Journal: Virchows Archiv : an international journal of pathology
This publication reviews the evolving role of molecular diagnostics in managing indeterminate thyroid nodules, a significant clinical challenge since 20-30% of fine-needle aspiration biopsies yield inconclusive results.
Molecular testing platforms such as Afirma GSC, ThyroSeq v3, and ThyroidPrint use gene expression, mutation analysis, and microRNA profiles to improve diagnostic accuracy.
These third-generation tests demonstrate:
- High sensitivity (91-100%)
- High negative predictive values (90-100%)
- Enabling avoidance of unnecessary surgeries in over half of cases with indeterminate cytology
The molecular classification into BRAF-like and RAS-like tumor profiles enhances diagnostic precision. Detection of mutations such as TERT promoter and TP53 guides prognosis and targeted therapy selection.
Challenges remain in test standardization, cost, and global access disparities.
Future directions include:
- Broader use of next-generation sequencing
- Liquid biopsies
- AI integration
- Multi-omic approaches
There is growing guideline support advocating molecular testing as part of multidisciplinary thyroid cancer care to optimize outcomes and limit overtreatment.