Clinical and molecular features of patients with IDH1 wild-type primary glioblastoma presenting unexpected short-term survival after gross total resection.

BACKGROUND: This study investigated the factors influencing short-term survivors (STS) after gross total resection (GTR) in patients with IDH1 wild-type primary glioblastoma. METHODS: We analyzed five independent cohorts who underwent GTR, including 83 patients from Kitasato University (K-cohort), and four validation cohorts of 148 patients from co-investigators (V-cohort), 66 patients from the Kansai Molecular Diagnosis Network for the Central Nervous System tumors, 109 patients from the Cancer Genome Atlas, and 40 patients from the Glioma Longitudinal AnalySiS. The study defined STS as those who had an overall survival ≤ 12 months after GTR with subsequent radiation therapy, and concurrent and adjuvant temozolomide (TMZ). RESULTS: The study included 446 patients with glioblastoma. All cohorts experienced unexpected STS after GTR, with a range of 15.0-23.9% of the cases. Molecular profiling revealed no significant difference in major genetic alterations between the STS and non-STS groups, including MGMT, TERT, EGFR, PTEN, and CDKN2A. Clinically, the STS group had a higher incidence of non-local recurrence early in their treatment course, with 60.0% of non-local recurrence in the K-cohort and 43.5% in the V-cohort. CONCLUSIONS: The study revealed that unexpected STS after GTR in patients with glioblastoma is not uncommon and such tumors tend to present early non-local recurrence. Interestingly, we did not find any significant genetic alterations in the STS group, indicating that such major alterations are characteristics of GB rather than being reliable predictors for recurrence patterns or development of unexpected STS.

Evaluation of the extracranial "multifocal arcuate sign," a novel MRI finding for the diagnosis of giant cell arteritis, on STIR and contrast-enhanced T1-weighted images.

BACKGROUND: While early diagnosis of giant cell arteritis (GCA) based on clinical criteria and contrast-enhanced MRI findings can lead to early treatment and prevention of blindness and cerebrovascular accidents, previously reported diagnostic methods which utilize contrast-enhanced whole head images are cumbersome. Diagnostic delay is common as patients may not be aware of initial symptoms and their significance. To improve current diagnostic capabilities, new MRI-based diagnostic criteria need to be established. This study aimed to evaluate the "multifocal arcuate sign" on short tau inversion recovery (STIR) and contrast-enhanced T1-weighted (CE-T1W) images as a novel extracranial finding for the diagnosis of GCA. METHODS: A total of 17 consecutive patients (including five with GCA) who underwent CE-T1W and whole-brain axial STIR imaging simultaneously between June 2010 and April 2020 were enrolled. We retrospectively reviewed their MR images. The "multifocal arcuate sign" was defined as "multiple distant arcuate areas with high signal intensity in extracranial soft tissues such as subcutaneous fat, muscles, and tendons." Extracranial abnormal high-signal-intensity areas were classified as "None," when no lesions were detected; "Monofocal," when lesions were detected only in one place; and "Multifocal," when lesions were detected in multiple places. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of "Multifocal" areas were calculated using cross tabulation. Fisher's exact test was used to compare "Multifocal" areas in five patients with GCA and those with other diseases. In addition, mean Cohen's kappa and Fleiss' kappa statistics were used to compare inter-reader agreement. RESULTS: The sensitivity, specificity, PPV, and NPV of the "multifocal arcuate sign" in patients with GCA were 60%, 92-100%, 75-100%, and 85-86%, respectively. Significantly more patients with GCA had "Multifocal" areas compared to those with other diseases (Fisher's exact test, p = 0.008-0.027). Mean Cohen's kappa and Fleiss' kappa for inter-reader agreement with respect to the five GCA patients were 0.52 and 0.49, respectively, for both STIR and CE-T1W sequences. CONCLUSIONS: The new radiologic finding of "multifocal arcuate sign" on STIR and CE-T1W images may be used as a radiologic criterion for the diagnosis of GCA, which can make plain MRI a promising diagnostic modality.

