# The Need for Standardization of PRAME Immunohistochemistry in Melanocytic Neoplasms

## TL;DR

This study shows that PRAME staining for melanoma diagnosis lacks consistency among pathologists, suggesting a need for standardized scoring methods.

## Contribution

The study demonstrates poor inter-rater reliability in PRAME scoring and proposes the need for standardized methods and AI tools.

## Key findings

- PRAME scoring showed poor inter-rater reliability (Kappa = 0.16) among dermatopathologists.
- H-score and percent PRAME positivity also showed low agreement (ICCs of 0.40 and 0.31, respectively).
- Variability in reporting language highlights the need for standardized scoring methods.

## Abstract

Accurate diagnosis of melanoma, a skin cancer originating from melanocytes, is crucial for the appropriate treatment of patients. Pathologists often use a laboratory stain called PRAME (PReferentially expressed Antigen in MElanoma) to help distinguish melanoma from benign skin lesions, but interpretation can be challenging. In this study, five dermatopathologists reviewed twenty-one borderline melanocytic skin lesions to evaluate the consistency of PRAME interpretation. We found that PRAME scoring lacks reproducibility among dermatopathologists for these challenging lesions. This variability highlights the need for more rigorous and standardized scoring methods in order to improve diagnostic accuracy. Future studies should explore whether artificial intelligence-based tools can help improve reliability.

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.