Pitfalls of Gene Expression Profiling for Cellular Blue Nevi

Summary: Gene expression profiling (GEP) has emerged as an important prognostic tool for cutaneous pigmented lesions of uncertain malignant potential. However, the sensitivities and specificities of GEP testing for cellular blue nevi are unknown. We report a case in which GEP testing was performed on a biopsy of a cellular blue nevus, leading to a false diagnosis of invasive malignant melanoma. A 25-year-old female presented with a 1.2 cm nodule on the left buttock. Excisional biopsy was performed with pathology demonstrating findings consistent with a cellular blue nevus with atypia. A commercially available GEP test was performed with a finding of “gene expression profile suggestive of melanoma.” Ultimately, it was determined that despite GEP testing, this lesion was not consistent with a blue nevus-like melanoma. This re-emphasizes the guidance provided by the American Society of Dermatopathology Appropriate Use Criteria (AUC), which discourages use of any ancillary testing for lesions that are histologically diagnosed as definitively benign or malignant melanomas. More studies are needed to assess the utility of GEP testing for cellular blue nevi. Thus, histopathology remains the gold standard for diagnostic evaluation of blue nevi.