DraftBlue Cross Blue Shield - Rhode IslandPolicy N/A

Molecular Markers in Fine Needle Aspirates of the Thyroid

Defines medical necessity, prior authorization, and coverage criteria for commercial and Medicare BlueCHiP products for molecular assays (e.g., Afirma, ThyraMIR, ThyGeNEXT, RosettaGX Reveal, ThyroSeq) used to evaluate indeterminate thyroid FNA cytology and to guide surgical planning.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMolecular Markers in Fine Needle Aspirates of the Thyroid

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateJul 1, 2020

Next Review DateN/A

Key ActionObtain prior authorization for BlueCHiP for Medicare (recommended for Commercial) via the payer online tool before ordering molecular thyroid testing.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

5named molecular tests addressed

Bethesda III-IV-VFNA cytology categories referenced

Requiredprior authorization

112 genesThyroSeq panel size

Provider updatesreferences cited

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Coverage Criteria for Molecular Testing of Thyroid FNA

Afirma (including Afirma BRAF and Afirma MTC)

Covered when ALL of the following are met:

Afirma general: Patient has one or more thyroid nodules with a history or characteristics suggesting malignancy (examples include nodule growth over time; hoarseness, difficulty swallowing or breathing; family history of thyroid cancer; history of exposure to ionizing radiation; presence of cervical adenopathy; a hard nodule compared with the rest of the gland); AND an indeterminate follicular pathology on fine needle aspiration (Bethesda indeterminate categories).

Afirma BRAF and Afirma MTC are medically necessary after a positive Afirma Genomic Sequencing Classifier result.

ThyraMIR, ThyGeNEXT (ThyGenX), RosettaGX Reveal

Covered when ALL of the following are met:

ThyraMIR/ThyGenX/RosettaGX Reveal: Patient has one or more thyroid nodules with history or characteristics suggesting malignancy (examples include nodule growth over time; hoarseness, difficulty swallowing or breathing; family history of thyroid cancer; history of exposure to ionizing radiation; presence of cervical adenopathy; a hard nodule compared with the rest of the gland) AND an indeterminate pathology on fine needle aspiration.

ThyraMIR is intended for use following a negative ThyGenX result as part of an algorithmic strategy; ThyGenX positive results inform preoperative planning; ThyraMIR negative results support active surveillance.

ThyroSeq

Covered when ALL of the following are met:

ThyroSeq: Thyroid nodule cytology in Bethesda diagnostic category III, IV, or V (indeterminate or suspicious cytologic findings on FNA) to assist in ruling in malignancy and guide initial surgical planning (to choose initial resection rather than staged surgery).

Intended for indeterminate or suspicious cytologic findings to inform extent of initial surgery.

Overall coverage linkage

Covered when ALL of the following are met

General coverage linkage: The listed molecular tests (eg, Afirma, ThyGeNEXT/ThyGenX, ThyraMIR, ThyroSeq) are covered when the specific medical criteria described in this policy are met and appropriate CPT/PLA codes are used.

See policy medical criteria section for exact patient selection details and applicable CPT/PLA codes.

Described testing algorithms

Algorithmic testing approaches (clinical use described)

Afirma malignancy classifiers: Afirma GEC/GSC with Afirma MTC and Afirma BRAF are mRNA expression–based malignancy classifiers intended to predict BRAF or medullary thyroid carcinoma–associated variants from FNA samples to inform preoperative planning; a positive result would influence decisions such as hemi- versus total thyroidectomy or performance of central neck dissection.

Described benefits include detection of variants not captured by single-variant PCR and informing surgical planning.

ThyGenX plus ThyraMIR reflex strategy: ThyGenX (NGS oncogene panel) is used first to detect oncogenic mutations; if ThyGenX is negative, reflex testing with the ThyraMIR microRNA expression classifier may be performed to provide high negative predictive value and potentially avoid diagnostic surgery, with ThyraMIR negative results supporting active surveillance.

Described clinical reflex testing pathway; sequence is a testing strategy rather than an explicit coverage step therapy requirement.

Coverage for laboratory-based molecular testing described in this policy is governed by the member's individual group or contract benefits. Refer to the member's Coverage or Subscriber Agreement for specific limitations on laboratory tests and to determine whether a given test is a covered benefit under that contract.

