Plasma Cell-Free DNA to Differentiate Malignant from Benign Thyroid Nodules

Area of Science:

• Endocrinology
• Oncology
• Molecular Diagnostics

Background:

• Molecular testing aids in thyroid nodule malignancy identification, especially for indeterminate cases.
• Plasma cell-free DNA (cfDNA) shows promise for diagnosing cancers in various tissues.
• This study investigates cfDNA levels in thyroid nodules to establish a malignancy cutoff.

Purpose of the Study:

• To analyze plasma cfDNA levels in patients with thyroid nodules.
• To establish a cfDNA cutoff value for differentiating malignant from benign thyroid nodules.
• To validate the diagnostic accuracy of the established cfDNA cutoff in indeterminate thyroid nodules.

Main Methods:

• Patients underwent ultrasonography and fine needle aspiration.
• Plasma cfDNA was extracted and quantified.
• A cfDNA cutoff was determined by comparing Bethesda 2 (benign) and Bethesda 5 & 6 (malignant) groups, then validated on Bethesda 3 & 4 (indeterminate) nodules.

Main Results:

• A cfDNA cutoff of 67.9 ng/mL demonstrated 100% sensitivity and 93% specificity for malignancy.
• In indeterminate nodules, the cfDNA cutoff achieved 100% sensitivity and 92.3% specificity.
• cfDNA-based classification showed strong agreement with histopathology (Cohen's kappa 0.94).

Conclusions:

• Plasma cfDNA levels can effectively differentiate malignant from benign thyroid nodules.
• The established cfDNA cutoff provides a reliable non-invasive method for thyroid nodule assessment.
• This approach may improve diagnostic accuracy and patient management for thyroid nodules.