PRAME expression in spindle cell melanoma, malignant peripheral nerve sheath tumour, and other cutaneous sarcomatoid neoplasms: a comparative analysis

Diagnosis of spindle cell/sarcomatoid melanoma may be challenging due to frequent loss of expression of melanocytic marker(s) and histomorphologic resemblance to various mesenchymal tumours, particularly malignant peripheral nerve sheath tumour (MPNST). Overexpression of PReferentially expressed Antigen in MElanoma (PRAME) supports a diagnosis of melanoma when evaluating challenging melanocytic tumours. PRAME expression in MPNST and other cutaneous sarcomatoid neoplasms, however, has not been well characterised. We aimed to determine the utility of PRAME immunostain in distinguishing spindle cell melanoma from MPNST and other sarcomatoid mimics. PRAME expression was scored by extent (0 to 4+) and intensity (0 to 3) of staining. A strong positive correlation was observed between the extent and intensity scores (r = 0.84). An extent score of 4+, defined by staining in 76-100% of tumour cells, was seen in 56% (23/41) of spindle cell melanomas, 18% (7/38) of MPNSTs, 15% (4/27) of cutaneous sarcomatoid squamous cell carcinomas (SCCs), 33% (5/15) of poorly differentiated cutaneous angiosarcomas, 12% (4/33) of atypical fibroxanthomas (AFXs), 4% (1/25) of pleomorphic dermal sarcomas (PDSs), and none (0/16) of the high-grade cutaneous leiomyosarcomas. A significant difference was found between spindle cell melanoma and all other examined sarcomatoid neoplasms except angiosarcoma. While diffuse (and often strong) PRAME expression is more frequently observed in spindle cell melanoma than MPNST, sarcomatoid SCC, AFX, PDS, and high-grade leiomyosarcoma, its limited sensitivity and specificity caution against its use as a standalone diagnostic marker. PRAME may complement other epigenetic or lineage-specific markers and should only be used as part of an immunohistochemical panel when evaluating these sarcomatoid neoplasms.