Spinal Dissemination of Pineal Parenchymal Tumors of Intermediate Differentiation Over 10 Years After Initial Treatment: A Case Report.

Pineal parenchymal tumors (PPTs) are rare, accounting for less than 0.3% of all primary central nervous system (CNS) tumors. Pineal parenchymal tumors of intermediate differentiation (PPTID) (WHO grade 2 or 3) show an intermediate prognosis between pineocytoma and pineoblastoma. The clinical course is unknown, and the optimal treatment for PPTID, especially for recurrence, has not been determined. We report a case of PPTID with spinal dissemination over 10 years after treatment and survival for four years. A 56-year-old woman presented with headaches and diplopia. Computerized tomography (CT) and magnetic resonance imaging (MRI) revealed a pineal mass, but leptomeningeal dissemination was not identified on whole-spine MRI. Microsurgical gross total tumor resection (GTR) was performed, and the pathological diagnosis was PPTID (grade 3). In addition, a later study found it to harbor a KBTBD4 mutation. She underwent whole-brain radiation therapy with a focal boost. The patient was unable to continue chemotherapy for severe myelosuppression after the first course of treatment. Eleven years after the surgery, she was unable to walk, and a whole-spine MRI revealed multiple masses at C3-4, T4, and cauda equina. Fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed accumulations of the same lesions. No recurrence was observed in the brain. A biopsy of the caudal portion was performed, and the histopathological findings were the same as those of the initial surgery. Spinal dissemination was refractory to chemotherapy but responded to whole spine radiotherapy with focal boost, and she remained tumor-free for four years. We considered good local control with a combination of GTR and subsequent radiation therapy to contribute to long-term survival. The timing of spinal radiation administration is controversial because of the tendency for late cerebrospinal dissemination. The importance of long-term follow-up of the spine and head is emphasized. In PPTID cases with good local control, withholding spinal radiation until spinal dissemination occurs may become a long-term treatment plan.

[Subdural hematoma with reversible cerebral vasoconstriction syndrome: a case report].

A 71-year-old man had persistent cervical pain secondary to thunderclap headache during sleep. MRI conducted the next morning revealed subdural hematoma and convexity subdural hemorrhage on the right occipital region, and the patient was hospitalized. MRA showed vascular narrowing in the bilateral PCA. Follow-up MRA on day 8 of admission showed aggravated vascular narrowing of PCA, indicative of reversible cerebral vasoconstriction syndrome (RCVS). The patient was treated with a calcium-channel antagonist. Post-discharge MRA showed improvement of PCA narrowing, and the diagnosis of RCVS was confirmed.

Diffusely infiltrating glioma with CREBBP-BCORL1 fusion showing overexpression of not only BCORL1 but BCOR: A case report.

BCORL1 encodes a transcriptional corepressor homolog to BCOR. BCORL1 rearrangements have been previously described as rare events, and among them, CREBBP-BCORL1 has been reported only in 2 cases of ossifying fibromyxoid tumors. Herein, we present the first case of diffusely infiltrating glioma with CREBBP-BCORL1 involving a 17-year-old female patient. Histologically, the tumor was composed of a diffusely infiltrative proliferation of small tumor cells with moderate cellularity showing prominent microcystic formation. DNA methylation analysis revealed that the current case and a previously reported anaplastic ependymoma with EP300-BCORL1 were clustered together in close proximity to but distinct from methylation class high-grade neuroepithelial tumor with BCOR alteration. RNA sequencing demonstrated high mRNA expression of not only BCORL1 but BCOR, and the latter was compatible with diffuse nuclear expression of BCOR detected by immunohistochemistry. Our findings suggest that central nervous system tumors with CREBBP/EP300-BCORL1 may exhibit diverse morphologies but form a distinct DNA methylation group and that BCORL1 fusion genes may lead to upregulation of both BCOR and BCORL1.

Brain abscess in an angiosarcoma patient during a disease-free interval.

This is the first case of an angiosarcoma patient with brain abscess, and it might be responsible for skin defect and cranial bone necrosis by surgical excision and radiation. Our patient was treated with 10 courses of triweekly paclitaxel therapy, radical radiotherapy (70 Gy), and surgical excision (2 cm margin apart from a lesion) for angiosarcoma. At two years after the operation he was diagnosed as brain abscess. Brain abscess was managed with antibiotic drugs and drainage, his clinical symptoms improved by these treatments. He achieves replace free survival without the exacerbation of angiosarcoma and brain abscess for three years.

