BlueCross BlueShield of Tennessee Medical Policy Manual

Molecular Markers in Fine Needle Aspirates of the Thyroid

DESCRIPTION

Thyroid nodules are a common clinical problem affecting approximately 5-7% of the U.S. adult population with the majority of thyroid nodules diagnosed as benign.  Fine needle aspiration (FNA) of the thyroid is currently the most accurate procedure to distinguish between benign and malignant thyroid lesions, reducing the rate of unnecessary thyroid surgery for individuals with benign nodules. Approximately 60-70% of thyroid nodules are classified cytologically as benign and 4-10% deemed malignant. The remaining 20-30% have equivocal findings, usually due to overlapping cytologic features between benign and malignant nodules.

Genetic alterations associated with thyroid cancer can be assessed using gene expression profiling, which refers to analysis of messenger RNA expression levels of many genes simultaneously. The Afirma® Gene Expression Classifier (Veracyte, Inc.) measures the gene expression of 142 genes to determine patterns associated with benign findings on surgical biopsy. The Afirma® Gene Expression Classifier is designed to evaluate thyroid nodules that have an “indeterminate” classification on fine needle aspirate as a method to select individuals who are low risk for cancer.

Molecular testing proposed as a method to identify thyroid malignancy is the use of genetic variant analysis panels.  Examples of available genetic variant analysis panels that evaluate point mutations and genetic rearrangements are as follows:

POLICY

MEDICAL APPROPRIATENESS

IMPORTANT REMINDERS

SOURCES

American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi.(2016). Medical guidelines for clinical practice for the diagnosis and management of thyroid nodules - 2016 update. Retrieved December 12, 2016 from https://www.aace.com/publications/guidelines.

American Thyroid Association. (2016). 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Retrieved December 9, 2016 from http://online.liebertpub.com/mwg-internal/de5fs23hu73ds/progress?id=CPh-aX_7qtn0eLvR0tbjKlIMLhk1s6m8bJaV0wt0YeQ,&dl.

Angell, T., Frates, M., Medici, M., Liu, X., Kwong, N., Cibas, E., et al. (2015). Afirma benign thyroid nodules show similar growth to cytologically benign nodules during follow up. The Journal of Clinical Endocrinology & Metabolism. Retrieved March 8, 2016 from http://press.endocrine.org/doi/10.1210/jc.2015-2658?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed.

BlueCross BlueShield Association. Medical Policy Reference Manual. (6:2017). Molecular markers in fine needle aspirates of the thyroid (2.04.78). Draft Policy. (55 articles and/or guidelines reviewed)

Brauner, E., Holmes, B., Krane, J., Nishino, M., Zurakowski, D., Hennessey, J., et al. (2015). Performance of the Afirma gene expression classifier in Hürthle cell thyroid nodules differs from other indeterminate thyroid nodules. Thyroid, 25 (7), 789-796. (Level 4 evidence)

Labourier, E., Shifrin, A., Busseniers, A., Lupo, M., Manganelli, M., Andruss, B., et al. (2015). Molecular testing for miRNA, mRNA, and DNA on fine-needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology. Journal of Clinical Endocrinology and Metabolism, 100 (7), 2473-2750. (Level 3 evidence)

National Comprehensive Cancer Network. (2017). NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Thyroid carcinoma (V.2.2017). Retrieved June 21, 2017 from the National Comprehensive Cancer Network.

Noureldine, S., Olson, M., Agrawal, N., Prescott, J., Zeiger, M., & Tufano, R. (2015). Effect of gene expression classifier molecular testing on the surgical decision-making process for patients with thyroid nodules. Journal of American Medical Association Otolaryngology--Head & Neck Surgery, 141 (12), 1082-1088.  Abstract retrieved March 8, 2016 from PubMed database.

Palmetto Government Benefit Adminstrators. (2017). Afirma assay by Veracyte coding and billing guidelines (M00015, V2). Retrieved February 15, 2017 from http://www.palmettogba.com/palmetto/MolDX.nsf/DocsCat/MolDx%20Website~MolDx~Browse%20By%20Topic~Covered%20Tests~8Q7MRU7038?open.

Sacks, W.L., Bose, S., Zumsteg, Z.S., Wong, R., Shiao, S.L., Braumstein, G.C., et al. (2016). Impact of Afirma gene expression classifier on cytopathology diagnosis and rate of thyroidectomy. Cancer, 124 (10), 722-728. Abstract retrieved December 12, 2016 from PubMed database.

Singer, J., Hanna, J., Visaria, J., Gu, T., McCoy, M., & Kloos, R. (2016). Impact of a gene expression classifier on the long-term management of patients with cytologically indeterminate thyroid nodules. Current Medical Research and Opinion, 32 (7), 1225-1232. (Level 4 evidence)

Sipos, J., Blevins, T., Shea, H., Duick, D., Lakhian, S., Michael, B., et al. (2016). Long-term non-operative rate of thyroid nodules with benign results on the afirma gene expression classifier. Endocrine Practice, 22 (6), 666-672. Abstract retrieved December 12, 2016 from PubMed database.

Valderrabano, P., Khazai, L., Leon, M., Thompson, Z., Ma, Z., Chung, C. (2017). Evaluation of ThyroSeq v2 performance in thyroid nodules with indeterminant cytology. Endocrine Related Cancer, 24 (3), 127-136. Abstract retrieved June 21, 2017 from PubMed database.

Winifred S. Hayes, Inc. Genetic Test Evaluation (GTE) Report. (2014, February; last update search February 2016). Afirma® thyroid FNA analysis. Retrieved March 8, 2016 from www.Hayesinc.com/subscribers. (31 articles and/or guidelines reviewed)

Witt, R. (2015). Outcome of thyroid gene expression classifier testing in clinical practice. Laryngoscope, 126 (2), 524-527. (Level 4 evidence)

Wong, K.S., Angell, T.E., Strickland, K.C., Alexander, E.K., Cibas, E.S., Krane, J.F. & Barletta, J.A. (2016). Noninvasive follicular variant of papillary thyroid carcinoma and the Afirma gene expression classifier. Thyroid, 26 (7), 911-915. Abstract retrieved December 12, 2016 from PubMed database.

Wu, J.X., Young, S., Hung, M.L., Li, N., Yang, S.E., Cheung, D.S., et al. (2016). Clinical factors influencing the performance of gene expression classifier testing in indeterminate thyroid nodules. Thyroid, 26 (7), 916-922. Abstract retrieved December 12, 2016 from PubMed database.

Yang, S, Sullivan, P., Zhang, J., Govind, R., Levin, M., Rao, J., & Moatamed, A. (2016). Has Afirma gene expression classifier testing refined the indeterminate thyroid category in cytology? Cancer Cytopathology, 124 (2), 100-109. (Level 4 evidence)

Yip, L., Nikiforova, M., Yoo, J., McCoy, K., Stang, M., Armstrong, M., et al. (2015). Tumor genotype determines phenotype and disease-related outcomes in thyroid cancer: a study of 1510 patients. Annals of Surgery, 262 (3), 519-525. Abstract retrieved March 8, 2016 from PubMed database.

ORIGINAL EFFECTIVE DATE:  10/12/2013

MOST RECENT REVIEW DATE:  8/23/2017

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