Missense mutation of NRAS is associated with malignant progression in neurocutaneous melanosis.

Neurocutaneous melanosis (NCM) is a rare congenital neurocutaneous syndrome characterized by congenital melanocytic nevus of skin and abnormal proliferation of leptomeningeal melanocytes. Early acquisition of post-zygotic somatic mutations has been postulated to underlie the pathogenesis of NCM. The pathogenesis of NCM remains to be fully elucidated, and treatment options have not been established. Here, we report for the first time, multiregional genomic analyses in a 3-year-old autopsied girl with leptomeningeal melanomatosis associated with NCM, in which a ventriculo-peritoneal (VP) shunt was inserted for the treatment of hydrocephalus. The patient expired six months after the onset due to respiratory failure caused by abdominal dissemination via VP shunt. We performed multiregional exome sequencing to identify genomic differences among brain and abdominal tumors, nevus, and normal tissues. A total of 87 somatic mutations were found in 71 genes, with a significantly large number of gene mutations found in the tumor site. The genetic alterations detected in the nevus were only few and not shared with other sites. Three mutations, namely GNAQ R183Q, S1PR3 G89S and NRAS G12V, considered pathogenic, were found, although S1PR3 mutations have not been previously reported in melanocytic tumors. GNAQ and S1PR3 mutations were shared in both tumor and normal sites. Moreover, the mutant allele frequencies of the two mutations were markedly higher in tumor sites than in normal sites, with copy-neutral loss-of-heterozygosity (CN-LOH) occurring in tumor. NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case. Multiregional comprehensive genetic analysis may lead to discovering novel driver mutations associated with tumorigenesis and targeted therapy.

Mechanical thrombectomy utilising a collateral pathway in a patient with dysgenesis of the internal carotid artery.

We describe a case of acute middle cerebral artery occlusion in a patient with ipsilateral internal carotid artery dysgenesis successfully treated with mechanical thrombectomy utilising a collateral pathway. During the procedure, a triaxial system using a balloon guiding catheter, flexible large lumen aspiration catheter and stent retriever was advanced from the left vertebral artery to the occluded left middle cerebral artery through the left posterior communicating artery. Because proximal aspiration from the balloon guiding catheter alone might have insufficient suction force due to the retrograde blood flow from large vascular communications (e.g. vertebral artery union), the tip of the flexible large lumen aspiration catheter was set at the proximal left middle cerebral artery, and distal aspiration was added during stent retrieval. A thrombolysis in cerebral infarction 2b result was achieved after the first pass. In this case, identification of carotid canal hypoplasia on computed tomography allowed for an immediate attempt of this alternative approach, avoiding a delay in the time to reperfusion.