Original ArticlesReduced H3K27me3 Expression Is Common in Nodular Melanomas of Childhood Associated With Congenital Melanocytic Nevi But Not in Proliferative NodulesBusam, Klaus J. MD; Shah, Kara N. MD, PhD; Gerami, Pedram MD; Sitzman, Thomas MD; Jungbluth, Achim A. MD; Kinsler, Veronica MD, PhDAuthor Information *Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY †Department of Pediatrics, Cincinnati Children’s Hospital, Cincinnati, OH ‡Department of Dermatology, Northwestern University, Chicago, IL §Great Ormond Street Hospital for Children ∥UCL Institute of Child Health, London, UK Conflicts of Interest and Source of Funding: Supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748. V.K. is funded by the Wellcome Trust, grant award number WT104076MA. The remaining authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Klaus J. Busam, MD, Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (e-mail: firstname.lastname@example.org). The American Journal of Surgical Pathology: March 2017 - Volume 41 - Issue 3 - p 396-404 doi: 10.1097/PAS.0000000000000769 Buy Metrics Abstract 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. Although 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. Significant loss of H3K27me3 expression was seen in 4 of 5 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 immunohistochemistry may be diagnostically useful for problematic cases. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.