Abstract

Dedifferentiated and undifferentiated melanomas are challenging to diagnose due to atypical histology and lack of expression of standard melanocytic markers (S100, SOX-10, HMB-45, and Melan-A). The molecular mechanisms driving dedifferentiation in melanoma remain unclear, and it is unknown whether this process contributes to immune evasion or represents an epithelial-mesenchymal transition. We employed Nanostring’s GeoMx Digital Spatial Profiler with next-generation sequencing to conduct high-resolution spatial differential gene expression analysis in a dedifferentiated melanoma with both well-differentiated and dedifferentiated components. The patient, a 72-year-old female with a history of melanoma, presented with a bone lesion on follow-up. Histologic examination of the bone lesion revealed a hypercellular spindle cell lesion, which was negative for melanocytic markers but exhibited weak BRAF positivity. Molecular analysis confirmed the diagnosis of melanoma. The GeoMx experiment, which focused on the differential gene expression of well-differentiated and dedifferentiated components, revealed significant overlap in upregulated genes with uveal melanoma and epithelial mesenchymal transition in the dedifferentiated component. Further investigations are ongoing to explore additional differentially altered pathways.