NRASQ61K mutated primary leptomeningeal melanoma in a child: case presentation and discussion on clinical and diagnostic implications

Background: 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. Case presentation: 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 BRAFV600E, GNAQQ209 and GNA11Q209 mutations but the presence of a NRASQ61K mutation. Conclusions: Our case adds some information to the limited experience of the literature, confirming the presence of the NRASQ61K 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.