There is a significant need for the development of diagnostic tools that can precisely distinguish Spitz nevi and spitzoid melanomas. Here, we report the development of a PCR-based quantitative diagnostic assay for spitzoid melanocytic lesions utilizing the expression ratio of neuropilin-2 and melan-A genes in primary tumor specimens. We find that the expression ratio of neuropilin-2/melan-A is significantly increased in spitzoid melanomas compared with Spitz nevi. The diagnostic potential of this quantitative assay was validated in two independent sets of patient samples as demonstrated in a receiver operating characteristic curve analysis showing an area under the curve value of 91.8%. Furthermore, the assay was found to quantitatively distinguish the clinical nature of atypical spitzoid melanocytic lesions that were diagnostically undetermined using histopathologic criteria alone. Our data indicate that this quantitative assay may be used as a tool in determining the diagnostic classification of histologically challenging spitzoid tumors. *Anna Eisenstein and Izabela P. Panova contributed equally to the writing of this article. Correspondence to Byungwoo Ryu, PhD, Department of Dermatology, Boston University School of Medicine, 609 Albany Street, J-502, Boston, MA 02118, USA Tel: +1 617 638 5535; fax: +1 617 638 5515; e-mail: ryub@bu.edu Correspondence to Rhoda M. Alani, MD, Department of Dermatology, Boston University School of Medicine, 609 Albany Street, J-507, Boston, MA 02118, USA Tel: +1 617 638 5517; fax: +1 617 638 5543; e-mail: alani@bu.edu Received August 10, 2017 Accepted October 27, 2017 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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