Gene Expression Profiling for Cutaneous Melanoma

POLICY NUMBER

A.2.04.146

DESCRIPTION

Laboratory tests have been developed that detect the expression of different genes in pigmented lesions or melanoma tumor tissue. Test results may help providers and patients decide whether to biopsy suspicious pigmented lesions, aid in the diagnosis of lesions with indeterminate histopathologic lesions or determine whether to perform sentinel lymph node biopsy in patients diagnosed with stage I or II cutaneous melanoma. This policy summarizes the evidence of three tests.

Cutaneous Melanoma

Cutaneous melanoma accounts for more than 90% of cases of melanoma. For many decades, melanoma incidence was rapidly increasing in the United States. However, recent estimates have suggested the rise may be slowing. In 2025, close to 105,000 new cases of melanoma are expected to be diagnosed, and more than 8,400 people are expected to die of melanoma.

Risk Factors

Exposure to solar ultraviolet radiation is a major risk factor for melanoma. Most melanomas occur on the sun-exposed skin, particularly those areas most susceptible to sunburn. Likewise, features that are associated with an individual’s sensitivity to sunlight, such as light skin pigmentation, red or blond hair, blue or green eyes, freckling tendency, and poor tanning ability are well-known risk factors for melanoma. There is also a strong association between high total body nevus counts and melanoma.

Several genes appear to contribute to melanoma predisposition such as tumor suppressor gene CDKN2A, melanocortin-1 receptor (MC1R) gene, and BAP1 variants. Individuals with either familial or sporadic melanoma have 2 to 3 times increased risk of developing a subsequent primary melanoma. Several occupational exposures and lifestyle factors, such as body mass index and smoking, have been evaluated as possible risk factors for melanoma.

Gene Expression Profiling

Gene expression profiling measures the activity of thousands of genes simultaneously and creates a snapshot of cellular function. Data for gene expression profiling are generated by several molecular technologies including DNA microarrays that measure activity relative to previously identified genes and RNA-Seq that directly sequences and quantifies RNA molecules. Clinical applications of gene expression profiling include disease diagnosis, disease classification, prediction of drug response, and prognosis.

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments. The Pigmented Lesion Assay®, myPath Melanoma®, and DecisionDx-Melanoma® tests are available under the auspices of the Clinical Laboratory Improvement Amendments. Laboratories that offer laboratory-developed tests must be licensed by the Clinical Laboratory Improvement Amendments for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.

POLICY

Gene expression testing, including but not limited to the Pigmented Lesion Assay, in the evaluation of individuals with suspicious pigmented lesions is considered investigational.

Gene expression testing, including but not limited to the myPath Melanoma test, in the evaluation of individuals with melanocytic lesions with indeterminate histopathologic features is considered investigational.

Gene expression testing, including but not limited to DecisionDx-Melanoma, in the evaluation of individuals with cutaneous melanoma is considered investigational for all indications.

POLICY EXCEPTIONS

None

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Genetic Counseling

Experts recommend formal genetic counseling for individuals who are at risk for inherited disorders and who wish to undergo genetic testing. Interpreting the results of genetic tests and understanding risk factors can be difficult for some individuals; genetic counseling helps individuals understand the impact of genetic testing, including the possible effects the test results could have on the individual or their family members. It should be noted that genetic counseling may alter the utilization of genetic testing substantially and may reduce inappropriate testing; further, genetic counseling should be performed by an individual with experience and expertise in genetic medicine and genetic testing methods.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

08/01/2019: New policy added. Approved by Medical Policy Advisory Committee.

06/19/2020: Policy reviewed; no changes.

12/16/2020: Code Reference section updated to add new CPT code 81529, effective 01/01/2021.

01/07/2022: Policy reviewed; no changes.

03/28/2022: Code Reference section updated to add new 04/01/2022 CPT code 0314U.

06/17/2022: Policy reviewed. Policy statements updated to change "patients" to "individuals."

11/09/2022: Code Reference section updated to add CPT codes 0089U and 0090U.

07/01/2023: Policy reviewed. Policy statements unchanged. Policy Guidelines updated to change "patients" to "individuals." Code Reference section updated to add new CPT code 0387U.

06/11/2024: Policy reviewed; no changes.

08/12/2025: Policy description updated regarding new data for melanoma. Policy statements unchanged.

10/01/2025: Code Reference section updated to add new CPT code 0578U.

SOURCE(S)

Blue Cross Blue Shield Association policy # 2.04.146

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

Investigational Codes

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