Original Investigation
December 2015

Association of Thyroid Nodule Size and Bethesda Class With Rate of Malignant Disease

Author Affiliations
  • 1Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey
  • 2Department of Public Health Sciences, The Pennsylvania State University, College of Medicine, Hershey
  • 3Department of Pathology, The Pennsylvania State University, College of Medicine, Hershey

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JAMA Otolaryngol Head Neck Surg. 2015;141(12):1089-1095. doi:10.1001/jamaoto.2015.1451

Importance  The ability to accurately stratify patients with thyroid nodules (TNs) preoperatively is imperative because most TNs are benign. The reliability of fine-needle aspiration biopsy (FNAB) in large TNs has been questioned in recent literature.

Objective  To determine whether TN size affects the reliability of FNAB results, and to determine the rates of malignant disease of each Bethesda class at Penn State Medical Center.

Design, Setting, and Participants  Retrospective electronic medical record review of patients undergoing FNAB followed by thyroidectomy from March 2010 through December 2013 at an academic, tertiary referral center. A total of 297 patients with 326 TNs were identified as part of a consecutive series.

Main Outcomes and Measures  The primary outcome was to determine the rate of malignant disease of TNs smaller than 3.0 cm or 3.0 cm or larger and of each Bethesda class. Statistical analysis included χ2 tests. The secondary outcome was to develop logistic regression models to estimate the probability of malignant disease on final pathologic diagnosis as predicted by TN size as well as TN size in conjunction with Bethesda class.

Results  Of the 297 patients, 233 were female (78.4%). The mean (SD) age was 51.0 (15.4) years. Of the 326 TNs, 143 were malignant on surgical histopathologic analysis (43.7%). The mean TN size was 2.0 (1.4) cm. Rates of malignant disease for Bethesda classes 1 to 6 were 0% (95% CI, 0%-26.0%), 6.0% (95% CI, 1.7%-14.6%), 30.2% (95% CI, 18.3%-44.3%), 23.5% (95% CI, 14.8%-34.2%), 72.4% (95% CI, 52.8%-87.3%), and 98.8% (95% CI, 93.5%-99.9%), respectively. Overall sensitivity and specificity (excluding class 1 TNs) were 97.2% and 36.8%, respectively. The false-negative rate of benign cytologic results was 6.0% (95% CI, 1.7%-14.6%); only 1 false-negative result occurred in TNs 3.0 cm or greater. Of the TNs smaller than 3.0 cm, 48.4% were malignant compared with 33.3% of TNs 3.0 cm or greater (P = .049). Both Bethesda class and TN size were significant variables (P < .05) within our logistic regression models indicating that higher Bethesda class and TN size smaller than about 2.0 cm were associated with increased probabilities of malignant disease.

Conclusions and Relevance  Our results suggest that smaller TNs (smaller than about 2.0 cm) are associated with increased probabilities of malignant disease irrespective of Bethesda class. Routine diagnostic thyroid lobectomy solely owing to TN size of 3.0 cm or greater need not be performed.