Diffuse PRAME Expression Is Highly Specific for Thin Melanomas in the Distinction from Severely Dysplastic Nevi but Does Not Distinguish Metastasizing from Non-Metastasizing Thin Melanomas

SIMPLE SUMMARY: Histological diagnoses within the spectrum from moderately dysplastic nevi to thin melanomas are neither accurate nor reproducible, emphasizing the need for more objective supplemental immunohistochemical markers. PRAME immunohistochemistry aids in differentiating unequivocal melanomas from unequivocal nevi. The aim of our study was to determine whether PRAME IHC also allows differentiation of severely dysplastic nevi from thin melanomas and whether PRAME is of prognostic significance in thin melanomas. We studied 70 thin melanomas, of which 35 metastasized and 35 did not metastasize and 35 severely dysplastic nevi. We found that diffuse PRAME expression was highly specific but only moderately sensitive for thin melanomas. Melanomas and severely dysplastic nevi with PRAME immunoreactivity had different staining patterns. Most Melanomas demonstrated diffuse PRAME staining of intraepidermal and dermal melanocytes while most severely dysplastic nevi showed a decreasing gradient with depth. PRAME did not allow for the differentiation of metastasizing and non-metastasizing melanomas. ABSTRACT: Background: PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is increasingly used as diagnostic adjunct in the evaluation of melanocytic tumors. The expression and prognostic significance of PRAME in melanomas ≤1.0 mm and its diagnostic utility in the distinction from severely dysplastic compound nevi (SDN) have not been studied. Methods: We investigated and compared the immunohistochemical PRAME expression in 70 matched thin metastasizing and non-metastasizing melanomas and 45 nevi from patients with long-term follow-up (35 SDN and 10 unequivocally benign compound nevi). Results: Diffuse PRAME staining in >75% of lesional epidermal and dermal melanocytes identified 58.6% of thin melanomas but did not distinguish metastasizing from non-metastasizing melanomas (p = 0.81). A superficial atypical melanocytic proliferation of uncertain significance, in which the final diagnostic interpretation favored a SDN was the only nevus with diffuse PRAME expression (1/45). Melanomas and SDN with PRAME immunoreactivity exhibited different staining patterns. Most melanomas (67.6%) showed uniform PRAME expression in the in situ and invasive component, whereas most SDN (81.0%) showed a decreasing gradient with depth. Conclusion: Diffuse intraepidermal and dermal PRAME staining is highly specific for melanomas in the distinction from SDN. PRAME expression is not a prognostic biomarker in melanomas ≤1.0 mm.