Abstract
While point mutations drive most melanomas, other genetic and genomic changes are observed and diagnosis has been accelerated through genomic studies. We present a case of melanoma with a EWSR1-PBX3 chromosomal rearrangement, previously only reported in myoepithelial tumors. A 49 year old male, Fitzpatrick I-II, presented with a new tender 1.1cm nodule on the left flank. It was reportedly present for 15 years, but with recent change and new tenderness 8 months prior to evaluation. It was sampled by excisional biopsy with suspicion of a cyst vs lipoma vs dermatofibroma. Immunohistochemistry (IHC) revealed that the atypical cells were S100, Sox10, and EMA positive. Pancytokeratin, GFAP, p63, MART1, and BRAFV600E were negative. The morphology and IHC profile were most suggestive of melanocytic lineage. Molecular studies were performed using the Tempus xT platform. The hybrid capture NGS panel tested 648 genes with single nucleotide variants, indels and translocations and showed EWSR1-PBX3 chromosomal rearrangement with a tumor mutation burden of 1.1 m/MB (13th percentile). This fusion was identified in both RNA and DNA. The EWSR-PBX3 chromosomal rearrangement has been previously reported in myopepithelial tumors but not melanoma. Additional testing with the Tempus mRNA expression tumor origin test was also highly suggestive of melanocytic lineage. We report the first case of invasive melanoma with a novel EWSR-PBX3 chromosomal rearrangement. The patient proceeded with WLE, SLNB and imaging with no evidence of metastatic disease. Surveillance imaging in the year after diagnosis remained negative.
