Introduction: The rates of atypia of undetermined significance (AUS) by fine-needle aspiration (FNA) and malignant outcomes have been estimated at < 7% and 5–15%, respectively. Initial AUS diagnosis is followed up clinically with serial ultrasounds, repeat FNA, molecular testing, or direct surgery. We investigated the incidence, follow-up modalities, and final outcomes of AUS in Newfoundland. Methods: All cases of AUS diagnosed at the Eastern Health Cytology Laboratory between 1 January 2010 and 31 December 2013 were identified. Electronic medical records were examined for follow-up modalities and final histologic diagnosis. The final outcomes were reported as benign, malignant, or undetermined. Results: Out of 3,285 thyroid FNAs, 181 (5.5%) were AUS. Fifty-seven (31.5%) had repeat FNA diagnosed as benign (38.6%), AUS (29.8%), or suspicious/malignant (8.8%). Eighty-four (46.4%) had surgery after the first AUS diagnosis, 39 (46.4%) of which were malignant. Twenty-four patients (13.3%) were followed up by serial ultrasound only, 2 (1.1%) by molecular testing, and 1 (0.6%) died of unrelated disease. Thirteen (7.2%) had no follow-up record. Our malignancy rate (MR) was 29.8%. Conclusion: The MR in our population was higher than the rate proposed by The Bethesda System for Reporting Thyroid Cytopathology. Repeat FNA can reduce the rate of unnecessary surgeries, but practice guidelines should consider individual and institutional circumstances. The ratio MR:ADR (AUS diagnostic rate) may be a better indicator of performance.

Cibas ES, Ali SZ: The Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol 2009; 132: 658–665.
Layfield LJ, Morton MJ, Cramer HM: Implications of the proposed thyroid fine-needle aspiration category of “follicular lesion of undetermined significance:” a five-year multi-institutional analysis. Diagn Cytopathol 2009; 37: 710–714.
Nayar R, Ivanovic M: 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 Cytopathol 2009; 117: 195–202.
Ozluk Y, Pehlivan E, Gulluoglu MG: 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 2011; 19: 761–771.
Theoharis CG, Schofield KM, Hammers L, et al: The Bethesda thyroid fine-needle aspiration classification system: year 1 at an academic institution. Thyroid 2009; 19: 1215–1223.
Shi Y, Ding X, Klein M, et al: Thyroid fine-needle aspiration with atypia of undetermined significance: a necessary or optional category? Cancer Cytopathol 2009; 117: 298–304.
Renshaw AA: Should “atypical follicular cells” in thyroid fine-needle aspirates be subclassified? Cancer Cytopathol 2010; 118: 186–189.
Jo VY, Stelow EB, Dustin SM, et al: Malignancy risk for fine-needle aspiration of thyroid lesions according to The Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol 2010; 134: 450–456.
Ho AS, Sarti EE, et al: Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS). Thyroid 2014; 24: 832–839.
Harvey AM, Mody DR, Amrikachi M: Thyroid fine needle aspiration reporting rates and outcomes before and after Bethesda implementation within a combined academic and community hospital system. Arch Pathol Lab Med 2013; 137: 1664–1668.
Mondal SK, Sinha S, Basak B, Roy DN, Sinha SK: The Bethesda System for reporting thyroid fine needle aspirates: a cytologic study with histologic follow-up. J Cytol 2013; 30: 94–99.
VanderLaan PA, Marqusee E, Krane JF: Clinical outcome for atypia of undetermined significance in thyroid fine needle aspirations. Should repeated FNA be the preferred initial approach? Am J Clin Pathol 2011; 135: 770–775.
Akhtar I, Liu X, et al: Understanding the management and clinical follow-up of “atypia of undetermined significance/follicular lesion of undetermined significance” (AUS/FLUS) category in thyroid FNA: a retrospective study in a tertiary care center. J Am Soc Cytopathol 2013; 2:S47.
Iskandar MZ, Bonomo G, Avadhani V: Evidence for overestimation of the prevalence of malignancy in indeterminate thyroid nodules classified as Bethesda category III. Surgery 2015; 157: 510–517.
Layfield LJ, Abrams J, Cochand-Priollet B, et al: Post-thyroid FNA testing and treatment options: a synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008; 36: 442–448.
Baloch ZW, Alexander EK, Gharib H, Raab SS: Overview of diagnostic terminology and reporting; in Ali AS, Cibas ES (eds): The Bethesda System for Reporting Thyroid Cytopathology: Definitions, Criteria and Explanatory Notes. New York, Springer, 2010.
Kamran SC, Marqusee E, et al: Thyroid nodule size and prediction of cancer. J Clin Endocrinol Metab 2013; 98: 564–570.
Moon WJ, Jung SL, Lee JH, et al; Thyroid Study Group, Korean Society of Neuro- and Head and Neck Radiology: Benign and malignant thyroid nodules: US differentiation – multicenter retrospective study. Radiology 2008; 247: 762–770.
Kuma K, Matsuzuka F, Yokozawa T, Miyauchi A, Sugawara M: Outcome of long-standing solitary thyroid nodules. World J Surg 1992; 16: 583–587.
Asanuma K, Kobayashi S, Shingu K, et al: The rate of tumor growth does not distinguish between malignant and benign thyroid nodules. Eur J Surg 2001; 167: 102–105.
Hung W, Anderson KD, Chandra RS, et al: Solitary thyroid nodules in 71 children and adolescents. J Pediatr Surg 1992; 27: 1407–1409.
Boelaert K, Horacek J, Holder RL, Watkinson JC, Sheppard MC, Franklyn JA: Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab 2006; 91: 4295–4301.
Frates MC, Benson CB, Doubilet PM, et al: Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography. J Clin Endocrinol Metab 2006; 91: 3411–3417.
Witt BL, Schmidt RL: Rapid onsite evaluation improves the adequacy of fine-needle aspiration for thyroid lesions: a systematic review and meta-analysis Thyroid 2013; 23: 428–435.
Witt B, Layfield L, Schmidt R: Impact of rapid on-site evaluation (ROSE) on the adequacy of fine needle aspiration cytology (FNAC) for thyroid lesions: a systematic review and meta-analysis. J Am Soc Cytopathol, 2012; 1:S67–S68.
Krane JF, VanderLaan PA, Faquin WC, Renshaw AA: The atypia of undetermined significance/follicular lesion of undetermined significance: malignant ratio. A proposed performance measure for reporting in The Bethesda System for Thyroid Cytopathology. Cancer Cytopathol 2012; 120: 111–116.
Fazeli R, Schneider EB, Ali SZ, Zeiger MA, Olson MT: Diagnostic frequency ratios are insufficient to measure laboratory precision with The Bethesda System for Reporting Thyroid Cytopathology. Acta Cytol 2015; 59: 225–232.
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