PRAME is a useful marker for the differential diagnosis of melanocytic tumours and histological mimics

Aims Although the morphological assessment of melanoma is generally straightforward, diagnosis can be especially difficult when the significant morphological and immunohistochemical results overlap with those of benign and malignant melanocytic tumours and histological mimics. This study assessed the potential diagnostic utility of measuring PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemically in naevi, melanomas and clear cell sarcomas (CCSs) in Chinese patients. Methods We examined the immunohistochemical expression of PRAME in 317 melanocytic naevi, 178 primary melanomas, 72 metastatic melanomas and 19 CCSs and compared the sensitivity and specificity of PRAME immunohistochemistry (IHC) in the differential diagnosis of melanocytic tumours and histological mimics. Results Of the 317 melanocytic naevi, 98.1%were completely negative for PRAME; six cases showed focal PRAME immunoreactivity in a minor population of lesional melanocytes. Diffuse nuclear immunoreactivity for PRAME was found in 89.9% of primary melanomas and 93.1% of metastatic melanomas. Regarding melanoma subtypes, PRAME was expressed in 100% of superficial spreading melanomas, 100% of melanomas arise in congenital naevus, 91.4% of nodular melanomas, 87.8% of acral lentigo melanomas, 80.0% of lentigo malignant melanomas, 60.0% of Spitz melanomas, 96.2% of mucosal melanomas and 80.0% of uveal melanomas. None of the two desmoplastic melanomas expressed PRAME. Of the 19 CCS cases, 89.5% were negative for PRAME and 10.5% showed focal weak PRAME immunoreactivity in a minor population of tumour cells. Conclusions Our findings indicate that PRAME may be a useful marker to support a suspected diagnosis of melanoma. In addition, lack of PRAME expression is a valuable hint to CCS in a suspected case, and then molecular confirmation of the presence of EWSR1 rearrangement is necessary.