Demonstration of 23-Gene Expression Profile Test Utility Within PRAME Immunohistochemistry Results: A Case Series

ABSTRACT: Histopathological examination using hematoxylin and eosin (H&E)-stained tissue is sufficient for diagnosing most melanocytic neoplasms as benign or malignant; however, diagnostic tools such as PRAME (preferentially expressed antigen in melanoma) immunohistochemistry (IHC) and the 23-gene expression profile (23-GEP) test can aid in the analysis of histopathologically ambiguous lesions, which can be referred to as diagnostically challenging, equivocal, indeterminate, or uncertain. When compared with the gold standard of H&E diagnosis by a dermatopathologist, PRAME IHC showed 83.2% sensitivity and 99.3% specificity in an initial validation cohort and 23-GEP showed 91.5% sensitivity and 92.7% specificity in an independent validation cohort. In addition, 23-GEP has been evaluated in 3 studies with patients with known outcomes (eg, metastasis) and has reported metrics of 90.4%-96.3% sensitivity and 87.3%-96.2% specificity in distinguishing benign versus malignant melanocytic neoplasms. In this study, we present the utility of the 23-GEP test within 8 equivocal cases with various PRAME IHC staining patterns. Cases underwent histopathological review and received at least 4 and up to 5 diagnoses each. In samples where PRAME IHC is inconclusive, conflicting, or ambiguous regarding a final diagnosis, the 23-GEP can provide additional diagnostic information to upgrade or downgrade the overall malignant potential of the lesion in question.