A 35-Gene Expression Profile Test for Use in Suspicious Pigmented Lesions Impacts Clinical Management Decisions of Dermatopathologists and Dermatologists

Purpose: Histopathological examination is sufficient for diagnosis of many melanocytic neoplasms, however, diagnostic discordance is common between dermatopathologists. A timely and confident diagnosis is optimal, especially in cases where both benign and malignant melanocytic neoplasms are considered in the differential diagnosis as treatment plans diverge significantly. A 35-gene expression profile (GEP) test that classifies melanocytic lesions into categories (benign, intermediate-risk and malignant), has reported accuracy metrics of 99.1% sensitivity, 94.3% specificity, 93.6% positive predictive value and 99.2% negative predictive value in a validation cohort of 503 samples. The clinical utility of the 35-GEP is described. Methods: Dermatopathologists (n=6) and dermatologists (n=14) were queried regarding diagnostic challenges and patient management strategies in 60 difficult-to-diagnose melanocytic neoplasms. Participants reviewed each lesion twice, once without the 35-GEP result and once with. Responses were evaluated for consistent trends in the utilization of the 35-GEP test result. Results: Dermatopathologists utilized the 35-GEP result to refine their diagnoses in lesions receiving a benign vs. malignant 35-GEP result (82.3% diagnostic downgrade vs. 94.9% diagnostic upgrade, respectively). Overall, diagnostic confidence was increased (51%), while additional work-up requests were decreased in cases with benign 35-GEP (72.1%) and increased with malignant 35-GEP (45.6%) results. Dermatologists utilized the 35-GEP result to gauge overall prognosis which was increased in 76.2% of responses for cases with a benign 35-GEP result and decreased in 94.2% of cases with malignant 35-GEP result. Case difficulty was increased in 54% of responses with a malignant 35-GEP result and decreased in 25% if a benign 35-GEP result was provided. Alterations in office visit frequency (25.9% increase in benign vs. 95.2% increase in malignant 35-GEP result) and re-excisions (76.7% decrease in re-excision in benign vs. 44.5% increase in re-excision in malignant 35-GEP result) were also influenced by the 35-GEP result. Conclusions: The diagnosis of challenging melanocytic neoplasms and subsequent clinical management decisions are influenced by 35-GEP results in a manner that agrees with the test result. The utility of the test provides the opportunity to improve patient care.