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.