Molecular testing of thyroid nodules
Updated: 6 days ago
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 and 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 assessment 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 Thyroid Print
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.
Frequently Asked Questions
Why would a biopsy be sent for molecular testing?
Molecular testing analyses genetic changes or patterns in the cells to provide additional information about the risk of cancer. This can help guide the decision between monitoring the nodule and proceeding to surgery.
What are the signs that a thyroid nodule is cancerous?
Most thyroid nodules that are cancerous cause no symptoms, and thyroid blood tests are usually normal even when cancer is present.
Signs that may raise concern include:
A lump that feels hard and fixed (doesn't move when you swallow)
Enlarged, firm lymph nodes in the neck alongside the nodule
Rapid growth noticed over weeks to months
Voice changes or persistent hoarseness
None of these confirm cancer on their own, and, if needed, a biopsy is what determines whether a nodule is suspicious.
How accurate is Molecular Testing for thyroid cancer?
Molecular testing can be highly accurate when used for appropriately selected thyroid nodules, particularly nodules with indeterminate biopsy results. However, its accuracy varies depending on the specific test.
What are the red flags on a thyroid ultrasound?
These are the ultrasound features doctors specifically look for when deciding whether a nodule needs a biopsy.
Solid composition
Hypoechoic appearance
Taller-than-wide shape
Irregular or poorly defined margins
Microcalcifications
Extension beyond the thyroid capsule
Suspicious lymph nodes nearby
What is the silent warning of Thyroid Cancer?
Thyroid cancer is sometimes called “silent” because it can develop without causing noticeable symptoms. A person may have a thyroid nodule or early thyroid cancer without pain, swallowing problems or voice changes, and thyroid blood tests such as TSH are usually normal even when cancer is present.
What foods should be avoided for papillary thyroid cancer?
There are no specific foods that need to be permanently avoided because you have papillary thyroid cancer. However, if radioactive iodine (RAI) treatment is planned, you may be advised to follow a temporary low-iodine diet, usually for about 1–2 weeks beforehand.
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