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Chordoid glioma (ChG) is a characteristic, slow growing, and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. Here we report the analysis of 16 ChG by whole-exome and RNA-sequencing. We found that 15 ChG harbor the same PRKCA D463H mutation. PRKCA encodes the Protein kinase C (PKC) isozyme alpha (PKCα) and is mutated in a wide range of human cancers. However the hot spot PRKCA D463H mutation was not described in other tumors. PRKCA D463H is strongly associated with the activation of protein translation initiation (EIF2) pathway. PKCα D463H mRNA levels are more abundant than wild-type PKCα transcripts, while PKCα D463H is less stable than the PCKα WT protein. Compared to PCKα WT , the PKCα D463H protein is depleted from the cell membrane. The PKCα D463H mutant enhances proliferation of astrocytes and tanycytes, the cells of origin of ChG. In conclusion, our study identifies the hallmark mutation for chordoid gliomas and provides mechanistic insights on ChG oncogenesis.

Background: Intraventricular tumors present difficult challenges to the neurosurgeon. Neurosurgeons have begun to explore the possibilities of using the endoscope in the radical resection of solid intraventricular lesions. There is a steep learning curve when dealing with such lesions with an endoscope., Objective: The aim of this study was to create a laboratory training model for neuroendoscopic surgery of intraventricular lesions guided by the navigation system. We believe this technique is more reliable than the traditional approach using contrast injection with C-arm x-ray guidance., Materials and Methods: Five formalin-fixated, latex-injected cadaveric heads were used. The arterial system was injected with red latex through the common carotid arteries, and the venous system was injected with blue latex through the internal jugular veins at the C6 vertebral level. The contrast-enhancing tumor polymer, Stratathane resin ST-504-derived polymer (SRSDP), was injected into the lateral ventricle via Frazier's point under direct endoscopic visualization and real-time neuronavigation guidance. When navigation was used for trajectory planning, the peel-away sheath was registered using a frameless navigational system (BrainLAB, Feldkirchen, Germany). A questionnaire was distributed to all participants in an endoscopic cadaveric course in which the models were used to evaluate the endoscopic tumor model., Results: Neurosurgeons participating in the course performed an endoscopic approach to resect the intraventricular tumor model through an ipsilateral frontal burr hole. The properties of the SRSDP mixture could be manipulated through varying concentrations of the materials used, in order to reach the desired consistency of a nodular solid lesion and possibility for piecemeal resection. The tumor model allowed participants to compare between normal and pathologic endoscopic anatomy in the same cadaveric head., Conclusion: This injectable tumor model with the combination of neuroendoscopy and navigation can improve the accuracy of the endoscopic approach and minimize the risk of cadaveric brain specimen damage that in return augments the feeling of lifelike conditions. Using this endoscopic injectable tumor model technique can assist neurosurgeons' preparation for the challenges associated with an endoscopic piecemeal resection of a solid lesion in the lateral or third ventricle., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Intraventricular schwannoma remains a rare entity in the literature. Controversy exists on the possible pathogenesis of such a tumor within cerebral ventricles. Literature is sparse on tumor characteristics and differences between pediatric and adult patients., Case Report: We present a case of intraventricular schwannoma in a 9-year-old patient presenting with headache, hemiparesis, and focal seizure. Brain CT scan and MRI revealed an intraventricular tumor within left atrium of lateral ventricle. The patient underwent total resection of the tumor via posterior parietal approach. Histopathological exam was in favor of schwannoma. Postoperative brain MRI and MRS showed no recurrence after 18 months., Conclusion: Our review of the literature indicates there are some significant differences between pediatric and adult cases in different aspects including gender predominance, intraventricular location, malignant transformation, tendency for recurrence, and surgical outcome. This needs to be taken into account in the literature.

Chordoid glioma of the third ventricle (CG3V) is a rare tumor developing in a stereotyped localization. It has been related to the circumventricular organ of the lamina terminalis, in the anterior part of the third ventricle, but its oncogenesis is poorly understood. TTF-1 transcription factor is involved in the development and adult physiology of the ventral forebrain. We studied the histopathologic and immunohistochemical features of a multicentric series of 17 cases of CG3V. We described additional histologic patterns (solid, fibrosing, and fusiform) to the typical chordoid pattern. TTF-1 was constantly expressed in CG3V, as in developing and adult lamina terminalis. The anti-TTF-1 SPT24 clone was more sensitive than the 8G7G3/1 clone. No mutation of IDH1 R132, IDH2 R172, or BRAF V600 codons was found. We showed TTF-1 as a useful marker for the diagnosis of CG3V and the understanding of its oncogenesis.

