Molecular Markers in Fine Needle Aspirates of the Thyroid
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Defines medical necessity, investigational uses, and clinical guidance for molecular marker (mutation analysis, gene expression classifiers, microRNA) testing on fine-needle aspiration (FNA) specimens of thyroid nodules for evaluation of thyroid carcinoma in BCBSNC members.
No material clinical or coverage changes in this revision.
Coverage Criteria
inv-01: Covered when ALL of the following are met
Covered when ALL of the following are met:
BCBSNC will provide coverage when medically necessary and criteria are met.
inv-02: Not covered / Investigational — list of investigational indications
The following are considered investigational (not covered):
Policy lists these explicitly as investigational and not covered.
inv-03: Coverage criteria for molecular testing in indeterminate nodules
Covered when molecular testing is used to inform management for indeterminate FNA in appropriate clinical context
NCCN/ATA/AACE guidance supports consideration of molecular testing in these indeterminate groups; results should be interpreted in clinical context.
NCCN recommends weighing these options for AUS/FLUS; choice of test depends on cytology and clinical question.
ATA strongly recommends use of certified laboratories for clinical testing.
Per ATA guidance and policy documentation requirements.
inv-04: Indications for molecular testing — guideline-aligned indications to complement cytology
Covered when aligned with guideline-based indications for use in indeterminate thyroid cytology and to complement cytologic evaluation:
Policy and guideline statements (AACE/ETA/NCCN/ATA) support use when it will influence management; testing not recommended to replace diagnostic surgery when evidence insufficient.
inv-05: Guideline scenarios to consider testing — scenarios per cited guidelines
Consider molecular testing in the following clinical scenarios per cited guidelines:
Derived from NCCN, ATA, ETA recommendations; consider shared decision-making and sonographic size thresholds when applicable.
inv-06: Medical necessity criteria — Covered when ALL of the following are met
Covered when ALL of the following are met
Policy inception and subsequent updates document these cytology categories as covered indications.
Policy historically specifies these test types as medically necessary when criteria are met.
MicroRNA profiling assays performed on thyroid fine-needle aspirate (FNA) specimens (for example, ThyraMIR) are designated as investigational and are not covered under this policy.
Molecular testing of thyroid FNA specimens for individuals under 18 years of age is considered investigational and is not recommended for routine use, as pediatric molecular diagnostics for thyroid nodules have not been validated.
Molecular testing is not recommended for nodules with cytology that already establishes benign or malignant status; guideline statements advise that molecular testing should complement, not replace, cytologic evaluation and generally are not recommended for nodules with established benign (Bethesda II) or malignant (Bethesda V–VI) cytologic characteristics.
Guideline guidance emphasizes that molecular testing is generally not recommended for nodules with established benign or malignant cytologic characteristics and that gene expression classifiers cannot be recommended to exclude malignancy and thereby replace diagnostic surgery when evidence is insufficient.
Policy updates explicitly added that tests are not covered for nondiagnostic/unsatisfactory (Bethesda I) specimens and for benign (Bethesda II) cytology; this change is reflected in the policy’s “When Not Covered” statements and implementation history.
Testing performed on thyroid FNA cytology categorized as Bethesda I, II, V, or VI is considered investigational (not medically necessary) per the policy and therefore not covered.
Molecular diagnostics have not been validated for routine pediatric use; therefore molecular testing in children and adolescents cannot be recommended at this time and is considered investigational for patients <18 years.
Routine application of gene expression classifiers to definitively exclude malignancy and to supplant diagnostic surgery is not supported by current evidence and is therefore not recommended.
The policy was specifically revised to clarify that molecular testing on nondiagnostic/unsatisfactory (Bethesda I) or benign (Bethesda II) cytology is not covered, and this exclusion is documented in the policy implementation history.
Billing and Coding
| not specified | Proprietary test names discussed: Afirma GSC, Afirma Xpression Atlas, ThyroSeq v2/v3, RosettaGX Reveal, NeoGenomics NeoTYPE |
| CPT 81445 | Listed in historical Billing/Coding updates |
| PLA 0018U | Listed in historical Billing/Coding updates |
| PLA 0026U | Listed in historical Billing/Coding updates |
| CPT 81546 | Added to Billing/Coding section |
| PLA 0204U | Added then later deleted per updates |
| PLA 0208U | Added then removed from Billing/Coding section |
| PLA 0245U | Added to Billing/Coding section |
| CPT 81455 | Added to Billing/Coding section |
| PLA 0287U | Added to Billing/Coding section effective 7/1/22 |
Provider Actions and Documentation
Prior authorization: verify benefits and document applicable cytology
Verify member benefits prior to ordering molecular testing and document that the FNA cytology is Bethesda-III (AUS/FLUS) or Bethesda-IV (FN/SFN) in an adult (≥18 years) when requesting prior authorization; member benefits may vary by plan.
- Prior authorization may be required per member benefit design.
- Document patient age and FNA cytology (Bethesda category) when submitting authorization or claim.
Prior authorization for molecular testing — considered for indeterminate FNA results (AUS/FLUS, FN/SFN)
When seeking prior authorization, indicate that molecular diagnostic testing is being requested to inform management of indeterminate FNA results (AUS/FLUS [Bethesda III] or FN/SFN [Bethesda IV]) and select the specific test based on the cytology and clinical question.
- Molecular diagnostics may be used to reclassify indeterminate lesions and to drive treatment decisions.
- Choice of precise molecular test depends on the cytology and clinical question being asked.