CSF TACI and BAFF levels in patients with primary CNS lymphoma as novel diagnostic biomarkers.

We used an enzyme-linked immunosorbent assay to measure pretreatment B cell-activating factor belonging to the tumour necrosis factor family (BAFF) and transmembrane activator and CAML-interactor (TACI) levels in CSF and serum collected from patients with primary central nervous system lymphoma (PCNSL) and control groups. The decision tree analysis of CSF TACI and BAFF levels for patients with a PCNSL diagnosis showed 100% sensitivity and 100% specificity when we attempted to differentiate PCNSL from glioblastoma and CNS inflammatory diseases. The combination of CSF TACI and BAFF levels may thus be a novel and useful diagnostic biomarker of PCNSL.

Significance of molecular classification of ependymomas: C11orf95-RELA fusion-negative supratentorial ependymomas are a heterogeneous group of tumors.

Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category.

Machine learning based on multi-parametric magnetic resonance imaging to differentiate glioblastoma multiforme from primary cerebral nervous system lymphoma.

PURPOSE: To evaluate the performance of a machine learning method based on texture features in multi-parametric magnetic resonance imaging (MRI) to differentiate a glioblastoma multiforme (GBM) from a primary cerebral nervous system lymphoma (PCNSL). MATERIALS AND METHODS: We included 70 patients who underwent contrast enhanced brain MRI at 3 T with brain tumors diagnosed as GBM (n = 45) and PCNSL (n = 25) in this retrospective study. Twelve histograms and texture parameters were assessed on T2-weighted images (T2WIs), apparent diffusion coefficient maps, relative cerebral blood volume (rCBV) map, and contrast-enhanced T1-weighted images (CE-T1WIs). A prediction model was developed using a machine learning method (univariate logistic regression and multivariate eXtreme gradient boosting-XGBoost) and the area under the receiver operating characteristic curve of this model was calculated via 10-fold cross validation. In addition, the performance of the machine learning method was compared with the judgments of two board certified radiologists. RESULTS: With the univariate logistic regression model, the standard deviation of rCBV offered the highest AUC (0.86), followed by mean value of rCBV (0.83), skewness of CE-T1WI (0.78), mean value of CET1 (0.78), and max value of rCBV (0.77). The AUC of the XGBoost was significantly higher than the two radiologists (0.98 vs. 0.84; p < 0.01 and 0.98 vs. 0.79; p < 0.01, respectively). CONCLUSION: The performance of machine learning based on histogram and texture features in multi-parametric MRI was superior to that of conventional cut-off method and the board certified radiologists to differentiate a GBM from a PCNSL.

BCL2 expression is associated with a poor prognosis independent of cellular origin in primary central nervous system diffuse large B-cell lymphoma.

PURPOSE: Primary central nervous system diffuse large B-cell lymphoma (CNS-DLBCL) is a distinct clinicopathological entity with a poor prognosis. Concurrent MYC and BCL2 overexpression predicts inferior prognosis in systemic DLBCL, although their prognostic significance remains unclear in primary CNS-DLBCL. METHODS: Pretreatment diagnostic biopsy samples were retrospectively evaluated for 79 patients with primary CNS-DLBCL who were treated between January 2001 and December 2017. Histological and immunohistochemical testing were performed to evaluate the patients' statuses for various markers, which were also evaluated for associations with survival outcomes. RESULTS: According to the Hans criteria, 26 patients (32.9%) had the germinal center B-cell subtype and 53 patients (67.1%) had the activated B-cell subtype. Forty-one cases (51.9%) were positive for MYC (expression of ≥ 40%), 33 cases (41.8%) were positive for BCL2 (expression of ≥ 70%), 22 patients (27.8%) were positive for both MYC and BCL2, and 27 patients (34.2%) were negative for both MYC and BCL2. There were no significant differences in survival between the germinal center and activated B-cell subtypes. Furthermore, MYC positivity was not associated with overall survival (p = 0.369) or progression-free survival (PFS) (p = 0.253). However, BCL2 positivity was significantly associated with poor overall survival (p = 0.039) and PFS (p = 0.036). Co-expression of MYC and BCL2 was not associated with survival. CONCLUSION: Our data suggest that evaluating BCL2 expression may help predict the prognosis in cases of primary CNS-DLBCL.

