The Diagnostic Utility of PRAME in Primary Cutaneous Dedifferentiated and Transdifferentiated Melanomas

Melanomas show a wide spectrum of clinical, morphological, immunohistochemical, and molecular features, which can impact treatment and prognosis. Dedifferentiated and transdifferentiated melanomas (DTM) are defined as melanomas which have lost conventional melanocytic morphologic and immunohistochemical features, showing sarcomatous morphology and/or immunohistochemical staining of other cell lineages, and as such, can be mistaken for other entities such as collision tumors and undifferentiated spindle cell tumors. In this series, we highlight the utility of preferentially expressed antigen in melanomas (PRAME) in diagnosing undifferentiated/dedifferentiated melanomas. Case 1 is a lentigo maligna melanoma with dedifferentiation on the scalp of an 85-year-old. Case 2 is a desmoplastic melanoma with leiomyosarcomatous transdifferentiation on the cheek of an 80-year-old. Case 3 is a desmoplastic melanoma with rhabdomyosarcomatous transdifferentiation arising from the temple of an 88-year-old. In all cases, conventional melanocytic immunohistochemical markers were positive in the conventional melanoma and negative in the dedifferentiated/transdifferentiated areas. However, PRAME was positive in both the conventional and dedifferentiated areas with varying intensity. Although PRAME immunoreactivity can be seen in other malignant spindle cell tumors, this study highlights the potential utility of PRAME immunohistochemistry when considering a diagnosis of DTM.