Diagnostic Utility of Preferentially Expressed Antigen in Melanoma (PRAME) and p16 Immunohistochemistry in Distinguishing Genital Melanomas From Benign Melanocytic Proliferations

Preferentially expressed antigen in melanoma (PRAME) expression is valuable for distinguishing malignant from benign melanocytic proliferations, and p16 has also been shown to aid in this distinction. However, data on the utility of these two immunohistochemistry stains in genital melanocytic lesions are limited. We retrospectively analyzed 56 genital melanocytic lesions, including 41 benign lesions and 15 melanomas (6 in situ and 9 invasive) with PRAME and p16 immunohistochemistry. All melanomas exhibited extensive PRAME positivity: 93.3% (14 of 15) had a 4+ score (>75% positive cells) and 1 had a 3+ score (51%-75% positive cells). In contrast, 87.8% (36 of 41) of benign lesions were PRAME negative, and none scored higher than 2+ (26%-50% positive cells). Using a 4+ cutoff, PRAME demonstrated a sensitivity of 93.3% and specificity of 100%. Lowering the cutoff to 3+ increased sensitivity to 100%. Complete or partial loss of p16 was observed in 60.0% (9 of 15) of melanomas but not in any benign lesions (0 of 41), resulting in a sensitivity of 60.0% and specificity of 100%. Our findings indicate that PRAME immunohistochemistry is highly sensitive and specific for genital melanoma. Loss of p16 expression, although not sensitive, is highly specific for genital melanomas and is, therefore, useful in challenging genital melanocytic lesions.