Thyroid nodules with benign findings at cytologic examination: Results of long-term follow-up with US

Purpose: To investigate the natural history of thyroid nodules found to be benign at initial fine-needle aspiration biopsy (FNAB) to determine the percentage of nodules that increased in volume by more than 50% as being an indicator of malignancy. Materials and Methods: This retrospective observational cohort study was approved by the institutional review board, and the need to obtain informed consent was waived. The study included 854 FNAB-confirmed benign thyroid nodules. Suspicious ultrasonographic (US) features included marked hypoechogenicity, irregular or microlobulated margin, microcalcification, and taller-than-wide shape. Univariate and multivariate generalized linear mixed models were used to assess the association with nodule growth greater than 50% in volume. Results: For the 854 nodules, the initial mean diameter was 19.92 mm (range, 3.10-60.00 mm), and the initial mean volume was 3.19 cm³ (range, 0.01-4.64 cm³). The majority (682 [79.9%] of 854) of thyroid nodules with benign cytologic results at initial FNAB did not grow more than 50% in volume during 4 years of mean follow-up (range, 7-101 months). More than 4 years of follow-up time versus less than 2 years, younger age, a cystic component of less than 25%, and nodule size 1 cm or larger versus less than 1 cm were independently associated with growth. There was only one malignant nodule (0.6%) among 172 thyroid nodules with a volume increase of 50% or greater during the entire follow-up time. Ten malignant nodules (overall malignancy rate: 1.2%) were detected among the 854 total nodules, and eight of these 10 nodules showed suspicious features at US. Conclusion: Repeat FNAB for nodules showing more than 50% growth in volume is unlikely to result in a diagnosis of malignancy. A positive FNAB result for malignancy is significantly more likely in the presence of suspicious US features.