For a small yet significant proportion of melanocytic lesions, histopathologic analysis may be unable to definitively evaluate malignant potential. These cases may signify a specific need for newer ancillary diagnostic technologies, including in vivo reflectance confocal microscopy (RCM) and gene expression profiling (GEP), both of which are highly sensitive in the diagnosis of melanoma. We report four cases of clinically suspicious melanocytic lesions that lacked definitive malignant features on histopathology and that were aided by use of RCM and GEP. Three of the four cases showed concordance between RCM and GEP in the diagnosis of melanoma. In one case, RCM was suggestive of melanoma; on the other hand, GEP and histopathology supported a final diagnosis of compound Spitz nevus. These cases support the role of RCM as a novel, non-invasive diagnostic tool to aid in the diagnosis of clinically suspicious melanocytic lesions with uncertain malignant potential, although RCM may have relatively lower accuracy for some atypical spitzoid lesions.

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