Medical Policy: 02.04.72
Original Effective Date: May 2018
Reviewed: May 2020
Revised: May 2020
This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.
Benefit determinations are based on the applicable contract language in effect at the time the
services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary
based on contract, and individual member benefits must be verified. Wellmark determines medical
necessity only if the benefit exists and no contract exclusions are applicable. This medical
policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document
was developed. Since that time, new technology may have emerged or new medical literature may
have been published. This Medical Policy will be reviewed regularly and be updated as scientific
and medical literature becomes available.
Gene expression profiling measures the activity of thousands of genes simultaneously and creates a snapshot of cellular function. Data for gene expression profiles are generated by several molecular technologies including DNA microarrays that measures 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.
Melanoma is a cancer that begins in the melanocytes. Other names for this cancer include malignant melanoma and cutaneous melanoma. Most melanoma cells still make melanin, so melanoma tumors are usually brown or black. But some melanomas do not make melanin and can appear pink, tan or even white. Melanomas can develop anywhere on the skin, but they are more likely to start on the trunk (chest and back) in men and on the legs in women. The neck and face are other common sites.
Risk factors for melanoma include skin type, personal history of prior melanoma, multiple clinically atypical moles or dysplastic nevi, a positive family history of melanoma, and rarely, inherited genetic mutations. Genetic counseling could be considered for individuals with a strong family history of invasive melanoma with or without pancreatic cancer. In addition to genetic factors, environmental factors including excess sun exposure and UV-based artificial tanning contribute to the development of melanoma. The interaction between genetic susceptibility and environmental exposure is illustrated in individuals with an inability to tan and fair skin that sunburns easily who have a greater risk of developing melanoma. However, melanoma can occur in any ethnic group and, also in areas of the body without substantial sun exposure.
As with nearly all malignancies, the outcome of melanoma depends on the stage at presentation. In the United States, it is estimated that 84% of patients with melanoma initially present with localized disease, 9% with regional disease, and 4% with distant metastatic disease. In general, the prognosis is excellent for patients who present with localized disease and primary tumors 1.0 mm or less in thickness, with 5-year survival achieved in more than 90% of patients. For patients with localized melanomas more than 1.0 mm in thickness, survival rates range from 50% to 90% depending on tumor thickness, ulceration and miotic rate. The likelihood of regional nodal involvement increases with increasing tumor thickness, as well as the presence of ulceration and miotic rate. When regional nodes are involved, survival rates are roughly halved.
There is increasing appreciation of the variations in specific genetic alternations among distinct clinical subtypes of melanoma. Currently described clinical subtypes of cutaneous melanoma are: non-chronic sun damage (non-CSD); melanoma on skin without chronic sun-induced damage; CSD: melanomas on skin with chronic sun-induced damage signified by the presence of marked elastosis; and acral; melanomas of the soles, palms, or sub-ungual sites.
Different subtypes of melanoma have been found to have very different genetic profiles, some of which have different therapeutic implications. Ina n analysis of 102 primary melanomas, the non-CSD subtype was found to have the highest proportion of BRAF mutations (56%) compared to CSD, acral and mucosal types (6%, 21% and 3% respectively). On the other hand, incidence of KIT aberrations was 28%, 36%, and 39% in CSD, acral and mucosal subtypes, respectively, but 0% in non-CSD subtypes. NRAS mutations were found in 5% to 20% of the subtypes.
Primary care physicians evaluate suspicious pigmented lesions to determine who should be referred to dermatology considering both a patient’s risk factors for melanoma as well as visual examination of the lesion. The visual examination assesses whether the lesion has features suggestive of melanoma. Criteria for features suggestive of melanoma have been developed. One checklist is the ABCDE checklist:
- Border irregularities
- Color variegation
- Diameter ≥ 6 mm
Standard of care for the assessment of clinically suspicious pigmented skin lesions is surgical biopsy and subsequent histopathology. However, histopathology is believed to have inherent limitations. Some lesions that are likely to be true melanomas based on clinical behavior do not meet the complete set of histologic criteria to establish a melanoma diagnosis. There is also considerable interrater variability with visual image and pattern recognition of skin lesions. In an effort to improve patient survival, a number of novel noninvasive techniques have been developed to classify pigmented skin lesions at an earlier stage.
