PRAME-negativity in sclerosing nevi with pseudomelanomatous features supports classification as an indolent lesion

Background: Some dysplastic nevi, termed sclerosing nevi with pseudomelanomatous features, may have florid fibroplasia associated with features that cause melanoma to be a prominent consideration in the differential diagnosis. PRAME (PReferentially expressed Antigen in MElanoma) immunohistochemistry (IHC) has been shown to be a useful marker in the distinction of melanoma and nevus. PRAME expression in such sclerosing nevi with pseudomelanomatous features has not been evaluated to our knowledge. Methods: Thirty-two sclerosing nevi with pseudomelanomatous features were stained with PRAME IHC, with positive labeling defined as staining of >75% of the cytomorphologically atypical lesional cells. Results: All 32 cases had variable cytologic atypia, bridging of elongated rete, fibroplasia, and a vertically oriented trizonal appearance. Some cases (23/32) had centrally located flattening of the rete ridge pattern bilaterally flanked by fibroplasia associated with elongated rete. PRAME labeling was negative (<1% labeling) in 28/32 cases. Four cases, also interpreted as having negative labeling with PRAME, showed only weak nuclear positivity of <50% of the melanocytes within the pseudomelanomatous foci. p16 staining was positive in 28/28 lesions. Conclusions: Rare sclerosing nevi with pseudomelanomatous features (4/32; similar to 13%) had weak PRAME labeling of 25%-50% of atypical foci. Twenty-eight of 32 lesions had virtually no labeling with PRAME. PRAME results support classifying sclerosing nevi with pseudomelanomatous features as indolent lesions.