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare variant of central nervous system primitive neuroectodermal tumor occurring exclusively in the pediatric population. We report a unique case of a 6-month male child presenting with a large intraventricular lesion. Histological examination revealed a tumor composed of primitive neuroectodermal cells in dense aggregates, interspersed by hypocellular areas containing small round cells widely dispersed in neuropil-like material. Few ependymal and occasional ependymoblastic rosettes were appreciated. Focal melanotic neuroepithelium recapitulating retinal differentiation was also seen. Documentation of such cases may expand the neuroectodermal differentiation spectrum of ETANTR.

Background: Combining anti-angiogenesis agents with cytotoxic agents for the treatment of malignant gliomas may affect the cytotoxic drug distribution by normalizing the blood-brain barrier (BBB). This study examines the intratumoral concentration of temozolomide (TMZ) in the presence and absence of the pan-VEGF receptor tyrosine kinase inhibitor, cediranib., Methods: Seven nude rats bearing U87 intracerebral gliomas had a microdialysis probe centered within the tumor. Ten-days after tumor implantation, TMZ (50 mg/kg) was given orally. The extracellular fluid (ECF) concentrations of TMZ within the tumor were assessed via microdialysis for 6 h following TMZ administration. Cediranib (6 mg/kg) was then given orally, and 12 h later, TMZ was re-administered with subsequent microdialysis collection. A subset of animals also underwent functional MRI to assess angiogenesis in vivo at post-inoculation days 12 and 21, before and after the cediranib treatment., Results: After dosing of oral TMZ only, ECF-TMZ mean-C(max) and area under the concentration curve(AUC(0-∞)) within the tumor were 0.59 μg/mL and 1.82 μg h/mL, respectively. Post-cediranib, ECF-TMZ mean-C(max) and AUC(0-∞) were 0.83 μg/mL and 3.72 ± 0.61 μg h/mL within the tumor, respectively. This represented a 1.4-fold (p = 0.3) and 2.0-fold (p = 0.06) increase in the ECF-TMZ C(max) and AUC(0-∞), respectively, after cediranib administration. In vivo MRI measurements of the various vascular parameters were consistent with a BBB "normalization" profile following cediranib treatment., Conclusions: In the U87 intracerebral glioma model, within the first day of administration of cediranib, the intratumoral concentrations of TMZ in tumor ECF were slightly, but not statistically significantly, increased when compared to the treatment of TMZ alone with radiographic evidence of a normalized BBB.

Atypical teratoid/rhabdoid tumor is a highly malignant tumor of the central nervous system, usually occurring in the posterior fossa in infants and young children. Supratentorial example is relatively rare, especially with involvement of the cerebral ventricle system. Herein, we reported 2 cases of atypical teratoid/rhabdoid tumor located in the septum pellucidum within the lateral and third ventricles and right parietooccipital region, respectively. Histopathologically, both of the tumors were composed of rhabdoid tumor cells and mesenchymal components, without primitive neuroectodermal tumor or epithelial differentiation. Immunohistochemical staining showed that these tumor cells reacted positively for vimentin, S-100 protein, synaptophysin, and neuron-specific enolase. Only 1 case was found to be epithelial membrane antigen reactive. The tumor cells lacked nuclear expression of INI1. These cases emphasize that atypical teratoid/rhabdoid tumor should be also considered in the list of differential diagnosis, even when these rhabdoid tumor cells do not arise in the predilection sites.

Circumventricular organs (CVOs) are specialized ventricular structures around the third and fourth ventricles of the brain. In humans, these structures are present during the fetal period and some become vestigial after birth. Some of these organs, such as the pineal gland (PG), subcommissural organ (SCO), and organum vasculosum of the lamina terminalis, might be the sites of origin of periventricular tumors, notably pineal parenchymal tumors, papillary tumor of the pineal region and chordoid glioma. In contrast to the situation in humans, CVOs are present in the adult rat and can be dissected by laser capture microdissection (LCM). In this study, we used LCM and microarrays to analyze the transcriptomes of three CVOs, the SCO, the subfornical organ (SFO), and the PG and the third ventricle ependyma in the adult rat, in order to better characterize these organs at the molecular level. Several genes were expressed only, or mainly, in one of these structures, for example, Erbb2 and Col11a1 in the ependyma, Epcam and Claudin-3 (CLDN3) in the SCO, Ren1 and Slc22a3 in the SFO and Tph, Aanat and Asmt in the PG. The expression of these genes in periventricular tumors should be examined as evidence for a possible origin from the CVOs. Furthermore, we performed an immunohistochemical study of CLDN3, a membrane protein involved in forming cellular tight junctions and found that CLDN3 expression was restricted to the apical pole of ependymocytes in the SCO. This microarray study provides new evidence regarding the possible origin of some rare periventricular tumors., (© 2012 Japanese Society of Neuropathology.)

