Undifferentiated Melanoma Mimicking Pleomorphic Dermal Sarcoma: Two Additional Cases With Follow-Up Data and Short...

Melanoma is known to have a high prevalence of somatic mutations, leading to a wide range of clinical and histological variability. This genetic plasticity can result in the partial or total loss of typical diagnostic clinical and immunohistochemical features of melanoma. Undifferentiated melanoma (UM) and dedifferentiated melanoma (DM) pose a significant diagnostic challenge due to their histological atypia and the absence of conventional melanocytic markers, often making them indistinguishable from pleomorphic dermal sarcoma (PDS). Accurate differentiation, however, is critical as UM and DM, unlike PDS, display a higher metastatic potential. Molecular analysis plays a crucial role in accurate diagnosis, particularly through the detection of mutations such as BRAF and NRAS, which are rarely found in true sarcomas. We present 2 cases of primary cutaneous UM initially misdiagnosed as PDS and later reclassified based on molecular findings. A comprehensive review of the literature was performed of reported cases of primary cutaneous undifferentiated and DM. Timely diagnosis is vital to allow access to effective targeted therapies, such as immune checkpoint inhibitors and BRAF/MEK inhibitors, which have shown promising responses, suggesting that undifferentiated and DM respond similarly to conventional melanoma despite their atypical presentation.