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SUMMARY The majority of supratentorial ependymomas (ST-ependymomas) have few mutations but frequently display chromothripsis of chromosome 11q that generates a fusion between C11orf95 and RELA (RELAFUS). Neural stem cells transduced with RELAFUS ex vivo form ependymomas when implanted in the brain. These tumors display enhanced NF-κB signaling, suggesting that this aberrant signal is the principal mechanism of oncogenesis. However, it is not known whether RELAFUS is sufficient to drive de novo ependymoma tumorigenesis in the brain and, if so, whether these tumors also arise from neural stem cells. We show that RELAFUS drives ST-ependymoma formation from periventricular neural stem cells in mice and that RELAFUS-induced tumorigenesis is likely dependent on a series of cell signaling pathways in addition to NF-κB., Graphical Abstract, In Brief The C11orf95-RELA fusion (RELAFUS) has been found in a distinct subset of supratentorial ependymomas. Ozawa et al. show that RELAFUS is sufficient to drive ST-ependymoma formation from periventricular neural stem cells in mice. Furthermore, they show that RELAFUS-induced tumorigenesis might depend on other cell signaling pathways in addition to NF-κB.

Carmustine wafers improve the survival of patients with high-grade gliomas, but several adverse events have been reported. A 42-year-old man with left Insulo-opercular anaplastic astrocytoma developed a massive intra-cavital hematoma with subarachnoid hemorrhage caused by ruptured pseudoaneurysm of the left middle cerebral artery (MCA) adjacent to the site of carmustine wafers implanted 6 months previously. Intraoperative finding demonstrated a dissection of the insular portion of the MCA, and pathological examination identified the resected pseudoaneurysm. This case demonstrates that carmustine wafers can cause changes in local vessels. Therefore, implantation of carmustine wafers near to important vessels passing close to the resection cavity should be considered with great caution.

We describe the clinicopathological features of 25 brainstem gliomas (BSGs). Twenty BSGs located in the pons and were all in children. Four BSGs located in the medulla oblongata were in 2 children and 2 adults. One (in a child) was located in the midbrain. Radiological findings on MR images were low-intensity on T1 weighted images and high-intensity on T2 weighted images. Mean survival when pontine glioma was treated by radiotherapy and/or use of temozolomide was 14 months, although 4 patients (3 cervicomedullary types and one focal type arising from midbrain) are alive. Follow up was from 5 months to 6 years. Histopathological features of 10 cases of the diffuse type were: 4 grade II astrocytomas, 4 grade III astrocytomas, and 2 glioblastomas. MIB-1 index was from 0.8 to 38 %. P53 was positive for 80 % of 15 tumors and there were no negative results. MGMT was positive in 60 % of 15 tumors and negative in 12.4 %. IDH1 was negative in 61.6 %. There was no positive result for IDH1 in this study. Thus, our histopathological results were indicative of high p53 immunoreactivity and no IDH1 immunoreactivity related to secondary malignant change.

This is the report of a histological and clinical investigation of 4 cases of glioblastoma, a rare tumor, in whom poor contrast enhancement of the tumor was visualized on magnetic resonance imaging (MRI). Among the 94 patients with first-occurrence glioblastoma treated between January 2000 and August 2011, 4 were enrolled in this retrospective study. There were 2 men and 2 women, ranging in age from 41 to 70 years (mean, 57 years). All the patients underwent tumor resection, postoperative irradiation, and chemotherapy. One died of local tumor recurrence after 36 months; the remaining three remain alive as of 25 to 72 months after the initial treatment. The histopathology was glioblastoma with nuclear pleomorphism and pseudopalisading necrosis in all cases. However, the typical vascular endothelial proliferation was not found in 3 cases. All glioblastomas were immunopositive for p53 and immunonegative for epidermal growth factor receptor (EGFR) and isocitrate dehydrogenase 1 (IDH1). These glioblastomas showing unclear contrast enhancement on MRI had similar clinical and pathological characteristics, but differed in characteristics from glioblastoma patients showing marked contrast enhancement of the tumor on MRI.