Despite the relatively low-grade of most central neurocytomas (CN), evidence suggests the existence of an aggressive subset with a propensity for recurrence. Recent studies have found the MIB-1 labeling index to be a prognostic indicator in CN. Here we review our experience with CN to analyze the relationships between extent of resection, adjuvant therapy, tumor histology, and clinical outcomes based on aggressive histology, as defined by MIB-1 labeling. A retrospective review was performed on histologically proven CN surgically resected from 1993 to 2009 at the University of California at San Francisco. Recurrence rates were analyzed using the Kaplan-Meier method with respect to MIB-1 labeling and extent of resection. All MIB-1 labeling indices were analyzed. A total of 18 patients were identified with a mean age of 30 years (range 17-58 years) and median follow-up of 40 months (5-173 months). The treatments were: gross total resection (GTR) alone (17% of patients), subtotal resection (STR) alone (50% of patients), STR plus radiotherapy (XRT: external beam or stereotactic radiosurgery: 28% of patients), or STR plus chemotherapy (5% of patients). The extent of resection and a MIB-1 labeling index >4% was predictive of recurrence (p<0.01). In the 33% of the patients in whom the tumor recurred, all had STR with MIB-1 labeling >4% with median time to recurrence of 23.5 months. The 2-year and 4-year recurrence rates in patients with MIB-1 labeling >4% were 50% and 75% respectively. No patient with a MIB-1 labeling index <4% who received STR alone had a recurrence. Thus, in patients with CN who were treated with STR, histology demonstrating a MIB-1 labeling index >4% can be a clinically useful prognostic indicator and can help guide adjuvant treatment., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Rationale and Objectives: Central neurocytomas (CNCs) are rare benign tumors typically located in the lateral ventricle of the central nervous system. The authors report five patients with CNCs and review 16 previously published studies that included 52 patients with CNCs to explore the magnetic resonance spectroscopic features of CNCs., Materials and Methods: Five patients with CNCs were retrospectively reviewed. They were examined using point-resolved spectroscopic series with short and/or long echo times. The integrals of choline, creatine, and the 3.55-ppm peak were determined using Magnetic Resonance User Interface software, and the metabolite ratios relative to creatine were obtained. In two cases, T2 relaxation times of choline and the metabolite resonance at 3.55 ppm were calculated using data points acquired with different echo times and an exponential decay model., Results: Consistent with previously published studies, all five patients showed highly increased choline and reduced N-acetylaspartate and creatine. Four patients in the present study and 35 in published data demonstrated prominent peaks at 3.55 ppm, which were assigned to glycine because of its relaxation pattern and long T2 relaxation time. In addition, increased in vivo glutamate and glutamine was also confirmed in three patients examined with short echo times. Alanine and lactate peaks were observed in three and two patients, respectively., Conclusions: The present study shows that the 3.55-ppm peak characteristic of CNC should be assigned to glycine according to its T2 relaxation time. Besides increased glycine and choline, the presence of glutamate or glutamine, which appears on series with short echo times, may further confirm the diagnosis of CNC., (Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.)

Central neurocytomas are low-grade tumors of neuronal origin located in the lateral ventricle that present predominantly with raised intracranial pressure. In this retrospective study, we investigated the clinical, radiological, histopathological and immunohistochemical features of eight patients (seven males and one female; age range 16-61 years; mean=35.1 years) with neurocytoma. Raised intracranial pressure was the most common presenting feature. In addition, one patient presented with marked visual deterioration and one presented with a visual field defect. All lesions were located in the lateral ventricle (right lateral ventricle: four patients, left lateral ventricle: three patients, both ventricles: one patients). Radiology showed marked intratumoral calcification in two patients. Total microsurgical excision was achieved in seven patients. Histopathology showed sheets of monotonously small-to-medium-sized neoplastic cells with uniform round-to-oval nuclei and inconspicuous nucleoli. Immunohistochemistry was positive for synaptophysin and neuron-specific enolase (NSE) in all tumors, and glial fibrillary acidic protein was focally positive in two patients. One patient had lipomatous differentiation within the tumor. No recurrence was noted in any of our patients until the last follow-up; however, there were two deaths in our series., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Primary malignant lymphoma is a non-Hodgkin lymphoma which occurs in the brain in the absence of systemic involvement. A 63-year-old woman presented to emergency service, complaining of sudden onset vomiting and dizziness. She was unconscious when she was admitted to the hospital. She had no complain, until a week ago when she experienced a headache nonresponding to analgesic. Preliminary diagnosis was cerebrovascular hemorrhage or intracranial mass. Magnetic resonance imaging and PET/CT yielded a mass filling all ventricles. Histopathology of the mass matched with malignant lymphoma located in the ventricles.

