Abstract
Primary melanocytic tumors of the CNS are extremely rare conditions, encompassing different disease processes including meningeal melanoma and meningeal melanocytosis. Its incidence range between 3-5%, with approximately 0.005 cases per 100,000 people. Tumor biological behavior is commonly aggressive, with poor prognosis and very low survivability, and a high recurrence rate, even after disease remission with multimodal treatments. Specific genetic alterations involving gene transcription, alternative splicing, RNA translation, and cell proliferation are usually seen, affecting genes like BRAF, TERT, GNAQ, SF3B1, and EIF1AX. Here we present an interesting case of a 59-year-old male presenting with neurologic symptoms and a further confirmed diagnosis of primary meningeal melanoma. Multiple therapy lines were used, including radiosurgery, immunotherapy, and chemotherapy. The patient developed two relapses and an evolving genetic makeup that confirmed the disease’s clonal origin. We also provide a review of the literature on the genetic basis of primary melanocytic tumors of the CNS.
Highlights
Melanocytic tumors that originate in the meninges are rare
The G15D mutation (c.44G> A) is found in up to more than 30% of uveal melanomas (UMs) and in primary melanomas of the meninges, where it usually co-occurs with other mutations in SF3B1, as in the present case (R625H mutation, c.1874G> A) (Supplementary Data includes a detailed description of the methods performed for the NGS assessment on the Ion TorrentTM OncomineTM Comprehensive Assay Plus)
The presence of BRAF, NRAS, HRAS and KIT mutations was ruled out, and during disease evolution, several alterations were found in GNAQ, EIF1AX, SF3B1, SDE2, PRDX2, CHIT1, TNIP, and telomerase reverse transcriptase gene (TERT)
Summary
Melanocytic tumors that originate in the meninges are rare. These tumors might present as focal (melanomas) or diffuse conditions (melanocytosis). The loss of chromosome 3 and BAP1 mutations have been detected in some melanocytic meningeal tumors [2, 3] These molecular differences have implications in targeted therapy [3]. The second sample’s genetic analysis revealed five new alterations in the TERT promoter (C228T), SDE, PDRX2, CHIT1, and TNIP genes As a complication, he had a CSF cyst plus bacterial meningitis that delayed the execution of new radiosurgery with gamma knife (16 Gy). After finding persistence of the GNAQ and TERT alterations in tumor tissue, he began treatment with temozolomide on the 5/ 28 schedule, maintaining the response to date At that time, he completed 58 months of survival.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
