title: NRAS(Q61K) mutated primary leptomeningeal melanoma in a child: case presentation and discussion on clinical and diagnostic implications.
abstract: Primary melanocytic neoplasms are rare in the pediatric age. Among them, the pattern of neoplastic meningitis represents a peculiar diagnostic challenge since neuroradiological features may be subtle and cerebrospinal fluid analysis may not be informative. Clinical misdiagnosis of neoplastic meningitis with tuberculous meningitis has been described in few pediatric cases, leading to a significant delay in appropriate management of patients. We describe the case of a child with primary leptomeningeal melanoma (LMM) that was initially misdiagnosed with tuberculous meningitis. We review the clinical and molecular aspects of LMM and discuss on clinical and diagnostic implications.
  
  
  
  A 27-month-old girl with a 1-week history of vomiting with mild intermittent strabismus underwent Magnetic Resonance Imaging, showing diffuse brainstem and spinal leptomeningeal enhancement. Cerebrospinal fluid analysis was unremarkable. Antitubercular treatment was started without any improvement. A spinal intradural biopsy was suggestive for primary leptomeningeal melanomatosis. Chemotherapy was started, but general clinical conditions progressively worsened and patient died 11 months after diagnosis. Molecular investigations were performed post-mortem on tumor tissue and revealed absence of BRAF(V600E), GNAQ(Q209) and GNA11(Q209) mutations but the presence of a NRAS(Q61K) mutation.
  
  
  
  Our case adds some information to the limited experience of the literature, confirming the presence of the NRAS(Q61K) mutation in children with melanomatosis. To our knowledge, this is the first case of leptomeningeal melanocytic neoplasms (LMN) without associated skin lesions to harbor this mutation. Isolated LMN presentation might be insidious, mimicking tuberculous meningitis, and should be suspected if no definite diagnosis is possible or if antitubercular treatment does not result in dramatic clinical improvement. Leptomeningeal biopsy should be considered, not only to confirm diagnosis of LMN but also to study molecular profile. Further molecular profiling and preclinical models will be pivotal in testing combination of target therapy to treat this challenging disease.
authors.affiliation: University-Hospital Pediatric Department, Bambino Gesù Children's Hospital IRCCS and University of Rome Tor Vergata School of Medicine, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Angelino
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital IRCCS, Piazza Sant'Onofrio 4, 00165, Rome, Italy.
authors.forename: Maria Debora
authors.initials: MD
authors.lastname: De Pasquale
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital IRCCS, Piazza Sant'Onofrio 4, 00165, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: De Sio
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital IRCCS, Piazza Sant'Onofrio 4, 00165, Rome, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Serra
authors.affiliation: Department of Pediatric Neurosurgery, Catholic University of the Sacred Heart, A. Gemelli University Polyclinic, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Massimi
authors.affiliation: Unit of Pathology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: De Vito
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital IRCCS, Piazza Sant'Onofrio 4, 00165, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Marrazzo
authors.affiliation: Unit of Infectious Disease, Department of Pediatrics, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lancella
authors.affiliation: Unit of Neurosurgery, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carai
authors.affiliation: Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University, Rome, Italy.
authors.forename: Manila
authors.initials: M
authors.lastname: Antonelli
authors.affiliation: Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University, Rome, Italy.|Neuromed IRCCS, Pozzilli, Isernia, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.affiliation: Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Gessi
authors.affiliation: Department of Diagnostic Imaging, Unit of Neuroradiology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Menchini
authors.affiliation: Department of Diagnostic Imaging, Unit of Neuroradiology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Scarciolla
authors.affiliation: Department of Diagnostic Imaging, Unit of Neuroradiology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Longo
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital IRCCS, Piazza Sant'Onofrio 4, 00165, Rome, Italy. angela.mastronuzzi@opbg.net.
authors.forename: Angela
authors.initials: A
authors.lastname: Mastronuzzi
mesh_terms: D002675:Child, Preschool; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008545:Melanoma / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008577:Meningeal Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D009154:Mutation
chemical_list: D008565:Membrane Proteins; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: Children; NRAS Q61K mutation; NRAS inhibitors; Primary leptomeningeal melanoma; Tuberculous meningitis