The expression of PD-1 ligands and IDO1 by macrophage/microglia in primary central nervous system lymphoma.

Recent progress in anti-tumor immunotherapy has focused on the significance of the tumor microenvironment in tumor progression and resistance to chemo/radio-therapy. Myeloid cells such as macrophages are predominant stromal components in hematological malignancies. In the present study, we investigated the regulation of programmed death-1 (PD-1) ligand expression in primary central nervous system lymphoma (PCNSL) using PCNSL cell lines and human monocyte-derived macrophages. TK PCNSL cell line-derived soluble factors induced overexpression of PD-1 ligands, indoleamine 2,3-dioxygenase (IDO1), and several other cytokines in macrophages. The expression of PD-1 ligands was dependent on the activation of signal transducer and activator of transcription 3. PD-L1 and IDO1 were overexpressed by macrophage/microglia in PCNSL tissues, and gene expression profiling indicated that IDO1 expression was positively correlated with the expression of macrophage and lymphocyte markers. Macrophage-derived factors did not influence the proliferation or chemo-sensitivity of cell lines. These data suggest that the expression of immunosuppressive molecules, including PD-1 ligands and IDO1, by macrophage/microglia may be involved in immune evasion of lymphoma cells.

Oligodendrocyte Progenitor Cells and Macrophages/Microglia Produce Glioma Stem Cell Niches at the Tumor Border.

Glioblastoma (GBM) usually develops in adult brain white matter. Even after complete resection, GBM recurs around the tumor removal cavity, where GBM cells acquire chemo-radioresistance. Characterization of the tumor border microenvironment is critical for improving prognosis in patients with GBM. Here, we compared microRNA (miRNA) expression in samples from the tumor, tumor border, and periphery by miRNA microarray. The top three of miRNAs showing higher expression in the tumor border were related to oligodendrocyte differentiation, and pathologically oligodendrocyte lineage cells were increased in the border, where macrophages and microglia also colocalized. Medium cultured with oligodendrocyte progenitor cells (OPCs) and macrophages induced stemness and chemo-radioresistance in GBM cells, similar to that produced by FGF1, EGF and HB-EGF, IL-1ß, corresponding to OPCs and macrophages, respectively. Thus, OPCs and macrophages/microglia may form a glioma stem cell niche at the tumor border, representing a promising target for prevention of recurrence.

Clinical significance of polyglutamylation in primary central nervous system lymphoma.

The therapeutic response to high-dose methotrexate (HD-MTX) therapy for primary central nervous system lymphoma (PCNSL) varies. Polyglutamylation is a reversible protein modification with a high occurrence rate in tumor cells. MTX incorporated into cells is polyglutamylated and strongly binds to dihydrofolate reductase without competitive inhibition by leucovorin (LV). Tumor cells with high polyglutamylation levels are selectively killed, whereas normal cells with lower polyglutamylation are rescued by LV. We hypothesized that the extent of polyglutamylation in tumor cells determines treatment resistance. Here, we investigated the therapeutic response of PCNSL to HD-MTX therapy with LV rescue based on polyglutamylation status. Among 113 consecutive PCNSL patients who underwent HD-MTX therapy in our department between 2001 and 2014, polyglutamylation was evaluated by immunostaining in 82 cases, with relationships between polyglutamylation and therapeutic response retrospectively examined. Human malignant lymphoma lines were used for in vitro experiments, and folpolyglutamate synthetase (FPGS), which induces polyglutamylation, was knocked down with short-hairpin RNA, and a stable cell line with a low rate of polyglutamylation was established. Cell viability after MTX treatment with LV rescue was evaluated using sodium butyrate (NaBu), a histone-deacetylase inhibitor that induces polyglutamylation by elevating FPGS expression. The complete response rate was significantly higher in the group with polyglutamylation than in the non-polyglutamylation group [58.1% (25/43) and 33.3% (13/39), respectively] (p < 0.05), and progression-free survival was also significantly increased in the group with polyglutamylation (p < 0.01). In vitro, the relief effect of LV after MTX administration was significantly enhanced after FPGS knockdown in al cell lines, whereas enhancement of FPGS expression by NaBu treatment significantly reduced this relief effect. These findings suggested that polyglutamylation could be a predictor of therapeutic response to HD-MTX therapy with LV rescue in PCNSL. Combination therapy with HD-MTX and polyglutamylation-inducing agents might represent a promising strategy for PCNSL treatment.

