Fluorescence in situ hybridization for distinguishing cellular blue nevi from blue nevus-like melanoma

Background: Blue nevus‐like melanomas are melanomas that arise in association with blue nevi or closely simulate the histopathologic appearance of a blue nevus, usually a cellular blue nevus (CBN). Although the majority of CBN can be readily distinguished from blue nevus‐like melanoma by conventional microscopy, there are a subset of cases where this distinction may be exceedingly difficult or impossible. Methods: In this study, we evaluated the ability of a fluorescence in situ hybridization (FISH) assay targeting 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1) and the centromere of chromosome 6 (Cep6) to distinguish between CBN and blue nevus‐like melanoma. We identified five cases of blue nevus‐like melanoma and 12 cases of CBN. Results: The FISH assay was performed with 100% sensitivity and 100% specificity. Three of five cases met the 6p25/Cep6 criteria, all five met the 6p25 gain criteria and three of five met the 6q23/Cep6 loss criteria. None of the cases met criteria for gains in 11q13. None of the 12 CBN met any criteria for melanoma. Conclusions: A combined analysis of clinical aspects, histopathologic changes and FISH analysis could potentially contribute significantly to the ability of pathologists to discriminate between blue nevus‐like melanoma and blue nevi in challenging cases. Gammon B, Beilfuss B, Guitart J, Busam KJ, Gerami P. Fluorescence in situ hybridization for distinguishing cellular blue nevi from blue nevus‐like melanoma.