Abstract

PRAME (PReferentially expressed Antigen in MElanoma) has proven useful as a treatment-targetable antigen for diagnosing and caring for challenging cutaneous melanocytic lesions and certain neural crest-derived ocular neoplasms. While PRAME expression by immunohistochemistry is currently known as a marker of melanocytic maturity, melanocytes are derived from neural crest embryologic precursors. Therefore, PRAME expression may have thus far untapped utility in evaluating other skin and soft tissue neoplasms with neural crest origins. A retrospective examination of various neural tumor cases--including neurofibroma, dermal nerve sheath myxoma, conventional and cellular schwannoma, and malignant peripheral nerve sheath tumor (MPNST) cases--revealed all lesions lacked PRAME expression by immunohistochemistry, except for within high-grade MPNST cases. This unique expression pattern may signify a gap in the current understanding of the derivation and in situ evolution of neural tumors and their relation to desmoplastic or spindle cell melanomas, as these are often considered within the differential diagnosis when working up a particular case. More practically, the discovery of PRAME expression in high-grade MPNST cases identifies a potential additional therapeutic target for patients whose malignancies have proven resistant to current treatment options. The findings of this study highlight the need for further research to elucidate PRAME's expression and usefulness as a therapeutic target in other neural crest-derived malignancies.