Description

Laboratory examination of cells in thyroid nodules acquired through fine needle aspiration (FNA) has been proposed to assist in exploring the possibility of thyroid cancer. These tests are used to detect molecular markers that are associated with thyroid cancer and are performed when cytopathology cannot determine if the nodule is malignant or benign. This classification is referred to as indeterminate.

Thyroid Nodules

Thyroid nodules are abnormal growths or lumps that develop in the thyroid gland. While most are benign, a small percentage are malignant. To determine the likelihood of malignancy, FNA is used to obtain cells from the nodule that are evaluated by cytopathology. FNA results are then assigned to one of 5 categories based on a classification system known as The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Results categorized as indeterminate warrant further evaluation, which may include repeat FNA, thyroid surgery and/or histopathology. Even with the additional examinations, the majority of cases are ultimately classified as benign. Testing for molecular markers in specimens already attained via FNA potentially eliminates the need for repeat FNA or for surgery.

Molecular Markers in Fine Needle Aspirates of Thyroid Nodules

Effective Date: 03/01/2023
Revision Date: 03/01/2023
Review Date: 03/01/2023
Policy Number: HUM-0552-012

Clinically Available Tests

• Afirma Genomic Sequencing Classifier (GSC) is a ribonucleic acid (RNA) sequencing technology platform that analyzes thousands of genes at one time to detect alterations.
• Afirma Xpression Atlas (XA) and Expanded Afirma XA evaluate FNA attained samples using RNA-sequencing to measure deoxyribonucleic acid (DNA) alterations and RNA fusions possibly linked to thyroid cancer. These are add-on tests to Afirma GSC. (Refer to Coverage Limitations section)
• ThyGeNEXT Thyroid Oncogene Panel is a DNA and RNA NGS-based test that analyzes genes and RNA fusions associated with thyroid cancer. ThyraMIR Thyroid miRNA Classifier is a microRNA (miRNA) profiling test performed reflexively to ThyGeNEXT. ThyraMIR evaluates the expression of miRNAs that may be associated with thyroid cancer. ThyGenNEXT and ThyraMIR are referred to as combination testing. (Refer to Coverage Limitations section)
• ThyroSeq Genomic Classifier (GC) uses an NGS platform to evaluate DNA and RNA of genes associated with thyroid cancer by examining indeterminate FNA.
• ThyroSeq CRC analyzes cytologically malignant FNA to aid in determining risk of recurrence. (Refer to Coverage Limitations section)
• Multigene (or expanded) panels analyze a broad set of genes simultaneously (as opposed to single gene testing that searches for variants in one specific gene) and have been proposed to evaluate the DNA of an individual with a personal and/or family history of more than one hereditary condition or syndrome. Panels often include medically actionable genes but may also include those with unclear medical management.

Molecular Markers in Fine Needle Aspirates of Thyroid Nodules
Effective Date: 03/01/2023
Revision Date: 03/01/2023
Review Date: 03/01/2023
Policy Number: HUM-0552-012

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

• Targeted (or focused) multigene panels analyze a limited number of genes targeted to a specific condition. (Refer to Coverage Limitations section)
• Single-site genetic testing to identify mutations associated with thyroid cancer have been proposed to assist in the reclassification of indeterminate nodules. Genes include, but may not be limited to, PAX8/PPARgamma, RET/PTC and TERT. (Refer to Coverage Limitations section)
• Molecular profiling for papillary thyroid carcinoma has also been proposed to determine risk of recurrence. An example includes Thyroid GuidePx. (Refer to Coverage Limitations section)

Testing for molecular markers in thyroid nodule specimens differs from germline genetic mutation testing. Analysis of molecular markers evaluates specimens for mutations acquired over an individual’s lifetime and are present only in the tissue sampled. Germline DNA is constant and identical in all body tissue types and mutations are inheritable.

For information regarding thyroid surgery, please refer to Thyroid Surgeries (Thyroidectomy & Lobectomy) Medical Coverage Policy.

Coverage Determination

Any state mandates for molecular markers in FNA of thyroid nodules take precedence over this medical coverage policy.

Humana members may be eligible under the Plan for any of the following molecular markers assays to assess thyroid nodules specimens obtained by FNA:

• Afirma GSC (81546) or ThyroSeq GC (0026U) to assess thyroid nodule specimens when the following criteria are met:
  1. Thyroid nodule 1 cm or greater on ultrasound; AND
  2. Indeterminate thyroid FNA cytopathology* described as:
• Molecular Markers in Fine Needle Aspirates of Thyroid Nodules
  Effective Date: 03/01/2023
  Revision Date: 03/01/2023
  Review Date: 03/01/2023
  Policy Number: HUM-0552-012

Atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) (Bethesda III); OR

Follicular neoplasm/suspicious for follicular neoplasm (FN), including Hurthle cell (Bethesda IV)

*Alternative terms for indeterminate thyroid FNA cytopathology include atypical follicular lesion, cellular follicular lesion or rule out neoplasm

Coverage Limitations

Humana members may NOT be eligible under the Plan for molecular markers in thyroid nodule specimens obtained by FNA for any indications or tests other than those listed above including, but may not be limited to:

• Afirma GSC or ThyroSeq GC for the following:
  • Evaluation of FNA thyroid cytopathology with Bethesda I, II, V or VI cytologic categories
  • Evaluation of thyroid nodule less than 1 cm
  • Repeat molecular marker testing of FNA aspirates for any indication
  • Testing more than 1 nodule when an individual presents with multiple nodules
• Afirma XA and Expanded XA (0204U)
• Evaluation of papillary thyroid carcinoma (eg, Thyroid GuidePx [0362U])
• Multigene and targeted multigene panels for the evaluation of indeterminate thyroid FNA cytopathology
• Single-site mutational analysis for the evaluation of indeterminate thyroid FNA cytopathology for any genes including, but may not be limited to:
  • DICER
  • EIF1AX

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

• NTRK
• PAX8/PPARgamma
• PIK3CA
• PTEN
• RAS (HRAS, KRAS, NRAS)
• RET/PTC
• TERT

• ThyGeNEXT (0245U)
• ThyraMIR (0018U)
• ThyroSeq CRC (0287U)
• Use of more than one molecular marker assay

These are considered experimental/investigational as they are not identified as widely used and generally accepted for any other proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language.

Additional information about thyroid nodules or cancer may be found from the following websites:

Background

• American Cancer Society
• American Thyroid Association
• National Library of Medicine

Medical Alternatives

Alternatives to molecular markers in FNA of thyroid nodules include, but may not be limited to:

• Watchful waiting (eg, observing for changes such as increase in size, worsening of symptoms or monitoring by repeat FNA or ultrasound)
• Surgery (thyroidectomy or thyroid lobectomy) (please refer to Thyroid Surgeries (Thyroidectomy & Lobectomy) Medical Coverage Policy)

Alternatives to molecular markers for evaluation of papillary thyroid carcinoma include, but may not be limited to:

• Staging systems to predict disease-specific survival (eg, tumor, node metastasis [TNM] classification scheme) and risk of disease recurrence (eg, American Thyroid Association [ATA] risk of recurrence staging system)

Physician consultation is advised to make an informed decision based on an individual’s health needs.

Humana may offer a disease management program for this condition. The member may call the number on his/her identification card to ask about our programs to help manage his/her care.

Any CPT, HCPCS or ICD codes listed on this medical coverage policy are for informational purposes only. Do not rely on the accuracy and inclusion of specific codes. Inclusion of a code does not guarantee coverage and or reimbursement for a service or procedure.