Medical records may be requested for determination of medical necessity
BCBSNC may request full medical records to determine medical necessity for billed services; when medical records are requested, letters of support alone are insufficient unless they include all specific information needed to make the determination.
- Medical records may be requested for services billed with listed codes.
- Letters of support/explanation are useful but not sufficient unless they include all specific information required.
Use current codes when submitting claims — billing/coding updates over time
Bill using current, valid CPT and PLA codes at the time of service; inclusion of a code in the policy’s Billing/Coding section does not guarantee reimbursement and codes have been added/removed over time.
- Use current codes listed in the policy at time of service.
- Inclusion of a code in Billing/Coding does not guarantee reimbursement; BCBSNC may request records to determine medical necessity.
No step therapy specified; molecular testing as adjunct for indeterminate FNAs
No step therapy is specified in this policy; molecular testing is described as an adjunct to inform management of indeterminate FNAs rather than as a mandated step before other interventions.
- Policy indicates molecular testing may be used instead of immediate surgery or repeat FNA in select indeterminate cases.
- No required step-therapy sequence is defined in the policy.
Alternatives to molecular testing — repeat FNA, second opinion, surgery, or surveillance
Before proceeding with molecular testing, consider and document alternative management options such as repeat FNA (with possible second-opinion pathology), diagnostic lobectomy, or surveillance as appropriate to clinical and sonographic features.
- Repeat FNA with second-opinion pathology may be considered.
- Diagnostic lobectomy or surveillance are acceptable alternatives depending on clinical context.
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Document cytology and age — confirm benefits and record FNA cytology and patient age
Confirm benefits and document the FNA cytology (Bethesda category) and patient age when ordering or billing for molecular testing; testing is medically necessary only when adult age and appropriate Bethesda-III or IV cytology criteria are met.
- Document patient age (≥18 years) and FNA cytology (Bethesda-III or IV).
- Verify member benefits prior to testing.
Required documentation and patient counseling — counseling about benefits/limitations and CLIA/CAP-certified labs
Document nodule size (>1 cm generally recommended for evaluation), cytology category, sonographic and clinical risk features, and that the patient was counseled on the benefits and limitations of testing; ensure testing is performed in a CLIA/CAP-certified (or international equivalent) laboratory when intended for clinical use.
- Document nodule size, cytology (eg, AUS/FLUS, FN/SFN), and sonographic/clinical features.
- Document patient counseling regarding benefits/limitations and use of CLIA/CAP-certified lab.
BCBSNC may request medical records; letters of support insufficient without full documentation
When BCBSNC requests records to determine medical necessity, provide full clinical documentation; letters alone are not sufficient unless they include all specific information needed for the determination.
- Provide full medical records when requested; letters of support are only adequate if they contain all required details.
- BCBSNC may request records for services billed with the listed codes.
Required clinical documentation — link medical necessity to indeterminate cytologic characterization
Include clinical documentation that ties medical necessity to indeterminate cytology (follicular cell neoplasm/suspicious for follicular neoplasm [FN/SFN] or atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS]) in adults being evaluated for thyroid carcinoma.
- Document that the specimen is FNA with cytology of FN/SFN or AUS/FLUS.
- Confirm patient is an adult (>18 years) being evaluated for thyroid carcinoma.
Testing performed for individuals under 18 or for Bethesda I, II, V, or VI is investigational
Ordering or performing molecular testing for individuals under 18 years of age or for FNAs with Bethesda I, II, V, or VI cytology is considered investigational and may be denied; avoid ordering/testing in these situations for coverage-seeking purposes.
- Testing for individuals under 18 years is investigational.
- Testing on Bethesda I (nondiagnostic), II (benign), V (suspicious for malignancy), or VI (malignant) cytology is investigational.
Adequacy and contextual interpretation — interpret results in clinical/radiographic/cytologic context
Ensure molecular test results are interpreted in the context of clinical, radiographic, and cytologic features; provide evidence of technical adequacy of the specimen because technically inadequate or context-free results may prompt repeat FNA or denial.
- Molecular markers should be interpreted within the context of each patient’s clinical, radiographic, and cytologic features.
- If molecular diagnostics are technically inadequate or not done, repeat FNA may be required.
Inclusion of a code does not guarantee reimbursement; BCBSNC may request records
Inclusion of a code in the Billing/Coding section does not guarantee reimbursement; BCBSNC may request medical records to determine medical necessity for the billed service.
- Inclusion of a code in the policy’s Billing/Coding list does not guarantee payment.
- BCBSNC may request records and will evaluate medical necessity when determining reimbursement.
Indication-based coverage limits — tests covered only for specified cytology categories in adults
Tests are covered only for specified cytology categories in adult patients (AUS/FLUS [Bethesda III] or FN/SFN [Bethesda IV]); cases outside those indications (eg, Bethesda I, II, V, VI or individuals <18 years) are documented as investigational and may be denied.
- Coverage is limited to adult patients with indeterminate cytology (Bethesda III or IV).
- Cases outside those indications are considered investigational/not covered.
Background
Thyroid nodules are common and FNA is the primary diagnostic approach; approximately 20–30% of FNAs yield indeterminate cytology (Bethesda III–IV). Molecular marker testing (mutation panels, gene expression classifiers, microRNA assays) may be used to refine malignancy risk for indeterminate nodules in adults, but guidelines and this policy emphasize that testing should complement cytology, be performed in certified laboratories, and be applied selectively when results are expected to influence management.
Definitions and Test Types
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