Large Cytologically Benign Thyroid Nodules Do Not Have High Rates of Malignancy or False-Negative Rates and Clinical Observation Should be Considered: A Meta-Analysis

Management of large thyroid nodules is controversial, as data are conflicting regarding overall rates of malignancy (ROM) in all nodules and frequency of false-negative fine-needle aspiration results (FNR) in cytologically benign nodules. This meta-analysis aimed to evaluate and compare ROM and FNR in small versus large nodules published in the literature. Methods: Articles indexed in PubMed, written in English, published electronically or in print on or prior to December 8 2017 were searched for "false negative thyroid size or cm" and "malignancy rates benign thyroid nodules." Three hundred fifty-two unique citations were identified. Multiple reviewers selected a final set of 35 articles that contained nodules stratified by size (3, 4, or 5 cm), with benign or all cytologic diagnoses, and with postsurgical histologic diagnoses. Multiple observers extracted data, including numbers of total, cytologically benign, and histologically malignant nodules. Size cutoffs of 3, 4, and/or 5 cm were analyzed in 14, 24, and 1 article, respectively. Results: ROM in all nodules ≥3 cm (13.1%) and ≥4 cm (20.9%) was lower than those <3 cm (19.6%) and <4 cm (19.9%; odds ratio [OR] = 0.72 [confidence interval (CI) 0.64-0.81] and OR = 0.85 [CI 0.77-0.95]). FNR in nodules ≥3 cm (7.2%) was not different from smaller nodules (5.7%; OR = 1.47 [CI 0.80-2.69]). FNR in nodules ≥4 cm (6.7%) was slightly higher than those <4 cm (4.5%; OR = 1.38 [CI 1.06-1.80]). The most frequently reported false-negative diagnosis was papillary thyroid carcinoma. Conclusions: Rates of malignancy and false-negative FNA results vary but, in most studies, are not higher in larger nodules. Patients with large, cytologically benign thyroid nodules need not undergo immediate surgical resection, as false-negative FNA rates are low and are expected to decrease in light of nomenclature revision of a subset of follicular variants of papillary thyroid carcinoma.