Aim: Many cases of suprasellar region germinoma occurs in diabetes insipidus (DI), but a patient initially may come to the hospital for the chief complaint of visual impairment. The aim of this study is to determine the etiology of initial symptom presentation and the outcomes of visual impairment and DI in suprasellar region germinoma. Methods: We investigated eleven cases of single lesion suprasellar germinomas that were diagnosed and treated in our hospital. For each, a magnetic resonance imaging (MRI) was performed. Results: At the hospital visit, decreased visual acuity was found in 5/11 cases, while DI was found in all cases. The decreased visual acuity was improved in 4/5 cases by treatment, but DI improved in only 2/11 cases. In 10 cases, DI occurred earlier than visual impairment. As the initial symptom, visual impairment occurred earlier than DI in only one case and did not improve by treatment. In this case, a pituitary stalk of the normal thickness could be identified by MRI, and the optic nerve was swollen. In ten cases except this case, no significant enlargement of optic nerve was detected, and a swollen pituitary stalk was confirmed. Conclusions: In suprasellar germinomas, it is rare, but the optic nerve can significantly swell at onset, while the pituitary stalk may be intact. In such cases, visual impairment occurs earlier than DI, and visual impairment may not be improved.

Aims and background Glioblastoma has a poor prognosis, with few therapeutic options if it recurs. We report a case in which we were able to inhibit the growth of a recurrent glioblastoma by weekly single-dose administration of interferon-beta. Case report A patient with recurrent glioblastoma after radiation and chemotherapy was treated with nimustine and interferon-beta. After 2 cycles of nimustine, the patient's leukocyte, neutrophil, and platelet counts showed grade 4 toxicity according to the National Cancer Institute's Common Toxicity Criteria. The patient was treated with a weekly single dose of interferon-beta at 6 × 106 IU. The tumor showed no remarkable changes after 18 months, and the patient's Karnofsky performance status remained at 50%. Conclusions The administration of interferon-beta produced long-term control in one case of glioblastoma and may be an effective therapy. Free full text available at www.tumorionline.it

A 63-year-old female developed left hemiparesis caused by intracranial intratumoral and peritumoral hemorrhage with cerebral herniation 4 days after cerebral angiography to evaluate right convexity and petrosal meningiomas. The cerebral angiography procedure may have caused the tumoral edema and intracranial hemorrhage because computed tomography on admission revealed the right convexity meningioma as slightly low density compared to before the hemorrhage. Administration of contrast medium is known to cause complications involving microcirculatory collapse and blood-brain barrier dysfunction associated with brain tumors. Therefore, the contrast medium may have affected the meningioma after cerebral angiography.

We report a usual case of papillary meningioma arising from tentorium cerebelli occurring in a 13-year-old boy. This patient presented a 3-month history of a mildly poor coordination of the left side of his body. Computed tomography showed a homogenous enhanced mass lesion in the left posterior fossa. At surgery, gross total resection of the tumor was accomplished. Upon 'microscopic examination, some tumor cells were arranged in the papillary pattern and a resulting diagnosis of papillary meningioma was made. Electron microscopic studies showed typical meningioma features such as interdigitations and desmosomes, which were, however, detectable in only few tumor cells. Cytological and ultrastructural features of pediatric papillary meningioma and of high-grade meningioma in general are sparse. Since papillary meningioma rarely presents in children, we report this case and review the literature.

It has been reported that tumor infiltration is correlated with the expression of autocrine motility factor (AMF) and its receptor 78 kDa glycoprotein (gp78). The purpose of the present study was to detect AMF and gp78 mRNA expression levels and their localization in high-grade astrocytomas (glioblastoma and anaplastic astrocytoma) and to determine whether AMF and gp78 are important prognostic factors. A total of 32 formalin-fixed and paraffin-embedded glioblastomas and 23 formalin-fixed and paraffin-embedded anaplastic astrocytomas was used. The expressions of AMF and gp78 mRNA were detected using the highly sensitive in situ hybridization method. The expression of AMF mRNA was detected in 27 of 32 glioblastomas (84.4%) and 11 of 23 anaplastic astrocytomas (47.8%). The positivity of AMF mRNA was significantly higher in glioblastomas than in anaplastic astrocytomas (P = 0.0094), but gp78 mRNA was detected in most cases and no statistical significance was observed. The overall survival of patients with AMF expression was significantly shorter than patients without AMF expression (P = 0.0175). In anaplastic astrocytomas, the overall survival of patients with AMF expression was also significantly shorter than in patients without AMF expression (P = 0.0058). This study demonstrated that AMF is a poor prognostic factor in high-grade astrocytomas.

