This document addresses the use of molecular markers for the evaluation of thyroid nodules to identify genetic mutations (mutation analysis) and to identify benign thyroid nodules preoperatively. Examples of these tests include, but are not limited to:

• Afirma^® Thyroid FNA Analysis (i.e., Genomic Sequencing Classifier, Medullary Thyroid Carcinoma Classifier, and Xpression Atlas) (Veracyte, South San Francisco, CA)
• ThyGeNEXT^® and ThyraMIR^® (Interpace Diagnostics, Parsippany, NJ)
• ThyroSeq^® (CBLPath, Rye Brook, NY)

Note: Please see the following related document for additional information:

• CG-GENE-14 Gene Mutation Testing for Cancer Susceptibility and Management

Clinical Indications

Medically Necessary:

Molecular marker evaluation of a thyroid nodule is considered medically necessary for use with fine needle aspirates when the following criteria are met:

1. Initial cytopathology is indeterminate (that is, atypia of undetermined significance [AUS], follicular lesion of undetermined significance [FLUS], suspicious for follicular neoplasm [SFN], follicular neoplasm [FN], or suspicious for malignancy [SUS]); and
2. One of the following gene expression classifiers will be used:
   1. Afirma Genomic Sequencing Classifier; or
   2. Afirma Medullary Thyroid Carcinoma (MTC) Classifier when results from the Genomic Sequencing Classifier are indeterminate; or
   3. ThyGeNEXT/ThyraMIR; or
   4. ThyroSeq Genomic Classifier.

Not Medically Necessary:

The use of molecular marker evaluation of thyroid nodules is considered not medically necessary for repeat testing of the same nodule and all other indications not listed above as medically necessary.

The use of other molecular marker evaluations of thyroid nodules (for example, Afirma Xpression Atlas) is considered not medically necessary.