PRAME Expression Is a Useful Tool in the Diagnosis of Primary and Metastatic Dedifferentiated and Undifferentiated Melanoma

Abstract

Although mostly recognized in the metastatic setting dedifferentiated and undifferentiated melanomas are increasingly recognized as cutaneous and, less commonly, mucosal primary tumors. Their diagnosis is challenging and dependent on sampling and recognition of a conventional melanoma precursor and/or detection of a mutation in a conventional melanoma driver gene. PRAME immunohistochemistry has recently become an important ancillary tool in the separation of melanoma from benign nevi, but no comprehensive studies exist regarding its value in the detection of dedifferentiated and undifferentiated melanomas and their separation from atypical fibroxanthoma and pleomorphic dermal sarcoma, the main differential diagnoses on sun-damaged skin. After retrieval from archival files, we performed PRAME immunohistochemistry on 11 primary and 10 metastatic dedifferentiated and undifferentiated melanomas, 11 atypical fibroxanthomas, and 10 pleomorphic dermal sarcomas. Nuclear staining was assigned extent (ranging from 0 to 4 and reflecting the percentage of PRAME-positive tumor nuclei) and intensity scores (graded as absent, weak, moderate, and strong, with assigned scores ranging from 0 to 3) with combined scores ranging from 0 to 7. Both primary and metastatic dedifferentiated and undifferentiated melanomas showed strong and diffuse nuclear PRAME staining with median combined scores of 7. Strong and diffuse staining was also seen in all conventional melanoma precursors except for desmoplastic melanoma. In contrast, PRAME staining in atypical fibroxanthoma and pleomorphic dermal sarcoma was patchy and weak with median combined scores of 2. Our data emphasize the diagnostic utility of PRAME staining as a first screening tool in the detection and workup of dedifferentiated and undifferentiated melanomas, both in the primary and metastatic settings. 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 found to be negative.