CPT 81546 Thyroid mRNA Profiling Reimbursement | OpenPayer

Summary & Overview

CPT 81546: Thyroid mRNA Gene Expression Profiling, Benign or Suspicious

CPT code 81546 designates a laboratory-based molecular diagnostic service that performs high‑throughput mRNA gene expression profiling on thyroid fine needle aspiration (FNA) specimens and applies an algorithmic analysis to report a binary result of “benign” or “suspicious” for thyroid cancer. This test informs clinical decision-making for indeterminate thyroid cytology by providing additional molecular risk stratification and can affect the need for diagnostic surgery or surveillance.

Key payers covered in this national overview include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise description of the clinical application and service setting, an explanation of what CPT code 81546 represents, and context on why molecular profiling matters for thyroid nodule management. The publication summarizes benchmarks and coverage considerations relevant to major payers, outlines common clinical scenarios in which the test is used, and highlights where policy updates and reimbursement practices commonly vary.

This summary is intended to orient clinicians, laboratory administrators, and policy analysts to the code’s clinical role, payer landscape, and the types of operational and coverage topics to expect in the full publication. Data not available in the input is noted where applicable.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicareCPT 81546molecular diagnosticsthyroid FNAgene expression profilingalgorithmic analysisthyroid cancerlab testing

Billing Code Overview

CPT code 81546 describes a molecular diagnostic test performed on a thyroid fine needle aspiration (FNA) specimen. The lab performs mRNA gene expression profiling across 10,196 genes and applies an algorithm that incorporates patient data and the laboratory results to produce a categorical report of “benign” or “suspicious” for thyroid cancer.

Service Type: Molecular diagnostic laboratory test — mRNA gene expression profiling with algorithmic analysis

Typical Site of Service: Clinical laboratory or reference molecular diagnostics laboratory receiving thyroid FNA specimens

Clinical & Coding Specifications

Clinical Context

A 45-year-old woman presents with a solitary thyroid nodule detected on palpation and confirmed by ultrasound. Fine needle aspiration (FNA) of the nodule is performed by an endocrinologist or head and neck surgeon; cytology returns an indeterminate or suspicious category (for example, Bethesda III–V). To refine malignancy risk and guide management, a laboratory performs mRNA gene expression profiling on the residual FNA specimen, analyzing expression of thousands of genes and applying an algorithm that incorporates the molecular results and patient data to generate a categorical report of benign or suspicious for thyroid cancer. Typical workflow: FNA specimen collection (clinic or radiology), specimen stabilization and shipment to the molecular laboratory, laboratory technical analysis (mRNA extraction, sequencing or expression profiling) and algorithmic interpretation, and return of the categorical result to the ordering clinician for surgical decision-making or surveillance planning.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	When reporting only the physician professional interpretation if separated from the lab technical processing.

CPT 81508: PAPP–A and hCG Laboratory Assay with Algorithmic Risk Score

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CPT 81536: Tumor Cell Culture, DAPI Staining, Predictive Drug Response Score

CPT-81595-MOLECULAR-TEST-HEART-TRANSPLANT-REJECTION-RISK

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CPT-81504-TUMOR-ORIGIN-RNA-EXPRESSION-CLASSIFIER

CPT 81504: RNA Expression Tumor Origin Classifier

CPT-81500-CA125-HE4-ALGORITHMIC-RISK-SCORE

CPT 81500: CA-125 and HE4 Laboratory Testing with Algorithmic Risk Score

CPT-81490-RA-DISEASE-ACTIVITY-SCORE-SERUM-BIOMARKER-PANEL

CPT 81490: RA Disease Activity Score from 12-Serum Biomarker Panel

CPT-81523-BREAST-TUMOR-NGS-MRNA-EXPRESSION-RISK-INDEX

CPT 81523: NGS Breast Tumor mRNA Expression Risk Index

CPT-81528-STOOL-DNA-AND-FECAL-HEMOGLOBIN-COLORECTAL-CANCER-SCREENING

CPT 81528: Stool DNA and Fecal Hemoglobin Colorectal Cancer Screening Test

CPT-81558-KIDNEY-TRANSPLANT-MRNA-GENE-EXPRESSION-PROFILING

CPT 81558: mRNA Gene Expression Profiling for Kidney Transplant Monitoring

CPT-81542-PROSTATE-CANCER-22-GENE-MRNA-RISK-SCORE

CPT 81542: mRNA 22-Gene Expression Profiling and Prostate Cancer Risk Score

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Taxonomy Code	Specialty	Notes
207RE0101X	Otolaryngology (ENT)	Performs thyroid FNA and coordinates diagnostic workup for thyroid nodules.
207K00000X	Endocrinology	Orders and interprets molecular testing for thyroid nodules as part of endocrine management.
207L00000X	General Surgery	Manages surgical decision-making for thyroid disease and may perform FNA or operative management.
207QA0000X	Radiology/Diagnostic Imaging	Performs ultrasound-guided FNA when image guidance is required.
2085P0200X	Pathology/Laboratory Medicine	Provides cytology interpretation and may coordinate specimen routing to molecular labs.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`E04.1`	Nontoxic single thyroid nodule	Common indication for FNA and subsequent molecular profiling to assess malignancy risk.
`E04.2`	Nontoxic multinodular goiter	Individual nodules within a multinodular gland may undergo FNA and molecular testing if cytology is indeterminate.
`E07.1`	Other hypersecretion of thyroid	Nodules associated with functional changes may still require evaluation; molecular testing considered when nodules are suspicious.
`R07.9`	Chest pain, unspecified	Not typically related; included only if clinical presentation prompts imaging that incidentally detects a thyroid lesion — otherwise rarely used.
`C73`	Malignant neoplasm of thyroid gland	Definitive diagnosis of thyroid cancer; molecular testing helps risk-stratify nodules and inform need for surgery.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`10021`	Fine needle aspiration without imaging guidance	Represents non–image-guided specimen collection that may provide the FNA material used for molecular profiling.
`10022`	Fine needle aspiration with imaging guidance	Represents ultrasound- or CT-guided FNA collection when image guidance is used prior to molecular testing.
`88172`	Cytopathology, assessment of fine needle aspirate; immediate cytologic evaluation	On-site adequacy assessment that may occur during FNA to ensure sufficient material for routine cytology and molecular testing.
`88305`	Surgical pathology, gross and microscopic examination	Pathology evaluation of cell block or tissue obtained from FNA; may be billed when additional cytologic blocks are processed prior to molecular referral.
`81399`	Unlisted molecular pathology procedure	Used when a specific molecular test lacks a unique CPT; historically used for novel assays but modern multigene panels may have dedicated codes like `81546`.
`81546`	Thyroid FNA mRNA gene expression profiling, algorithmic analysis, report benign or suspicious	The molecular diagnostic test that performs mRNA profiling and algorithmic interpretation to report a categorical result guiding management.

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