St8sia1-deficiency in mice alters tumor environments of gliomas, leading to reduced disease severity.

Ganglioside GD3/GD2 are over-expressed in various neuroectoderm-derived tumors. Previous studies indicated that GD3 is involved in the enhancement of cancer properties such as rapid growth and increased invasiveness. However, little is known about the functions of GD3/GD2 in glioma cells and glioma microenvironments. To clarify the functions of GD3/GD2 in gliomas, we used a mouse glioma model based on the RCAS/Gtv-a system. At first, we compared the gliomas size between wild-type (WT) and GD3 synthase (GD3S) knockout (KO) mice, showing a less malignant histology and slower tumor growth in GD3S-KO mice than in WT mice. Immunohistochemistry of glioma sections from WT and GD3S-KO mice revealed that reactive microglia/macrophages showed different localization patterns between the two genetic types of mice. CD68+ cells were more frequently stained inside glioma tissues of GD3S-KO mice, while they were stained mainly around glioma tissues in WT mice. The number of CD68+ cells markedly increased in tumor tissues of GD3S-KO mice at 2 weeks after injection of transfectant DF-1 cells. Furthermore, CD68+ cells in GD3S(-/-) glioma tissues expressed higher levels of inducible nitric oxide synthase. We observed higher expression levels of pro-inflammatory cytokine genes in primary-cultured glioma cells of WT mice than in GD3S-KO mice. DNA microarray data also revealed differential expression levels of various cytokines and chemokines in glioma tissues between WT and GD3S-KO mice. These results suggest that expression of GD3S allows glioma cells to promote polarization of microglia/macrophages towards M2-like phenotypes by modulating the expression levels of chemokines and cytokines.

Lack of GD3 synthase (St8sia1) attenuates malignant properties of gliomas in genetically engineered mouse model.

High expression of gangliosides GD3 and GD2 is observed in human gliomas. The functions of GD3 and GD2 in malignant properties have been reported in glioma cells in vitro, but those functions have not yet been investigated in vivo. In this study, we showed that deficiency of GD3 synthase (GD3S, St8sia1) attenuated glioma progression and clinical and pathological features in a platelet-derived growth factor B-driven murine glioma model. Lack of GD3S resulted in the prolonged lifespan of glioma-bearing mice and low-grade pathology in generated gliomas. Correspondingly, they showed reduced phosphorylation levels of Akt, Erks, and Src family kinases in glioma tissues. A DNA microarray study revealed marked alteration in the expression of various genes, particularly in MMP family genes, in GD3S-deficient gliomas. Re-expression of GD3S restored expression of MMP9 in primary-cultured glioma cells. We also identified a transcription factor, Ap2α, expressed in parallel with GD3S expression, and showed that Ap2α was critical for the induction of MMP9 by transfection of its cDNA and luciferase reporter genes, and a ChIP assay. These findings suggest that GD3S enhances the progression of gliomas by enhancement of the Ap2α-MMP9 axis. This is the first report to describe the tumor-enhancing functions of GD3S in vivo.

Foxr2 promotes formation of CNS-embryonal tumors in a Trp53-deficient background.

BACKGROUND: Embryonal tumors in the central nervous system (CNS) are primary, aggressive, and poorly differentiated pediatric brain tumors. We identified forkhead box R2 (Foxr2) as an oncogene for medulloblastoma through a transposon-based insertional mutagenesis screen. Foxr2 translocation has been identified in a subset of human embryonal tumors of the CNS, designated as CNS neuroblastoma with Foxr2 activation (CNS NB-Foxr2); however, the in vivo functions of Foxr2 remain elusive. METHODS: We analyzed the effect of Foxr2 overexpression in the mouse brain by generating a transgenic strain that expresses Foxr2 in the entire brain under a transformation related protein 53 (Trp53)-deficient background. We performed histological analysis of tumors and characterized tumor-derived sphere-forming cells. We investigated gene expression profiles of tumor-derived cells. RESULTS: Foxr2 and Trp53 loss promoted tumor formation in the olfactory bulb (OB) and brainstem (BS). The tumors showed the common morphological features of small round blue cell tumors, exhibiting divergent, mainly neuronal and glial, patterns of differentiation, which corresponds to the definition of CNS-embryonal tumors. Importantly, all mice developed CNS-embryonal tumors. In the OB, early proliferative lesions consisting of oligodendrocyte transcription factor 2 (Olig2+) cells were observed, indicating that Foxr2 expression expanded Olig2+ cells in the OB. Tumor-derived cells formed spheres in vitro and induced tumors that recapitulated the parental tumor upon transplantation, indicating the presence of tumor-initiating cells. Gene expression profiling revealed that OB and BS tumor cells were enriched for the expression of the genes specific to CNS NB-Foxr2. CONCLUSION: Our data demonstrate that Foxr2 plays a causative role in the formation of CNS-embryonal tumors.