We report a rare case of ependymoma with vacuolar features, signet cells, pigmentation and numerous Rosenthal fibers arising in the fourth ventricle of a 35-year-old woman. The tumor was composed of cells with cytoplasmic vacuoles, signet cells and clear cells. The clear cells were compactly arranged resembling oligodendroglioma. Pseudovascular and ependymal rosettes were observed only in focal areas. Additionally, some tumor cells contained brown cytoplasmic pigment, which was histochemically compatible with lipofuscin and neuromelanin. On immunohistochemical examination, the tumor cells were positive for S100, glial fibrillary acidic protein and vimentin, and negative for synaptophysin, cytokeratin, neurofilament and HMB45. Epithelial membrane antigen staining showed dot-like and small vesicular reactivity. The case is presented to increase familiarity with these extraordinary variants of ependymoma.

Background: Central neurocytoma is a rare primary brain tumour, mostly localised in the lateral ventricles in relation to the foramen of Monro., Objectives: To report a case of a rare central neurocytoma with a complete loss of Synaptophysin expression and provide the differential diagnosis., Methods and Results: We describe a case of a 34-year old man with a headache, unsteady gait and dim vision. MRI demonstrated a tumorous expansion localised in both lateral ventricles. The patient underwent a subtotal resection. Histology showed a picture consistent with central neurocytoma, but tumour was completely negative for Synaptophysin. We describe our approach in such a diagnostically difficult case., Conclusions: In the rare case of Synaptophysin-negative central neurocytoma, its neuronal differentiation should be substantiated by electron-microscopic examination. Unfortunately in the routine work, biopsy samples are usually fixed in formalin fixative which does not preserve ultrastructure well. In such situations, an accurate diagnosis is disputable and based on careful assessment of the histological features, exclusion of tumours with similar morphology and detailed correlation with MRI pictures (Fig. 4, Ref. 6). Full Text (Free, PDF) www.bmj.sk.

Gliosarcomas are uncommon variants of glioblastoma bearing the histological hallmark of two distinct tumor components (high grade glial and sarcomatous). They share similarities with glioblastomas as far as clinico-epidemiological and prognostic factors are concerned. They are commonly cortically-surfacing lesions occurring mostly in the supratentorial compartment. Intraventricular location of a gliosarcoma is very uncommon and reported only once before. We report one such case where the lesion was subependymal and protruded into the ventricle giving the appearance of a truly intraventricluar tumor. We discuss this case and review the relevant literature.

The aim of this study was to assess the usefulness of proton MR spectroscopy in the diagnosis of intraventricular tumours. Fifty-two intraventricular tumours pertaining to 16 different tumour types were derived from our database. All cases had single-voxel proton MR spectroscopy performed at TE at both 30 and 136 ms at 1.5 T. The Mann-Whitney U test was used to search for the most discriminative datapoints each tumour type. Characteristic trends were found for some groups: high Glx and Ala in meningiomas (p < 0.001 and p < 0.01, respectively), high mobile lipids in metastasis (p < 0.001), high Cho in PNET (p < 0.001), high mI + Gly in ependymoma (p < 0.001), high NAC (p < 0.01) in the absence of the normal brain parenchyma pattern in colloid cysts, and high mI/Gly and Ala in central neurocytoma. Proton MR spectroscopy provides additional metabolic information that could be useful in the diagnosis of intraventricular brain tumors.

Tumors containing both neuronal and glial components are a rare heterogeneous group with unique features that require further subclassification. The rosette-forming glioneuronal tumor of the fourth ventricle is one of a number of recently described glioneuronal tumors, which has been accorded official WHO nosologic status only in 2007. We describe the clinical and pathologic features of two patients with rare rosette-forming glioneuronal tumors of the fourth ventricle, one of which was associated with dysgenetic tricho-rhinopharyngeal type I syndrome.

Subependymomas of the lateral ventricles are rare tumors. We present two patients with subependymomas of the lateral ventricle, who underwent gross total resection of the tumor via transcallosal approach. The patient, with increased Ki-67 labeling index had recurrence of tumor two years after the initial operation. We emphasize at the risk of recurrence which is probably correlated with Ki-67 labeling index.

