tests, thyroid antibodies, scintigraphy, and histopathological results were evaluated. Of the 268 patients’ results, 276 nodules are evaluated. Malignancy rates were 24.3 % in the AUS group, 19.8 % in the FLUS group, and 22.8 % in both groups. In the evaluation of all nodules, the predictive features of malignancy are hypoechogenicity and peripheral vascularization of the nodule. We determined that the malignancy rates in these nodules are higher than that in the literature rate. This high ratio may be due to the fact that we studied only patients who underwent surgery. The ultrasonographic features alone may be insufficient to predict the malignancy; therefore, all the clinical and ultrasonographic features must be considered in the evaluation of the thyroid nodules. In addition, we think that the recommended management of repeat FNAB in these groups must be reconsidered with the clinical and ultrasonographic features.

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References

  1. Cakir B, Aydin C, Korukluoğlu B, Ozdemir D, Sisman IC, Tüzün D, Oguz A, Güler G, Güney G, Kuşdemir A, Sanisoglu SY, Ersoy R (2011) Diagnostic value of elastosonographically determined strain index in the differential diagnosis of benign and malignant thyroid nodules. Endocrine 39:89–98

    Article  PubMed  CAS  Google Scholar 

  2. Rago T, Scutari M, Santini F, Loiacono V, Piaggi P, Di Coscio G, Basolo F, Berti P, Pinchera A, Vitti P (2010) Real-time elastosonography: useful tool for refining the presurgical diagnosis in thyroid nodules with indeterminate or nondiagnostic cytology. J Clin Endocrinol Metab 95:5274–5280

    Article  PubMed  CAS  Google Scholar 

  3. Moon WJ, Baek JH, Jung SL, Kim DW, Kim EK et al (2011) Ultrasonography and the ultrasound-based management of thyroid nodules: consensus statement and recommendations. Korean J Radiol 12:1–14

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  Google Scholar 

  5. Carrillo JF, Frias-Mendivil M, Ochoa-Carrillo FJ, Ibarra M (2000) Accuracy of fine-needle aspiration biopsy of the thyroid combined with an evaluation of clinical and radiologic factors. Otolaryngol Head Neck Surg 122:917–921

    Article  PubMed  CAS  Google Scholar 

  6. 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  PubMed  CAS  PubMed Central  Google Scholar 

  7. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167–1214

    Article  PubMed  Google Scholar 

  8. Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedüs L, Vitti P (2010) 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. Endocr Pract 16:468–475

    Article  PubMed  Google Scholar 

  9. Schlumberger MJ, Filetti S, Hay ID (2011) Nontoxic diffuse and nodular goiter and thyroid neoplasia. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR. Williams textbook of endocrinology. 11nd ed. Saunders Elsevier, pp 412–417.

  10. Frates MC, Benson CB, Charboneau JW, Cibas ES, Clark OH, Coleman BG, Cronan JJ, Doubilet PM, Evans DB, Goellner JR, Hay ID, Hertzberg BS, Intenzo CM, Jeffrey RB, Langer JE, Larsen PR, Mandel SJ, Middleton WD, Reading CC, Sherman SI, Tessler FN (2006) Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Ultrasound Q 22:231–238

    Article  PubMed  Google Scholar 

  11. Bongiovanni M, Krane JF, Cibas ES, Faquin WC (2012) The atypical thyroid fine-needle aspiration: past, present, and future. Cancer Cytopathol 120:73–86

    Article  PubMed  Google Scholar 

  12. Baloch ZW, Cibas ES, Clark DP, Layfield LJ, Ljung BM, Pitman MB, Abati A (2008) The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation. Cytojournal 5(6):1–17

    Article  PubMed  PubMed Central  Google Scholar 

  13. Jo VY, Stelow EB, Dustin SM, Hanley KZ (2010) Malignancy risk for fine-needle aspiration of thyroid lesions according to the Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol 134:450–456