Enhancement of malignant properties of human glioma cells by ganglioside GD3/GD2.

Sialic acid-containing glycosphingolipids, gangliosides, are considered as cancer associated antigens in neuro-ectoderm-derived tumors such as melanomas and neuroblastomas. In particular, gangliosides GD3 and GD2 are expressed in human gliomas. It has been reported that their expression levels increase along with increased malignant properties. However, the implication of GD3/GD2 in human glioma cells has never been clarified, at least to the best of our knowledge. In this study, we introduced the cDNA of GD3 synthase (GD3S)(ST8SIA1) into a glioma cell line, U-251MG, that expresses neither GD3 nor GD2, thereby establishing transfectant cells U-251MG-GD3S(+) expressing high levels of GD3 and GD2 on the cell surface. In these U-251MG­GD3S(+) cell lines, signaling molecules such as Erk1/2, Akt, p130Cas, paxillin and focal adhesion kinase were activated, leading to the enhancement of invasion activity and motility. It was then demonstrated that the U-251MG-GD3S(+) cells could proliferate under culture conditions with low or no serum concentrations without undergoing cell cycle arrest by escaping the accumulation of p16 and p21. All these results suggested that GD3 and GD2 highly expressed in gliomas confer increased invasion and mobility, cell growth abilities under low serum conditions, and increased ratios of the S-G2/M phase in the cell cycle.

Significance of perivascular tumour cells defined by CD109 expression in progression of glioma.

In the progression of glioma, tumour cells often exploit the perivascular microenvironment to promote their survival and resistance to conventional therapies. Some of these cells are considered to be brain tumour stem cells (BTSCs); however, the molecular nature of perivascular tumour cells has not been specifically clarified because of the complexity of glioma. Here, we identified CD109, a glycosylphosphatidylinositol-anchored protein and regulator of multiple signalling pathways, as a critical regulator of the progression of lower-grade glioma (World Health Organization grade II/III) by clinicopathological and whole-genome sequencing analysis of tissues from human glioma. The importance of CD109-positive perivascular tumour cells was confirmed not only in human lower-grade glioma tissues but also in a mouse model that recapitulated human glioma. Intriguingly, BTSCs isolated from mouse glioma expressed high levels of CD109. CD109-positive BTSCs exerted a proliferative effect on differentiated glioma cells treated with temozolomide. These data reveal the significance of tumour cells that populate perivascular regions during glioma progression, and indicate that CD109 is a potential therapeutic target for the disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Phase I, multicenter, open-label, dose-escalation study of sonidegib in Asian patients with advanced solid tumors.

Sonidegib is a selective inhibitor of Smoothened receptor, which is a key regulator of the Hedgehog signaling pathway. The purpose of this study was to determine the maximum tolerated dose based on dose-limiting toxicity (DLT) and the recommended dose (RD) of sonidegib in Asian patients with advanced solid tumors. This was an open-label, single-arm, multicenter, two-group, parallel, dose-escalation, phase I study undertaken in Asian patients; group 1 included patients from Japan and group 2 included patients from Hong Kong and Taiwan. Dose escalation was guided by a Bayesian logistic regression model dependent on DLTs in cycle 1 and other safety findings. A total of 45 adult Asian patients with confirmed advanced solid tumors were enrolled. Group 1 included 21 patients (12 treated with 400 mg q.d. [once daily] and 9 treated with 600 mg q.d.) and group 2 included 24 patients (12 treated with 400 mg q.d., 8 treated with 600 mg q.d., and 4 treated with 800 mg q.d.). Elevation in creatine kinase was the DLT in both groups. The most common adverse events suspected to be related to sonidegib in both patient groups were increase in creatine kinase levels, myalgia, fatigue, and abnormal hepatic function. The RD of 400 mg q.d. was defined in both groups. Difference in tolerability was noted between the East Asian patients and Western population. The RD in East Asian patients (400 mg q.d.) was lower than in patients from Europe and the USA (800 mg q.d. and 250 mg twice daily). (Registered with Clinicaltrials.gov: NCT01208831.).