A 58-year-old man presented with a rare case of Rathke's cleft cyst (RCC) manifesting as headache and visual disturbance. Goldman's perimeter showed he had bitemporal hemianopia. Magnetic resonance imaging revealed a solid intrasellar lesion. He underwent surgery via a right pterional approach. The lesion was red, solid, and fibrous. Histological examination revealed a few columnar epithelial cells with poor cilia in a xanthogranulomatous lesion. Only 13 cases of RCC with granulomatous change have been diagnosed by pathological examination, including 4 xanthogranulomatous cases. Xanthogranuloma of the sellar region is relatively rare. The etiology is still unknown. We speculate that xanthogranulomas of the sellar region may be caused by reaction to the presence of RCC.

An 88-year-old man presented with Rathke’s cleft cyst (RCC) manifesting as complete cavernous sinus syndrome. He had no headache, endocrinological symptom, or blood abnormality. Neuroimaging revealed a cystic intrasellar lesion with lateral extension. The patient underwent surgery by a transsphenoidal approach. Histological examination revealed squamous and cuboidal epithelium. The diagnosis was RCC. RCC is rarely symptomatic, but enlargement and compression of the surrounding structures usually causes headache, visual field defects, or symptoms of pituitary dysfunction. The present case shows that RCC may manifest as complete cavernous sinus syndrome.

A 55-year old female was referred to the Department of Neurosurgery, Kitasato Hospital, because of a hearing impairment. Neuroimaging revealed a typical meningioma attached to the falx in the right frontal region. During surgery, an encapsulated, circumscribed, reddish-gray, slightly hard tumor attached to the falx was completely removed by an interhemispheric approach. On light microscopy, many of the tumor cells contained eosinophilic inclusions with single or multiple vacuoles that displaced the cytoplasm. The nuclei of the tumor cells were eccentric. There were no signs of malignancy in the specimen. Electron microscopy revealed that most of the eosinophilic inclusions were composed of filaments measuring 12 nm in diameter. There have been several reports of benign meningiomas with eosinophilic inclusions composed of intermediate filaments. The microscopic differences between these types of tumor and rhabdoid meningiomas are very subtle, and it is important the two types of tumors are not confused. Benign meningiomas with eosinophilic inclusions comprising intermediate filaments, for example the tumor described in this report, have been diagnosed as granulofilamentous meningiomas, which is a subtype of benign meningioma.

A 58-year-old man presented with a rare case of Rathke's cleft cyst (RCC) manifesting as headache and visual disturbance. Goldman's perimeter showed he had bitemporal hemianopia. Magnetic resonance imaging revealed a solid intrasellar lesion. He underwent surgery via a right pterional approach. The lesion was red, solid, and fibrous. Histological examination revealed a few columnar epithelial cells with poor cilia in a xanthogranulomatous lesion. Only 13 cases of RCC with granulomatous change have been diagnosed by pathological examination, including 4 xanthogranulomatous cases. Xanthogranuloma of the sellar region is relatively rare. The etiology is still unknown. We speculate that xanthogranulomas of the sellar region may be caused by reaction to the presence of RCC.

This study is a histological and clinical investigation of four cases of cerebellar glioblastoma, a rare tumor. The cases included three males and one female, from 33 to 67 years in age (mean 49 years). Tumor resection, postoperative irradiation and chemotherapy were performed in all cases. Two patients died of local tumor recurrence after 14 and 27 months. Another patient relapsed after 10 months; however, after additional tumor resection and second line chemotherapy, she remains disease-free 41 months after the initial treatment. The fourth patient has not relapsed in the 6 months since initial treatment. The histopathology of all cases was glioblastoma with pseudopalisading necrosis. However, low-grade glioma histopathology was found in three patients. All glioblastomas were immunopositive for p53 and immunonegative for epidermal growth factor receptor (EGFR) and isocitrate dehydrogenase 1 (IDH1). These adult cerebellar glioblastoma cases had similar clinical and pathological characteristics, and had different characteristics compared with supratentorial glioblastomas.