    Article  PubMed  Google Scholar 

  14. Cibas ES, Ali SZ (2009) The Bethesda System for Reporting Thyroid Cytopathology. Thyroid 19:1159–1165

    Article  PubMed  Google Scholar 

  15. Faquin WC (2009) Diagnosis and reporting of follicular-patterned thyroid lesions by fine needle aspiration. Head Neck Pathol 3:82–85

    Article  PubMed  PubMed Central  Google Scholar 

  16. Broome JT, Solorzano CC (2011) The impact of atypia/follicular lesion of undetermined significance on the rate of malignancy in thyroid fine-needle aspiration: evaluation of the Bethesda System for Reporting Thyroid Cytopathology. Surgery 150:1234–1241

    Article  PubMed  Google Scholar 

  17. Jadhav S, Lila A, Bandgar T, Shah N (2012) Promise and pitfalls of molecular markers of thyroid nodules. Indian J Endocrinol Metab 16:162–166

    Google Scholar 

  18. Teixeira GV, Chikota H, Teixeira T, Manfro G, Pai SI, Tufano RP (2012) Incidence of malignancy in thyroid nodules determined to be follicular lesions of undetermined significance on fine-needle aspiration. World J Surg 36:69–74

    Article  PubMed  Google Scholar 

  19. Filie AC, Asa SL, Geisinger KR, Logani S, Merino M, Nikiforov YE, Clark DP (2008) Utilization of ancillary studies in thyroid fine needle aspirates: a synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. Diagn Cytopathol 36:438–441

    Article  PubMed  Google Scholar 

  20. Fadda G, Rossi ED, Raffaelli M, Pontecorvi A, Sioletic S, Morassi F, Lombardi CP, Zannoni GF, Rindi G (2011) 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

    Article  PubMed  CAS  Google Scholar 

  21. Cochand-Priollet B, Dahan H, Laloi-Michelin M, Polivka M, Saada M, Herman P, Guillausseau PJ, Hamzi L, Poté N, Sarfati E, Wassef M, Combe H, Raulic-Raimond D, Chedin P, Medeau V, Casanova D, Kania R (2011) Immunocytochemistry with cytokeratin 19 and anti-human mesothelial cell antibody (HBME1) increases the diagnostic accuracy of thyroid fine-needle aspirations: preliminary report of 150 liquid-based fine-needle aspirations with histological control. Thyroid 21:1067–1073

    Article  PubMed  CAS  Google Scholar 

  22. Luu MH, Fischer AH, Stockl TJ, Pisharodi L, Owens CL (2011) Atypical follicular cells with equivocal features of papillary thyroid carcinoma is not a low-risk cytologic diagnosis. Acta Cytol 55(6):526–530

    Article  PubMed  Google Scholar 

  23. Renshaw AA (2010) Should "atypical follicular cells" in thyroid fine-needle aspirates be subclassified? Cancer Cytopathol 118:186–189

    Article  PubMed  Google Scholar 

  24. Olson MT, Clark DP, Erozan YS, Ali SZ (2011) Spectrum of risk of malignancy in subcategories of 'atypia of undetermined significance'. Acta Cytol 55:518–525

    Article  PubMed  Google Scholar 

  25. Renshaw AA (2011) Subclassification of atypical cells of undetermined significance in direct smears of fine-needle aspirations of the thyroid: distinct patterns and associated risk of malignancy. Cancer Cytopathol 119:322–327

    Article  PubMed  Google Scholar 

  26. DeLellis RA, Williams ED (2004) Thyroid and parathyroid tumors. In: DeLellis RA, Lloyd R, Heitz PU, Eng C (eds) WHO classification of tumors, pathology and genetics—tumors of endocrine organs. France, IARC Press, Lyon, pp 49–97

    Google Scholar 

  27. Dincer N, Balci S, Yazgan A, Guney G, Ersoy R, Cakir B, Guler G (2013) Follow-up of atypia and follicular lesions of undetermined significance in thyroid fine needle aspiration cytology. Cytopathology 24:385–390

