Abstract
Background and clinical significance: Cutaneous melanomas sometimes display unusual histopathological features, reminiscent of various other malignancies, either primary or metastatic. However, due to the highly aggressive nature of cutaneous melanomas, an accurate and timely diagnosis is mandatory. This requires extensive histopathological and immunohistochemical analyses and molecular tests, if needed. Case presentation: In this respect, we present two cases of primary cutaneous melanomas exhibiting rhabdoid features and genuine divergent rhabdomyosarcomatous differentiation confirmed by immunoreactivity for myogenin and loss of positivity for some melanocytic markers. We discuss the diagnosis approach for these particularly rare entities, highlighting the most useful immunohistochemical panel. Additionally, we also provide an extensive review of all the previously reported similar lesions, focusing on the epidemiological, histopathological, immunohistochemical and molecular features, as well as discussing the prognostic and treatment options for rhabdomyosarcomatous cutaneous melanomas. Conclusions: These rare cases of primary cutaneous melanomas with rhabdomyosarcomatous differentiation underscore the diagnostic challenges posed by such unusual histopathological variants. In order to establish the correct diagnosis a comprehensive immunohistochemical workup, including both melanocytic and myogenic markers, is required. These findings are supported by a detailed review of the literature, emphasizing the importance of recognising these rare melanoma subtypes for providing the appropriate prognostic assessment, and therapeutic management.