Abstract

Histopathological examination is sufficient for many melanocytic neoplasms; however, high rates of diagnostic discordance are reported. Timely and confident diagnoses are optimal, especially in cases where both benign and malignant melanocytic neoplasms are in the differential diagnosis as treatment plans diverge significantly. Here, the performance of the 35-gene expression profile (GEP) test in a novel cohort of 525 patients to aid in the diagnosis of melanocytic neoplasms is presented. Performance was assessed within the clinically available ?18-yo population in an independent set of 261 benign and 264 malignant lesions; lesions were included if 2/3 dermatopathologist reviews were concordant and excluded if lesions received conflicting diagnoses of benign and malignant. When lesions with spitzoid features were excluded from analysis, the test demonstrated 96.0% sensitivity, 92.2% specificity, 93.8% PPV and 95.0% NPV; 2.3% intermediate-risk rate. Of note, lesions designated as benign by dermatopathologist review and malignant by 35-GEP (misclassified benign lesions), demonstrated higher reviewer discordance (48.3%) compared to the full cohort (25.3%). In lesions with spitzoid features, (n=56), the test demonstrated 100% sensitivity and 68.3% specificity; 8.9% intermediate-risk rate. Spitz lesions had higher rates of dermatopathologist discordance when compared to other benign subtypes (64.4% vs. 25.4%) indicating histopathological ambiguity. In conclusion, two independent validation cohorts totaling 1,028 lesions of the 35-GEP indicate the test is highly accurate. The 35-GEP test was developed to refine diagnoses of melanocytic neoplasms by providing clinicians with an objective adjunctive tool that can be interpreted in the context of clinical, laboratory and histological features with a low intermediate-risk rate.

Financial Disclosure:
The poster abstract presenter listed below disclosed the following information about their financial interests. The ASDP Ethics Committee has reviewed these disclosures and determined that no conflicts of interest exist between financial relationships and educational content being presented.

Speaker	Company	Affiliation/Relationship
Gregory A. Hosler, MD, PhD	Castle Biosciences, Inc.	Consultant