Primary peripheral T-cell lymphoma, not otherwise specified, of the central nervous system in a child.

Primary peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is a rare disease that infrequently involves the central nervous system (CNS), and it is even rarer in pediatric patients. Here, we report of a 13-year-old male with primary CNS PTCL-NOS who exhibited a malignant clinical course with recurrence after radiochemotherapy followed by bone marrow transplantation; he died 43 months after diagnosis. Pathology revealed the proliferation of cytotoxic T-cells and clonal T-cell receptor gene rearrangements. Although the optimal therapy for PTCL remains controversial, intensive radiochemotherapy may be required for some patients.

Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with Platelet-derived Growth Factor Receptor α and Yes Kinase.

There have been a few studies on the ganglioside expression in human glioma tissues. However, the role of these gangliosides such as GD3 and GD2 has not been well understood. In this study we employed a genetically engineered mouse model of glioma to clarify the functions of GD3 in gliomas. Forced expression of platelet-derived growth factor B in cultured astrocytes derived from p53-deficient mice resulted in the expression of GD3 and GD2. GD3-positive astrocytes exhibited increased cell growth and invasion activities along with elevated phosphorylation of Akt and Yes kinase. By enzyme-mediated activation of radical sources reaction and mass spectrometry, we identified PDGF receptor α (PDGFRα) as a GD3-associated molecule. GD3-positive astrocytes showed a significant amount of PDGFRα in glycolipid-enriched microdomains/rafts compared with GD3-negative cells. Src kinase family Yes was co-precipitated with PDGFRα, and its pivotal role in the increased cell invasion of GD3-positive astrocytes was demonstrated by silencing with anti-Yes siRNA. Direct association between PDGFRα and GD3 was also shown, suggesting that GD3 forms ternary complex with PDGFRα and Yes. The fact that GD3, PDGFRα, and activated Yes were colocalized in lamellipodia and the edge of tumors in cultured cells and glioma tissues, respectively, suggests that GD3 induced by platelet-derived growth factor B enhances PDGF signals in glycolipid-enriched microdomain/rafts, leading to the promotion of malignant phenotypes such as cell proliferation and invasion in gliomas.

Anaplastic meningioma with rapid growth after omental flap transposition: a case report and experimental study.

Meningiomas occasionally display aggressive behavior, but the mechanisms of malignant transformation remain unclear. We encountered the case of a 65-year-old man with a 10-year history of recurrent meningioma. The patient had undergone multiple tumor resections, radiotherapy treatments, and reconstructive surgeries due to wound infection. After the third resection of the tumor and reconstruction with an omental flap, the tumor demonstrated rapid growth and lung metastasis. The final pathological diagnosis was anaplastic meningioma. Because the drastic change of the tumor was observed after omental flap transposition, we investigated the effect of the omentum on tumor cells and performed histopathological analyses of meningiomas using a mouse model. We found that meningioma cells have a high affinity to the omentum and show a growth advantage when co-cultured with adipocytes. Immunohistochemical staining revealed that meningioma cells adjacent to the omentum strongly expressed fatty acid-binding protein 4, a lipid transfer protein, in both mouse and human. Our results suggest that tumor cells can receive lipid supply from omental adipocytes, and the surrounding tissues may induce tumor progression. We conclude that although omental tissue is an ideal material for reconstruction surgery, close follow-up is recommended in meningioma patients when used for cranioplasty.

Assessment of tumor cells in a mouse model of diffuse infiltrative glioma by Raman spectroscopy.

