Journal of Clinical & Experimental Dermatology Research
Open Access

Abstract

Proliferative Nodules in Congenital Nevi - A Histopathologic, Genetic and Immunohistochemical Reappraisal

Meera Brahmbhatt, Shi Yang and Meera Mahalingam

Although histopathology is the gold standard for the classification of melanocytic proliferations, in some such as the proliferative nodule, an equivocal diagnosis can be diagnostically extremely challenging based on histopathologic features alone. The purpose of this study was to review the histologic features of proliferative nodules and to ascertain the utility of immunohistochemistry and analyses of oncogenic mutations in signaling components of the MAP kinase pathway as diagnostic adjuncts. Genomic DNA for genotyping was isolated per protocol using techniques that included laser capture microdissection to isolate nevus cells from proliferative nodules (n=3) and age-matched congenital nevi (CN, n=3). Direct DNA sequencing was performed on BRAF codon 600; NRAS1 codons 12 and 13; NRAS2 codons 60 and 61, KRAS codons 12 and 13 and GNAQ. Immunohistochemical analyses were performed using antibodies to nestin, CD133, p53, c-kit and bcl-2. While all 3 cases of proliferative nodules exhibited mitoses, features of concern were not noted in any. Of the genes analyzed, no mutations were identified in any of the PN. Immunohistochemistry revealed the following: nestin in 1 PN (3+) and in 2 CN (both 3+); CD133 negative in all PN and CN; p53 in 1 PN (2+) and 0 in CN; c-kit in 2 PN (2+/3+) and in 3 CN (2+/3+/3+) and bcl-2 in 2 PN (both 3+) and 2 CN (both 3+). Our findings, albeit limited by sample size, suggest that proliferative nodules do not appear to possess a distinctive or unifying genomic signature. In light of evidence indicating that progression to malignant melanoma involves genetic pathways instrumental to stem cell biology, that absence of a sizeable population of stem cells in 2 of 3 of proliferative nodules in the current study supports their putative benign biologic behavior.