Next-generation sequencing improves the diagnosis of thyroid FNA specimens with indeterminate cytology



The assessment of thyroid nodules is a common clinical challenge. Fine-needle aspiration (FNA) is the standard preoperative tool for thyroid nodule diagnosis. However, up to 30% of the samples are classified as indeterminate. This often leads to unnecessary surgeries. In this study, we evaluated the added value of next-generation sequencing (NGS) for helping in the diagnosis of FNA samples.

Methods and Results

We retrospectively analysed 34 indeterminate FNA samples for which surgical resection was performed. DNA was obtained from cell blocks or from stained smears and subjected to NGS to analyse mutations in 50 genes. Mutations in BRAF, NRAS, KRAS and PTEN that are known to be involved in thyroid cancer biology were detected in 7 FNA samples. The presence of a mutation in these genes was a strong indicator of cancer because 5 (71%) of the mutation-positive FNA samples had malignant diagnosis after surgery. Moreover, the cancer risk in nodules with indeterminate cytological diagnosis but with a negative molecular test was of only 8%.


This study demonstrates that thyroid FNA can be successfully analysed by NGS. The detection of mutations known to be involved in thyroid cancer improves the sensitivity of thyroid FNA diagnosis.

5 Replies

  • Thank you

  • Hi Clutter,

    This sounds like it is along the lines of the Affirma test you can currently get in certain parts of the USA. This sort of genetic sequencing seems to be the way forwards. Lets hope it doesn't take too long before it can be implemented everywhere!


  • Hi Melissa,

    Yes, it does. Not only will it prevent needless surgery for inconclusive FNAs but I imagine positive FNA would mean total thyroidectomy rather than hemi and follow up completion. I wonder how long it will be until the FNA can determine what type of cancer?

    How are you doing now?

  • It's good to hear about advances like this. The consultant who did my ultrasound gave me several reasons why he thought my nodule wasn't cancerous but, as the next FNA with a different consultant was a 3, I still ended up electing to have surgery as I wasn't sure how reliable that reasoning was. In the end, he was proved right. Once NGS becomes standard practice, as you say, it should eliminate those unnecessary ops. However, my nodule was said to be over-producing hormone, so maybe I needed mine?

  • Same here. Nodule was compressing windpipe and gullet so had to go. FNA 3 but histology was stage II Hurthle cell carcinoma. Not sure whether it may have been better to hang on to the other side which was cancer free, but it wasn't doing any good in the 3 months between hemi & TT and RAI would have cooked it, if Hashimoto's didn't destroy it in time, so, no regrets.

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