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Update on Molecular Testing for Cytologically Indeterminate Thyroid Nodules

Bose, Shikha, MD; Sacks, Wendy, MD; Walts, Ann E., MD

Advances in Anatomic Pathology: March 2019 - Volume 26 - Issue 2 - p 114–123
doi: 10.1097/PAP.0000000000000211
Review Articles

Fine needle aspiration biopsy (FNAB) and ultrasonography are the most common modalities for the diagnosis and follow up of thyroid nodules. FNAB is able to distinguish benign from malignant nodules with high sensitivity and specificity; however, 20% to 30% of nodules are diagnosed as indeterminate with a risk of malignancy varying from 10% to 75% based on the 2017 revision of the Bethesda System for Reporting Thyroid Cytopathology. Molecular tests are being increasingly used to triage this group of nodules. Several molecular tests are commercially available and newer upgrades are being developed to either “rule in” or “rule out” malignancy with greater accuracy. The Afirma gene expression classifier and its recent upgrade (the Afirma gene sequencing classifier), Thryoseq v2, a next generation sequencing test and its recent upgrade (the v3), RosettaGX Reveal based on microRNA alterations, and ThyGenX/ThyraMIR, a combination test, are currently on the market. Familiarity with these tests, their performance, and postvalidation publications will enable appropriate test selection and improve triage of patients for appropriate therapy. The underlying rate of malignancy at different institutions and the interobserver variability in cytologic and histologic diagnosis of thyroid lesions are important factors that impact the performance of the various molecular tests.

Cedars-Sinai Medical Center, Los Angeles, CA

The authors have no funding or conflicts of interest to disclose.

Reprints: Shikha Bose, MD, South Tower, Room 8720, Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048 (e-mail:

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