Genetic and genomic analyses of melanocytic tumors have yielded new opportunities for improvements in diagnostic accuracy for the distinction of nevus from melanoma and better selection of patients affected by melanoma for targeted treatment. Since chromosomal copy number changes are commonly found in malignant melanoma, but rare in melanocytic nevi, cytogenetic assays have emerged as a promising ancillary study for the workup of melanocytic tumors with ambiguous light microscopic features. Comparative genomic hybridization (CGH) permits assessment of the full set of chromosomes, but requires a significant amount of lesional tissue, and may fail to detect aberrations in a minor subpopulation of tumor cells. Fluorescence in situ hybridization (FISH) is the cytogenetic assay of choice for limited amounts of tissue. FISH targets only specific chromosomes, with inherent limitations in test sensitivity and specificity. FISH analysis is also heavily dependent on individual experience. Molecular studies have identified distinct sets of mutations in melanoma and/or nevi. These mutations have become clinically relevant for targeted therapy of patients with advanced disease, especially for the treatment of patients with metastatic melanoma carrying the BRAF(V600) or KIT mutations. However, mutation analysis can on occasion also be used for diagnostic purposes.
