# A Comparative Study Between Copy Number Alterations and PRAME Immunohistochemical Pilot Study in Challenging Melanocytic Lesions

## TL;DR

This study compares PRAME immunohistochemistry and molecular testing for diagnosing difficult melanocytic lesions, finding that PRAME is specific but not sensitive enough to replace other methods.

## Contribution

The study provides a direct comparison of PRAME immunohistochemistry and molecular testing in challenging melanocytic lesions.

## Key findings

- PRAME showed high specificity (96.2%) and negative predictive value (78.1%) but low sensitivity (12.5%) in challenging cases.
- Molecular testing demonstrated higher sensitivity (75%) and perfect specificity (100%) in the same cases.
- PRAME is best used as an adjunct, especially when a benign diagnosis is suspected.

## Abstract

Melanoma is a significant public health concern due to its rising incidence and mortality. While most melanocytic lesions can be readily classified as benign nevi or malignant melanoma, diagnostically challenging lesions remain difficult to categorize due to their overlapping clinical and histological features. Ancillary tools such as immunohistochemistry, FISH, and SNP array have been developed to enhance diagnostic accuracy. This study evaluates the diagnostic performance of PRAME, a tumor-associated antigen, to molecular testing in 34 diagnostically challenging and 9 non-diagnostically challenging melanomas. In diagnostically challenging cases, PRAME showed high specificity (96.2%) and negative predictive value (78.1%) but low sensitivity (12.5%), whereas molecular testing demonstrated higher sensitivity (75%) and specificity (100%). These findings suggest that while the utility of PRAME is limited as a standalone test, it does serve as a useful confirmatory adjunct, especially when a benign diagnosis is favored.

Introduction: Diagnostic uncertainty for ambiguous lesions that fall on the spectrum between nevi and melanoma remains a significant challenge and can have consequences for patient management. Methods: This study aimed to compare the diagnostic utility of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry to molecular testing (FISH and SNP array) in 34 diagnostically challenging melanocytic lesions and 9 non-diagnostically challenging melanomas. Results: We conclude that while PRAME immunohistochemistry demonstrates high specificity (96.2%) in diagnostically challenging melanocytic lesions, its low sensitivity (12.5%) suggests that it should not replace histopathological evaluation in rendering the final diagnosis. Conclusions: These findings suggest that PRAME may serve as a useful adjunct in the diagnostic workup, particularly due to its high negative predictive value, but should be used in conjunction with other established diagnostic modalities.