Distant recurrence in the cerebellar dentate nucleus through the dentato-rubro-thalamo-cortical pathway in supratentorial glioma cases.

BACKGROUND: Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway. METHODS: A total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed. RESULTS: Of the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway. CONCLUSION: Distant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF.

The MDM2-p53 Axis Represents a Therapeutic Vulnerability Unique to Glioma Stem Cells.

The prevention of tumor recurrence by the successful targeting of glioma stem cells endowed with a tumor-initiating capacity is deemed the key to the long-term survival of glioblastoma patients. Glioma stem cells are characterized by their marked therapeutic resistance; however, recent evidence suggests that they have unique vulnerabilities that may be therapeutically targeted. We investigated MDM2 expression levels in glioma stem cells and their non-stem cell counterparts and the effects of the genetic and pharmacological inhibition of MDM2 on the viability of these cells as well as downstream molecular pathways. The results obtained showed that MDM2 expression was substantially higher in glioma stem cells than in their non-stem cell counterparts and also that the inhibition of MDM2, either genetically or pharmacologically, induced a more pronounced activation of the p53 pathway and apoptotic cell death in the former than in the latter. Specifically, the inhibition of MDM2 caused a p53-dependent increase in the expression of BAX and PUMA and a decrease in the expression of survivin, both of which significantly contributed to the apoptotic death of glioma stem cells. The present study identified the MDM2-p53 axis as a novel therapeutic vulnerability, or an Achilles' heel, which is unique to glioma stem cells. Our results, which suggest that non-stem, bulk tumor cells are less sensitive to MDM2 inhibitors, may help guide the selection of glioblastoma patients suitable for MDM2 inhibitor therapy.

Effect of cerebrospinal fluid area mask correction on 123I-FP-CIT SPECT images in idiopathic normal pressure hydrocephalus.

BACKGROUND: Cerebrospinal fluid (CSF) area mask correction reduces the influence of low [123I]-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) accumulation in the volume of interest (VOI) by CSF area dilatation on the specific binding ratio (SBR) calculated using the Southampton method. We assessed the effect of CSF area mask correction on the SBR for idiopathic normal pressure hydrocephalus (iNPH) characterized by CSF area dilatation. METHODS: We enrolled 25 patients with iNPH who were assessed using 123I-FP-CIT single-photon emission computed tomography (SPECT) before shunt surgery or the tap test. The SBRs with and without CSF area mask correction were calculated, and changes in quantitative values were verified. Additionally, the number of voxels in the striatal and background (BG) VOI before and after CSF area mask correction were extracted. The number of voxels after correction was subtracted from that before correction, and the volume removed by the CSF area mask correction was calculated. The volumes removed from each VOI were compared to verify their effect on SBR. RESULTS: The images of 20 and 5 patients with SBRs that were decreased and increased, respectively, by CSF area mask correction showed that the volumes removed from the BG region VOI were higher and lower, respectively than those in the striatal region. CONCLUSIONS: The SBR before and after CSF area mask correction was associated with the ratio of the volume removed from the striatal and BG VOIs, and the SBR was high or low according to the ratio. The results suggest that CSF area mask correction is effective in patients with iNPH. TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000044826. 11/07/2021.

The Real-World status and risk factors for a poor prognosis in elderly patients with primary central nervous system malignant lymphomas: a multicenter, retrospective cohort study of the Tohoku Brain Tumor Study Group.