Glioma of infiltrative nature is challenging for surgeons to achieve tumor-specific and maximal resection. Raman spectroscopy provides structural information on the targeted materials as vibrational shifts. We utilized Raman spectroscopy to distinguish invasive tumors from normal tissues. Spectra obtained from replication-competent avian sarcoma-(RCAS-) based infiltrative glioma cells and glioma tissues (resembling low-grade human glioma) were compared with those obtained from normal mouse astrocytes and normal tissues. In cell analysis, the spectra at 950-1000, 1030, 1050-1100, 1120-1130, 1120-1200, 1200-1300, 1300-1350, and 1450 cm(-1) were significantly higher in infiltrative glioma cells than in normal astrocytes. In brain tissue analysis, the spectra at 1030, 1050-1100, and 1200-1300 cm(-1) were significantly higher in infiltrative glioma tissues than in normal brain tissues. These spectra reflect the structures of proteins, lipids, and DNA content. The sensitivity and specificity to predict glioma cells by distinguishing normal cells were 98.3% and 75.0%, respectively. Principal component analysis elucidated the significance of spectral difference between tumor tissues and normal tissues. It is possible to distinguish invasive tumors from normal tissues by using Raman spectroscopy.

Papillary glioneuronal tumor with a high proliferative component and minigemistocytes in a child.

Papillary glioneuronal tumor (PGNT) is a rare type of primary brain tumor. Although PGNT has traditionally been defined as a clinically indolent neoplasm, several cases with high proliferative activity and tumor recurrence have recently been reported. We report a case of PGNT in a 12-year-old boy who presented with epilepsy and harbored a 64 mm cystic tumor with a high proliferative component in the right temporal lobe. (11) C-methionine positron emission tomography (PET) showed high uptake in the solid mass. Gross total resection of the tumor mass was achieved and the patient became seizure-free without any neurological deficits. Histologically, the tumor contained two distinct areas of a vasocentric papilliform structure and a desmoplastic component. Minigemistocytic cells and small necrotic regions were observed adjacent to the pseudopapillae. Immunohistochemical analyses revealed both glial and neuronal differentiation. The Ki-67 proliferation index was high (14%) in the area corresponding to the high uptake region in the (11) C-methionine PET. No tumor recurrence was observed 20 months after surgery. High proliferative PGNTs are rare and to our knowledge this is only the third pediatric case of PGNT with atypical features reported in the literature. Hence, we here review the reported cases of PGNT and discuss the clinical, radiological and histological features of this malignancy.

[Intracranial germinoma masquerading as a granulomatous inflammation, diagnostic failure after brain biopsy].

We report the case of a 33-year-old man with diplopia, sleepiness, and paresthesia of the left upper limb that were slowly progressive. On admission, he presented with restriction in the vertical movement of the eyes and abduction of the right eye, and horizontal and convergence nystagmus. Slight weakness of the left upper limb, bilateral Babinski sign, and truncal ataxia were also noted. Cerebral magnetic resonance imaging was performed, and gadolinium-enhanced T1-weighted imaging revealed a mass lesion that involved the diencephalon and the corpus callosum, which was invariably enhanced. Specimens obtained using a brain biopsy showed epithelioid granuloma with the presence of foreign body giant cells and lymphocytic infiltration. Prednisolone was administrated because we suspected neurosarcoidosis, but the clinical symptoms worsened with the enlargement of the lesion. A re-evaluation of the biopsy specimens using immunohistochemistry revealed tumor cells of germinoma that were scattered among the lymphocytes and positive for periodic acid-Schiff staining, placental alkaline phosphatase, and c-kit. A combination of chemotherapy and radiation resulted in clinical improvement and marked reduction of the mass lesion in size. We concluded that the possibility of germinoma should be considered in case granulomatous inflammation is observed in brain biopsy specimens.

Secondary hematological malignancies associated with temozolomide in patients with glioma.

BACKGROUND: The alkylating agent temozolomide (TMZ) is widely used for the treatment of gliomas. Although reports of treatment-related myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) associated with TMZ are accumulating, it remains unclear whether TMZ has the same leukemogenic potential as other alkylating agents. METHODS: We performed a single-institution retrospective analysis using a database of 359 glioma patients given nimustine (ACNU)-based therapy, TMZ-based therapy, or combination therapy, who were followed up for a minimum of 2 months, between January 1990 and December 2009, at the National Cancer Center Hospital in Japan. RESULTS: Of the 359 patients, 225 received ACNU alone or ACNU plus other chemotherapeutic drugs (ACNU-based group; median follow-up period, 31.4 mo), 63 patients received ACNU-based therapy followed by TMZ therapy (ACNU-TMZ group; median follow-up period, 19.1 mo), and 71 patients received TMZ alone or TMZ plus other chemotherapeutic drugs (TMZ-based group; median follow-up period, 16.9 mo). Three patients in the ACNU-based group developed MDS/AML (incidence rate: 2.9 cases per 1000 person-years), 2 patients in the ACNU-TMZ group developed MDS/AML (13.0 cases per 1000 person-years), and 1 patient in the TMZ-based group developed ALL (9.9 cases per 1000 person-years). CONCLUSIONS: Despite the limitations of this study, published reports and our results suggest that TMZ induces secondary hematological malignancies, particularly ALL, and might shorten the latency period when used in combination with other chemotherapeutic agents.

