Background: Brain metastases with hematoma are clinically important as they indicate the potential for rapid neurological deterioration. Non-uterine leiomyosarcoma-derived brain metastases are particularly rare, and their clinical features, including the bleeding rate, are unclear. Herein, we present a rare case of thigh leiomyosarcoma-derived brain metastasis with intratumoral hematoma and review previous case reports. Case Description: A 68-year-old man with a right thigh leiomyosarcoma presented with multiple brain metastases. The patient received stereotactic radiotherapy; however, he reported sudden right-sided hemiparesis. We found a right frontal irradiated lesion with intratumoral hemorrhage and performed gross total tumor resection. Histopathological examination showed highly atypical cells with prominent necrosis and hemorrhage. Abnormal thin-walled vessels were prominent within the brain tumor, and vascular endothelial growth factor was diffusely expressed immunohistopathologically. To date, 11 cases of brain metastasis from non-uterine leiomyosarcoma, including the present case, have been reported. Of note, six patients had hemorrhage. Three out of six patients presented with hemorrhage before therapeutic intervention, three cases were from residual sites after surgery or radiation. Conclusion: More than half the patients with non-uterine leiomyosarcoma-derived brain metastases presented with intracerebral hemorrhage. Furthermore, these patients are at risk of developing rapid neurological deterioration due to intracerebral hemorrhage.

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IDH-wildtype and IDH-mutant glioma have different genetical and metabolic background although their histological appearances are similar. To reveal the difference in metabolites between IDH-wildtype and IDH-mutant glioma, two artificial cell lines made from normal human astrocyte, NHAE6E7hTERTRas (IDH-wildtype) and NHAE6E7hTERTIDHmut (IDH-mutant), were investigated. Capillary electrophoresis- and ion chromatography-coupled mass spectrometry revealed the lower amount of glutamine, glutamate and 2-oxoglutarate in NHAE6E7hTERTIDHmut cells than NHAE6E7hTERTRas cells. Pharmacological or genetical inhibition of GLUD1 which converts glutamate to 2-oxoglutarate, suppressed proliferation of the cells by inducing ROS and apoptosis in NHAE6E7hTERTIDHmut cells. ROS inhibitor, NAC suppressed GLUD1 inhibitor-induced ROS, apoptosis, and cytotoxicity in NHAE6E7hTERTIDHmut cells, revealing that cytotoxicity by GLUD1 inhibitor was at least partially due to the inhibitor-induced ROS. Exogeneous dimethyl 2-oxoglutarate rescued the cytotoxicity by GLUD1 inhibitor, suggesting decreased 2-oxoglutarate was associated with GLUD1 inhibitor-induced cytotoxicity. Mutant IDH1 overexpressed glioma cell line showed similar sensitivity to GLUD1 inhibitor to NHAE6E7hTERTIDHmut, which suggested that the difference of sensitivity to GLUD1 inhibitor was due to the status of mutant IDH. In conclusion, GLUD1 inhibitor will be new therapeutic options for IDH-mutant glioma.

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Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma confined to the brain, eyes, and the spinal cord. The mechanism of central nervous system (CNS) tropism in PCNSL has not been fully elucidated. Diffuse large B cell lymphomas (DLBCLs) occasionally present with distant recurrence, which can involve inside and outside the CNS. Secondary central nervous system lymphomas (SCNSLs) are CNS relapse of systemic lymphoma. PCNSLs also rarely present with systemic relapse. We have previously reported in our study of whole exome sequencing that PCNSLs harbor frequent mutations in genes of B cell receptor pathway members and aberrant somatic hypermutation (aSHM) target genes. Although several genetic alterations were identified as more frequent in PCNSLs compared with systemic lymphomas, specific genetic alterations which serve as the driver for CNS tropism in PCNSLs has not been identified. In order to search for mutations which might serve as driver mutations in the CNS, we have performed targeted sequencing in paired samples from patients with recurrent lymphomas, either SCNSLs or PCNSL systemic relapses, using Ion Torrent multiplex PCR. Mutational profiles were compared between the primary and recurrent tumor. Six cases (four SCNSL cases and two PCNSL systemic relapse cases) were analyzed. Of note, in the SCNSL cases, several de novo mutations were enriched only among the recurrent CNS tumors. Among these mutations, BTG2 mutations were observed in 3/4 (75%), and B2M and KLHL14 mutations were observed in 2/4 (50%) cases. In the two PCNSL systemic relapse cases, KMT2D mutations were enriched only in the recurrent systemic tumors. It is suggested that these de novo mutations in the recurrent CNS tumors might serve as driver mutations in the CNS. Further analysis in larger cohorts, and functional studies are required in order to validate these findings.