BACKGROUND: Elderly patients with primary central nervous system malignant lymphoma (EL-PCNSL) may not be given sufficient treatment due to their poor pre-treatment Karnofsky Performance Status (KPS) and comorbidities. Therefore, a retrospective, cohort study was performed to evaluate risk factors associated with a poor prognosis of EL-PCNSL in the Tohoku Brain Tumor Study Group. METHODS: Patients aged ≥ 71 years with PCNSL were enrolled from eight centers. Univariate analysis was performed with the log-rank test. A Cox proportional hazards model was used for multivariate analysis. RESULTS: Three of the total 142 cases received best supportive care (BSC). Treatment was given to 30 cases without a pathological diagnosis, 3 cases with cerebrospinal fluid (CSF) cytology, and 100 cases with a pathological diagnosis. After confirmation of no differences in progression-free survival (PFS) and overall survival (OS) between the group treated without pathology and the groups diagnosed by pathology or CSF cytology and between median age ≥ 76 years and < 76 years, a total of 133 patients were studied. The median pre-treatment KPS was 50%. Median PFS and median OS were 16 and 24 months, respectively. Risk factors associated with poor prognosis on Cox proportional hazards model analysis were pre-treatment cardiovascular disease and central nervous system disease comorbidities, post-treatment pneumonia and other infections, and the absence of radiotherapy or chemotherapy. CONCLUSIONS: Pre-treatment comorbidities and post-treatment complications would affect the prognosis. Radiation and chemotherapy were found to be effective, but no conclusions could be drawn regarding the appropriate content of chemotherapy and whether additional radiotherapy should be used.

A surgical case of pediatric spinal medulloepithelioma.

Embryonal tumor with multilayered rosettes (ETMR), C19MC-altered was introduced to the World Health Organization classification of central nervous system tumors in 2016. It is characterized by amplification or fusion of the chromosome 19 microRNA cluster (C19MC) locus at 19q13.42. Medulloepithelioma also an ETMR but lacks C19MC alteration. We report a rare case of spinal medulloepithelioma in a 2-year-old boy and review the literature.

Efficacy and safety of nivolumab in Japanese patients with first recurrence of glioblastoma: an open-label, non-comparative study.

BACKGROUND: An open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence glioblastoma. METHODS: Patients with first recurrence of histologically confirmed World Health Organization Grade IV glioma, after treatment with temozolomide and radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression (Response Assessment in Neuro-Oncology criteria) or toxicity. Primary endpoint was 1-year overall survival rate assessed by Bayesian approach. The prespecified efficacy criterion was that the Bayesian posterior probability threshold for exceeding the 1-year overall survival of bevacizumab (34.5%) from the Japanese phase 2 study (JO22506) would be 93%. RESULTS: Of the 50 enrolled patients, 44 (88.0%) had recurrent malignant glioma (glioblastoma, gliosarcoma), and of these, 26 (59.1%) had at least one measurable lesion at baseline. The Bayesian posterior mean 1-year overall survival (90% Bayesian credible intervals) with nivolumab was 54.4% (42.27-66.21), and the Bayesian posterior probability of exceeding the threshold of the 1-year overall survival rate of bevacizumab (34.5%) was 99.7%. Median (90% confidence interval) overall and progression-free survival was 13.1 (10.4-17.7) and 1.5 (1.4-1.5) months, respectively. One partial response was observed (objective response rate 1/26 evaluable patients [3.8%]). Treatment-related adverse event rates were 14.0% for Grade 3-4 and 2.0% for Grade 5; most adverse events resolved and were manageable. CONCLUSIONS: The 1-year overall survival with nivolumab monotherapy in Japanese patients with glioblastoma met the prespecified efficacy criterion. The safety profile of nivolumab was consistent with that observed in other tumor types. CLINICAL TRIAL REGISTRATION: JapicCTI-152967.

Arterial spin labeling magnetic resonance imaging at short post-labeling delay reflects cerebral perfusion pressure verified by oxygen-15-positron emission tomography in cerebrovascular steno-occlusive disease.