Spontaneous Repeated Disappearance and Recurrence of Multiple Spinal Intradural Arachnoid Cysts in a Child.

BACKGROUND: Spinal intradural arachnoid cysts are rare in the pediatric population. We present a rare case of intradural spinal arachnoid cysts that spontaneously and repeatedly disappeared and reoccurred. CASE DESCRIPTION: A 2-year-and-8-months-old boy presenting with lower extremity weakness was found to have spinal intradural arachnoid cysts in cervical and thoracolumbar regions at separate times. Although spontaneous disappearance of both lesions was observed, surgical treatment was finally performed for the symptomatic recurrent thoracolumbar lesion. CONCLUSIONS: To the best of our knowledge, this is the first report of spontaneously disappearing and recurring spinal arachnoid cysts.

Additive Value of 3T 3D CISS Imaging to Conventional MRI for Assessing the Abnormal Vessels of Spinal Dural Arteriovenous Fistulae.

INTRODUCTION: We investigated the additive value of the 3T 3D constructive interference in steady state (CISS) sequence to conventional MRI for the evaluation of spinal dural arteriovenous fistulae (SDAVF). MATERIALS AND METHODS: We included 16 consecutive patients (15 men, 1 woman; age range 42-81 years; mean 64 years) with SDAVF who underwent 3T MRI and digital subtraction angiography (DSA) before treatment. Two neuroradiologists independently evaluated the presence of abnormal vessels on 3D CISS-, T2- and T1-weighted images (T1WI, T2WI), and contrast-enhanced T1WI using a 3-point grading system. Interobserver agreement was assessed by calculating the κ coefficient. RESULTS: The SDAVF site was the cervical region in one patient, the thoracic region in 12 patients, the lumbar region in two, and the sacral region in one. For the visualization of abnormal vessels, the mean score was significantly higher for 3D CISS than the other sequences (P < 0.05). In 12 of 16 cases (75%) both readers made definite positive findings on additional 3D-CISS images. Interobserver agreement was excellent for 3D CISS images (κ = 1.0), good for T1WI (κ = 0.78; 95% confidence interval [CI] 0.54-1.00) and T2WI (κ = 0.74; 95% CI 0.48-1.00) and moderate for contrast-enhanced T1WI (CET1WI) (κ = 0.50; 95% CI 0.21-0.80). CONCLUSION: For the assessment of abnormal vessels of SDAVF, the 3T 3D CISS sequence adds value to conventional MRI.

Differentiating Between Primary Central Nervous System Lymphomas and Glioblastomas: Combined Use of Perfusion-Weighted and Diffusion-Weighted Magnetic Resonance Imaging.

OBJECTIVE: The purpose of this study was to determine whether combined diffusion-weighted imaging and dynamic susceptibility contrast-enhanced perfusion-weighted imaging magnetic resonance imaging can be used to differentiate between common malignant brain tumors, including lymphomas and high-grade gliomas. METHODS: We evaluated 87 patients with histologically confirmed brain tumors, including 33 primary central nervous system lymphomas (PCNSLs) and 54 glioblastomas (GBMs). All patients underwent conventional magnetic resonance imaging, diffusion-weighted imaging, and perfusion-weighted imaging before surgical removal of the lesion or stereotactic biopsy. RESULTS: The maximum relative cerebral blood volume (rCBV) ratios of GBMs were significantly higher than those of PCNSLs (P < 0.0001). The maximum rCBVs helped to distinguish PCNSLs from GBMs with 97.0% sensitivity, 90.7% specificity, and 0.98 area under the curve. The minimum apparent diffusion coefficients (ADCs) of PCNSLs were significantly lower than those of GBMs (P < 0.0001). At an rCBV cutoff value of 4.0 and a minimum ADC of 1.0 × 10-3 mm2/second, it was possible to differentiate between PCNSLs and GBMs. CONCLUSIONS: The combination of rCBV and ADC can facilitate the differentiation between PCNSLs and GBMs.