Commercially Available Gene Expression Profiling (GEP)
- DecisionDx Melanoma (Castle Biosciences): DecisionDx- Melanoma is a gene expression profile (GEP) test that was designed to identify the risk of recurrence or metastasis in Stage I, II and III melanoma based on the biological profile of 31 genes (28 prognostic genes and 3 control genes) within a patient’s tumor tissue.
The test is used to:
- Inform patients individual treatment plan; and
- Whether to perform the SLNB surgical procedure; and
- Determining the appropriate level of follow-up, imaging and referrals.
DecisionDx-Melanoma is performed on formalin-fixed, paraffin embedded (FFPE) primary tumor tissue from either a biopsy or excision.
- myPath Melanoma (Myriad Genetics, Inc): Per the manufacturers website myPath melanoma test is used as an adjunct to histopathology when the distinction between a benign nevus and a malignant melanoma cannot be made by histopathology alone. The test measures 23 genes for which expression patterns differ between malignant melanoma and benign nevi. These genes are involved in cell differentiation, cell signaling, and immune response signaling. The genes included in myPath Melanoma testing are:
- PRAMER a single gene involved in cell differentiation
- S100A7, S100A8, S100A9, S100A12 and P13, a group of genes involved in multiple cell signaling pathways
- CCL5, CD38, CXCL10, CXCL9, IRF1, LCP2, PTPRC and SELL involved in tumor immune response signaling
- Nine housekeeping gene that are measured to normalize RNA expression for analysis CLTC, MRFAPI, PPP2CA, PSMA1, RPL13A, RPL8, RPS29, SLC25A3 and TXNLI
An algorithm is applied that combines measurements of gene expression, assigns a weight to each gene component and establishes a threshold value. The result is a single numerical score that classifies a melanocytic lesion as “likely benign”, “likely malignant” or “indeterminant.”
- Pigmented Lesion Assay (PLA) (DermTech): Per the manufacturers website the Pigmented Lesion Assay (PLA) is a non-invasive gene expression tests to identity subtle malignancy changes thereby enhancing early melanoma detection. Using adhesive patches, skin tissue is sampled across an entire lesion. RNA is extracted from the collected skin cells and RT-PCR is used to assess the expression analysis of two genes, PRAME and LINC00518 allows DermTech to distinguish between melanoma and non-melanoma. DermTech’s PLA can aid in the physician’s biopsy decision. The test is intended on pigmented lesion suspicious for melanoma that the physical would like additional information prior to surgical biopsy.
- PLA Uses Include:
- Lesion that meet one or more ABCDE criteria
- Lesion being followed for change
- Lesions in sensitive areas
- Lesion on patients with potential risks to surgical biopsy including patients who are anti-coagulated, at risk for infection, and at risk for poor wound healing or elevated abnormal scarring
- Lesions on patients what are needle averse or biopsy fatigued
- PLA negative lesions are generally monitored
- PLA positive lesions are generally surgically biopsied to establish diagnosis
Summary of Evidence
The evidence is currently insufficient to support the use of the Pigmented Lesion Assay (PLA) to accurately differentiate melanoma lesions from nonmelanoma lesions. Study limitations include the small study populations, lack of generalizability of study results to more diverse melanoma subtypes, lack of blinding primary readers, as well as early reports of insufficient RNA obtained from study samples. Independent prospective clinical utility studies are currently lacking, and it is unclear if the use of PLA versus conventional diagnostic tools lead to changes in health care decision making and improvements in patient survival. Current practice standards and clinical management guidelines do not include the use of gene expression profiling for suspicious pigmented lesions. Gene expression profiling testing for melanoma is not recommended outside of clinical trials. Additional well-designed randomized controlled trials (RCTs) in larger patient populations with diverse melanoma subtypes are needed to add to the evidence based and corroborate the early study findings. The evidence is insufficient to determine the effects of the technology on net health outcomes.
