PRAME and HMB-45 panel for distinguishing primary melanocytic tumors

Introduction: The utility of a single immunohistochemistry for PRAME (PReferentially expressed Antigen in MElanoma) can vary, with published literature showing sensitivity between 67% and 81%. Previously, one technical study explored the use of double staining for HMB45 and PRAME on a small subset of melanocytic tumors suggesting a potential diagnostic benefit. The aim of this study was to assess the value of a dual panel of PRAME and HMB45 in primary melanocytic tumors.
Methods and materials: A total of 259 tumors from a two-year period span were retrieved from the department’s archives. All tumors were reviewed by two experienced dermatopathologists and classified as one of the following: benign nevi, dysplastic nevi, and malignant melanoma. Only the cases with agreement on the classification were included. Specimens included 141 nevi, 32 dysplastic nevi, and 86 malignant melanomas. New sections were stained with PRAME and HMB45, respectively. For PRAME, a nuclear, and for HMB45, a cytoplasmic staining, was considered positive and scored as described in the literature on a scale from 0 to 4+.
Results: We report superior sensitivity and specificity for diffuse 4+ PRAME positivity, 73% and 96% respectively, when compared to HMB45, 57% and 86% respectively. No nevi showed double 4+ positivity, however, sensitivity for the double positivity was only 47,6%.
Discussion and conclusion: Our results confirm the superiority of PRAME over HMB45 in differential diagnosis of melanocytic tumors. However, a combined staining can significantly increase specificity rendering a benign diagnosis more unlikely in a setting of double 4+ diffuse positivity.