Predictive Value of a Genomic Classifier in Indeterminate Thyroid Nodules Based on Nodule Size

Area of Science:

• Endocrinology
• Oncology
• Genetics

Background:

• Genomic classifiers aid in managing indeterminate thyroid nodules (ITNs).
• The impact of ITN size on diagnostic accuracy of genomic classifiers remains understudied.

Purpose of the Study:

• To evaluate the diagnostic performance of a genomic classifier (ThyroSeq) in relation to ITN size.
• To assess the association between genetic signatures and cancer risk in ITNs.

Main Methods:

• A retrospective case series of 218 ITNs from patients undergoing genomic classifier testing and surgery.
• Analysis of diagnostic metrics (PPV, NPV, sensitivity, specificity) stratified by ITN size (<2 cm, 2-4 cm, >4 cm).

Main Results:

• The overall cancer prevalence was 23.9%.
• Positive predictive value (PPV) and negative predictive value (NPV) improved with increasing ITN size (e.g., PPV 25% and NPV 79% for <2 cm vs. PPV 50% and NPV 89% for >4 cm).
• Test specificity was significantly higher for larger ITNs (40% for >4 cm vs. 15% for <2 cm, P=.01).

Conclusions:

• ThyroSeq test performance, particularly specificity, improves with larger indeterminate thyroid nodule size.
• Large ITNs with negative genomic classifier results have a low risk of malignancy.
• Initial thyroid lobectomy may be a sufficient management strategy for genomic classifier-negative ITNs >4 cm.