Abstract

Atypical spitzoid melanocytic neoplasms can be diagnostically challenging for dermatopathologists. Molecular assays and immunohistochemical markers are being explored as ancillary methods to assist in the diagnostic work-up. One such example is preferentially expressed antigen in melanoma (PRAME) immunohistochemistry, a nuclear stain commonly positive in melanomas but not in nevi. In this study, we investigated PRAME immunoreactivity in a set of 59 atypical spitzoid melanocytic neoplasms with known clinical outcomes. We compared PRAME status to: 1) the clinical outcomes, 2) the morphologic diagnoses, and 3) the status of TERT promoter mutation. There were three cases of melanoma with spitzoid features with subsequent metastatic disease. Two of them (66.7%) had diffuse ( ≥75%) positive nuclear PRAME staining in tumor cells. One lacked PRAME expression. Diffuse PRAME expression was seen in 7/21 (33.3%) cases diagnosed as melanoma and 6/56 (10.7%) with uneventful outcome (P=0.006). Only one benign tumor 1/38 (2.6%) showed diffuse PRAME expression (P=0.001). Four of 8 tumors with a TERT promoter mutation were diffusely PRAME positive compared to 4/51 cases without TERT promoter mutation (P=0.001). Our results show that there is a statistically significant correlation between diffuse PRAME expression and the diagnosis, outcome, and TERT promoter mutation status of atypical spitzoid melanocytic neoplasms. Therefore, immunohistochemistry for PRAME can help support a suspected diagnosis. However, because of occasional false-positive and negative test results, correlation with the clinical and microscopic findings as well as results from other tests is needed for the interpretation of diagnostically challenging spitzoid melanocytic neoplasms.

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