Molecular Markers in Fine Needle Aspiration of the Thyroid
Customize your policy alerts
Sign up for all Blue Cross Blue Shield - Rhode Island policy alerts
Know when Blue Cross Blue Shield - Rhode Island releases new policies or updates existing guidance.
Monitor payer policy activity
Policy governing medical necessity and coverage of molecular marker and genomic tests used to evaluate indeterminate thyroid fine needle aspiration (FNA) samples for members of Blue Cross Blue Shield - Rhode Island (Medicare Advantage and Commercial products).
No material clinical or coverage changes in this revision.
Coverage Criteria for Molecular Testing of Indeterminate Thyroid FNA
Afirma GSC (rule-out)
Afirma GSC may be considered medically necessary when ALL of the following are met
Patients must have both conditions
Afirma BRAF and Afirma MTC (reflex)
Afirma BRAF and Afirma MTC
Used to inform preoperative planning such as choice of hemi- versus total thyroidectomy or need for central neck dissection
ThyraMIR / ThyGeNEXT / RosettaGX Reveal
These microRNA and NGS panel services may be considered reasonable and necessary when ANY of the following apply
Applies to ThyraMIR (0018U), ThyGeNEXT (0245U), and RosettaGX Reveal (81479)
ThyroSeq (single-use per nodule)
ThyroSeq testing may be considered medically necessary ONCE per nodule when ALL of the following are met
Testing is limited to once per nodule
ThyroSeq CRC (rule-in for surgical planning)
ThyroSeq CRC may be considered medically necessary when
Used to inform extent of initial surgery
Covered testing strategies and intended clinical use
Coverage and intended testing strategies as described in the policy:
Afirma GSC has CPT 81546; Afirma Xpression Atlas (0204U) is not covered
Examples: ThyGeNEXT/ThyGenX code 0245U; ThyraMIR code 0018U
Afirma Xpression Atlas (CPT 0204U) is not covered for Medicare Advantage Plans and is considered not medically necessary for Commercial Products due to insufficient evidence demonstrating an effect on health outcomes. Providers should not expect coverage of this test for members under either product line.
The policy explicitly lists CPT 0204U (Afirma Xpression Atlas: mRNA, gene expression analysis of 593 genes) as not covered for Medicare Advantage Plans and not medically necessary for Commercial Products because available evidence is insufficient to determine clinical benefit.
Short summary: Afirma Xpression Atlas (CPT 0204U) is not covered / not medically necessary for the products addressed in this policy.
Coverage distinction: Afirma Xpression Atlas (CPT 0204U) is specifically designated as not covered for Medicare Advantage Plans and not medically necessary for Commercial Products. This contrasts with other proprietary thyroid molecular tests in the policy that have specific CPT/PLA codes and may be medically necessary when policy criteria are met.
CPT / PLA / Billing Codes
| 81546 | Afirma Genomic Sequencing Classifier (GSC) - listed in header as CPT 81546 |
| 81479 | Afirma BRAF / Afirma MTC / RosettaGX Reveal - miscellaneous molecular pathology |
| 0018U | ThyraMIR - Oncology (thyroid), microRNA profiling by RT-PCR of 10 microRNA sequences, utilizing fine needle aspirate, algorithm reported as a positive or negative result for moderate to high risk of malignancy |
| 0245U | ThyGeNEXT - Oncology (thyroid), mutation analysis of 10 genes and 37 RNA fusions and expression of 4 mRNA markers using next-generation sequencing, fine needle aspirate, report includes associated risk of malignancy expressed as a percentage |
| 0026U | ThyroSeq - Oncology (thyroid), DNA and mRNA of 112 genes, next-generation sequencing, fine needle aspirate of thyroid nodule, algorithmic analysis reported as a categorical result ("Positive, high probability of malignancy" or "Negative, low probability of malignancy") |
| 0287U | ThyroSeq CRC - Oncology (thyroid), DNA and mRNA, next generation sequencing analysis of 112 genes, fine needle aspirate or formalin fixed paraffin-embedded (FFPE) tissue, algorithmic prediction of cancer recurrence, reported as a categorical risk result (low, intermediate, high) |
| 0204U | Afirma Xpression Atlas - Oncology (thyroid), mRNA, gene expression analysis of 593 genes (including BRAF, RAS, RET, PAX8, and NTRK) for sequence variants and rearrangements, utilizing fine needle aspirate, reported as detected or not detected |