Intravascular lymphoma of the central nervous system presenting as multiple cerebral infarctions.

A 67-year-old woman presented with an acute onset of left-sided weakness. Magnetic resonance (MR) imaging revealed multiple cerebral infarctions and gadolinium-enhanced lesions in both cerebral hemispheres. Her symptoms once improved after starting steroid treatment; however, soon developed consciousness disturbance and hemiparesis on the left side. She was referred to our hospital where she underwent stereotactic needle biopsy, that revealed an intravascular large B-cell lymphoma in the cerebrum. She received high-dose methotrexate chemotherapy followed by whole-brain radiation therapy, and the MR findings improved. However, her medical condition gradually worsened, and she died 6 months after disease onset. Intravascular lymphoma (IVL) limited to the central nervous system (CNS) is very rare, and the optimal treatment for this medical condition has not been established yet. IVLs showing only neurologic manifestations might be overlooked or misdiagnosed as cerebral infarctions. Here, we present a case of CNS IVL, with its radiographic and pathologic features and treatment with high-dose methotrexate chemotherapy.

Immunohistochemical analysis-based proteomic subclassification of newly diagnosed glioblastomas.

Recent gene expression and copy number profilings of glioblastoma multiforme (GBM) by The Cancer Genome Atlas (TCGA) Research Network suggest the existence of distinct subtypes of this tumor. However, these approaches might not be easily applicable in routine clinical practice. In the current study, we aimed to establish a proteomics-based subclassification of GBM by integrating their genomic and epigenomic profiles. We subclassified 79 newly diagnosed GBM based on expression patterns determined by comprehensive immunohistochemical observation in combination with their DNA copy number and DNA methylation patterns. The clinical relevance of our classification was independently validated in TCGA datasets. Consensus clustering identified the four distinct GBM subtypes: Oligodendrocyte Precursor (OPC) type, Differentiated Oligodendrocyte (DOC) type, Astrocytic Mesenchymal (AsMes) type and Mixed type. The OPC type was characterized by highly positive scores of Olig2, PDGFRA, p16, p53 and synaptophysin. In contrast, the AsMes type was strongly associated with strong expressions of nestin, CD44 and podoplanin, with a high glial fibrillary acidic protein score. The median overall survival of OPC-type patients was significantly longer than that of the AsMes-type patients (19.9 vs 12.8 months). This finding was in agreement with the Oncomine analysis of TCGA datasets, which revealed that PDGFRA and Olig2 were favorable prognostic factors and podoplanin and CD44 were associated with a poor clinical outcome. This is the first study to establish a subclassification of GBM on the basis of immunohistochemical analysis. Our study will shed light on personalized therapies that might be feasible in daily neuropathological practice.

A novel method of intracranial injection via the postglenoid foramen for brain tumor mouse models.

OBJECT: Mouse models have been widely used in developing therapies for human brain tumors. However, surgical techniques such as bone drilling and skin suturing to create brain tumors in adult mice are still complicated. The aim of this study was to establish a simple and accurate method for intracranial injection of cells or other materials into mice. METHODS: The authors performed micro CT scans and skull dissection to assess the anatomical characteristics of the mouse postglenoid foramen. They then used xenograft and genetically engineered mouse models to evaluate a novel technique of percutaneous intracranial injection via the postglenoid foramen. They injected green fluorescent protein-labeled U87MG cells or virus-producing cells into adult mouse brains via the postglenoid foramen and identified the location of the created tumors by using bioluminescence imaging and histological analysis. RESULTS: The postglenoid foramen was found to be a well-conserved anatomical structure that allows percutaneous injection into the cerebrum, cerebellum, brainstem, and basal cistern in mice. The mean (± SD) time for the postglenoid foramen injection technique was 88 ± 15 seconds. The incidence of in-target tumor formation in the xenograft model ranged from 80% to 100%, depending on the target site. High-grade gliomas were successfully developed by postglenoid foramen injection in the adult genetically engineered mouse using virus-mediated platelet-derived growth factor B gene transfer. There were no procedure-related complications. CONCLUSIONS: The postglenoid foramen can be used as a needle entry site into the brain of the adult mouse. Postglenoid foramen injection is a less invasive, safe, precise, and rapid method of implanting cells into the adult mouse brain. This method can be applied to both orthotopic xenograft and genetically engineered mouse models and may have further applications in mice for the development of therapies for human brain tumors.

