INTRODUCTION: Leptomeningeal metastases are occurring at higher frequency in 
cancer patients. The prognosis of leptomeningeal metastases is poor and standard 
treatment, which includes radiotherapy and chemotherapy, is mostly ineffective. 
Melanoma represents one of the tumors with the highest incidence of 
leptomeningeal metastases. For such a disease, the BRAF inhibitors have recently 
been demonstrated to be effective on melanoma brain metastases harboring the 
V600EBRAF mutation.
CASE PRESENTATION: We report a case of a 39-year-old Italian woman with advanced 
melanoma with brain, lung and peritoneum metastases harboring the V600EBRAF 
mutation. In August 2010 she was enrolled into the BRIM3 trial and after the 
randomization process she received dacarbazine. After two cycles, there was 
evidence of disease progression in her peritoneum and lung. For this reason, she 
was enrolled into another clinical trial with the GSK2118436 BRAF inhibitor, 
dabrafenib, as a second line of therapy. She had a partial response that was 
maintained until 13 weeks of treatment. In January 2011 she developed symptoms 
typical for brain metastases and received a diagnosis of leptomeningeal 
involvement of melanoma cells after an examination of her cerebral spinal fluid; 
magnetic resonance imaging was negative for meningitis or brain metastases. 
Analysis of her cerebral spinal fluid sample confirmed that the melanoma cells 
still carried the V600EBRAF mutation. After a few days, our patient went into a 
coma and died.
CONCLUSION: Starting with a clinical case, we discuss the pathogenesis of 
leptomeningeal metastases and whether the leptomeninges may represent a 
sanctuary where melanoma cells may generate resistance and/or BRAF inhibitors 
cannot reach an adequate concentration for significant activity. We assess 
whether treatment with BRAF inhibitors in melanoma patients should be 
interrupted as soon as disease progression appears or continued beyond 
progression, through the administration of additional compounds.