BACKGROUND: Arterial transit time correction by data acquisition with multiple post-labeling delays (PLDs) or relatively long PLDs is expected to obtain more accurate imaging in cases of the cerebrovascular steno-occlusive disease. However, there have so far been no reports describing the significance of arterial spin labeling (ASL) images at short PLDs regarding the evaluation of cerebral circulation in ischemic cerebrovascular disease. PURPOSE: To clarify the role of short-PLD ASL in cerebrovascular steno-occlusive disease. MATERIAL AND METHODS: Fifty-three patients with cerebrovascular steno-occlusive disease were included in this study. All patients underwent ASL magnetic resonance imaging and 15O-PET within two days of each modality. To compare the ASL findings with each parameter of PET, the right-to-left (R/L) ratio, defined as the right middle cerebral artery (MCA) value/left MCA value, was calculated. RESULTS: There is a significant correlation between the ASL images at a short PLD and the ratio of cerebral blood flow and cerebral blood volume by 15O-PET, which may accurately reflect the cerebral perfusion pressure. A receiver operating characteristic curve analysis indicated that ASL images at PLD 1000 and 1500 ms were more accurate than at PLD 2000-3000 ms for the detection of a ≥10% change in the PET cerebral blood flow. CONCLUSION: ASL images at shorter PLDs may be useful at least as a screening modality to detect the changes in the cerebral circulation in cerebrovascular steno-occlusive disease. We must evaluate ASL images at multiple PLDs while considering the arterial transit time of each case at present.

Postcentral gyrus resection of opercular gliomas is a risk factor for motor deficits caused by damaging the radiologically invisible arteries supplying the descending motor pathway.

BACKGROUND: Postoperative motor deficits are among the worst morbidities of glioma surgery. We aim to investigate factors associated with postoperative motor deficits in patients with frontoparietal opercular gliomas. METHODS: Thirty-four patients with frontoparietal opercular gliomas were retrospectively investigated. We examined the postoperative ischemic changes and locations obtained from MRI. RESULTS: Twenty-one patients (62%) presented postoperative ischemic changes. Postoperative MRI was featured with ischemic changes, all located at the subcortical area of the resection cavity. Six patients had postoperative motor deficits, whereas 28 patients did not. Compared to those without motor deficits, those with motor deficits were associated with old age, pre- and postcentral gyri resection, and postcentral gyrus resection (P = 0.023, 0,024, and 0.0060, respectively). A merged image of the resected cavity and T1-weighted brain atlas of the Montreal Neurological Institute showed that a critical area for postoperative motor deficits is the origin of the long insular arteries (LIAs) and the postcentral gyrus. Detail anatomical architecture created by the Human Connectome Project database and T2-weighted images showed that the subcortical area of the operculum of the postcentral gyrus is where the medullary arteries supply, and the motor pathways originated from the precentral gyrus run. CONCLUSIONS: We verified that the origin of the LIAs could damage the descending motor pathways during the resection of frontoparietal opercular gliomas. Also, we identified that motor pathways run the subcortical area of the operculum of the postcentral gyrus, indicating that the postcentral gyrus is an unrecognized area of damaging the descending motor pathways.

Relationships between recurrence patterns and subventricular zone involvement or CD133 expression in glioblastoma.

INTRODUCTION: We previously reported that CD133 expression correlated with the recurrence pattern of glioblastoma (GBM). Subventricular zone (SVZ) involvement may also be associated with distant recurrence in GBM. Therefore, we herein investigated whether the combined analysis of SVZ involvement and CD133 expression is useful for predicting the pattern of GBM recurrence. MATERIALS AND METHODS: We retrospectively analyzed 167 cases of GBM. Tumors were divided into four groups based on spatial relationships between contrast-enhanced lesions (CEL) and the SVZ or cortex (Ctx) on MRI. The initial recurrence pattern (local/distant) was obtained from medical records. To identify factors predictive of recurrence, we examined CD133 expression by immunohistochemical, clinical (age, sex, KPS, Ki-67 labeling index, surgery, and MRI characteristics), and genetic (IDH1, MGMT, and BRAF) factors. RESULTS: The CD133 expression rate was higher in SVZ-positive tumors than in SVZ-negative tumors (P = 0.046). Distant recurrence was observed in 21% of patients, and no significant difference was noted in recurrence patterns among the four groups. However, strong CD133 expression was associated with a shorter time to distant recurrence in univariate, multivariate, and propensity-matched scoring analyses (P < 0.0001, P = 0.001, and P = 0.0084, respectively). In the combined analysis, distant recurrence was the most frequent (70%) in group III (SVZ-negative, Ctx-positive) GBM and those with high CD133 expression rates (≥ 15%). CONCLUSION: An integrated analysis of CD133 expression and MRI-based tumor classification may be useful for predicting the recurrence pattern of GBM.

