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


RESULTS
We analysed retrospectively 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 seven FNA samples. The presence of a mutation in these genes was a strong indicator of cancer because five (71%) of the mutation-positive FNA samples had a malignant diagnosis after surgery. Moreover, there was only an 8% cancer risk in nodules with an indeterminate cytological diagnosis but with a negative molecular test.


CONCLUSIONS
This study demonstrates that thyroid FNA can be analysed successfully by NGS. The detection of mutations known to be involved in thyroid cancer improves the sensitivity of thyroid FNA diagnosis.
Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Marie
M
Le Mercier
Nicky
N
D'Haene
Nancy
N
De Nève
Oriane
O
Blanchard
Caroline
C
Degand
Sandrine
S
Rorive
Isabelle
I
Salmon
D000328:Adult; D044963:Biopsy, Fine-Needle; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000235:genetics*
molecular diagnosis; next-generation sequencing; thyroid FNA; thyroid cancer