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Thyroid Nodules >4cm With Atypia Of Undetermined Significance Cytology Independently Associate With Malignant Pathology
*Caroline Lynch, *Mridula Bethi, Tammy M Holm
University of Cincinnati, Cincinnati, OH

Objective: The risk of malignancy from nodules with atypia of undetermined significance (AUS) cytology is estimated between 5-15% though more recent studies suggest rates upwards of 48%. This study sought to characterize pre-operative predictors of malignancy to aid in clinical decision makingMethods: We performed a single institution retrospective review of all adult patients with unilateral thyroid nodules demonstrating AUS cytology between March 1, 2013-June 1, 2019 who underwent surgical resection (n=266). Univariate and multivariate logistical analysis was performed using clinical and demographic variables to identify potential pre-operative characteristics associated with malignant disease.Results: Malignancy was identified on final pathology in 24.7% of patients with AUS cytology. Age, gender, exposure to ionizing radiation, family history of thyroid cancer, Hashimoto’s disease, Afirma suspicious results, and smoking were not associated with malignancy on both univariate and multivariate analysis. Nodule size >4cm independently associated with malignancy risk on both univariate (OR 2.44, 1.09-5.43, p<0.03) and multivariate (OR 2.96, 1.27-6.87, p<0.02) analysis. Conclusion: The results of this study demonstrate that nodules with AUS cytology >4cm are strongly associated with malignancy. We recommend strong consideration of surgery for all patients with thyroid nodules >4cm and AUS cytology.
Table 1. Characteristics of patients undergoing thyroid surgery for nodule with AUS

All patients(N=266)
Age, mean in years, (SD)53.3 (14.0)
Asian/Pacific Islander3.9%
African American19.1%
Native American0.4%
Risk factors
History of Hashimoto’s thyroiditis21.9%
History of ionizing radiation11.3%
Family history of thyroid cancer8.6%
Pre-operative characteristics
Size of nodule, mean in cm (SD)2.7 (1.2)
Nodule > 4cm, %11.3%

Needing Levothyroxine15.2%
Afirma testing22.7%
Afirma suspicious (of tested)82.8%
Post-operative pathology
Follicular adenoma8.6%
Hurthle cell adenoma2.7%
Other benign61.7%
Classic papillary thyroid cancer6.6%
Follicular variant papillary thyroid cancer12.1%
Follicular thyroid cancer1.2%
Hurthle cell cancer0.4%
Other malignant4.3%

Table 2. Characteristics associated with presence of thyroid cancer1 on surgical pathology
Univariate analysisMultivariable analysis
Odds ratio(95% CI)P valueOdds ratio(95% CI)P value
Age0.99(0.97 – 1.01)0.2090.505
Gender0.86(0.44 – 1.69)0.6690.952
Non-white0.74(0.37 – 1.48)0.4000.362
Smoking0.94(0.52 – 1.71)0.8460.813
History of Hashimoto’s1.63(0.85 – 3.13)0.1411.76(0.90 – 3.45)0.100
History of ionizing radiation0.46(0.15 – 1.36)0.1600.362
Family history of thyroid cancer0.89(0.32 – 2.53)0.8300.614
Nodule > 4cm2.44(1.09 – 5.43)0.0302.96(1.27 – 6.87)0.016
Surgeon1.85(0.88 – 3.92)0.1062.06(0.95 – 4.48)0.068
Pre-operative levothyroxine0.91(0.40 – 2.03)0.8090.330
Afirma suspicious1.03(0.50 – 2.12)0.9440.746

1Thyroid cancer = classic papillary thyroid cancer, follicular variant papillary thyroid cancer, follicular thyroid cancer, Hurthle cell cancer, other malignant

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