Indeterminate Thyroid Nodules and Advances in Molecular Pathology

The recommended practice is that thyroid nodules with indeterminate to suspicious imaging features undergo fine needle aspiration (FNA). The Bethesda System for Reporting Thyroid Cytopathology (The Bethesda System, TBS)1,2 was set up with accompanying risk of malignancy (ROM) summaries to help guide management decisions so as to avoid overtreatment of indolent thyroid lesions3. TBS has indeterminate risk categories with varying ROM. The indeterminate categories include: Atypia of Undetermined Significance (AUS, TBS III)4, Follicular Neoplasm (TBS IV), and according to some, Suspicious for Malignancy (TBS V)5, with ROM ranging from 6% (TBS III) to 75% (TBS V)1. Prior to the advent of commercially available molecular tests, surgical excision was advised for all nodules with FNA results that were suspicious, positive, or repeatedly indeterminate for malignancy. Presently, molecular testing has been incorporated by many practicing physicians to help some patients with indeterminate FNA results avoid surgery. Our review paper describes the three commercially available thyroid-specific molecular tests and will summarize the common molecular drivers associated with papillary thyroid carcinoma (PTC) and follicular patterned lesions, in order to help the practicing pathologist and clinician better interpret the results of these tests and incorporate this information into their management of cytologically indeterminate thyroid lesions.

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