Background: Differentiating Spitz nevi from melanoma can be difficult. Pagetoid spread of melanocytes is among the features making diagnosis difficult. Rare reports of isolated pagetoid Spitz nevi exist. Observations: We present a unique case of multiple pagetoid Spitz nevi initially diagnosed as multiple in situ melanomas. Germline karyotyping, CDK4 and CDKN2A sequencing, and comparative genomic hybridization ofHRAS, BRAF, KRAS, RAF1, CDKN2A, Rb1, MAP2K1, MAP2K2, PTEN, and PTPN11 genes did not identify mutations in this case. Germline and somatic sequencing of BRAF exon 15 revealed no mutations at V600D/E/K. In addition, singlenucleotide polymorphism microarray analysis (330K) on lesional and normal skin revealed no genome-wide copy number changes or loss of heterozygosity. Conclusions: Clinicians should be aware of the occurrence of multiple pagetoid Spitz nevi to avoid morbidity associated with the misdiagnosis of multiple melanomas. The genetic mechanisms of pagetoid spread of melanocytes are not fully understood.
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