The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma.

Gliomas are the most frequently occurring primary brain tumor in the central nervous system of adults. Glioblastoma multiformes (GBMs, WHO grade 4) have a dismal prognosis despite the use of the alkylating agent, temozolomide (TMZ), and even low grade gliomas (LGGs, WHO grade 2) eventually transform to malignant secondary GBMs. Although GBM patients benefit from promoter hypermethylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) that is the main determinant of resistance to TMZ, recent studies suggested that MGMT promoter methylation is of prognostic as well as predictive significance for the efficacy of TMZ. Glioma-CpG island methylator phenotype (G-CIMP) in the global genome was shown to be a significant predictor of improved survival in patients with GBM. Collectively, we hypothesized that MGMT promoter methylation might reflect global DNA methylation. Additionally in LGGs, the significance of MGMT promoter methylation is still undetermined. In the current study, we aimed to determine the correlation between clinical, genetic, and epigenetic profiles including LINE-1 and different cancer-related genes and the clinical outcome in newly diagnosed 57 LGG and 54 GBM patients. Here, we demonstrated that (1) IDH1/2 mutation is closely correlated with MGMT promoter methylation and 1p/19q codeletion in LGGs, (2) LINE-1 methylation levels in primary and secondary GBMs are lower than those in LGGs and normal brain tissues, (3) LINE-1 methylation is proportional to MGMT promoter methylation in gliomas, and (4) higher LINE-1 methylation is a favorable prognostic factor in primary GBMs, even compared to MGMT promoter methylation. As a global DNA methylation marker, LINE-1 may be a promising marker in gliomas.

Long-term survival in patients with newly diagnosed primary central nervous system lymphoma treated with dexamethasone, etoposide, ifosfamide and carboplatin chemotherapy and whole-brain radiation therapy.

In the present study, we aimed to evaluate the safety and efficacy of DeVIC (dexamethasone, etoposide, ifosfamide and carboplatin) chemotherapy for the treatment of patients with primary central nervous system lymphoma (PCNSL). We retrospectively examined 21 patients with newly diagnosed PCNSL who received DeVIC chemotherapy followed by whole-brain radiation therapy (WBRT). The median progression-free survival (PFS) in all patients was 37.4 months and the median duration of overall survival (OS) was 47.8 months. Notably, the median duration of OS was significantly longer in patients who achieved a complete response (CR) after DeVIC chemotherapy (49.0 months) than in those without CR (12.8 months). Furthermore, we found that the overall response rate to the initial DeVIC chemotherapy was 95.2%. No treatment-related deaths were observed. Our study investigated the efficacy of DeVIC chemotherapy in PCNSL patients, and found it to result in favorable survival outcomes in these patients, thus warranting further investigation of it as a therapeutic measure against PCNSL.

Rhabdoid glioblastoma in a child: case report and literature review.

Rhabdoid glioblastoma is a rare type of glioblastoma characterized by cells resembling rhabdomyoblasts. Several reports have identified its aggressive clinical course and the pathological differences from other primary brain tumors. We report a case of rhabdoid glioblastoma in a 12-year-old boy who presented with headache and harbored a 70-mm solid tumor in the left temporal lobe. The tumor was surgically excised, but early tumor recurrence and leptomeningeal spread developed, and the patient died of the disease 4.9 months after surgery. Histologically, the tumor contained two distinct patterns of glioblastoma and rhabdoid cells with necrosis and hemorrhage. Immunohistochemical analysis revealed that both cells were positive for glial fibrillary acid protein, vimentin, and INI1, which is consistent with the reported diagnosis of rhabdoid glioblastoma. Genetic studies confirmed no loss of the INI1 gene and identified hemizygous deletion of the CDKN2A gene. We review reported cases of rhabdoid glioblastoma and summarize the clinical, radiological, and histological features.