For individuals who have melanocytic lesions with indeterminate histopathologic features who receive gene expression profiling (GEP) with the myPath Melanoma test added to histopathology to aid in diagnosis of melanoma, the evidence includes retrospective and prospective observational studies. No direct evidence of clinical utility was identified. Current practice standards and clinical management guidelines do not include the use of gene expression profiling for melanocytic lesions with indeterminate histopathologic features. Gene expression profiling testing for melanoma is not recommended outside of clinical trials. Additional well-designed randomized controlled trials (RCTs) are needed to compare diagnosis and health outcomes of those evaluated with histopathology alone and those with myPath Melanoma as an adjunct to histopathology. The evidence is insufficient to determine the effects of the technology on net health outcomes.
Treatment plans for cutaneous melanoma are based upon individual risk of recurrence. Decisions made post-diagnosis include recommendation for sentinel lymph node biopsy (SNLB), followed by management decisions such as surveillance, frequency of follow-up, and interdisciplinary consultations including possible adjuvant therapy use. These have traditionally been guided by clinicopathologic factors, but discordance exists, as melanoma deaths have occurred in patients diagnosed with disease considered to be early stage by such factors, including a negative SLNB. Gene expression profiling (GEP) testing to include DecisonDx-Melanoma has been proposed to optimize patient care as a predictor of risk of recurrence, distant metastasis and death in stage I-III melanoma and assist in guiding SLNB decisions. While studies have shown some promise in certain clinical situations, current practice standards and clinical management guidelines at this time do not indicate the use of gene expression profiling for the management of cutaneous melanoma. At this time gene expression profiling (GEP) for cutaneous melanoma is not recommended outside of clinical trials. The 2019 guideline by the American Academy of Dermatology regarding care for the management of primary cutaneous melanoma states the following: “There is insufficient evidence to recommend routine molecular profiling assessment for baseline prognostication. Evidence is lacking that molecular classification should be used to alter patient management outside of current guidelines (e.g., NCCN and AAD). The criteria for and the utility of prognostic molecular testing, including GEP, in aiding clinical decision making (e.g., SLNB eligibility, surveillance intensity, and/or therapeutic choice) needs to be evaluated in the context of clinical study or trial.” The National Comprehensive Cancer Network (NCCN) Cutaneous Melanoma Version 2.2020 guideline recommendation stats the following regarding molecular prognostic testing: “Commercially available GEP tests are marketed as being able to classify cutaneous melanoma into separate categories based on risk of metastasis. However, it remains unclear whether these tests provide clinically actionable prognostic information when used in addition to or in comparison with known clinicopathologic factors or multivariable nomograms that incorporate patient sex, age, tumor location and thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and SLNB status. Furthermore, the impact of these tests on treatment outcomes or follow-up schedules has not been established.” Additional well-designed randomized controlled trials (RCTs) are needed to determine the clinical utility of gene expression profiling of cutaneous melanoma compared with traditional clinical factors to guide medical management and improve clinical outcomes to include established follow-up schedules. The evidence is insufficient to determine the effects of the technology on net health outcomes.
Practice Guideline and Position Statements
National Comprehensive Cancer Network (NCCN)
Cutaneous Melanoma Version 2.2020
Principles of Molecular Testing
Emerging Molecular Technologies for Cutaneous Melanoma Diagnosis and Prognostication
- Commercially available GEP tests are marketed as being able to classify cutaneous melanoma into separate categories based on risk of metastasis. However, it remains unclear whether these tests provide clinically actionable prognostic information when used in addition to or in comparison with known clinicopathologic factors or multivariable nomograms that incorporate patient sex, age, tumor location and thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and SLNB status. Furthermore, the impact of these tests on treatment outcomes or follow-up schedules has not been established.
- Various (mostly retrospective) studies of prognostic GEP testing suggest its role as an independent predictor of worse outcome, though not superior to Breslow thickness or SNL status. It remains unclear whether this GEP profile is reliably predictive of outcome across the risk spectrum of melanoma. Prospective validation studies (as have been performed in breast cancer) are required to more accurately define the clinical utility of molecular testing prior to widespread implementation of GEP for prognostication of cutaneous melanoma, and in particular to determine its role in guideline surveillance imaging, SLNB, and adjuvant treatment decisions. Existing and emerging GEP platforms and other prognostic techniques should also be compared with optimized contemporary multivariable phenotypic models (i.e., the AJCC 8th edition melanoma risk calculator/prognostic tool in development).
