ArticleThe New England journal of medicine2012
Preoperative diagnosis of benign thyroid nodules with indeterminate cytology.
Article in The New England journal of medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 369 papers, 8 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized Trial Comparing Performance of Molecular Markers for Indeterminate Thyroid Nodules
Validation of a Multi-Genetic Test for the Diagnosis of Indeterminate Thyroid Nodules
Who cites it
369 citing papers in PubMed, 8 syntheses or guidelines pooled it, 1,154 citations in OpenAlex.
- Real-World Performance of the Afirma Genomic Sequencing Classifier (GSC)-A Meta-analysis.The Journal of clinical endocrinology and metabolism · 2023Pooled it
- Assessing Bias and Limitations of Clinical Validation Studies of Molecular Diagnostic Tests for Indeterminate Thyroid Nodules: Systematic Review and Meta-Analysis.Thyroid : official journal of the American Thyroid Association · 2022Pooled it
- Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis.Frontiers in endocrinology · 2021Pooled it
- Diagnostic reliability of elastography in thyroid nodules reported as indeterminate at prior fine-needle aspiration cytology (FNAC): a systematic review and Bayesian meta-analysis.European radiology · 2020Pooled it
- Pooled it
- Evaluation of 167 Gene Expression Classifier (GEC) and ThyroSeq v2 Diagnostic Accuracy in the Preoperative Assessment of Indeterminate Thyroid Nodules: Bivariate/HROC Meta-analysis.Endocrine pathology · 2019Pooled it
- Pooled it
- The Diagnostic Performance of Afirma Gene Expression Classifier for the Indeterminate Thyroid Nodules: A Meta-Analysis.BioMed research international · 2019Pooled it
- Bethesda III and IV Thyroid Nodules Managed Nonoperatively After Molecular Testing With Afirma GSC or Thyroseq v3.The Journal of clinical endocrinology and metabolism · 2023Trial
- A Novel Risk Stratification System for Thyroid Nodules With Indeterminate Cytology-A Pilot Cohort Study.Frontiers in endocrinology · 2020Trial
- Evaluation of the Italian cytological subclassification of thyroid indeterminate nodules into TIR-3A and TIR-3B: a retrospective study of 290 cases with histological correlation from a single institution.Journal of endocrinological investigation · 2018Trial
- The Diagnostic Performance of Afirma Genomic Sequencing Classifier in Black and Hispanic Patients With Indeterminate Thyroid Nodules.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2026Article
- National Trends in Thyroidectomy and Molecular Diagnostic Utilization: A Medicare Analysis (2016-2023).The Laryngoscope · 2026Article
- Five Advances in the Last 50 Years That Have Impacted Endocrine Surgery.World journal of surgery · 2026Review
- A seven-gene diagnostic and prognostic signature for papillary thyroid carcinoma.Discover oncology · 2026Article
- A targeted proteomics assay for the preoperative diagnosis of thyroid nodules.Cell reports. Medicine · 2026Article
- Article
- Utilities of next-generation sequencing in the surgical management of thyroid nodules in China.BMC endocrine disorders · 2026Article
- Chemical-enhanced thyroid cell detection using photonic crystal biosensors with phase-change materials.RSC advances · 2026Article
- Artificial intelligence-assisted risk stratification of thyroid nodules with atypia of undetermined significance.European thyroid journal · 2026Article
309 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundApproximately 15 to 30% of thyroid nodules evaluated by means of fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign. A novel diagnostic test that measures the expression of 167 genes has shown promise in improving preoperative risk assessment.
methodsWe performed a 19-month, prospective, multicenter validation study involving 49 clinical sites, 3789 patients, and 4812 fine-needle aspirates from thyroid nodules 1 cm or larger that required evaluation. We obtained 577 cytologically indeterminate aspirates, 413 of which had corresponding histopathological specimens from excised lesions. Results of a central, blinded histopathological review served as the reference standard. After inclusion criteria were met, a gene-expression classifier was used to test 265 indeterminate nodules in this analysis, and its performance was assessed.
resultsOf the 265 indeterminate nodules, 85 were malignant. The gene-expression classifier correctly identified 78 of the 85 nodules as suspicious (92% sensitivity; 95% confidence interval [CI], 84 to 97), with a specificity of 52% (95% CI, 44 to 59). The negative predictive values for "atypia (or follicular lesion) of undetermined clinical significance," "follicular neoplasm or lesion suspicious for follicular neoplasm," or "suspicious cytologic findings" were 95%, 94%, and 85%, respectively. Analysis of 7 aspirates with false negative results revealed that 6 had a paucity of thyroid follicular cells, suggesting insufficient sampling of the nodule.
conclusionsThese data suggest consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results. (Funded by Veracyte.).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.