    Article  PubMed  CAS  Google Scholar 

  28. VanderLaan PA, Marqusee E, Krane JF (2011) Clinical Outcome for atypia of undetermined significance in thyroid fine-needle aspirations: should repeated fna be the preferred initial approach? Am J Clin Pathol 135:770–775

    Article  PubMed  Google Scholar 

  29. Singh RS, Wang HH (2011) Eliminating the "Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance" category from the Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol 136:896–902

    Article  PubMed  Google Scholar 

  30. Rago T, Di Coscio G, Basolo F, Scutari M, Elisci R, Berti P, Miccoli P, Romani R, Faviana P, Pinchera A, Vitti P (2007) Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hurthle cell thyroid lesions: results from a series of 505 consecutive patients. Clin Endocrinol (Oxf) 66:13–20

    CAS  Google Scholar 

  31. Bonzanini M, Amadori P, Morelli L, Fasanella S, Pertile R, Mattiuzzi A, Marini G, Niccolini M, Tirone G, Rigamonti M, Dalla Palma P (2011) Subclassification of the "grey zone" of thyroid cytology; a retrospective descriptive study with clinical, cytological, and histological correlation. J Thyroid Res 2011:251680

    Article  PubMed  PubMed Central  Google Scholar 

  32. Nayar R, Ivanovic M (2009) The indeterminate thyroid fine-needle aspiration: experience from an academic center using terminology similar to that proposed in the 2007 National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. Cancer 117:195–202

    PubMed  Google Scholar 

  33. Yassa L, Cibas ES, Benson CB, Frates MC, Doubilet PM, Gawande AA, Moore FD Jr, Kim BW, Nosé V, Marqusee E, Larsen PR, Alexander EK (2007) Long-term assessment of a multidisciplinary approach to thyroid nodule diagnostic evaluation. Cancer 11:508–516

    Article  Google Scholar 

  34. Yang J, Schnadig V, Logrono R, Wasserman PG (2007) Fine-needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations. Cancer 111:306–315

    Article  PubMed  Google Scholar 

  35. Theoharis CG, Schofield KM, Hammers L, Udelsman R, Chhieng DC (2009) The Bethesda thyroid fine-needle aspiration classification system: year 1 at an academic institution. Thyroid 19:1215–1223

    Article  PubMed  Google Scholar 

  36. Layfield LJ, Morton MJ, Cramer HM et al (2009) Implications of the proposed thyroid fine-needle aspiration category of ‘follicular lesion of undetermined significance’: a five year multi-institutional analysis. Diagn Cytopathol 37:710–714

    Article  PubMed  Google Scholar 

  37. Rabaglia JL, Kabbani W, Wallace L et al (2010) Effect of the Bethesda system for reporting thyroid cytopathology on thyroidectomy rates and malignancy risk in cytologically indeterminate lesions. Surgery 148:1267–1272

    Article  PubMed  Google Scholar 

  38. Faquin WC, Baloch ZW (2010) Fine-needle aspiration of follicular patterned lesions of the thyroid: Diagnosis, management, and follow-up according to National Cancer Institute (NCI) recommendations. Diagn Cytopathol 38:731–739

    PubMed  Google Scholar 

  39. Onder S, Firat P, Ates D (2013) The Bethesda system for reporting thyroid cytopathology: an institutional experience of the outcome of indeterminate categories. Cytopathology Sep 2. doi:10.1111/cyt.12091

  40. Choi YJ, Baek JH, Ha EJ, Lim HK, Lee JH, Kim JK, Song DE, Shong Y, Hong SJ (2013) 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 Aug 15. doi:10.1089/thy.2012.0635

  41. Horne MJ, Chhieng DC, Theoharis C, Schofield K, Kowalski D, Prasad ML, Hammers L, Udelsman R, Adeniran AJ (2012) Thyroid follicular lesion of undetermined significance: Evaluation of the risk of malignancy using the two-tier sub-classification. Diagn Cytopathol 40:410–415