Monocyte chemoattractant protein 1 expression and proliferation in primary central nervous system lymphoma.

Whether the poor prognosis of primary central nervous system lymphoma (PCNSL) compared with systemic diffuse large B cell lymphoma (DLBCL) is attributable to the immune privilege of the intracerebral location or to intrinsic differences in the biological characteristics of two types of lymphoma remains unclear. Monocyte chemoattractant protein 1 (MCP-1) is essential to support tumor cell survival and growth, and the present study aimed to compare MCP-1 expression in PCNSL and peripheral DLBCL. The present study included 19 patients with PCNSL and 16 patients with DLBCL, all of whom had tissue diagnosis and lymphoma tissue samples available for analysis. Histology included immunohistochemistry using antibodies against a panel of lymphoma markers, antibodies specific to MCP-1, and antibodies specific to tumor-associated macrophages. MCP-1 expression was quantified using immunostaining scoring. RNA extraction and reverse transcription-quantitative polymerase chain reaction were used to determine MCP-1 mRNA expression. In addition, a human brain-derived lymphoma cell line, HKBML, was stimulated with MCP-1 and cell proliferation was measured by 5-bromo-2'-deoxyuridine incorporation. The expression levels of MCP-1 mRNA and MCP-1 protein were significantly increased in PCNSL compared with peripheral DLBCL. MCP-1 induced tyrosine phosphorylation of mitogen-activated protein kinase in HKBML cells, as analyzed by western blotting. The results of the present study indicated that MCP-1 expression in PCNSL promoted cell proliferation in an autocrine manner.

A nationwide multi-institutional retrospective study to identify prognostic factors and develop a graded prognostic assessment system for patients with brain metastases from uterine corpus and cervical cancer.

BACKGROUND: The prevalence of brain metastases (BM) from uterine cancer has recently increased because of the improvement of overall survival (OS) of patients with uterine cancer due to its early detection and improved local control as a result of new effective treatments. However, little information is available regarding their clinical characteristics and prognosis, because oncologists have encountered BM from uterine cancer on rare occasions. METHODS: Records from 81 patients with uterine BM were collected from 10 institutes in Japan. These were used in a multi-institutional study to identify prognostic factors and develop a graded prognostic assessment (GPA) for patients with BM from uterine cancer. RESULTS: Median OS after the development of BM was 7 months (95% confidence interval, 4 to 10 months). Multivariate analysis revealed that there were survival differences according to the existence of extracranial metastases and number of BM. In the present uterine-GPA, a score of 0 was assigned to those patients with ≥5 BM and extracranial metastasis, a score of 2 was assigned to those patients with one to four BM or without extracranial metastasis, and a score of 4 was assigned to those patients with one to four BM and without extracranial metastasis. The median OS for patients with a uterine-GPA scores of 0, 2, and 4 was 3, 7, and 22 months, respectively. A survival analysis confirmed the presence of statistically significant differences between these groups (p < 0.05). The results were validated by data obtained from the National Report of Brain Tumor Registry of Japan. CONCLUSION: Uterine GPA incorporates two simple clinical parameters of high prognostic significance and can be used to predict the expected survival times in patients with BM from uterine cancer. Its use may help in determining an appropriate treatment for individual patients with BM.

Benefit of 3T Diffusion-weighted Imaging in Comparison to Contrast-enhanced MR Imaging for the Evaluation of Disseminated Lesions in Primary Malignant Brain Tumors.

