PRAME Immunohistochemistry for Differentiating Pigmented Lesions of the Vulva and Perineum

Special site pigmented lesions often present a diagnostic challenge for clinicians and for pathologists. Lesions of the genital region present even further challenges due to the sensitivity of the anatomic location and preference to defer physical exam and biopsy. Even after biopsy, the diagnostic challenge persists owing to the frequent presence of atypical features in these sites and the technical difficulties associated with performing complete excisions. Immunohistochemistry plays a crucial role in the classification and categorization of these lesions. PRAME (PReferentially expressed Antigen in MElanoma) is a nuclear receptor and transcriptional regulator that regulates cell differentiation, growth, and apoptosis. Immunohistochemistry for PRAME has proven valuable in assisting pathologists to classify various cutaneous melanocytic proliferations all over the human body. Our study sought to investigate the use of PRAME in determining the biologic nature of pigmented lesions of the genital region. A search of medical records identified 53 cases of genital pigmented lesions for review. Each case received MART1 and PRAME IHC for evaluation and classification by two board certified dermatopathologists. The results found that PRAME was negative (zero nuclear staining) in a total of 32 benign lesions (i.e., melanosis including macules and lentigos as well as nevi). One dysplastic nevus showed focal weak PRAME expression in less than 10% of lesional melanocytes. PRAME was overwhelmingly positive (4+ staining, > 75% of nuclei) in 90% of the malignant lesions (i.e., invasive melanoma and melanoma in situ). Overall, we conclude that PRAME remains a valuable tool in the diagnostic workup of diagnosing pigmented lesions of the genital region.