    Article  PubMed  Google Scholar 

  42. Ozluk Y, Pehlivan E, Gulluoglu MG, Poyanlı A, Salmaslioglu A, Colak N et al (2011) The use of the Bethesda Terminology in thyroid fine-needle aspiration results in a lower rate of surgery for nonmalignant nodules: A report from a reference center in Turkey. Int J Surg Pathol 19:761–771

    Article  PubMed  Google Scholar 

  43. Tee YY, Lowe AJ, Brand CA, Judson RT (2007) Fine-needle aspiration may miss a third of all malignancy in palpable thyroid nodules: a comprehensive literature review. Ann Surg Nov 246:714–720

    Article  Google Scholar 

  44. Baloch ZW, Hendreen S, Gupta PK, LiVolsi VA, Mandel SJ, Weber R, Fraker D (2011) Interinstitutional review of thyroid fine-needle aspirations: impact on clinical management of thyroid nodules. Diagn Cytopathol 25:231–234

    Article  Google Scholar 

  45. Tan GH, Gharib H (1997) Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med 126:226–231

    Article  PubMed  CAS  Google Scholar 

  46. Cheung K, Roman SA, Wang TS, Walker HD, Sosa JA (2008) Calcitonin measurement in the evaluation of thyroid nodules in the United States: a cost-effectiveness and decision analysis. J Clin Endocrinol Metab 93:2173–2180

    Article  PubMed  CAS  Google Scholar 

  47. Erdoğan MF, Güllü S, Başkal N, Uysal AR, Kamel N, Erdoğan G (1997) Omeprazole: calcitonin stimulation test for the diagnosis follow-up and family screening in medullary thyroid carcinoma. J Clin Endocrinol Metab 82:897–899

    Article  PubMed  Google Scholar 

  48. Costante G, Meringolo D, Durante C, Bianchi D, Nocera M, Tumino S, Crocetti U, Attard M, Maranghi M, Torlontano M, Filetti S (2007) Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. J Clin Endocrinol Metab 92:450–455

    Article  PubMed  CAS  Google Scholar 

  49. Karges W, Dralle H, Raue F, Mann K, Reiners C, Grussendorf M, Hüfner M, Niederle B, Brabant G (2004) German Society for Endocrinology (DGE) - Thyroid Section. Calcitonin measurement to detect medullary thyroid carcinoma in nodular goiter: German evidence-based consensus recommendation. Exp Clin Endocrinol Diabetes 112:52–58

    Article  PubMed  CAS  Google Scholar 

  50. Baskin HJ (2000) Ultrasound of thyroid nodules. In: Baskin HJ (ed) Thyroid Ultrasound and Ultrasound-Guided FNA Biopsy. Kluwer Academic Publishers, Boston, MA, pp 71–86

    Chapter  Google Scholar 

  51. Deveci MS, Deveci G, LiVolsi VA, Baloch ZW (2006) Fine-needle aspiration of follicular lesions of the thyroid. Diagnosis and follow-up. Cytojournal 3:1–6

    Article  Google Scholar 

  52. Choi YJ, Yun JS, Kim DH (2009) Clinical and ultrasound features of cytology diagnosed follicular neoplasm. Endocrin J 56:383–389

    Article  Google Scholar 

  53. Banks ND, Kowalski J, Tsai HL, Somervell H, Tufano R, Dackiw AP, Marohn MR, Clark DP, Umbricht CB, Zeiger MA (2008) A diagnostic predictor model for indeterminate or suspicious thyroid FNA samples. Thyroid 18:933–941

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Neslihan Çuhaci.

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Malignancy rate of thyroid nodules in thyroid cytopathology defined as follicular lesion of undetermined significance and atypia of undetermined significance.

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Çuhaci, N., Arpaci, D., Üçler, R. et al. Malignancy Rate of Thyroid Nodules Defined as Follicular Lesion of Undetermined Significance and Atypia of Undetermined Significance in Thyroid Cytopathology and Its Relation with Ultrasonographic Features. Endocr Pathol 25, 248–256 (2014). https://doi.org/10.1007/s12022-014-9298-7

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