Biopsy: NCCN Recommendations
Patients presenting with suspicious pigmented lesions optimally should undergo an excisional biopsy (elliptical, punch, or saucerization), preferably with 1to 3 mm negative margins. The orientation of the excisional biopsy should always be planned with definitive treatment in mind (e.g., a longitudinal orientation in the extremities parallel to lymphactics). With the increasing use of lymphatic mapping and sentinel node biopsy, biopsies should also be planned so as not to interfere with the procedure. In this regard, wider margins for the initial diagnostic procedure should be avoided.
Excisional biopsy may be inappropriate for certain sites (including the face, palmar surface of the hand, sole of the foot, ear, distal digit or sublingual lesion) or for very large lesions. In these instances a full-thickness incisional or punch biopsy of the clinically thickest portion of the lesion is an acceptable option. These procedures should provider accurate primary tumor microstaging, without interfering with definitive local therapy. If the initial biopsy is inadequate to make a diagnosis or accurately microstage the tumor (based on evaluation by a dermatopathologist) for treatment planning, re-biopsy with narrow margin excision should be considered. Shave biopsy may compromise pathologic diagnosis and complete assessment of Breslow thickness. However, it is acceptable in a low suspicion setting.
Molecular Characterization of the Primary Tumor
Gene expression profiling for melanoma could be an enormously valuable contribution to understanding the biopsy of the disease. However, the difficulty of embracing gene expression profiling as an independent predictor of outcome is illustrated by the inconsistency of results across studies aimed at defining the most predictive gene sets for melanoma. Comparison of the gene signatures identified in these studies show minimal overlap in specific genes thought to be predictive of outcome. The identification and validation of a prognostic gene expression profile is a complicated multi-step and often multi-step process, and there are many ways in which specifics of study design and methodology can impact the end result. The lack of overlap in gene signatures identified as prognostic for melanoma is likely due to substantial differences in study design and methodology. Efforts to develop gene expression profiling prognostic assays for other types of cancer have also resulted in limited for partial overlap in the “gene signature” identified by different studies.
American Academy of Dermatology
In 2019, the American Academy of Dermatology updated their 2011 guideline regarding care for the management of primary cutaneous melanoma which states: Recommendations for baseline and surveillance studies and follow-up:
- Baseline radiologic imaging and laboratory studies are not recommended for asymptomatic patients with newly diagnosed stage 0-II primary CM.
- Radiologic imaging and laboratory studies for CM at baseline should be performed only to evaluate specific signs or symptoms of synchronous metastasis (regional nodal or distant).
- The use of LN ultrasound is encouraged at baseline or in surveillance in the setting of an equivocal LN on physical examination, and for surveillance when
- The patient meets criteria for SLNB but does not undergo the procedure;
- SLNB is not possible or not technically successful (eg, because of failure of lymphoscintigraphic dye migration and inability to identify a draining SLN); or
- CLND is not performed in the setting of a positive SLNB; and
- When radiology expertise in the use of nodal ultrasound surveillance for CM is available.
- Regular clinical follow-up is recommended as the most important means of detecting CM recurrence. Findings from the history (review of systems) and physical examination should direct the need for further radiologic or laboratory studies to detect local, regional, and distant metastatic disease.
- Collaboration with medical oncology is recommended for patients with high-risk CM (stage IIB and IIC) and those with a positive SLNB result for discussion of surveillance imaging and clinical comanagement.
- Surveillance follow-up schedule and consideration of radiographic imaging varies according to the risk of disease recurrence (as determined by stage of disease and other factors) and risk of new primary CM (determined by mole pattern, presence of atypical nevi, and family history). Laboratory studies are not recommended for surveillance of asymptomatic patients with CM.
- Patient education on self-examination of the skin and LN for the detection of recurrent disease or new primary CM is recommended.