Clinical impact of revisions to the WHO classification of diffuse gliomas and associated future problems.

The publication of the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 WHO CNS) represented a major change in the classification of brain tumors. It is essential to determine the IDH and 1p/19q statuses of diffuse gliomas to ensure that the final diagnosis is accurate. The integrated diagnostic method outlined in the 2016 WHO CNS has enabled more precise prediction of the prognoses of diffuse gliomas. However, there are further two points that need to be addressed when planning future clinical trials. The first is the problems with the WHO grading system for diffuse gliomas. The second is that examinations for IDH mutations and 1p/19q co-deletion are not sufficient on their own to accurately predict the prognosis of diffuse glioma patients. Risk of an IDH-mut diffuse glioma should be evaluated based on a combination of clinical factors (age and the resection rate), molecular factors (the presence/absence of CDKN2A deletion), and histological factors (morphology and the mitotic index). Glioblastoma (GBM) have also been classified according to their IDH status; however, the frequency of IDH gene mutations is only 5-10% in GBM. Other molecular markers such as MGMT methylation, pTERT mutations and EGFR amplification could be more important to predict clinical outcome. Therefore, the next revision of the classification of diffuse gliomas will propose a detailed classification based on additional markers. In the near future, treatments for diffuse gliomas will be chosen according to the molecular profile of each tumor.

[Seven Patients with Pituitary Metastases Treated at Our Department:Case Reports].

Pituitary metastases(PM)are rare and show a poor prognosis. However, recent advances in diagnostic imaging could increase the chances of PM being diagnosed without a history of cancer. Furthermore, it was unclear whether adjuvant therapy could increase the survival of patients with PM or not. To clarify the clinical course of patients with PM, we report seven cases of PM with a literature review. Most patients showed symptomatic adenohypophyseal dysfunction(AD)and diabetes insipidus(DI)as initial symptoms. All patients underwent radiotherapy for PM and showed good local tumor control. However, except for one patient with improved DI, neither AD nor DI improved with radiotherapy. As for the prognosis, three patients with PM without a history of cancer survived longer than those with a history of cancer(20.3 vs. 11.7 months, respectively). In summary, early diagnosis and appropriate hormone replacement therapies are important in PM. Improvement of the general condition enables adjuvant therapy to prolong patient survival.

[Multiloculated Hydrocephalus Complicated by Meningitis and Ventriculitis Treated with Staged Fenestration:A Case Report].

Multiloculated hydrocephalus following severe meningitis with ventriculitis is often therapeutically challenging. Neonatal meningitis is commonly associated with ventricular inflammation, and approximately 30% of patients show septum formation. Although placement of a single ventriculoperitoneal shunt system could serve as optimal treatment for a multiloculated cerebrospinal cavity that is converted into a single chamber, multiple devices are often required for disease stability. We report a case of multiloculated hydrocephalus that occurred after meningitis in a patient who was successfully treated with a single shunt system using staged multimodality treatments.

[Intracranial Pseudoaneurysm Arising after Radiotherapy for Oligodendroglioma:A Case Report].

