Molecular testing of thyroid nodules

Molecular Testing for Thyroid Nodules

What is Molecular Testing?

Molecular testing is an advanced laboratory technique that analyses the genetic material (DNA and RNA) within thyroid nodule cells obtained during a fine needle aspiration (FNA) biopsy. By looking for specific gene mutations, gene fusions, and other genetic alterations, molecular testing helps determine whether a thyroid nodule is likely to be benign (non-cancerous) or malignant (cancerous).

It is particularly helpful when traditional cytology (microscopic examination of cells) cannot give a clear answer.

Why Is Molecular Testing Useful?

Most thyroid nodules are benign. However, around 15–30% of nodules fall into an indeterminate category after FNA biopsy. These are classified as:

• Bethesda Category III (AUS/FLUS – Atypia of Undetermined Significance)

• Bethesda Category IV (Follicular Neoplasm or Suspicious for Follicular Neoplasm)

In these situations, cytology alone cannot reliably distinguish between benign and malignant nodules. Traditionally, many patients proceeded to diagnostic surgery to remove half of the thyroid simply to obtain a definitive diagnosis — and a significant proportion of those nodules ultimately proved benign.

Molecular testing reduces uncertainty and helps guide decision-making:

• It can “rule out” cancer, allowing patients to safely avoid surgery.

• It can “rule in” cancer, helping plan the appropriate extent of surgery.

• It provides more personalised risk assessment.

The Tests Available: ThyroSeq v3 vs Idylla ThyroidPrint

In New Zealand, two commonly used molecular platforms are:

ThyroSeq v3 Genomic Classifier

I predominantly use ThyroSeq v3, a comprehensive genomic classifier that:

• Uses Next Generation DNA and RNA sequencing

• Analyses 112 genes

• Detects:

  • Gene mutations

  • Gene fusions

  • Copy number alterations

Importantly, ThyroSeq has both:

• Rule-out capability (high negative predictive value)

• Rule-in capability (identifies high-risk mutations and specific tumour types)

This means it not only tells us when surgery may be avoided, but also when cancer is likely — and often identifies the type of tumour, which assists with surgical planning.

Idylla ThyroidPrint

Idylla ThyroidPrint:

• Analyses 10 genes

• Functions primarily as a rule-out test

• Is performed at the time of your appointment

• Provides faster results

While it has a strong ability to rule out cancer, it does not provide the same depth of genomic information or tumour characterisation as ThyroSeq.

Turnaround Time

• ThyroSeq results take longer because the sample is sent for advanced genomic sequencing.

• Idylla ThyroidPrint is performed during your appointment, so results are available much sooner.

If the primary goal is to avoid unnecessary surgery, the short delay with ThyroSeq is generally not clinically problematic. In return, patients receive more detailed and comprehensive information.

Cost in New Zealand

The cost of ThyroSeq v3 is:

• $2,400 NZD for the first nodule

• $1,400 NZD for each additional nodule

The cost of Idylla ThyroidPrint is similar overall.

Some private health insurance policies may cover molecular testing, but you should confirm this directly with your insurance provider.

Summary

For patients with indeterminate thyroid nodules (Bethesda III or IV), molecular testing can significantly reduce uncertainty and help avoid unnecessary surgery.

While both ThyroSeq and Idylla ThyroidPrint have strong rule-out capability, I favour ThyroSeq v3 because it:

• Uses comprehensive next-generation sequencing

• Analyses a far larger number of genes

• Provides both rule-in and rule-out capability

• Identifies specific tumour types

This allows for more precise, personalised decision-making and better surgical planning when required.

If you would like to discuss whether molecular testing is appropriate for your thyroid nodule, please contact our clinic for further advice.