PURPOSE: We aimed to determine whether 3T diffusion-weighted imaging (DWI) has an additive value relative to contrast-enhanced MR imaging for the detection of disseminated lesions in patients with primary malignant brain tumors. METHODS: We included consecutive 12 patients with nodular disseminated lesions of primary malignant brain tumors that were confirmed by surgery or follow-up MR imaging. All underwent conventional MR imaging, DWI at b = 1000 and 3000 s/mm2, post-contrast T1-weighted and 3D gradient-echo imaging at 3T. For the largest lesion per person, two radiologists independently evaluated the presence of additional information on DWI compared with postcontrast MR images using a 4-point scoring system. On DW images, one radiologist measured the lesion-to-brain contrast ratio (LBCR). RESULTS: Compared with postcontrast studies, radiologists 1 and 2, respectively, assigned more apparent lesion conspicuity in 2 (17%) and 1 (8%) DWI at b = 1000 s/mm2 and 4 (33%) and 5 (42%) DWI at b = 3000 s/mm2 studies. For one of them, the mean score was significantly higher for b = 3000 s/mm2 than b = 1000 s/mm2 (P < 0.05). Interobserver agreement for DWI at b = 1000 s/mm2 and b = 3000 s/mm2 was very good (κ = 0.85; 95% CI, 0.63-1.00) and excellent (κ = 0.93; 95% CI, 0.78-1.00), respectively. The mean LBCR was significantly higher for DWI at b = 3000 s/mm2 than DWI at b = 1000 s/mm2 (P < 0.01). CONCLUSION: In the detection of disseminated lesions in patients with primary malignant brain tumors, 3T DWI has an additive value relative to contrast-enhanced MR imaging. DWI at b = 3000 s/mm2 may be more useful than DWI at b = 1000 s/mm2.

Quality of Life and Clinical Features of Long-Term Survivors Surgically Treated for Pediatric Craniopharyngioma.

OBJECTIVE: Several studies have reported treatment methods and results for pediatric craniopharyngiomas; however, few have evaluated patients' quality of life (QOL) after long-term follow-up. To evaluate treatment options, we assessed the QOL of patients with pediatric craniopharyngioma approximately 19 years after surgery and analyzed factors affecting QOL. METHODS: Twenty-six survivors who underwent resection of craniopharyngiomas at <15 years of age enrolled in this study and their physical condition was assessed. QOL was assessed by a short-form health survey (SF-36 version 2) for patients older than 19 years of age or by Child Health Questionnaire Parent Form-50 for patients 18 years of age and younger. Patients were divided into good and fair QOL groups according to their physical and mental summary scores. Factors affecting the QOL of both groups were evaluated. RESULTS: Median follow-up time was 19.1 years (range, 2.8-44.1 years). Twenty-two (84.6%) patients were employed or in school; 14 (53.8%) had visual deficits. Panhypopituitarism was diagnosed in 22 of 26 (84.6%) subjects. SF-36 analysis indicated that patients had significantly lower scores for general and mental health. Visual deficits, obesity, and complications during follow-up significantly affected the fair QOL group long-term. Patients' basic characteristics, initial resection rates, times of operation or irradiation did not significantly affect long-term QOL. CONCLUSION: Long-term survivors lived independently but had a lower overall QOL. Not only monitor short-term results based on estimation of the initial resection or recurrence rate, it is important to preserve visual and hypothalamic function and monitor arising complications for extended periods to improve patients' long-term QOL.

A case of an epithelioid glioblastoma with the BRAF V600E mutation colocalized with BRAF intact low-grade diffuse astrocytoma.

Epithelioid glioblastomas are one of the rarest histological variants of glioblastomas, which are not formally recognized by the World Health Organization (WHO) classification. Epithelioid glioblastomas usually occur as primary lesions, but there have been several reports of secondary epithelioid glioblastomas or epithelioid glioblastomas with pre- or co-existing lesions to date. The serine/threonine-protein kinase B-Raf (BRAF) V600E mutation has been found at a high frequency of 54% in epithelioid glioblastomas. We present a case of a 26-year-old female patient with an epithelioid glioblastoma with the BRAF V600E mutation in her right frontal lobe. In the present case, a low-grade diffuse astrocytoma component had colocalized with the epithelioid glioblastoma. The component presented prominent calcification on neuroimages as well as by histology, and low-grade diffuse astrocytoma was considered to be a precursor lesion of an epithelioid glioblastoma. However, the BRAF V600E mutation was detected only in epithelioid glioblastoma but not in low-grade diffuse astrocytoma. To the best of our knowledge, this is the first report demonstrating a discrepancy in the BRAF V600E mutation states between epithelioid glioblastoma and colocalized low-grade astrocytoma.