Primary Melanocytic Tumors of the Central Nervous System: a Review with Focus on Molecular Aspects

• Published in: Brain pathology (Zurich, Switzerland) Vol. 25; no. 2; pp. 209 - 226
• Main Authors: Küsters-Vandevelde, Heidi V.N., Küsters, Benno, van Engen-van Grunsven, Adriana C.H., Groenen, Patricia J.T.A., Wesseling, Pieter, Blokx, Willeke A.M.
• Format: Journal Article
• Language: English
• Published: Switzerland Blackwell Publishing Ltd 01.03.2015; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: Animals; brain; central nervous system; Central Nervous System Neoplasms - genetics; Central Nervous System Neoplasms - metabolism; GNA11; GNAQ; GTP Phosphohydrolases - genetics; GTP-Binding Protein alpha Subunits - genetics; GTP-Binding Protein alpha Subunits, Gq-G11; Humans; leptomeningeal melanocytic neoplasms; Medical research; Melanocytes - metabolism; melanocytoma; melanoma; Melanoma - genetics; Melanoma - metabolism; melanotic schwannoma; Membrane Proteins - genetics; Meningeal Neoplasms - genetics; Meningeal Neoplasms - metabolism; metastasis; molecular; mosaic RASopathy; Mutation; Nervous system; neurocutaneous melanosis; NRAS; Review; Signal Transduction; neurocutaneous melanosis; melanoma; brain; central nervous system; NRAS; mosaic RASopathy; metastasis; GNA11; GNAQ; melanocytoma; molecular; melanotic schwannoma; leptomeningeal melanocytic neoplasms
• ISSN: 1015-6305; 1750-3639
• DOI: 10.1111/bpa.12241

Primary melanocytic tumors of the central nervous system (CNS) represent a spectrum of rare tumors. They can be benign or malignant and occur in adults as well as in children, the latter often in the context of neurocutaneous melanosis. Until recently, the genetic alterations in these tumors were largely unknown. This is in contrast with cutaneous and uveal melanomas, which are known to harbor distinct oncogenic mutations that can be used as targets for treatment with small‐molecule inhibitors in the advanced setting. Recently, novel insights in the molecular alterations underlying primary melanocytic tumors of the CNS were obtained, including different oncogenic mutations in tumors in adult patients (especially GNAQ, GNA11) vs. children (especially NRAS). In this review, the focus is on molecular characteristics of primary melanocytic tumors of the CNS. We summarize what is known about their genetic alterations and discuss implications for pathogenesis and differential diagnosis with other pigmented tumors in or around the CNS. Finally, new therapeutic options with targeted therapy are discussed.