Proliferative Nodules in Congenital Nevi - A Histopathologic, Genetic and Immunohistochemical ReappraisalMeera Brahmbhatt1, Shi Yang2 and Meera Mahalingam3*
- *Corresponding Author:
- Meera Mahalingam
Department of Dermatology
Boston University School of Medicine
609 Albany Street, J-301
Boston, MA 02118, USA
Tel: 617 638 5574
Fax: 617 638 5575
Email: [email protected]
Received date: November 11, 2010; Accepted date: December 06, 2010; Published date: December 07, 2010
Citation: Brahmbhatt M, Yang S, Mahalingam M (2010) Proliferative Nodules in Congenital Nevi - A Histopathologic, Genetic and Immunohistochemical Reappraisal. J Clin Exp Dermatol Res 1:105. doi: 10.4172/2155-9554.1000105
Copyright: © 2010 Brahmbhatt M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
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.