Next Generation Sequencing in Differential Diagnosis of Childhood Melanoma From Spitz Nevus: A Case Report

Abstract

Melanomas are uncommon in children and share many of the characteristics of benign Spitz nevi in their clinical presentation as well as histopathology. Therefore, the diagnosis could be challenging. Currently, molecular diagnostic tools are being explored to aid the diagnosis in the pediatric melanoma. Melanomas often harbor multiple gene mutations and gene number variations, including BRAF (7q34), CCND1 (11q13), RREB1 (6p25), Cep 6, MYB (6q23), PIK3CA (3q26), PTEN (10q23), CDKN2A (9p21), c-KIT (4q12) and MYC (8q24), but these changes are rare in benign melanocytic nevi, including Spitz nevus of which the signature gene abnormalities had been recently revealed. Next generation sequencing (NGS) is a new molecular technique allowing the detection of a broad spectrum of genome abnormalities simultaneously, thus providing a potential powerful tool for assisting the diagnosis of childhood melanoma. We herein present a 12-year-old female with a melanocytic neoplasm showing histopathologic features highly suggestive of malignant melanoma. A variety of molecular analysis studies were employed including NGS, which revealed BRAF mutation, BRAF copy number addition, and CDKN2A and PTEN deletion. Fluorescence in situ hybridization studies were also used, which not only confirmed the gene number variation in BRAF, CDKN2A and PTEN, but also revealed gain in MYC. These results added valuable information in the diagnosis of melanoma. This case demonstrated the usefulness of molecular analysis as the ancillary tools in assisting the diagnosis of childhood melanoma. Int J Clin Pediatr. 2014;3(1):22-28 doi: http://dx.doi.org/ 10.14740 / ijcp148e