From Diagnosis to Prognosis: Using MyPath^® Melanoma and DecisionDx^®-Melanoma to Help Guide Patient Management Decisions

Every dermatologist knows the challenge of the “gray zone” melanocytic lesion—the one that looks suspicious but doesn’t fit neatly into benign or malignant categories. That’s where gene expression profile (GEP) testing can help. MyPath Melanoma and DecisionDx-Melanoma work together to bring molecular clarity to ambiguous cases and guide risk-aligned patient management, all from the same biopsy sample with no additional clinical testing needed.

Both tests provide complementary insights that sup-port more informed diagnostic and management deci-sions. MyPath Melanoma provides clarity for diagnostically ambiguous lesions, helping clinicians determine with greater confidence whether a suspicious lesion is potentially benign or malignant. Once a diagnosis of melanoma is rendered, DecisionDx-Melanoma then offers prognostic insight into a tumor’s molecular risk, identifying patients at low or high risk of poor melanoma outcomes, such as metastasis to the lymph nodes or distant organs. Together, they give clinicians a clearer path, from initial diagnosis to long-term management, using information derived from a single biopsy sample.

MYPATH MELANOMA

MyPath Melanoma is a 23-gene expression profile (23-GEP) test that helps dermatologists and dermatopatholo-gists distinguish benign from potentially malignant lesions by providing results of “suggestive of benign,” “intermedi-ate,” or “suggestive of malignant.” Using RNA extracted from the biopsy sample, the test evaluates gene expression patterns to deliver objective, clinically proven results that support more confident diagnostic decisions.1 With high sensitivity and specificity demonstrated across multiple studies, MyPath Melanoma provides important clarity when histopathologic findings are less than certain. In comparison to standard immunohistochemical (IHC) stains, MyPath Melanoma is designed to provide a broader dynamic range of information to allow for resolution and help discriminate lesions in which IHC may be inconclusive. Performance of MyPath Melanoma has been reported in lesions with expert or consensus histopathological assessment (91.5% sensitivity, 92.7% specificity) and lesions with known outcomes (90.4% to 96.3% sensitivity, 87.3% to 96.2% specificity).²

MyPath Melanoma can also be used by dermatologists and/or dermatologic surgeons to better determine the appropriate surgical care and follow-up for their biopsied pigmented skin lesion—examples of which are discussed here (Figure 1).³ MyPath Melanoma is particularly useful for lesions in patients who are poor candidates for surgery because the test result can be used to determine if a patient needs an excision surgery, and if so, the extent of healthy skin margins. In particular, very old or young patients and those with lesions in functionally or cosmetically sensitive sites (eg, face, fingers, foot, genitals, and distal lower extremi-ties) can benefit from MyPath Melanoma testing to spare unnecessary surgery. Figure 1 provides examples of how each test result is used for certain types of lesions. This level of personalized care allows for tissue-sparing techniques that minimize downtime and recovery, or avoidance of surgery altogether, which can be a great relief for patients.

Specifically, if a pathology report does not suggest exci-sion, but clinical concern remains, MyPath Melanoma can be used to guide the next steps: a “suggestive of malignant” result can prompt excision, an “intermediate result” can prompt a re-shave, and a “suggestive of benign” result can prompt a “wait and watch” situation. 

If excision is recommended on a pathology report regarding lesions with atypia and/or early/evolving melano-ma in situ, MyPath Melanoma can be used to direct next steps. Generally, the test result may be considered alongside other clinical and pathologi-cal information as part of the overall decision-making pro-cess regarding the potential de-escalation or escalation of a surgical approach, depending on the type of lesion (Figure 1).

     * Face, finger, foot, genitals, distal lower extremity
     ** May do MSS ir CCPDMA/staged excision wtih 5 mm margins

 DECISIONDX-MELANOMA

When MyPath Melanoma returns a result of “suggestive of malignant” and the patient is diagnosed with invasive melanoma, clinicians can then order DecisionDx-Melanoma using the same tumor tissue to gain additional prognostic information that can guide downstream clinical management decisions. DecisionDx-Melanoma is a 31-gene expression profile (31-GEP) test that evaluates RNA expression to predict the risk of sentinel lymph node (SLN) positivity, recurrence, metastasis, and mortality in patients with stage I–III invasive cutaneous mel-anoma. Test results identify patients as low (Class 1A), inter-mediate (Class 1B/2A), or high risk (Class 2B). Additionally, DecisionDx-Melanoma integrates the 31-GEP risk score with clinical and pathological factors to provide a precise, person-alized risk of SLN biopsy (SLNB) positivity (i31-SLNB).

