The Need for Standardization of PRAME Immunohistochemistry in Melanocytic Neoplasms

Accurate diagnosis of melanomas is crucial for proper evaluation and treatment. One immunohistochemical stain frequently utilized is PRAME (PReferentially expressed Antigen in MElanoma), a tumor-associated antigen expressed in most melanomas. This study aims to evaluate the reproducibility of PRAME scoring performed by dermatopathologists at an academic tertiary referral medical center. A blinded survey was designed featuring 21 melanocytic neoplasms stained with PRAME and H&E. For each case, five dermatopathologists provided a PRAME score from 0-4+, percent PRAME positivity, values for H-score, and a descriptive interpretation. Absolute agreement across raters was assessed using a Kappa statistic for PRAME score and intraclass correlations (ICCs) for H-score and PRAME percentage. Statistical analysis indicated poor inter-rater reliability for PRAME score (Kappa = 0.16), percent PRAME positivity (ICC = 0.31), and H-score (ICC = 0.40). Reporting language varied among pathologists. Our study demonstrated that the interpretation of PRAME immunohistochemistry lacks reproducibility, especially for challenging lesions. This suggests that a more rigorous, defined, and reproducible scoring method should be investigated for equivocal cases. Future studies may explore the utility of artificial intelligence software in the interpretation of PRAME for borderline lesions to improve reliability and standardize scoring.