Meningiomas usually present as benign tumors corresponding to WHO grade I. The development of the papillary variant of meningiomas with cyst formation in the central nervous system is extremely rare. We report a case of cystic papillary meningioma in a young female occurring in the lateral ventricle with invasion of brain parenchyma and dissemination of subarachnoid space. The tumor exhibits a marked peritumoral cyst, with contrast enhancement on magnetic resonance imaging (MRI) in accordance with type 2 of Zee's classification of cystic meningioma. Histologically, the tumor displays a classical perivascular pseudopapillary pattern with focal necrosis and subarachnoid space dissemination. Tumor cells are diffusely positive for epithelial membrane antigen (EMA) and vimentin, but lack immunoreactivity for cytokeratin (CK) and glial fibrillary acidic protein (GFAP). MIB-1 labeling is high, accounting for 5% of tumor focally. A diagnosis of primary intraventricular cystic papillary meningioma with subarachnoid space dissemination (WHO grade III) was made. To our knowledge, there is no report describing the radiological and histological characteristics of cystic papillary meningioma presenting in the lateral ventricle. In addition, the biological behavior and the clinical outcome of this tumor are also discussed.

Subependymomas (SE) are slow-growing brain tumors that tend to occur within the ventricles of middle-aged and elderly adults. The World Health Organization classifies these tumors within the ependymoma group. Previous limited analysis of this tumor type had not revealed significant underlying cytogenetic abnormalities. We have used microarray comparative genomic hybridization to study a series of SE (n = 12). A whole-genome array at 0.97-Mb resolution showed copy number abnormalities in five of 12 cases (42%). Two cases (17%) showed regions of loss on chromosome 6. More detailed analysis of all cases using a chromosome 6 tile-path array confirmed the presence of overlapping regions of loss in only these two cases. One of these cases also showed trisomy chromosome 7. Monosomy of chromosome 8 was seen in a further two cases (17%), and a partial loss on chromosome 14 was observed in one additional case. This is the first array-based, genome-wide study of SE. The observation that five of 12 cases examined (42%) at 0.97-Mb resolution showed chromosomal copy number abnormalities is a novel finding in this tumor type.

Purpose: To evaluate with 1H-magnetic resonance spectroscopy (MRS) the metabolites rations of the foramen of Monro's region in patients with tuberous sclerosis complex (TSC)., Method: Twelve patients with TSC and an age and gender-matched control group underwent MR imaging at a 1.5T scanner, and 1H-MRS at the foramen of Monro level with a multivoxel acquisition. Similar volumes of interest were selected in each side of the foramen of Monro and in the basal ganglia (lentiform nuclei). The obtained N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) peak amplitude values and ratios were studied. The statistical analysis was performed and p<0.05 was considered statically significant., Results: There was no significant difference between the NAA/Cr and Cho/Cr ratios near to the foramen of Monro and basal ganglia of the TSC patients compared with the controls (p>0.05)., Conclusion: The NAA/Cr and Cho/Cr ratios near to the foramen of Monro and basal ganglia of TSC patients are similar to the rations obtained in the control group.

We report a 6-year-old boy who presented with a medulloblastoma demonstrating classic, myoblastic, neuronal, glial, and melanotic differentiation and manifesting as severe morning headache. Magnetic resonance imaging revealed a mass lesion with cystic components in the cerebellar vermis. He underwent suboccipital craniotomy and total resection of the tumor. The specimen consisted of three morphologically distinct components. The first component consisted of densely packed cells with round-to-oval highly hyperchromatic nuclei surrounded by scanty cytoplasm. Immunohistochemical staining revealed diffuse expression of neurofilament protein and focal expression of desmin and myoglobin. The second component consisted of long spindle-shaped cells with elongated nuclei and eosinophilic cytoplasm. Immunohistochemical staining revealed diffuse expression of neurofilament protein, desmin, and myoglobin. The third component consisted of cells with small, densely hyperchromatic nuclei and scanty cytoplasm in a fine fibrillary background. Mature ganglion cells and melanotic tumor cells were also observed. Immunohistochemical staining revealed diffuse expression of synaptophysin and neurofilament protein, and focal expression of glial fibrillary acidic protein, S-100 protein, desmin, and myoglobin. The diagnosis was medulloblastoma with myoblastic, neuronal, astrocytic, and melanotic differentiation. Medulloblastoma demonstrating multipotent differentiation is rare, but the features observed in this case support the idea that medulloblastoma originates from multipotent stem cells.