Patients with a low-risk (Class 1A) DecisionDx-Melanoma result and <5% predicted i31-SLNB risk may safely consider a conservative management approach, including forgoing SLNB. Studies have determined that patients with <5% i31-SLNB-predicted risk have low rates of SLN positivity, indicating that the test accurately identifies a low-risk popu-lation who can safely forgo SLNB, reducing risk of procedure-related complications and healthcare-related costs.^4-6 On the other hand, patients with a higher-risk (Class 1B/2A or Class 2B) DecisionDx-Melanoma result and ≥5% predicted SLNB positivity risk (≥5% i31-SLNB) have a demonstrated higher risk of a positive SLN and should consider undergoing SLNB. Studies have found that DecisionDx-Melanoma is more accurate in predicting SLN positivity than American Joint Committee on Cancer (AJCC) staging, online nomograms using clinical and pathological factors, and other GEP-based tests, including CP-GEP.^4,5,7-9

Further, patients identified as low risk by DecisionDx-Melanoma may be recommended for less intensive follow-up and treatment management plans. The DecisionDx-Melanoma test results can provide more confidence for clinicians who are recommending less intensive management, knowing that patients with low-risk results consistently have better outcomes than patients with high-risk results, including low risks of SLN positivity, recurrence, metastasis, and death. Conversely, higher-risk patients may benefit from increased management plans, including more frequent follow-up schedules and surveillance imaging to identify recurrence and metastases earlier to improve outcomes. Recent reports confirm use of DecisionDx-Melanoma to make clinical management decisions, including SLNB decisions and surveillance imaging, helps to safely avoid unnec-essary biopsy procedures (and associated adverse effects), identify recurrence earlier, and improve outcomes.^5,10

The risk stratification and clinical utility of DecisionDx-Melanoma have been validated in numerous retrospective, prospective, and real-world patient cohorts, comprising more than 50 peer-reviewed publications including over 10,000 patients—representing the largest evidence base of any GEP test for melanoma prognosis.^11,12 Incorporating DecisionDx-Melanoma results with AJCC staging has been shown to significantly enhance prediction of recurrence and mortality risk compared with staging alone.⁵ The test’s results also inform SLNB decisions, surveillance imaging, follow-up frequency, and treatment planning—supporting more personalized care, efficient resource use, and improved patient outcomes.^10,13

Figure 2. MyPath Melanoma and DecisionDx-Melanoma flowchart. When a pathology report returns a diagnostically ambiguous result for a suspected cutaneous melanoma lesion, MyPath Melanoma is a GEP test that provides additional clarity. MyPath Melanoma returns one of three results: “suggestive of benign,” “intermediate,” or “suggestive of malignant.” If MyPath Melanoma returns a “suggestive of malignant” result and the final diagnosis is rendered as an invasive melanoma, DecisionDx-Melanoma (31-GEP) testing can be performed on the original tumor biopsy tissue to provide prognostic information about the risk of SLN positivity, recurrence, metastasis, and mortality. This prognostic information can help clinicians and patients make risk-aligned, personalized treatment and follow-up management plans.

CONCLUSIONS

Together, MyPath Melanoma and DecisionDx-Melanoma enable clinicians to deliver more risk-aligned, personalized care for patients with suspected or confirmed melanoma, all using the same tumor tissue sample. MyPath Melanoma is designed to help clarify diagnostically ambiguous lesions, safely sparing patients unnecessary surgery while supporting escalation of care in cases when needed. If MyPath Melanoma returns a “suggestive of malignant” result and the final diagnosis is rendered as an invasive melanoma, DecisionDx-Melanoma can add personalized prognostic information to help inform SLNB decisions, follow-up frequency, and surveillance strategies. Integrating both tests into clinical workflows can improve decision-making precision, optimize use of healthcare resourc-es, and ultimately enhance patient outcomes. 

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2. Goldberg MS, Cockerell CJ, Rogers JH, et al. Appropriate Statistical Methods to Assess Cross-study Diagnostic 23-Gene Expression Profile Test Performance for Cutaneous Melanocytic Neoplasms. The American Journal of Dermatopathology. 2024;46(12):833. doi:10.1097/DAD.0000000000002808
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