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.