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Second, it is important to evaluate for the presence of symptoms that impact whether the patient is planning to pursue surgery. If the patient has compressive symptoms, hoarseness secondary to posterior extension of the nodule, or cosmetic concerns about the nodule and is planning to undergo surgery regardless of the molecular result, then the addition of molecular testing to a cytologically indetermi­nate FNA currently may not impact decision-making or treatment.

Once you have considered the above factors, and if you have decided to proceed with molecular testing, then the next step is to consider which molecular test to use. The two most common commercially available tests in the United States are Veracyte Arma Genomic Sequencing Classier (GSC) + Genome Atlas, and ThyroSeq version 3 (v3) [4]. For this discussion, we will focus on these two tests since they have the most data and have undergone direct comparison (Table3.2).

Arma GSC +Genome Atlas The newest version of the Arma molecular test

(GSC) has been available commercially since 2017. GSC evaluates genomic con­tent of thyroid nodules through RNA sequencing technology that helps evaluate more than 10,000 genes, of these 1115 are core genes that drive the prediction behavior of the model, while the remaining genes improve classier stability. This technology includes sequencing of nuclear and mitochondrial transcript level RNA, changes in genomic copy number and loss of heterozygosity. The updated platform has multiple classiers including a benign vs malignant classier with additional Hurthle cell and Hurthle neoplasm cassettes, a parathyroid classier, a medullary thyroid cancer classier, and a BRAF V600E classier. It can also identify RET/ PTC1 and RET/PTC3 fusions if present [4, 6, 7, 9]. A GSC benign result indicates a 4% cancer probability while a GSC suspicious result indicates a 50% cancer prob­ability [12]. In 2018, Veracyte launched the Arma Xpression Atlas (XA) which was most recently updated in March 2020. Similar to Arma GSC, it uses RNA sequencing to identify an additional 905 variants and 235 fusions in 593 genes. To perform molecular testing using Arma GSC+Genoma Atlas, samples need to be collected at the time of the FNA. Veracyte recommends obtaining two additional passes at the time of FNA biopsy, and placing them in a solution provided by the company [4, 6, 7, 9]. This analysis cannot be done on stained slides at a later time after the FNA.