- There is insufficient evidence to recommend routine molecular profiling assessment for baseline prognostication. Evidence is lacking that molecular classification should be used to alter patient management outside of current guidelines (e.g., NCCN and AAD). The criteria for and the utility of prognostic molecular testing, including GEP, in aiding clinical decision making (e.g., SLNB eligibility, surveillance intensity, and/or therapeutic choice) needs to be evaluated in the context of clinical study or trial.
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 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.
See also the following medical policies:
- 02.04.53 Gene Expression Profiling for Uveal Melanoma
- 02.04.41 Genetic Testing for Familial Cutaneous Malignant Melanoma
Gene expression profiling (GEP) testing in the evaluation of patients with suspicious pigmented lesions, including but not limited to Pigmented Lesion Assay (PLA) is considered investigational. The evidence is insufficient to determine the effects of the technology on net health outcomes.
Gene expression profiling (GEP) testing in the evaluation of patients with melanocytic lesions with indeterminate histopathologic features, including but not limited to myPath Melanoma test is considered investigational. The evidence is insufficient to determine the effects of the technology on net health outcomes.
Gene expression profiling (GEP) testing in the evaluation of patient with cutaneous melanoma as a predictor of risk of recurrence, distant metastasis and death in stage I-III melanoma and assist in guiding SLNB decisions, including but not limited to DecisionDx-Melanoma is considered investigational. The evidence is insufficient to determine the effects of the technology on net health outcomes.
Procedure Codes and Billing Guidelines:
To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes and / or diagnosis codes.
- 81479 Unlisted molecular pathology procedure
- 81529 Oncology (cutaneous melanoma), mRNA, gene expression profiling by real-time RT-PCR of 31 genes (28 content and 3 housekeeping), utilizing formalin-fixed paraffin-embeded tissue, algorithm reported a recurrence risk, including likelihood of sentinel lymph node metastasis (DecisionDX Melanoma)
- 81599 Unlisted multianalyte assay with algorithmic analysis procedure
- 84999 Unlisted chemistry procedure
- 0089U Oncology (melanoma), gene expression profiling by RT-PCR, PRAME and LINC00518, superficial collection using adhesive patch(es) (Pigmented Lesion Assay (PLA) DermTech)
- 0090U Oncology (cutaneous melanoma), mRNA gene expression profiling by RT-PCR of 23 genes (14 content and 9 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a categorical result (ie, benign, indeterminate, malignant) (myPath Melanoma)
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. Jan 2018;68(1):7-30. PMID 29313949
- Gandini S, Sera F, Cattaruzza MS, et al. Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors. Eur J Cancer. Sep 2005;41(14):2040-2059. PMID 16125929
- Caini S, Gandini S, Sera F, et al. Meta-analysis of risk factors for cutaneous melanoma according to anatomical site and clinico-pathological variant. Eur J Cancer. Nov 2009;45(17):3054-3063. PMID 19545997
- Goldstein AM, Chan M, Harland M, et al. Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. J Med Genet. Feb 2007;44(2):99-106. PMID 16905682
- Wendt J, Rauscher S, Burgstaller-Muehlbacher S, et al. Human determinants and the role of melanocortin-1 receptor variants in melanoma risk independent of UV radiation exposure. JAMA Dermatol. Jul 1 2016;152(7):776-782. PMID 27050141
- Wiesner T, Obenauf AC, Murali R, et al. Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet. Aug 28 2011;43(10):1018-1021. PMID 21874003
- Chen T, Fallah M, Forsti A, et al. Risk of next melanoma in patients with familial and sporadic melanoma by number of previous melanomas. JAMA Dermatol. Jun 2015;151(6):607-615. PMID 25671687
- Jiang AJ, Rambhatla PV, Eide MJ. Socioeconomic and lifestyle factors and melanoma: a systematic review. Br J Dermatol. Apr 2015;172(4):885-915. PMID 25354495
- Abbasi NR, Shaw HM, Rigel DS, et al. Early diagnosis of cutaneous melanoma: revisiting the ABCD criteria. Jama. Dec 8 2004;292(22):2771-2776. PMID 15585738
- Wilson RL, Yentzer BA, Isom SP, et al. How good are US dermatologists at discriminating skin cancers? A number-needed-to-treat analysis. J Dermatolog Treat. Feb 2012;23(1):65-69. PMID 21756146
- Gershenwald JES, R.A.; Hess, K.R.; et al. Melanoma of the Skin. Chicago, IL: American Joint Committee on Cancer; 2017.
- Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therap. N Engl J Med. Nov 10 2016;375(19):1845-1855. PMID 27717298
- Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. Nov 9 2017;377(19):1824-1835. PMID 28891423
- Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanomas. N Engl J Med. Nov 9 2017;377(19):1813-1823. PMID 28891408
- National Center for Biotechnology Information. PRAME preferentially expressed antigen in melanoma. 2018;
- DermTech. Pigmented Lesion Assay: Non-invasive gene expression analysis of pigmented skin lesions. Performance and Development Notes. 2015;
- Wachsman W, Morhenn V, Palmer T, et al. Noninvasive genomic detection of melanoma. Br J Dermatol. Apr 2011;164(4):797-806. PMID 21294715
- Gerami P, Alsobrook JP, 2nd, Palmer TJ, et al. Development of a novel noninvasive adhesive patch test for the evaluation of pigmented lesions of the skin. J Am Acad Dermatol. Aug 2014;71(2):237-244. PMID 24906614
- Gerami P, Yao Z, Polsky D, et al. Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. J Am Acad Dermatol. Jan 2017;76(1):114-120 e112. PMID 27707590
- Vestergaard ME, Macaskill P, Holt PE, et al. Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting. Br J Dermatol. Sep 2008;159(3):669-676. PMID 18616769
- Murzaku EC, Hayan S, Rao BK. Methods and rates of dermoscopy usage: a cross-sectional survey of US dermatologists stratified by years in practice. J Am Acad Dermatol. Aug 2014;71(2):393-395. PMID 25037790
- Engasser HC, Warshaw EM. Dermatoscopy use by US dermatologists: a cross-sectional survey. J Am Acad Dermatol. Sep 2010;63(3):412-419, 419.e411-412. PMID 20619490
- Bossuyt PM, Irwig L, Craig J, et al. Comparative accuracy: assessing new tests against existing diagnostic pathways. Bmj. May 6 2006;332(7549):1089-1092. PMID 16675820
- Ferris LK, Jansen B, Ho J, et al. Utility of a noninvasive 2-gene molecular assay for cutaneous melanoma and effect on the decision to biopsy. JAMA Dermatol. Jul 1 2017;153(7):675-680. PMID 28445578
- Myriad. n.d. Understanding the myPath® Melanoma Results;
- Clarke LE, Warf MB, Flake DD, 2nd, et al. Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. J Cutan Pathol. Apr 2015;42(4):244-252. PMID 25727210
- Gaiser T, Kutzner H, Palmedo G, et al. Classifying ambiguous melanocytic lesions with FISH and correlation with clinical long-term follow up. Mod Pathol. Mar 2010;23(3):413-419. PMID 20081813
- Vergier B, Prochazkova-Carlotti M, de la Fouchardiere A, et al. Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases. Mod Pathol. May 2011;24(5):613-623. PMID 21151100
- Clarke LE, Flake DD, 2nd, Busam K, et al. An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi. Cancer. Feb 15 2017;123(4):617-628. PMID 27768230
- Ko JS, Matharoo-Ball B, Billings SD, et al. Diagnostic distinction of malignant melanoma and benign nevi by a gene expression signature and correlation to clinical outcomes. Cancer Epidemiol Biomarkers Prev. Jul 2017;26(7):1107-1113. PMID 28377414
- Cockerell C, Tschen J, Billings SD, et al. The influence of a gene-expression signature on the treatment of diagnostically challenging melanocytic lesions. Per Med. Mar 2017;14(2):123-130. PMID 28757886
- Cockerell CJ, Tschen J, Evans B, et al. The influence of a gene expression signature on the diagnosis and recommended treatment of melanocytic tumors by dermatopathologists. Medicine (Baltimore). Oct 2016;95(40):e4887. PMID 27749545
- National Comprehensive Cancer Network (NCCN). Cutaneous Melanoma. Version 2.2020
- Castle Biosciences. Cutaneous Melanoma: DecisionDx-Melanoma Overview. n.d.;
