QHow have MyPath’s sensitivity, specificity, and reproducibility held up across studies, and what does that consistency mean for managing melanocytic lesions?

The MyPath 23-gene expression profile (23-GEP) test has consistently demonstrated strong diagnostic performance across multiple independent studies, reinforcing its role as a reliable molecular adjunct in the evaluation of melanocytic lesions.

In a large, multi-center study we conducted (Performance of the 23-GEP Test by Histopathological Evaluation), MyPath showed a sensitivity of 91.5% and specificity of 92.5% for distinguishing benign from malignant melanocytic neoplasms. These metrics closely mirrored those of the original validation studies, confirming high performance across histologic patterns, demographics, and institutional practices.

This consistency was further validated in our 2023 publication (Appropriate Statistical Methods to Assess Cross-Study Diagnostic 23-GEP Test Performance), where we applied rigorous cross-validation to assess performance across diverse cohorts and real-world settings and demonstrated remarkable reproducibility. One reason the test holds up under these variations is that the gene panel targets fundamental molecular pathways involved in melanocytic neoplasia—such as cell cycle regulation and immune signaling—making it broadly applicable across morphologic subtypes and populations.

Still, no test is without limitations. Gray zones remain, particularly in severely atypical spitzoid tumors or lesions with overlapping features of nevoid melanoma and deep penetrating nevus. These are precisely the cases where molecular support proves most valuable—offering objective insight that can clarify ambiguous histopathologic findings and reduce interobserver variability.

In our dermatopathology laboratory, we use MyPath almost daily. It has become an essential tool for enhancing diagnostic confidence, particularly in borderline cases. In many instances, the molecular result has tipped the balance in favor of a definitive diagnosis when histology alone was equivocal.

Beyond diagnostic metrics, the clinical impact is substantial. A published study showed that dermatologists changed their management in nearly half of cases based on MyPath results—highlighting its value not just in pathology, but in patient care decisions.

In summary, the 23-GEP test has demonstrated durable sensitivity, specificity, and reproducibility across diverse settings. Its molecular insight adds critical clarity in diagnostically challenging cases, making it a trusted component of our diagnostic workflow.

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References:

1. Goldberg MS, Cockerell CJ, Rogers JH, Siegel JJ, Russell BH, Hosler GA, Marks E. Appropriate statistical methods to assess cross-study diagnostic 23-gene expression profile test performance for cutaneous melanocytic neoplasms. Am J Dermatopathol. 2024;46(12):833–838. doi:10.1097/DAD.0000000000002808
2. Goldberg MS, Motaparthi K, Hosler GA, Cockerell CJ, Estrada SI, Depcik-Smith ND, Plaza JA. Performance of the 23-gene expression profile (23-GEP) test by histopathological evaluation in an independent, multi-center performance cohort of cutaneous melanocytic neoplasms. SKIN. 2023;7(6):s265. doi:10.25251/skin.7.supp.265
3. Witkowski A, Jarell AD, Ahmed KL, Siegel JJ, Russell BH, Rogers JH, Goldberg MS, Fernandes NF, Ludzik J, Farberg AS. A clinical impact study of dermatologists’ use of diagnostic gene expression profile testing to guide patient management. Melanoma Manag. 2024;11(1):MMT68. doi:10.2217/mmt-2023-0002