Intracranial pseudoaneurysms arising after radiotherapy for brain tumors are a relatively rare occurrence and associated with high-volume radiotherapy such as stereotactic radiosurgery. Herein, the authors report a rare case of intracranial pseudoaneurysm after conventional radiotherapy for oligodendroglioma. Case:A 46-year-old female incidentally presented with an intracranial hemorrhage from a middle temporal artery aneurysm. Four years earlier, she underwent surgical resection and conventional radiation therapy for oligodendroglioma. The aneurysm was successfully treated with middle cerebral artery(MCA)aneurysm trapping, in conjunction with a parietal branch superficial temporal artery-MCA bypass, to prevent re-rupture. Formation of intracranial pseudoaneurysm after conventional radiotherapy is extremely rare. However, the occurrence of cerebral aneurysm(s), as well as vascular stenosis during follow-up for brain tumors treated with radiotherapy, should be considered.

[A Case of Atypical Meningioma with Liver Metastasis at 9 Years after Initial Surgery].

Metastatic meningiomas are extremely rare, and generally have poor prognosis. We report a case of atypical meningioma with good clinical course despite metastasis 9 years after the initial surgery. CASE:A 58-year-old woman visited a nearby hospital with complaints of hemiplegia and aphasia. MRI showed a large left frontal meningioma;she was referred to our department where she underwent a tumor resection(Simpson Grade I). Histopathological finding revealed fibrous meningioma in the prominent part of the tumor. Additionally, a small lesion with high Ki-67 labeling index was identified;therefore, the final diagnosis was atypical meningioma. Nine years postoperatively, a hepatic mass found incidentally and was resected by digestive surgery;a histological diagnosis of metastatic atypical meningioma was established. Thirteen years after the first operation, routine MRI showed enlargement of the local recurrent lesions in the tumor resection cavity. She underwent a reoperation(Simpson Grade I)at our department, and subsequently, discharged without any neurological deficits. Findings were not suggestive of atypical meningioma. Studies report three good prognostic factors in patients with metastatic meningioma-histologically benign primary tumor, long interval between initial diagnosis and metastasis, and asymptomatic metastatic lesion.

[A Case of Unruptured Internal Carotid Artery Aneurysm with Improved Endocrinological Function after Treatment].

We experienced a case of unruptured internal carotid artery aneurysm improved endocrinological function after the treatment. A 68-year-old woman was admitted to our hospital complaining of general fatigue, dizziness, and decreased visual acuity. Radiological examination revealed unruptured large aneurysm at the right anterior carotid artery compressing on the pituitary gland. We underwent right STA-MCA bypass and trapping of right internal carotid artery. Post-operative course was uneventful. Although visual function was not improved, her endocrinological function was improved 8 months after surgery by thrombosed and shrunken aneurysm. The mechanism of panhypopituitarism due to aneurysm has been suggested to involve mechanical compression on the pituitary gland, pituitary stalk, or hypophyseal artery. Although it was unclear about the improvement of endocrine function after the treatment of aneurysm, some cases could recover the hypopituitarism after enough follow-up period.

[Diffuse Leptomeningeal Glioneuronal Tumor with Subarachnoid Hemorrhage:A Case Report].

Diffuse leptomeningeal glioneuronal tumor(DLGNT)is a rare primary neoplasm of the central nervous system, and is a condition that is newly listed in the 2016 World Health Organization(WHO)classification of tumors of the central nervous system. We report an adult case of DLGNT that was characteristically merged with subarachnoid hemorrhage. A 46-year-old woman reported persistent dizziness upon walking. MRI of the brain revealed a diffuse, infiltrating lesion with high intensity on FLAIR around the cerebellopontine angle to the lateral ventricle and in the leptomeninges of the spinal cord. The lesion on the cerebellopontine angle showed high intensity on T1 weighted images with contrast enhancement. Since diffuse glioma and meningeal carcinomatosis were suspected, we performed an endoscopic biopsy for the lesion in the right lateral ventricle. Although the tumor was tentatively diagnosed as WHO grade II diffuse astrocytoma, a definitive diagnosis could not be obtained. One month after surgery, the patient presented with acute headache and dizziness. CT showed subarachnoid hemorrhage in the cerebellopontine angle. To decompress the intracranial pressure and prevent re-bleeding, and to obtain enough tissue samples for definitive diagnosis, we removed the enhanced lesion and hematoma at the cerebellopontine angle. Tumor tissue was composed of oligodendroglial-like cells and was positive for GFAP, Olig2, synaptophysin, and S100 protein, although it was negative for IDH1R132H. Fluorescent in situ hybridization showed KIAA1566-BRAF fusion; however, neither 1p loss nor 1p19q co-deletion was observed. Together with histological and radiological findings, the tumor was ultimately diagnosed as DLGNT. The patient received maintenance chemotherapy with temozolomide, and the tumor was stable at 18 months after surgery.

