The formation of a nodule within a congenital melanocytic nevus (CMN) raises concerns about
possible melanoma. Most new nodular growths that develop during childhood, however, are
benign proliferative nodules (PN); melanoma is very rare. The distinction of melanoma from PN
can at times be difficult clinically and histopathologically, requiring ancillary molecular tests for
diagnosis. While the application of molecular methods has revealed new insights into the
mutational and genomic landscape of childhood melanomas, little is known about epigenetic
events that may drive the growth of a melanoma or PN in a CMN. In this study we compared the
expression of H3K27me3, a key regulator in chromatin remodelling-controlled transcription, in
PNs and pediatric nodular melanomas arising within medium-sized to large CMN by
immunohistochemistry (IHC). Significant loss of H3K27me3 expression was seen in four of five
melanomas, but not in any of the 20 PNs. This observation suggests that epigenetic events likely
play a role in the pathogenesis of melanoma developing in the dermis or subcutis of CMN.
Furthermore, assessing for H3K27me3 expression by IHC may be diagnostically useful for
problematic cases