The frequency and clinical features of Epstein-Barr virus (EBV)-associated primary central nervous system lymphoma (PCNSL) in elderly patients were investigated in this study. Thirty-three PCNSL cases were enrolled in the retrospective study. Biopsies were performed, and tissue was embedded in paraffin and sectioned. In-situ hybridization of EBV-encoded small RNAs was then conducted. Specimens were scored as having one of three possible results: negative (no EBV-positive cells), slightly positive (50% EBV-positive cells), and strongly positive (50% EBV-positive cells). Fifteen cases were negative for EBV expression. Sixteen cases were slightly positive, and two cases (68 and 79 years of age) were strongly positive. The incidence of strongly positive EBV expression in PCNSL was 6.1%. The incidence of strongly positive EBV expression in PCNSL patients ≥65 years of age was 13%. Median survival time differed significantly among PCNSL patients treated with high-dose methotrexate and radiotherapy. Importantly, the strongly EBV-positive PCNSL cases had the worst outcomes, and the EBV-negative PCNSL cases had the best outcomes. These results suggest that EBV infection may affect the treatment outcome of PCNSL. In the future, examination of EBV expression in PCNSL patients who receive individualized treatment may be useful.

When methotrexate (MTX) salvage chemotherapy is performed for primary brain malignant lymphoma, use of leucovonrin rescue must often be extended due to delays in the degradation of blood concentration. We examined whether delay in MTX blood concentration degradation could be prevented by chai-ling-tang (Sairei-to) which has diuretic action. In the five cases examined were MTX blood concentration 72 hours after MTX administration was more than 1 x 10(-7) M. A single dose of 3 g of chai-ling-tang was administered three times on the day the MTX salvage chemotherapy was subsequently performed. MTX blood concentration at 72 hours post MTX administration and subsequent chai-ling-tang administration was less than 1 x 10(-7) M in all five cases. In addition, urea nitrogen and creatinine levels in serum increased and creatinine clearance decreased following MTX administration, however these changes induced by MTX administration were reduced by chai-ling-tang administration. Chai-ling-tang was effective in preventing an MTX deferent delay in MTX high-dose therapy by improving renal blood flow.

The present study was conducted to determine whether any correlation exists between the expression of DJ-1 and WHO grading of the tumor or patient prognosis, and to analyze the function of this oncogene in astrocytomas. Twenty-nine formalin-fixed and paraffin-embedded glioblastomas (grade IV), 21 anaplastic astorocytomas (grade III), and 14 diffuse astrocytomas (grade II) were immunohistochemically studied to identify the expression of DJ-1 protein. The expression of DJ-1 was detected both in the nucleus and cytoplasm of tumor cells; however, such expression varied from case to case. While there was no difference in the cytoplasmic expression of DJ-1 among astrocytomas, its nuclear expression was inversely correlated with the WHO grading of astrocytomas. Moreover, the overall survival of patients with maintained (group 1) or mixed (groups 2 and 3) was significantly longer than those with decreased (group 3) expression (p=0.0063). The present study demonstrated that the survival of patients with astrocytomas was correlated with the nuclear DJ-1 status of the tumor. We herein demonstrated for the first time that the DJ-1 molecule might therefore play an important role as a tumor suppressor in astrocytomas.

A 63-year-old female developed left hemiparesis caused by intracranial intratumoral and peritumoral hemorrhage with cerebral herniation 4 days after cerebral angiography to evaluate right convexity and petrosal meningiomas. The cerebral angiography procedure may have caused the tumoral edema and intracranial hemorrhage because computed tomography on admission revealed the right convexity meningioma as slightly low density compared to before the hemorrhage. Administration of contrast medium is known to cause complications involving microcirculatory collapse and blood-brain barrier dysfunction associated with brain tumors. Therefore, the contrast medium may have affected the meningioma after cerebral angiography.

Here, we describe the first reported autopsy findings following gamma knife surgery for thalamic pain. A 62-year-old man presented with thalamic pain after treatment for thalamic malignant lymphoma. He was treated with narcotic drugs, but his pain was uncontrollable. Treatment using gamma knife surgery on the pituitary gland using a maximum dose of 180 Gy, led to the control of his intractable pain with lower doses of drugs. His death was pain-free and was caused by a recurrence of the tumor, six months after gamma knife surgery. An autopsy was performed and necrosis was present in the area of the pituitary gland where it borders the pituitary stalk. Half of the adenohypophysis was not necrotic, and necrosis was not found in the pituitary stalk.