- Gerami P, Cook RW, Wilkinson J, et al. Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res. Jan 1 2015;21(1):175-183. PMID 25564571
- Zager JS, Gastman BR, Leachman S, et al. Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. BMC Cancer. Feb 5 2018;18(1):130. PMID 29402264
- Wong SL, Balch CM, Hurley P, et al. Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline. J Clin Oncol. Aug 10 2012;30(23):2912-2918. PMID 22778321
- Wrightson WR, Wong SL, Edwards MJ, et al. Complications associated with sentinel lymph node biopsy for melanoma. Ann Surg Oncol. Jul 2003;10(6):676-680. PMID 12839853
- Soong SJ, Ding S, Coit DG, et al. AJCC: Individualized melanoma patient outcome prediction tools. n.d.;
- Callender GG, Gershenwald JE, Egger ME, et al. A novel and accurate computer model of melanoma prognosis for patients staged by sentinel lymph node biopsy: comparison with the American Joint Committee on Cancer model. J Am Coll Surg. Apr 2012;214(4):608-617; discussion 617-609. PMID 22342785
- Faries MB, Steen S, Ye X, et al. Late recurrence in melanoma: clinical implications of lost dormancy. J Am Coll Surg. Jul 2013;217(1):27-34; discussion 34-26. PMID 23643694
- Hsueh EC, DeBloom JR, Lee J, et al. Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. J Hematol Oncol. Aug 29 2017;10(1):152. PMID 28851416
- Gerami P, Cook RW, Russell MC, et al. Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol. May 2015;72(5):780-785 e783. PMID 25748297
- Berger AC, Davidson RS, Poitras JK, et al. Clinical impact of a 31-gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. Curr Med Res Opin. Sep 2016;32(9):1599-1604. PMID 27210115
- Farberg AS, Glazer AM, White R, et al. Impact of a 31-gene expression profiling test for cutaneous melanoma on dermatologists' clinical management decisions. J Drugs Dermatol. May 1 2017;16(5):428-431. PMID 28628677
- Schuitevoerder D, Heath M, Cook RW, et al. Impact of gene expression profiling on decision-making in clinically node negative melanoma patients after surgical staging. J Drugs Dermatol. Feb 1 2018;17(2):196-199. PMID 29462228
- Dillon LD, Gadzia JE, Davidson RS, et al. Prospective, multicenter clinical impact evaluation of a 31-gene expression profile test for management of melanoma patients. Skin. 2018;2(2):111-121.
- Zager JS, Gastman BR, Messina J, et. al. Performance of a 31-gene expression profile in a previously unreported cohort of 334 cutaneous melanoma patients. J Clin Oncol 2016 34 (15 suppl): p 9581
- Hsueh EC, Schwartz T, Lizalek JM, et. al. Prospective validation of gene expression profiling in primary cutaneous melanoma. J Clin Oncol 2016 34 (15 suppl) p. 9581
- Ferris LK et. al. Identification of high risk cutaneous melanoma tumors is improved when combining online American Joint Committee on Cancer Individualized Melanoma Patient Outcome Prediction Tool with a 31 gene expression profile based classification. J Am Acad Dermatol 2017
- Morton DL, et. al. Final trial report of sentinel node biopsy versus nodal observation in melanoma. N. Engl J Med 2014 370 (7): p 599-609
- Podlipnik S. et. al. Performance of diagnostic tests in an intensive follow-up protocol for patients with American Joint Committee on Cancer (AJCC) stage IIB, IIC, and III localized primary melanoma: A prospective cohort study. J Am Acad Dermatol 2016 75(3): p. 516-24
- UpToDate. Tumor Node Metastasis (TNM) Staging System and Other Prognostic Factors in Cutaneous Melanoma. Antonio C. Buzaid M.D., Jeffrey E. Gershenwald M.D., FACS Topic last updated February 19, 2019.
- UpToDate: Staging Work-Up and Surveillance after Treatment of Melanoma. Anthony C. Buzaid M.D., Jeffrey E. Gershenwald M.D., FACS. Topic last updated March 26, 2018.