Services that are determined to be not medically necessary or that are specifically designated as non‑covered benefits under the member's contract are excluded from coverage. Providers may not bill the member for such services unless the member has been informed and has provided prior written agreement to assume financial responsibility.

Historically, many patients with indeterminate thyroid FNA cytology proceed to diagnostic surgery because cytology has limited specificity. The policy notes that roughly 80% of patients with indeterminate cytology undergo surgical resection and postoperative pathology shows a malignancy rate varying from 6% to 30%. Molecular testing has been developed to improve risk stratification of indeterminate nodules and potentially reduce unnecessary diagnostic surgery and enable more informed preoperative planning.

Determinations that a test is not medically necessary will result in noncoverage in accordance with the member's subscriber agreement, certificate, or employer agreement; those documents supersede this policy. For member‑specific benefit or eligibility questions, contact the payer's provider call center as benefit determinations are made at the contract level.

Coding and Billing

Named CPT code referencesCPT

81545

Afirma (listed CPT in document)

Other referenced CPT/HCPCSCPT

0018U	ThyraMIR
81445	ThyGenX (listed as CPT 81445 in document)
Unlisted CPT	RosettaGX Reveal thyroid microRNA test (no specific CPT assigned)

ThyroSeq codingCPT

0026U

ThyroSeq (document lists 0026U)

Covered CPT/PLA/Temporary CodesmixedCovered

81445	Brand Name = ThyGeNEXTR; Targeted genomic sequence analysis solid organ neoplasm, DNA analysis, and RNA analysis when performed, 5-50 genes
81545	Brand Name = Afirma; Oncology (thyroid), gene expression analysis of 142 genes, utilizing fine needle aspirate, algorithm reported as categorical result
0018U	Brand Name = ThyraMIR; Oncology (thyroid), microRNA profiling by RT-PCR of 10 microRNA sequences, utilizing fine needle aspirate, algorithm reported as positive or negative
0026U	Brand Name = ThyroSeq; Oncology (thyroid); DNA and mRNA of 112 genes, next-generation sequencing, fine needle aspirate, algorithmic analysis reported as categorical result

Unlisted codesCPT

UNLISTED

Tests without specific CPT codes should be filed using an appropriate unlisted code.

Provider Actions, Authorization, and Claims

Prior Authorization

Prior Authorization Required

Prior authorization is required for BlueCHiP for Medicare and recommended for Commercial products. Participating providers must obtain prior authorization via the online tool. All services that are reported with unlisted CPT codes require prior authorization so the payer can determine what service was rendered and whether the service is covered or medically necessary.

Prior authorization required for BlueCHiP for Medicare; recommended for Commercial Products.
Prior authorization obtained via the online tool for participating providers.

Billing Rule

Authorization for Unlisted/Novel Tests

Services billed with unlisted CPT codes (for tests without an assigned specific CPT) require authorization prior to payment to establish the specific test performed and determine coverage. Providers should file claims using the appropriate unlisted CPT when no specific CPT exists and follow the Coding section for details.

Background

Thyroid nodules are common and most are benign. Fine needle aspiration (FNA) cytology reduces unnecessary surgery but yields indeterminate results in a substantial minority of cases. Indeterminate cytologic categories (Bethesda III–V) present diagnostic uncertainty: many patients with these findings proceed to surgery because cytology alone has low specificity. Molecular assays (including variant analysis, NGS panels, gene‑expression classifiers, and microRNA classifiers) are intended to improve risk stratification of indeterminate nodules and to inform the need for and extent of initial surgery.

Key Definitions and Test Descriptions

inv-24: Bethesda diagnostic category III — AUS/FLUS

DefinitionAtypia/follicular lesion of undetermined significance (AUS/FLUS).

Bethesda categoryCategory III

Clinical contextIndeterminate cytologic finding on thyroid FNA that may prompt consideration of molecular testing to further risk-stratify and guide management.

inv-25: Bethesda diagnostic category IV — Follicular neoplasm or suspicion for a follicular neoplasm

DefinitionFollicular neoplasm or suspicion for a follicular neoplasm.

Bethesda categoryCategory IV

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMolecular Markers in Fine Needle Aspirates of the Thyroid

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateJul 1, 2020

Next Review DateN/A

Key ActionObtain prior authorization for BlueCHiP for Medicare (recommended for Commercial) via the payer online tool before ordering molecular thyroid testing.