Incidence of initial spinal metastasis in glioblastoma patients and the importance of spinal screening using MRI.

PURPOSE: Intracranial glioblastomas with simultaneous spinal lesions prior to chemoradiation therapy or craniotomy, defined as initial spinal metastasis, are not well understood. Herein, we investigated intracranial glioblastoma and demonstrated the importance of spinal screening using gadolinium enhanced spinal magnetic resonance imaging (Gd-MRI). METHODS: Consecutive adult patients with intracranial glioblastoma were treated between 2010 and 2014 and received spinal screening using Gd-MRI. Spinal screening was performed regardless of spine-related symptoms, and patients presenting with and without initial spinal metastasis (spinal and non-spinal groups, respectively) were compared based on patient demographics, tumor characteristics, radiological and molecular features, and overall survival (OS). RESULTS: During the study period, 116 glioblastoma cases were treated and 87 of these (76%) underwent spinal screening. Among these patients, 11 (13%) were included in the spinal group, and 76 (87%) were included in the non-spinal group. All patients of the spinal group were free of symptoms related to spinal lesions. Compared with the non-spinal group, intracranial lesions of the spinal group presented higher incidences of intracranial dissemination and were located at subventricular zones (P = 0.0012 and 0.020, respectively). MIB-1 labeling index, molecular alterations such as IDH1 mutation, TERT promoter mutation, and immunoreactivity of ATRX and MGMT did not differ between two groups. OS was significantly shorter in the spinal group than in the non-spinal group (P = 0.0054). CONCLUSIONS: This study revealed a relatively high incidence of spinal metastasis. A subset of glioblastoma patients benefited from spinal screening, through which early detection of asymptomatic spinal metastasis was achieved.

[Natural History of Patients with Asymptomatic FLAIR High-signal Lesions Suspected of Lower-grade Gliomas].

The distribution of MRI scans has increased the chance of diagnosing asymptomatic FLAIR high-signal lesions. Herein, we retrospectively analyzed 14 asymptomatic FLAIR high-signal lesions to evaluate their natural course. Fifteen symptomatic(epilepsy)patients with FLAIR high-signal lesions were also analyzed as controls. As a result, all symptomatic patients underwent surgery and were diagnosed with lower-grade gliomas(n=14)and a dysembryoplastic neuroepithelial tumor(n=1). Among the 14 lower-grade gliomas, 11 gliomas were isocitrate dehydrogenase(IDH)-mutant. As previously reported, these results showed that FLAIR high-signal lesions with epilepsy are closely associated with IDH-mutant gliomas. On the other hand, 12 of the 14 asymptomatic patients showed no changes in the size of the lesion and symptoms during the follow-up period. Only 2 patients(14.3%)revealed increased lesions within 38 and 25 months, who were diagnosed with high-grade gliomas. Although there was no difference in the apparent diffusion coefficient value between asymptomatic and symptomatic lesions, low-intensity T1WI on MRI might be useful to discriminate lower-grade gliomas from non-tumor lesions. In conclusion, there is no need for immediate surgery for true asymptomatic lesions; however, we must undergo routine follow-up MRI scans.