Purpose: Central neurocytomas (CNCs) are rare neuronal tumors that have a favorable prognosis and lower rate of recurrence compared with other intraventricular neoplasms. Although it may be difficult to distinguish CNC on conventional neuroimaging, typical MR spectroscopy (MRS) features have been reported. We describe the MRI and MRS features of CNC., Materials and Methods: Eight patients with CNC were reviewed. Three patients underwent presurgical in vivo single-voxel MRS at short echo time (TE, 35 ms) and multi-voxel MR spectroscopic imaging at long TE (144 ms). The surgically resected tumor specimen of one of these patients was also studied ex vivo using high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance., Results: All eight tumors were located in the lateral ventricles. In six patients, CNC extended into the third ventricle, and in two patients the tumor showed further contiguous intraventricular dissemination into the fourth ventricle. In all three patients who underwent MRS, a characteristic metabolite peak was detected at 3.55 parts per million (ppm) at both long and short TE. HRMAS confirmed the presence of elevated glycine (Gly) at 3.55 ppm, without increase in the concentration of myo-inositol found at the same chemical shift. Elevated choline (at 3.2 ppm) was also seen in all three patients., Conclusion: On MRS, CNCs have a typical appearance with a metabolite peak at 3.55 ppm due to increased Gly, and this feature may be helpful in presurgical diagnosis. Although they are rare benign intraventricular tumors, in atypical cases, CNCs can show extensive intraventricular dissemination into the fourth ventricle.

Purpose: We evaluated the automated magnetic resonance spectroscopic (MRS) characteristics of intra- and extraventricular neurocytomas., Materials and Methods: One extra- and 4 intraventricular neurocytomas were studied. Automated single-voxel proton MRS was performed with a 1.5 T MR scanner. The results of 6 total automated MR spectra were analyzed for each tumor., Results: Lactate resonance was detected as a doublet in 3 MR spectra of 2 intraventricular neurocytomas. A peak corresponding to N-acetylaspartate (NAA) was small in 5 MR spectra of 4 intraventricular neurocytomas. Creatine (Cr) resonance was detected in all 6 MR spectra. Prominent choline (Cho) resonance was found in all 6 MR spectra. The myoinositol (MI) and/or glycine (Gly) peaks were large in 3 MR spectra of 2 intraventricular neurocytomas., Conclusion: The presence of the NAA signal and high MI and/or Gly signals may be characteristic features of intraventricular neurocytomas. A combination of prominent Cho resonance and detectable Cr resonance is a common feature of both intra- and extraventricular neurocytomas.

Objective: To study the clinicopathologic features of pilomyxoid astrocytoma (PmA)., Methods: The clinical and pathologic features in 3 cases of PmA were analyzed. Immunohistochemical study for glial fibrillary acidic protein (GFAP), CD34 and Ki-67 was performed on paraffin-embedded sections by standard EnVision method., Results: All the 3 cases occurred in female patients at the age of 10 months, 10 years and 19 years respectively. Two cases were located in the third ventricle, while the remaining case was located at the optic pathway. Histologically, the tumor was composed of bipolar spindle cells setting in a strikingly mucinous background. There was a marked proliferation of vessels within the tumor. In some areas, the tumor cells exhibited an angiocentric growth pattern. The biphasic pattern noted in a classic pilocytic astrocytoma was not found in PmA. Rosenthal fibers and eosinophilic granular bodies were also not identified. Immunohistochemcal study showed that the tumor cells were diffusely positive for GFAP. The Ki-67 labeling index measured less than 1%. CD34 highlighted mainly the vascular networks., Conclusions: PmA is a distinctive variant of pilocytic astrocytoma with subtle histologic differences. Compared with conventional pilocytic astrocytoma, PmA behaves more aggressively. Some cases tend to occur in older children and adolescents. Immunohistochemical study for GFAP is helpful in differential diagnosis.

Objective: To study the clinicopathologic features of subependymal giant cell astrocytoma., Methods: The clinical and pathologic characteristics of 18 cases of subependymal giant cell astrocytoma were retrospectively analyzed., Results: Amongst the 18 cases studied, there was a male predominance (male-to-female ratio = 2:1). The age of patients ranged from 7 to 54 years (mean age = 18.2 years). The tumor often occurred in the lateral ventricles (16/18, 88.9%). Most patients presented with headache and vomiting (11/18, 61.1%), followed by visual disturbance (3/18, 16.7%). Eleven patients (61.1%) had clinical features of tuberous sclerosis, usually in the form of facial angiofibroma (8/18, 44.4%). Computerized tomography was performed in 10 cases, in which 7 cases were of high density and 5 cases showed contrast enhancement. MRI revealed isointense mass lesion on T1WI (7/11, 63.6%), highly intense lesion on T2WI (10/11, 90.9%) and contrast enhancement in some cases (9/11, 81.8%). Four patients had follow-up information available and all of them were alive from 1 to 5 years (mean = 3.5 years). Histologically, there were bundles of spindle cells mixed with clusters of gemistocytes and ganglion-like cells. The spindle cells showed immunoreactivity for glial fibrillary acidic protein (18/18, 100%), while the gemistocytes and ganglion-like cells expressed synaptophysin (14/18, 77.8%). Most of the cases (16/18, 88.9%) had MIB-1 index