- Plasseraud KM, Cook RW, Oelschlager K, et. al. Clinical performance and management outcomes with the DecisionDx-UM gene expression profile test in prospective multicenter study. J Oncol. May 2016;2016:5325762. PMID 27446211
- Bichakjian C, Halpern A, Johnson T, et. al. Guidelines of Care for the Management of Primary Cutaneous Melanoma. American Academy of Dermatology. J Am Acad Dermatol 2011;65:1032-47
- Swetter S, Tsao H, Bichakjian C, et. al., America Academy of Dermatology Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol 2019;80:208-50
- Palmetto GBA myPath Melanoma assay
- Palmetto GBA has issued a draft local coverage determination for DecisionDx-Melanoma
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. PMID 29313949
- Ferris LK, Gerami P, Skelsey MK, et. al. Real-world performance and utility of noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions. Melanoma Research 2018;28(5):478-482
- Ferris LK, Rigel DS, Siegel DM, et.al. Impact on clinical practice of a non-invasive gene expression melanoma rule-out tests: 12-month follow-up of negative test results and utility data from large US registry study. Dermeatol Only J. 219;25(5):2
- Dubin DP, Dinehart SM, Farberg AS. Level of evidence review for a gene expression profile test for cutaneous melanoma. Am J Clin Dermatol 2019 Dec;20(6):763-770. PMID 313593351
- Svoboda, R.M., Glazer, A.M., Farberg, A.S. & Rigel, D.S. Factors Affecting Dermatologists' Use of a 31-Gene Expression Profiling Test as an Adjunct for Predicting Metastatic Risk in Cutaneous Melanoma. J Drugs Dermatol 17, 544-547 (2018). PMID: 29742186
- Gastman, B.R. et al. Identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria. J Am Acad Dermatol 80, 149-157 e4 (2019). PMID:30081113
- Keller, J. et al. Prospective validation of the prognostic 31-gene expression profiling test in primary cutaneous melanoma. Cancer Med 8, 2205-2212 (2019). PMID:30950242
- Vetto, J.T. et al. Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling. Future Oncol 15, 1207-1217 (2019). PMID:30691297
- Cook, R.W. et al. Analytic validity of DecisionDx-Melanoma, a gene expression profile test for determining metastatic risk in melanoma patients.Diagn Pathol 13, 13 (2018). PMID:29433548
- Gastman, B.R. et al. Performance of a 31-gene expression profile test in cutaneous melanomas of the head and neck. Head Neck 41, 871-879 (2019). PMID:30694001
- Greenhaw, B.N., Zitelli, J.A. & Brodland, D.G. Estimation of Prognosis in Invasive Cutaneous Melanoma: An Independent Study of the Accuracy of a Gene Expression Profile Test. Dermatol Surg 44, 1494-1500 (2018). PMID:29994951
- Marks, E. et al. Establishing an evidence-based decision point for clinical use of the 31-gene expression profile test in cutaneous melanoma. SKIN J Cutaneous Med 3, 239-249 (2019)
- Podlipnik, S. et al. Early outcome of a 31-gene expression profile test in 86 AJCC stage IB-II melanoma patients. A prospective multicentre cohort study. J Eur Acad Dermatol Venereol 33, 857-862 (2019). PMID:30702163
- May 2020 - Annual Review, Policy Revised
- May 2019 - Annual Review, Policy Renewed
- May 2018 - New Policy created
Wellmark medical policies address the complex issue
of technology assessment of new and emerging treatments, devices,
drugs, etc. They are developed to
assist in administering plan benefits and constitute neither offers of
coverage nor medical advice. Wellmark medical policies contain only a
partial, general description of plan or program benefits and do not
constitute a contract. Wellmark does not provide health care services
and, therefore, cannot guarantee any results or outcomes.
Participating providers are independent contractors in private
practice and are neither employees nor agents of Wellmark or its
affiliates. Treating providers are solely responsible for medical
advice and treatment of members. Our medical policies may be updated
and therefore are subject to change without notice.
*CPT® is a registered trademark of the American Medical Association.