Protoporphyrin IX (PPIX) fluorescence-guided brain tumor resection using 5-aminolevulinic acid labeling is one of the most valuable tools available to determine the extent of glioma infiltration, but requires repeated spectroscopic evaluation of the tissue. The present method informs the surgeon of residual tumor in real time using spectrum analysis of PPIX fluorescence and an audible alert system. The target region was illuminated with a laser with a peak wavelength of 405 +/- 1 nm in addition to the usual microscope halogen lamp during tumor resection. Analysis of the spectrum detected the PPIX peak using a difference in relative intensity exceeding 500 at 636 nm and 632 nm, when an audible alert was transmitted to the surgeon. Using this method, infiltration of glioma was detected and confirmed histologically in three of six glioblastomas. The surgeon can detect tumor infiltration far more objectively and with less effort using this system during tumor resection.

We performed a pathological study to identify the locus of production of protoporphyrin IX (PPIX) in human metastatic brain tumors. Patients with metastatic brain tumors (n = 11) received 1 g of 5-aminolevulinic acid (5-ALA) perorally 2 h before undergoing surgery. The target region was exposed to laser light with a peak wavelength of 405 +/- 1 nm and an output of 40 mW. Tissue samples from the tumor bulk and surrounding areas were examined by histological and fluorescence methods. Of the 11 tumors, 9 manifested PPIX fluorescence in the tumor bulk and peritumoral brain tissue. Our findings indicate that PPIX fluorescence can be observed in peritumoral edematous areas that are free of neoplastic cells, because PPIX produced by neoplastic cells leaks into the surrounding edematous area.

Intraoperative 5-aminolevulinic acid (5-ALA)-induced fluorescence guidance for resection of malignant brain tumors was correlated with histological examination to investigate false positive findings in 42 patients with malignant glioma and six patients with metastatic brain tumor. Patients received a single 1 g oral dose of 5-ALA 2 hours before surgery. The tumor site was illuminated with a laser with a peak wavelength of 405 +/- 1 nm and output of 40 mW. Samples with strong fluorescence were obtained from the tumor bulk and samples with weak fluorescence from the tumor cavity. Fluorescence was observed in 36 of the 42 malignant gliomas and four of the six metastatic brain tumors. No tumor cells were found in fluorescent samples from six of the 36 malignant gliomas and all four metastatic brain tumors. Five of the six malignant gliomas were recurrent cases. Fluorescence was found in areas of peritumoral edema or inflammatory cell and reactive astrocyte infiltration. Intraoperative 5-ALA-induced fluorescence guidance is useful for the resection of initial malignant glioma since false positive results are rare, but only non-eloquent weak positive areas should be resected. In contrast, all weak positive areas of recurrent malignant gliomas must be resected. Weak positive areas of the peritumoral edema surrounding metastatic brain tumors should be removed carefully as false positive results are common.

PURPOSE: Our hospital introduced an intraoperative computed tomography (CT) for reasons such as its broad utility, safety and economy, despite an increase in intraoperative magnetic resonance imaging (MRI). We would like to verify existence value of our intraoperative CT system for neurosurgical procedures. MATERIALS AND METHODS: We performed intraoperative CT scans for the patients with 16 gliomas and 1 anterior cerebral artery partially thrombosed large aneurysm, which was treated by A2 side to side anastomosis and proximal occlusion, using a CT with 900mm opening size, radiolucent skull clamp and three types of pin made by stainless, titan, and sapphire, respectively. We assessed the residual tumors with plain and enhanced CT scans. In the cases of non-contrast tumors, small titan clips were applied on the wall of resection cavity to clarify the residual tumors. We also use 3-dementional CT angiography (3DCTA) for evaluating the hemodynamics. The time from the preparation to take images to restarting operation, image quality including the amount of halation caused by pins, and incidence during these procedures, were evaluated. RESULT: We could obtain CT scans all of these cases, regardless of the patients' position. All the surgical instruments were just put on the table below the breast. The amount of halation with sapphire pins was minimum, however even with them, it was difficult to evaluate the detailed residual tumors just beneath the location of pins. CTA was useful, especially for demonstrating the hemodynamics after resection of insulo-opercular gliomas and bypass/clipping. Total time to take CT scans was 15–40 (mean, 27) minutes. There had occurred no incidence including anesthesia. CONCLUSION: MRI is better than CT at the point of spatial resolution, but CT can be defined as an useful system in its easy-to-use, safety, and vascular evaluation.