DOI: 10.1210/clinem/dgae112 ISSN: 0021-972X

Outcomes of cytologically indeterminate thyroid nodules managed with Genomic Sequencing Classifier

Sara Ahmadi, Anupam Kotwal, Athanasios Bikas, Pingping Xiang, Whitney Goldner, Anery Patel, Elena G Hughes, Xochitl Longstaff, Michael W Yeh, Masha J Livhits
  • Biochemistry (medical)
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Abstract

Context

Molecular testing can refine the risk of malignancy in thyroid nodules with indeterminate cytology to decrease unnecessary diagnostic surgery.

Objective

This study was performed to evaluate the outcomes of cytologically indeterminate thyroid nodules managed with Afirma genomic sequencing classifier (GSC) testing.

Design, setting, patients, and intervention

Adult patients who underwent a biopsy at three major academic centers between July 2017 and June 2021 with Bethesda III or IV cytology were included. All patients had surgery or minimum follow-up of 1 year ultrasound surveillance.

Main outcome measures

The primary outcomes were the sensitivity, specificity, PPV, and NPV of GSC in Bethesda III and IV nodules.

Results

The median nodule size of the 834 indeterminate nodules was 2.1 cm and the median follow-up was 23 months. GSC's sensitivity, specificity, PPV, and NPV across all institutions were 95%, 81%, 50%, and 99% for Bethesda III nodules and 94%, 82%, 65%, and 98% for Bethesda IV nodules, respectively. The overall false negative rate was 2%. The NPV of GSC in thyroid nodules with oncocytic predominance was 100% in Bethesda III nodules and 98% in Bethesda IV nodules. However, the PPV of oncocytic nodules was low (17% in Bethesda III nodules and 45% in Bethesda IV nodules). Only 22% of thyroid nodules with benign GSC results grew during surveillance.

Conclusions

GSC is a key tool for managing patients with indeterminate cytology, including the higher-risk Bethesda IV category. GSC benign thyroid nodules can be observed similarly to thyroid nodules with benign cytology.

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