Thyroid disease

Utility of genomic sequencing classifier in managing cytologically indeterminate oncocytic thyroid nodules

J Clin Endocrinol MetabPublished Retrospective diagnostic accuracy study

Authors' conclusion

Afirma GSC has a high BCR and improved performance over earlier generation molecular tests in oncocytic thyroid nodules, particularly for Bethesda IV. However, the PPV in Bethesda III nodules remains low, especially in the presence of Hashimoto's thyroiditis.

Study context

Population
Adults with Bethesda III and IV thyroid nodules with oncocytic predominance who underwent FNA biopsy and Afirma genomic sequencing classifier (GSC) testing, July 2017–December 2023
Participants
359 nodules
Comparison
Bethesda III vs Bethesda IV
Outcome
Benign call rate (BCR), sensitivity, specificity, PPV and NPV of Afirma GSC
Methodological detailsmulticenter
  • Multicenter

Performance

As reported in the abstract

Afirma GSC performance
Test or modelBenign call rate (BCR)SensitivitySpecificityPPVNPV
Bethesda III81%89%86%24%99%
Bethesda IV74%94%87%50%99%

Benign call rate (BCR)

Bethesda III81%
Bethesda IV74%

Sensitivity

Bethesda III89%
Bethesda IV94%

Specificity

Bethesda III86%
Bethesda IV87%

PPV

Bethesda III24%
Bethesda IV50%

NPV

Bethesda III99%
Bethesda IV99%

Further findings

Hashimoto's thyroiditis

Concurrent Hashimoto's thyroiditis significantly reduced specificity and PPV in Bethesda III nodules

TIRADS classification

TIRADS classification did not affect BCR or PPV in Bethesda III or IV nodules

Original publication

Utility of genomic sequencing classifier in managing cytologically indeterminate oncocytic thyroid nodules. J Clin Endocrinol Metab. Published 6 February 2026. doi:10.1210/clinem/dgag044

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