Evaluating the Diagnostic Concordance of MyPath Melanoma Assay and PRAME Immunohistochemistry in Challenging Melanocytic Lesions.

Background: The 23-gene expression signature (GES) assay (myPath Melanoma) is a well-established molecular test for analyzing challenging melanocytic lesions, alongside fluorescence in situ hybridization (FISH) and single nucleotide polymorphism (SNP) array. However, routine use of these tests is often limited by high costs, long turnaround times, significant tissue requirements, and limited accessibility. This study aimed to evaluate the diagnostic concordance of PRAME immunohistochemistry (IHC) and the GES assay in difficult melanocytic lesions to determine whether PRAME IHC, widely available in pathology laboratories, could serve as a surrogate for GES. In addition, we correlated these methods with SNP array and FISH analyses, where available, to assess their diagnostic value in challenging melanocytic lesions.

Methods: We conducted a single-institution retrospective analysis of 56 diagnostically ambiguous melanocytic lesions that underwent ancillary GES testing. All 56 cases were evaluated for PRAME IHC, while 35 had FISH results, 16 had SNP array results, and 3 had both FISH and SNP results. Two board-certified dermatopathologists independently reviewed hematoxylin and eosin (H&E)-stained slides, PRAME IHC slides, and other available immunostains, along with GES results, FISH, and/or SNP array results, classifying each lesion as benign or malignant.

Results: Fifty-six cutaneous melanocytic lesions with challenging histopathologic features were evaluated. Diagnostically ambiguous categories included dysplastic nevi versus melanoma (29 cases, 51.8%), spitzoid lesions (19 cases, 33.9%), nevoid lesions (7 cases, 12.5%), and blue nevus-like lesions (1 case, 1.8%). Of these, 38 cases (67.9%) were ultimately classified as benign, while 18 cases (32.1%) were classified as malignant.PRAME IHC showed a significant association with malignancy, with an 83.9% concordance rate (χ2 = 21.37, P = 0.0001), accurately classifying 47 out of 56 cases. GES demonstrated an 82.1% concordance rate (χ2 = 18.68, P = 0.0001), accurately classifying 46 out of 56 cases. FISH showed a 77.1% agreement with the final diagnosis (χ2 = 7.63, P = 0.005), correctly categorizing 27 out of 35 cases. Although the number of cases were relatively small, SNP array analysis correctly identified all 16 cases (χ2 = 16, P = 0.0001).

Conclusions: This study supports PRAME IHC as a useful surrogate for the GES assay in the evaluation of challenging melanocytic lesions. PRAME IHC offers a cost-efficient, accessible, and practical ancillary tool that can be rapidly integrated into routine clinical practice for diagnostically ambiguous melanocytic lesions.