ArticleCytopathology : official journal of the British Society for Clinical Cytology2026
Malignancy Risk, Molecular Mutations, and Surgical Outcomes of Thyroid Nodules Classified as Atypia of Undetermined Significance in the Bethesda System: A Comprehensive Analysis.
Article in Cytopathology : official journal of the British Society for Clinical Cytology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- EIF1AX Mutations in thyroid nodules and advanced thyroid carcinoma: a systematic review and meta-analysis.Virchows Archiv : an international journal of pathology · 2026Review
- On the Prognostic Implications of Nuclear Atypia in Bethesda III Thyroid Nodules.Cytopathology : official journal of the British Society for Clinical Cytology · 2026Article
- Molecular Testing and Surgical Outcomes in Bethesda III and IV Thyroid Nodules: A Retrospective Cohort Study.Cancers · 2025Article
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8 authors.
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Abstract
objectivesThyroid nodules classified as atypia of undetermined significance (AUS) within the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) present a diagnostic challenge, with a risk of malignancy (ROM) of 5% to 50%. In 2017, TBSRTC introduced AUS subcategories to enhance ROM assessment. This study explores the correlation between AUS subclassification, molecular mutations, and surgical outcomes.
methodsRetrospective analysis was performed of 114 AUS cases with molecular profiling by ThyroSeqV3 and surgical follow-up. AUS subcategories as defined by TBSRTC included: AUS-Architectural, AUS-Nuclear, AUS-Nuclear and Architectural, and AUS-Hürthle cell. Pathology diagnoses were categorised as benign, malignant, or borderline, including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).
resultsOf the 114 nodules, 32.5% were AUS-Architectural, 28.9% AUS-Nuclear and Architectural, 18.4% AUS-Nuclear, 19.3% AUS-Hürthle cell, and 0.9% AUS-Not Otherwise Specified. Papillary carcinoma, predominantly follicular variant, was the most common diagnosis (47.4%), followed by benign lesions (34.2%) and NIFTP (9.6%). RAS family mutations were the most prevalent molecular alteration (34.2%) followed by DICER1, EIF1AX, EXH1 mutations, CNA and GEP (29.8%). THADA fusions, PTEN, TSHR and BRAFK601E mutations were identified in 10.5% of cases, while high-risk mutations such as BRAF V600E, TERT, and TP53 were found in 8.8% of cases. AUS subcategories demonstrated distinct molecular profiles and were linked to varying surgical outcomes.
conclusionsAUS subcategorization is associated with specific molecular profiles and surgical outcomes, supporting the subclassification of AUS cases per TBSRTC guidelines for improved risk stratification and clinical management. Further prospective studies with larger cohorts are necessary for validation.
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