We describe three unusual tumours characterized by a mixture of glial and neuronal differentiation, involvement of the posterior fossa and formation of rosettes. Mixed glial-neuronal tumours of the posterior fossa are rare and poorly described neoplasms. However, several distinctive entities have appeared in the literature over recent years under a variety of different names. Our cases demonstrate the morphological features of the 'rosette-forming glioneuronal tumour of the fourth ventricle', a recently identified tumour characterised by its unique location, neurocytic pseudo-rosette formation and the presence of a low grade astrocytoma component. The long term prognosis of these tumours remains unclear. However, the clinical data available including the cases presented here, along with the histological features, suggest that these are low grade tumours with a good prognosis after surgical resection.

The reported liponeurocytoma of the left lateral ventricle in a 35-year-old man represents the fifth recorded case of a supratentorial intraventricular liponeurocytoma. In this location, liponeurocytomas are very exceptional, whereas it is the typical site for classic central neurocytomas. Conversely, neurocytomas of the cerebellum are predominantly liponeurocytomas with until now more than 25 reported cases. Thus, cerebellar liponeurocytoma is the most frequent neuroepithelial CNS tumor with adipose-like cells followed by ependymomas with a lipid component and supratentorial intraventricular liponeurocytoma. Adipose-like cells in neurocytomas may originate by lipidization of tumor cells, metaplastic transformation of neuroectodermal cells into fat cells or by true adipocytic differentiation. The present case showed also focal glial differentiation with GFAP-positivity of some tumor cells as often seen in cerebellar liponeurocytomas but much rarer in central neurocytomas. Pathogenetic and nosologic implications of supratentorial intraventricular liponeurocytomas are discussed. Future WHO tumor classification should consider that liponeurocytomas are not restricted to the cerebellum. Reports on cerebellar liponeurocytomas with a less favorable clinical course suggest a WHO grade II for liponeurocytomas.

Background: Medulloblastoma is the most common malignant central nervous system tumour in children but, in contrast, quite rare in adults. Hemispheric, rather than midline, cerebellar medulloblastomas are more common in older children and adults. We present the unusual case of a 71-year-old man who presented with a fourth ventricular mass that proved to be a medulloblastoma., Methods: A 71-year-old man presented with progressive balance problems, slurred speech and double vision. A CT scan of the brain revealed a hyperattenuating, partially calcified, avidly enhancing mass within the fourth ventricle. Diffusion weighted MRI showed restricted diffusion within the mass. The patient underwent a midline suboccipital craniotomy and a subtotal resection was achieved., Results: Histological examination showed a densely cellular neoplasm composed of small cells with a tendency towards neuroblastic rosette formation. Most cells were strongly positive for neuron-specific enolase and synaptophysin. Ultrastructurally, tumour cells showed evidence of neuronal differentiation. These findings were consistent with a classical medulloblastoma., Conclusion: Adult medulloblastoma should be considered in the differential diagnosis of a partially calcified hyperattenuating mass within the fourth ventricle.

April 2005. A woman aged 24 years presented with symptoms related to a tumor in the fourth ventricle. Cytologically, the tumor was biphasic with areas typical of a classic ependymoma, including rosettes, and other areas containing grossly atypical giant cells. Many tumor cells were GFAP-positive and ultrastructural examination revealed microvilli and cilia. The histopathologic abnormalities place this tumor among the ependymomas. Its focal giant cell phenotype is very rare, but has been reported in 4 intracranial or filum ependymomas.

