High-risk and intermediate-high-risk results from the ThyroSeq v2 and v3 thyroid genomic classifier are associated with neoplasia: Independent performance assessment at an academic institution

Background: The ThyroSeq panel tests for genetic alterations to risk-stratify cytologically indeterminate nodules. The authors assessed the test performance of the tests, including the latest version (v3), at an academic center.

Methods: Results from ThyroSeq testing (v2 and v3) were reviewed over 2 years, and patient demographics, cytology diagnoses, results of ThyroSeq testing, and histopathologic diagnoses on resection (if available) were collected.

Results: One hundred eighty-five nodules were tested from 178 patients, including 94 nodules tested with v2 and 91 nodules tested with v3. Overall, 28 of 185 nodules (15%) yielded a high-risk or intermediate-high-risk mutation (HRM). Of the patients with these nodules, 19 of 25 (76%) had neoplastic nodules, and 11 of 25 (44%) had a malignancy or a noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Only 16 of 147 nodules (11%) that were negative or had low-risk genetic alterations underwent resection, with 1 false-negative result (a papillary thyroid carcinoma tested with v2). No false-negative results were identified with v3. Two nodules had TP53 mutations identified, both of which were benign on resection. Nodules with HRM that were tested with v2 and v3 had a positive predictive value (PPV) for malignancy of 57% and 39%, respectively, and a PPV for neoplasm of 86% and 72%, respectively. The negative predictive values for v2 and v3 were 92% and 100%, respectively.

Conclusions: The PPV of an HRM result on ThyroSeq v3 was low for malignancy or NIFTP, and the PPV for neoplasm was higher. RAS-type mutations were the most commonly identified in both benign and malignant nodules. Thyroseq v3 had a lower PPV for both malignancy/NIFTP and neoplasm than v2 but did not produce any false-negative results.