| 0245U | Oncology (thyroid), mutation analysis of 10 genes and 37 RNA fusions and expression of 4 mRNA markers using next-generation sequencing, fine needle aspirate, report includes associated risk of malignancy expressed as a percentage |
| 81546 | Oncology (thyroid), mRNA, gene expression analysis of 10,196 genes, utilizing fine needle aspirate, algorithm reported as a categorical result (eg, benign or suspicious) |
| 0018U | Oncology (thyroid), microRNA profiling by RT-PCR of 10 microRNA sequences, utilizing fine needle aspirate, algorithm reported as a positive or negative result for moderate to high risk of malignancy |
| 0026U | Oncology (thyroid), DNA and mRNA of 112 genes, next-generation sequencing, fine needle aspirate of thyroid nodule, algorithmic analysis reported as a categorical result ("Positive, high probability of malignancy" or "Negative, low probability of malignancy") |
| 0287U | Oncology (thyroid), DNA and mRNA, next generation sequencing analysis of 112 genes, fine needle aspirate or formalin fixed paraffin-embedded (FFPE) tissue, algorithmic prediction of cancer recurrence, reported as a categorical risk result (low, intermediate, high) |
| 0204U | Oncology (thyroid), mRNA, gene expression analysis of 593 genes (including BRAF, RAS, RET, PAX8, and NTRK) for sequence variants and rearrangements, utilizing fine needle aspirate, reported as detected or not detected |
| 81479 | Unlisted molecular pathology procedure |
Provider Actions, Authorization, and Billing Guidance
Prior Authorization Required
Prior authorization is required for Medicare Advantage Plans and is recommended for Commercial Products. Unlisted molecular pathology CPT codes (eg, 81479) must have prior authorization to establish what service is being rendered and to determine coverage or medical necessity. Laboratories are not permitted to obtain clinical authorization or participate in the authorization process on behalf of the ordering physician; only the ordering physician may submit and manage authorizations and appeals. If a laboratory provides a service that was not authorized, the service will be denied and the participating laboratory is financially liable and may not bill the member.
- Prior authorization required for Medicare Advantage; recommended for Commercial.
- All unlisted genetic/molecular testing CPT codes (eg, 81479) require prior authorization.
- Laboratories may not obtain authorization on behalf of ordering physicians; unauthorized lab services will be denied and financial liability rests with the lab.
Algorithmic/Reflex Testing
Some commercial vendor tests are performed in an algorithmic or reflex sequence (one test first, then a second test only if the first is negative or indeterminate). These reflex strategies affect ordering, authorization, and billing workflows because the initial test result determines whether the reflex test is performed and authorized.
- Afirma pathway: Afirma GSC may be followed by Afirma BRAF or Afirma MTC as clinically indicated.
- ThyGenX/ThyraMIR pathway: ThyGenX is performed first; if ThyGenX is negative, reflex to ThyraMIR to provide a high negative predictive value and potentially avoid surgery.
Reflex Testing Sequence (ThyGenX → ThyraMIR)
The policy describes a specific reflex testing sequence for ThyGenX and ThyraMIR: perform ThyGenX (eg, CPT 0245U) first to identify patients who "rule in" for surgical management; if ThyGenX is negative, reflex to ThyraMIR (eg, CPT 0018U) to "rule out" malignancy and support active surveillance instead of surgery.
Background and Clinical Context
Thyroid nodules are common and most are benign; sampling by fine needle aspiration (FNA) is the standard diagnostic method to distinguish benign from malignant lesions. Despite FNA’s utility, approximately 20–30% of nodules yield indeterminate cytology (Bethesda categories III–V), which often prompts diagnostic surgery. Molecular testing of FNA samples is intended to improve diagnostic accuracy by either ruling out malignancy (to avoid surgery) or ruling in malignancy (to guide definitive surgical planning).
Definitions and Key Terms
Policy Revision History
OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.