Abstract

Dedifferentiated and undifferentiated melanomas are increasingly recognized as cutaneous and mucosal primaries. Their diagnosis is challenging and dependent on recognition of a conventional melanoma precursor or detection of mutations in known melanoma driver genes. PRAME immunohistochemistry has become an important ancillary tool separating melanoma from nevi, but its value in the diagnosis of dedifferentiated and undifferentiated melanomas and their separation from atypical fibroxanthoma and pleomorphic dermal sarcoma is unknown. After retrieval from archival files, we performed PRAME immunohistochemistry on eleven primary and ten metastatic dedifferentiated and undifferentiated melanomas, eleven atypical fibroxanthomas and ten pleomorphic dermal sarcomas. Nuclear staining was assigned extent (ranging from 0-4 and reflecting the percentage of PRAME positive tumor nuclei) and intensity scores (graded as absent, weak, moderate and strong, with scores ranging from 0-3) with combined scores ranging from 0 to 7. Primary and metastatic dedifferentiated and undifferentiated melanomas showed strong and diffuse nuclear PRAME staining (median combined score: 7). PRAME staining was also seen in conventional melanoma precursors except for desmoplastic melanoma. In contrast, PRAME staining in atypical fibroxanthoma and pleomorphic dermal sarcoma was patchy and weak (median combined score: 2). Our data emphasize the diagnostic utility of PRAME staining as a first screening tool in the detection and work-up of dedifferentiated and undifferentiated melanomas. PRAME immunohistochemistry is particularly helpful as it is also positive in tumors without a recognizable conventional melanoma precursor and in those associated with desmoplastic melanomas, where PRAME is typically negative.