SourceLink

On This Page

Use an Unlisted CPT code when a specific CPT is not assigned for the test.
All Unlisted CPT-coded tests require authorization to determine coverage and medical necessity.

Documentation Required

Clinical Documentation to Support Medical Necessity

Clinical documentation must support the medical necessity of molecular testing. Documentation should include evidence of indeterminate fine needle aspiration (FNA) cytology and relevant clinical features that increase pretest probability of malignancy (examples: nodule growth, hoarseness or dysphagia, family history of thyroid cancer, prior ionizing radiation exposure, cervical adenopathy, or a firm nodule). For reflex/algorithmic testing, include documentation of prior test results (e.g., ThyGenX result prior to ThyraMIR reflex; Afirma GSC result prior to Afirma BRAF/MTC) and the clinical rationale for sequencing.

Document indeterminate FNA cytology.
Document clinical features that raise malignancy risk (nodule growth, hoarseness, family history, ionizing radiation exposure, cervical adenopathy, hard/firm nodule).
Include prior test results and rationale for reflex/algorithmic testing (e.g., ThyGenX negative with plan for ThyraMIR reflex).

Note

Described Testing Sequence

Sequential (algorithmic/reflex) testing strategies described in this policy must be followed and documented. Example sequences include: perform ThyGenX (Thyroid Oncogene Panel) first; if ThyGenX is negative, reflex to ThyraMIR microRNA expression testing to obtain a high negative predictive value and potentially avoid surgery. For Afirma, Afirma GSC may be supplemented by Afirma BRAF or Afirma MTC classifiers when indicated; a positive Afirma BRAF or MTC result informs preoperative planning. Document the stepwise test order and how each result affects management.

ThyGenX first; if negative, reflex to ThyraMIR.
Afirma GSC with reflex to Afirma BRAF or Afirma MTC as clinically indicated to inform surgical planning.

Denial Risk

Member Financial Liability Risk

If services are determined to be not medically necessary or are non-covered benefits, coverage may be denied and the member may be financially liable unless a written agreement is obtained in advance. Providers should verify member-specific benefits and eligibility prior to testing and inform members if there is potential for out-of-pocket liability.

Benefits and eligibility are determined by the member's subscriber agreement; contact the provider call center for member-specific benefit information.
Non-medically necessary or non-covered services may be denied; members may be billed only if notified and a written agreement obtained in advance.

Clinical significance

Indeterminate cytologic finding on thyroid FNA used to identify nodules for potential molecular testing to inform surgical planning.

inv-26: Bethesda diagnostic category V — Suspicious for malignancy

DefinitionSuspicious for malignancy.

Bethesda categoryCategory V

Clinical significanceCytology indicates higher likelihood of malignancy; molecular testing may be used to assist in preoperative planning.

inv-27: Afirma BRAF / Afirma MTC — mRNA expression–based malignancy classifiers

Test typemRNA expression–based malignancy classifiers to evaluate for BRAF variants (Afirma BRAF) and medullary thyroid carcinoma–associated variants (Afirma MTC).

Intended usePredict malignancy from an FNA sample with increased pretest probability to inform preoperative planning (e.g., hemi- vs total thyroidectomy, central neck dissection).

RationaleDesigned to detect variants that may be missed by single-variant PCR due to low sensitivity or low-frequency variants; may perform on small FNA samples where DNA quantity is limited.

inv-28: ThyGenX — NGS oncogene panel for thyroid FNA

Test typeNGS oncogene panel (ThyGenX Thyroid Oncogene Panel) assessing multiple hotspot mutations associated with papillary and follicular carcinomas.

Intended useAssess patients with indeterminate thyroid FNA results to predict malignancy and inform preoperative surgical planning when positive.

Testing contextPerformed at a clinical laboratory (Interpace Diagnostics/Asuragen) as part of an algorithmic approach with reflex testing if negative.

inv-29: ThyraMIR — microRNA expression–based classifier used reflexively after negative ThyGenX

Test typeMicroRNA expression–based classifier intended for use following a negative ThyGenX result.

PurposeProvides a high negative predictive value to help rule out malignancy and potentially avoid surgery when used as a reflex test after negative ThyGenX.

Algorithmic roleUsed reflexively after ThyGenX negative results in combined testing strategy (ThyGenX first, ThyraMIR reflex if negative).