Abstract

Histopathologic evaluation can effectively diagnose most melanocytic neoplasms; however, lesions considered to be difficult-to-diagnose pose challenges for accurate classification of malignant potential, which can lead to over- or under-treatment. Ancillary testing to provide additional information is available for such cases. The validated diagnostic 23-GEP test provides an objective result of benign, malignant, or intermediate. In this large, independent cohort, the performance of the 23-GEP in its current laboratory is presented. Lesions from patients ≥18 years old were enrolled from eight centers or from melanoma cases clinically submitted for prognostic 31-GEP testing. Lesions were independently reviewed by 3–5 dermatopathologists and included in the study if they were fully concordant or non-concordant without conflicting diagnoses (i.e., both benign and malignant designations) or majority of unknown malignant potential designations, resulting in a cohort (n=1456) of benign nevi (n=525) and malignant melanomas (n=931). Accuracy metrics and two-tailed 95% confidence intervals (CIs) were calculated using resampling x10,000 iterations to establish a balanced number of benign versus malignant samples. The 23-GEP performance within this cohort was 89.8% (95% CI, 86.6–92.7%) sensitivity, 92.6% (89.8–95.2%) specificity, 92.7% (90.2–95.1%) positive predictive value, and 89.7% (86.8–92.5%) negative predictive value; 7.7% of lesions received an intermediate result. These metrics do not deviate significantly from previously published studies. These data demonstrate that the 23-GEP has an overall accuracy of 91.2% (89.0–93.1%), further supporting its use as an ancillary test that can be integrated with clinical and histopathologic information to guide final diagnosis.