Introduction: The use of multigene panels in thyroid nodule diagnosis is still limited, due to high costs and need for ad hoc sampling. Since BRAF-V600E is the commonest genetic alteration in differentiated thyroid cancer, this is the mostly tested genetic parameter in clinical practice.
Aim: To evaluate the use of BRAF mutation analysis in wash-out liquid from fine needle aspiration (FNA) in clinical practice, characterizing the cases in which it is requested, and the consequences of genetic test result on therapeutic decisions.
Methods: We considered all the subjects tested for BRAF-V600E among those attending the Endocrinology Unit of Modena for FNA between January 2014 and November 2018. After written informed consent, washing fluid was collected together with cytological sample and stored at –20°C. If the clinician deemed it necessary, the sample was thawed, DNA was extracted and genetic test was performed by the high-resolution melting protocol previously described1. We collected cytology of nodules according to the 2010 SIAPEC-IAP Italian Consensus, and when surgical treatment was performed, histology.
Results: Out of a total of 7112 subjects submitted to FNA, BRAF analysis was requested for 681 (9.6%), for a total of 898 nodules: 97% of nodules were indeterminate at cytology, mainly TIR3A (low risk); 2% suspicious or diagnostic for cancer, and genetic test was requested to estimate prognosis; 1% were suspect nodules at ultrasonography with unsuspicious cytology. Only 22 nodules were mutant (BRAF+).Most of them were already high risk or suspicious lesions at cytology (64%). One third were TIR3A. Considering the prevalence of BRAF mutation among cytological classes of the whole group, only 1% of TIR3A were BRAF+. Twenty BRAF+ patients were addressed to surgery (one lost at follow-up, one refused): 5% underwent hemithyroidectomy, 25% total thyroidectomy and 70% total thyroidectomy plus central lymph nodes dissection. They all had papillary thyroid cancer. Since 64% of BRAF+ were TIR3B-4-5 at cytology, they had surgical indication even before the genetic test. Among the 14 subjects treated with central neck dissection, only 2 had suspect metastasis before surgery; among those who would have had no indication, one third had metastases (only 1 among TIR3A and 2 among TIR3B).
Conclusions: Despite the development of panels, single gene tests are still requested, mainly for nodules with indeterminate low risk cytology. BRAF mutation in TIR3A is rare and leads clinicians to more invasive surgery, with questionable clinical utility.
1. Marino et al. Eur Thyroid J 2015 4(2) 73–81.
05 - 09 Sep 2020
European Society of Endocrinology