The most recurrent fusion of central nervous system high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1) is MN1 rearrangement. Here, we report the case of a 36-year-old man with spinal cord astroblastoma showing Ewing Sarcoma breakpoint region 1/EWS RNA-binding protein 1 (EWSR1)-BEN domain-containing 2 (BEND2) fusion. The patient presented with back pain, gait disturbance and dysesthesia in the lower extremities and trunk. Magnetic resonance imaging showed an intramedullary tumor at the T3-5 level, displaying homogeneous gadolinium enhancement. Partial tumor removal was performed with laminectomy. Histological examinations demonstrated solid growth of epithelioid tumor cells showing high cellularity, a pseudopapillary structure, intervening hyalinized fibrous stroma, and some mitoses. Astroblastoma was diagnosed, classified as HGNET-MN1 by the German Cancer Research Center methylation classifier. MN1 alteration was not detected by fluorescence in situ hybridization (FISH), but EWSR1-BEND2 fusion was detected by FISH and RNA sequencing. Previously, a child with EWSR1-BEND2 fusion-positive spinal astroblastoma classified as HGNET-MN1was reported. In conjunction with that, the present case provides evidence that EWSR1-BEND2 fusion is identified in the entity of HGNET-MN1. Taken together, the BEND2 A Self-archived copy in Kyoto University Research Information Repository https://repository.kulib.kyoto-u.ac.jp 5 alteration rather than MN1 may determine the biology of a subset of the central nervous system HGNET-MN1 subclass. Keywords astroblastoma, CNS high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1), Ewing Sarcoma breakpoint region 1/EWS RNA-binding protein 1 (EWSR1), BEN domain-containing 2 (BEND2), EWSR1-BEND2 fusion

Background:Arachnoid cysts originating from the velum interpositum are very rare, and their existence as a clinicopathologic entity remains controversial. We report a case of a patient with an arachnoid cyst of the velum interpositum presenting with memory disturbance, focusing on the anatomical origin of the lesion and the physiological mechanisms causing memory disturbance.Case Description:A 65-year-old man with a large cystic lesion in the velum interpositum experienced progressive memory disturbance and enlargement of the lesion 6 months before referral to our institution. Neuropsychological evaluation on admission demonstrated severe memory disturbance. Radiological examination did not reveal hydrocephalus, but the bilateral fornices and thalami were compressed by the cyst. The patient underwent endoscopic cystoventriculostomy via the frontal horn of the right lateral ventricle through a frontal burr hole. Histopathology of the sample was consistent with that of an arachnoid cyst, and the endoscopic findings suggested that the cyst originated from the tela choroidea, which covers the velum interpositum. The symptoms resolved after surgery with significant improvement in neuropsychological test scores.Conclusion:Arachnoid cysts of the velum interpositum are rare but distinct clinicopathologic entities that originate from the tela choroidea. The lesions can cause memory disturbance without hydrocephalus due to compression of the fornices and thalami, but this can be reversed by surgery.

Background Mutations in driver genes such as IDH and BRAF have been identified in gliomas. Meanwhile, dysregulations in the p53, RB1, and MAPK and/or PI3K pathways are involved in the molecular pathogenesis of glioblastoma. RAS family genes activate MAPK through activation of RAF and PI3K to promote cell proliferation. RAS mutations are a well-known driver of mutation in many types of cancers, but knowledge of their significance for glioma is insufficient. The purpose of this study was to reveal the frequency and the clinical phenotype of RAS mutant in gliomas. Methods This study analysed RAS mutations and their clinical significance in 242 gliomas that were stored as unfixed or cryopreserved specimens removed at Kyoto University and Osaka National Hospital between May 2006 and October 2017. The hot spots mutation of IDH1/2, H3F3A, HIST1H3B, and TERT promoter and exon 2 and exon 3 of KRAS, HRAS, and NRAS were analysed with Sanger sequencing method, and 1p/19q codeletion was analysed with multiplex ligation-dependent probe amplification. DNA methylation array was performed in some RAS mutant tumours to improve accuracy of diagnosis. Results RAS mutations were identified in four gliomas with three KRAS mutations and one NRAS mutation in one anaplastic oligodendroglioma, two anaplastic astrocytomas (IDH wild-type in each), and one ganglioglioma. RAS-mutant gliomas were identified with various types of glioma histology. Conclusion RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma.

The characteristics of IDH-wild-type lower-grade astrocytoma remain unclear. According to cIMPACT-NOW update 3, IDH-wild-type astrocytomas with any of the following factors show poor prognosis: combination of chromosome 7 gain and 10 loss (+ 7/− 10), and/or EGFR amplification, and/or TERT promoter (TERTp) mutation. Multiplex ligation-dependent probe amplification (MLPA) can detect copy number alterations at reasonable cost. The purpose of this study was to identify a precise, cost-effective method for stratifying the prognosis of IDH-wild-type astrocytoma. Sanger sequencing, MLPA, and quantitative methylation-specific PCR were performed for 42 IDH-wild-type lower-grade astrocytomas surgically treated at Kyoto University Hospital, and overall survival was analysed for 40 patients who underwent first surgery. Of the 42 IDH-wild-type astrocytomas, 21 were classified as grade 4 using cIMPACT-NOW update 3 criteria and all had either TERTp mutation or EGFR amplification. Kaplan–Meier analysis confirmed the prognostic significance of cIMPACT-NOW criteria, and World Health Organization grade was also prognostic. Cox regression hazard model identified independent significant prognostic indicators of PTEN loss (risk ratio, 9.75; p < 0.001) and PDGFRA amplification (risk ratio, 13.9; p = 0.002). The classification recommended by cIMPACT-NOW update 3 could be completed using Sanger sequencing and MLPA. Survival analysis revealed PTEN and PDGFRA were significant prognostic factors for IDH-wild-type lower-grade astrocytoma.