Abstract
Primary melanocytic tumors of central nervous system represent rare tumors arising from melanocytes of the leptomeninges. These neoplasms include focal forms like melanocytoma and primary malignant melanoma and diffuse forms like leptomeningeal melanocytosis and primary leptomeningeal melanomatosis. The clinical diagnosis remains challenging, with clinical and radiologic features overlapping with other more common diseases. Here we present a case of a 38 years old male with primary diffuse leptomeningeal melanomatosis with presence of a NRASQ61K mutation without features of neurocutaneous melanosis.
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References
Louis DN, Hiroko O (2016) WHO classification of tumours of the central nervous system, 4th edn. Lyon, France
Küsters-Vandevelde HVN, Küsters B, Van Engen-Van Grunsven ACH et al (2015) Primary melanocytic tumors of the central nervous system: a review with focus on molecular aspects. Brain Pathol 25:209–226. https://doi.org/10.1111/bpa.12241
Liubinas SV, Maartens N, Drummond KJ (2010) Primary melanocytic neoplasms of the central nervous system. J Clin Neurosci 17:1227–1232. https://doi.org/10.1016/j.jocn.2010.01.017
Smith AB, Rushing EJ, Smirniotopoulos JG (2009) Pigmented lesions of the central nervous system: radiologic–pathologic correlation. RadioGraphics 29:1503–1524. https://doi.org/10.1148/rg.295095109
Brat DJ, Giannini C, Scheithauer BW, Burger PC (1999) Primary melanocytic neoplasms of the central nervous systems. Am J Surg Pathol 23:745–754
Bhatia R, Kataria V, Vibha D et al (2016) Mystery case: neurocutaneous melanosis with diffuse leptomeningeal malignant melanoma in an adult. Neurology 86:e75–e79. https://doi.org/10.1212/WNL.0000000000002396
Trinh V, Medina-Flores R, Taylor CL et al (2014) Primary melanocytic tumors of the central nervous system: report of two cases and review of literature. Surg Neurol Int 5:147. https://doi.org/10.4103/2152-7806.142795
Pirini MG, Mascalchi M, Salvi F et al (2003) Primary diffuse meningeal melanomatosis: radiologic–pathologic correlation. Am J Neuroradiol 24:115–118
Kim DH, Choi CY, Lee CH, Joo M (2015) Primary intracranial leptomeningeal melanomatosis. J Korean Neurosurg Soc 58:554–556. https://doi.org/10.3340/jkns.2015.58.6.554
Fujimori K, Sakai K, Higashiyama F et al (2017) Primary central nervous system malignant melanoma with leptomeningeal melanomatosis: a case report and review of the literature. Neurosurg Rev. https://doi.org/10.1007/s10143-017-0914-0
Küsters-Vandevelde HVN, van Engen- van Grunsven IACH, Coupland SE et al (2015) Mutations in G protein encoding genes and chromosomal alterations in primary leptomeningeal melanocytic neoplasms. Pathol Oncol Res 21:439–447. https://doi.org/10.1007/s12253-014-9841-3
van de Nes J, Gessi M, Sucker A et al (2016) Targeted next generation sequencing reveals unique mutation profile of primary melanocytic tumors of the central nervous system. J Neurooncol 127:435–444. https://doi.org/10.1007/s11060-015-2052-2
Küsters-Vandevelde HVN, Creytens D, van Engen-van Grunsven ACH et al (2016) SF3B1 and EIF1AX mutations occur in primary leptomeningeal melanocytic neoplasms; yet another similarity to uveal melanomas. Acta Neuropathol Commun 4:5. https://doi.org/10.1186/s40478-016-0272-0
Gessi M, Hammes J, Lauriola L et al (2013) GNA11 and N-RAS mutations: alternatives for MAPK pathway activating GNAQ mutations in primary melanocytic tumours of the central nervous system. Neuropathol Appl Neurobiol 39:417–425. https://doi.org/10.1111/j.1365-2990.2012.01288.x
Kinsler VA, Thomas AC, Ishida M et al (2013) Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS. J Investig Dermatol 133:2229–2236. https://doi.org/10.1038/jid.2013.70
Koelsche C, Hovestadt V, Jones DTW et al (2015) Melanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles. Brain Pathol 25:202–208. https://doi.org/10.1111/bpa.12228
Ma M, Ding ZL, Cheng ZQ et al (2018) Neurocutaneous melanosis in an adult patient with intracranial primary malignant melanoma: case report and review of the literature. World Neurosurg 114:76–83. https://doi.org/10.1016/j.wneu.2018.02.007
Kinsler VA, Chong WK, Aylett SE, Atherton DJ (2008) Complications of congenital melanocytic naevi in children: analysis of 16 years’ experience and clinical practice. Br J Dermatol 159:907–914. https://doi.org/10.1111/j.1365-2133.2008.08775.x
Marghoob AA, Dusza S, Oliveria S, Halpern AC (2004) Number of satellite nevi as a correlate for neurocutaneous melanocytosis in patients with large congenital melanocytic nevi. Arch Dermatol 140:171–175. https://doi.org/10.1001/archderm.140.2.171
Brunsvig KL, Zenobi M, Rilliet B et al (2011) Primary leptomeningeal melanocytosis in a 10-year-old girl: a challenging diagnosis with a poor prognosis. J Child Neurol 26:1444–1448. https://doi.org/10.1177/0883073811409749
Sutton BJ, Tatter SB, Stanton CA, Mott RT (2011) Leptomeningeal melanocytosis in an adult male without large congenital nevi: a rare and atypical case of neurocutaneous melanosis. Clin Neuropathol 30:178–182
Kolin DL, Geddie WR, Ko HM (2017) CSF cytology diagnosis of NRAS-mutated primary leptomeningeal melanomatosis with neurocutaneous melanosis. Cytopathology 28:235–238. https://doi.org/10.1111/cyt.12366
Angelino G, De Pasquale MD, De Sio L et al (2016) NRASQ61K mutated primary leptomeningeal melanoma in a child: case presentation and discussion on clinical and diagnostic implications. BMC Cancer. https://doi.org/10.1186/s12885-016-2556-y
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Internal Funding, Department of Pathology and Diagnostics, University and Hospital Trust of Verona (AM, FUR 2016).
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IG: study design; data collection; data interpretation; manuscript preparation; literature search; review and approval of the final manuscript. LC: study design; data collection; data interpretation; manuscript preparation; review and approval of the final manuscript. CG: data collection; data interpretation; review and approval of the final manuscript. MZ: review and approval of the final manuscript. AM: data collection; data interpretation; review and approval of the final manuscript. GR: review and approval of the final manuscript. VC: review and approval of the final manuscript. GC: data collection, data interpretation, review and approval of the final manuscript. AV: review and approval of the final manuscript. GDS: language editing, review and approval of final manuscript. LN: review and approval of the final manuscript. MG: data interpretation, manuscript preparation, review and approval of the final manuscript. AE: data interpretation; review and approval of the final manuscript.
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This study was approved by the institutional review board of the University of Verona in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments.
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Informed consent was acquired from the family of the patient in order to perform autopsy and subsequent investigations.
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Girolami, I., Cima, L., Ghimenton, C. et al. NRASQ61K mutated diffuse leptomeningeal melanomatosis in an adult patient with a brief review of the so-called “forme fruste” of neurocutaneous melanosis. Brain Tumor Pathol 35, 217–223 (2018). https://doi.org/10.1007/s10014-018-0328-x
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DOI: https://doi.org/10.1007/s10014-018-0328-x