Next-Generation Sequencing Enhances the Diagnosis Efficiency in Thyroid Nodules

Area of Science:

• Oncology
• Genetics
• Pathology

Background:

• Fine-needle aspiration (FNA) has limitations in diagnosing indeterminate thyroid nodules.
• The Bethesda System for Reporting Thyroid Cytopathology includes uncertain cytology results.
• Next-generation sequencing (NGS) technology offers efficient genetic profiling of pathological tissues.

Purpose of the Study:

• To evaluate the efficacy of combining FNA cytology with NGS genetic analysis for thyroid nodule diagnosis.
• To determine if NGS can improve diagnostic accuracy beyond cytology alone.
• To explore the role of genetic background in refining thyroid nodule diagnosis.

Main Methods:

• DNA extraction from 73 FNA thyroid nodule samples.
• Exome sequencing using the ThyroLead panel and BRAF mutation testing via ARMS-qPCR.
• Collection of clinical data including cytology, BRAF status, and surgical pathology.

Main Results:

• NGS detected various genetic alterations including single nucleotide variants, fusion genes, and microsatellite instability-high status.
• BRAF V600E mutation was the most frequent in malignant nodules.
• Combining FNA cytology with NGS increased diagnostic sensitivity from 0.582 to 0.855 (P < 0.001) without significantly affecting specificity.

Conclusions:

• NGS enhances preoperative diagnostic sensitivity for thyroid nodules when used with FNA.
• Genetic profiling provides valuable information for guiding medication and treatment strategies.
• Integrating cytology and genetic alterations offers a more precise diagnostic approach for thyroid nodules.