Diagnostic Utility of PRAME Immunohistochemistry for Distinguishing Acral Melanoma From Acral Melanocytic Nevi

Introduction Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry helps distinguish non‐acral melanocytic lesions, but few studies have addressed its value in acral lesions. We aimed to identify an optimal PRAME cut‐off score to differentiate acral melanoma (AM) from acral melanocytic nevi (AMN). Methods Formalin‐fixed, paraffin‐embedded specimens of AM, AMN, and small biopsy of atypical melanocytic lesions (AMLs) were included. PRAME staining was performed. Expression was categorized into five groups: 0 (0%), 1+ (1%–25%), 2+ (26%–50%), 3+ (51%–75%), and 4+ (> 75%). PRAME nuclear expression was compared between AM and AMN to identify the best cut‐off score, which was then assessed in small‐sized biopsies of AML specimens. Results We analyzed 62 AMs, 62 AMNs, and 23 AMLs. A PRAME score of ≥ 3+ optimally differentiated AM from AMN (sensitivity 80.6%, specificity 98.4%, positive predictive value 98%, and negative predictive value 83.6%). PRAME expression score ≥ 3+ was strongly associated with AM, whereas AMN showed expression score < 3+ ( p < 0.001). However, one AM was completely negative for PRAME, and one AMN exhibited strong PRAME staining. Conclusions PRAME immunohistochemistry with a cut‐off of ≥ 3+ is useful for differentiating AM from AMN. However, false positivity and negativity of PRAME expression must be considered.