Next-Generation Sequencing of Nevus Spilus–Type Congenital Melanocytic Nevus: Exquisite Genotype–Phenotype Correlation in Mosaic RASopathies

TO THE EDITOR Nevus spilus is a descriptive term used to denote any cutaneous lesion with a café-au-lait macular background and superimposed on more pigmented areas. Small single nevus spilus are relatively common, and they have recently been described to be due to somatic activating HRAS mutations (Sarin et al., 2014). Larger superficial lesions with small superimposed junctional nevi in association with phakomatosis pigmentokeratotica have also been found to contain HRAS mutations (Groesser et al., 2013). However, another nevus spilus–type phenotype has also been well described in which large café-au-lait macules have superimposed lesions that are indistinguishable both clinically and histopathologically from medium/large congenital melanocytic nevi (CMN), exhibit a wide variety of colors and sizes (Schaffer et al., 2001a, b), and continue to develop postnatally in many cases. This is termed nevus spilus–type CMN. In our experience, there may be delayed appearance of the café-au-lait background after birth, but the lesion is still usually predictable on the basis of clustering of many CMN in one anatomical area. Smaller separate lesions in the same individual are often indistinguishable clinically from caféau-lait macules, and are so faint that they can be easily missed (Figure 1). Our primary aim in this study was to look for the genetic basis of this defined phenotypic subset of CMN, in the context of the recent discovery that NRAS Q61K and Q61R mutations are the cause of most causes of multiple CMN (Kinsler et al., 2013b). In particular, we were interested in determining the mutation in See related commentary on pg 2493 LETTER TO THE EDITOR