Polysialic acid (PSA) is thought to attenuate neural cell adhesion molecule (NCAM) adhesion, thereby facilitating neural cell migration and regeneration. Although the expression of PSA has been shown to correlate with the progression of certain tumors such as small cell lung carcinoma, there have been no studies to determine the roles of PSA in gliomas, the most common type of primary brain tumor in humans. In this study, we first revealed that among patients with glioma, PSA was detected more frequently in diffuse astrocytoma cells, which spread extensively. To determine directly the role of PSA in glioma cell invasion, we transfected C6 glioma cells with polysialyltransferases to express PSA. In those transfected cells, PSA is attached mainly to NCAM-140, whereas the mock-transfected C6 cells express equivalent amounts of PSA-free NCAM-140. Both PSA negative and positive C6 cell lines exhibited almost identical growth rates measured in vitro. However, PSA positive C6 cells exhibited increased invasion to the corpus callosum, where the mock-transfected C6 glioma cells rarely invaded when inoculated into the brain. By contrast, the invasion to the corpus callosum by both the mock-transfected and PSA positive C6 cells was observed in NCAM-deficient mice. These results combined indicate that PSA facilitates tumor invasion of glioma in the brain, and that NCAM-NCAM interaction is likely attenuated in the PSA-mediated tumor invasion.

Although the coincidence of multiple sclerosis (MS) and central nervous system (CNS) tumors has been reported in over 30 cases in English literature, meningioma growth was associated with interferon-beta (INF-b) treated MS only in two of them. We report the case of a 19-year-old woman with clinically possible, laboratory supported MS, and a concomitant right intraventricular tumor with magnetic resonance imaging (MRI) characteristics consistent with meningioma (similar signal with grey matter on T1 and T2-weighted images and homogenous, intense enhancement). Two years after initiation of INF-b treatment, follow-up brain MRI revealed enlargement of the intraventricular mass and relative increase in the number of white matter lesions without significant clinical deterioration. She underwent almost total resection of the mass and histology confirmed the diagnosis of papillary meningioma. Based on the immunohistochemistry results, we speculate that INF-b resulted in meningioma growth by enhancing platelet derived growth factor (PDGF) receptors or/and down-regulating transforming growth factor receptors on the tumor itself.

Background: Published research on the clinicopathologic features of extraventricular ependymal neoplasms of the cerebral hemispheres has been scant., Methods: Thirty-two archival cases were studied to investigate the prognostic impact of clinicopathologic parameters including flow cytometry, the proliferation (Ki-67) labeling index, and p53 expression., Results: Among these 32 cases were 2 subependymomas, 19 ependymomas, and 11 anaplastic ependymomas. No significant gender predilection was observed, and 45% of patients were in their second or third decade of life. The left cerebral hemisphere was 1.5 times more commonly involved. On available imaging studies, lesions were often cystic, with or without a mural nodule. Tumors expressed glial fibrillary acidic protein (87%), S-100 protein (77%), cytokeratin (43%), and epithelial membrane antigen (17%). Ki-67 proliferation index paralleled tumor grade. Immunoreactivity for p53 protein was observed in the 2 cases of subependymoma, in 10 of 11 anaplastic ependymomas, and in 6 of 17 ependymomas. Flow cytometry performed in 27 tumors revealed diploidy in 20 cases and aneuploidy in 4 cases (3 anaplastic and 1 classic ependymomas), with S-phase fraction ranging from 0.2-9.7. Eleven subjects were additionally treated with radiotherapy, and 3 with chemotherapy. Follow up was available in 25 (78%) patients., Conclusions: The results of the current study suggest that there is no significant relation between histopathology, Ki-67 proliferation index, p53 immunolabeling, tumor ploidy, and biologic behavior., (Published 2005 by the American Cancer Society.)

In the central nervous system, tuberous sclerosis complex (TSC) is characterized by a range of lesions including cortical tubers, white matter heterotopias, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). Recent studies have implicated an important role for the TSC genes TSC1 and TSC2, in a signaling pathway involving the mammalian target of rapamycin (mTOR) kinase. We performed immunohistochemical and genetic analyses on SEGAs from 7 TSC patients, 4 with mutations in TSC1, and 3 with mutations in TSC2. SEGA cells show high levels of phospho-S6K, phospho-S6, and phospho-Stat3, all proteins downstream of and indicative of mTOR activation. Such expression is not seen in histologically normal control tissue. Five of 6 SEGAs also showed evidence of biallelic mutation of TSC1 or TSC2, suggesting that SEGAs develop due to complete loss of a functional tuberin-hamartin complex. We conclude that TSC SEGAs likely arise through a two-hit mechanism of biallelic inactivation of TSC1 or TSC2, leading to activation of the mTOR kinase.

Aquaporins are selective water channel proteins that play a central role in the homeostasis of human body water. The choroid plexus (CP) is considered to be the main cerebrospinal fluid (CSF)-producing structure. In this study, six specimens of normal human CP obtained during surgery were analyzed by immunohistochemistry techniques for aquaporin-1 (AQP1) expression and distribution. Intense, uniformly distributed AQP1 immunostaining was observable in the apical but not the basolateral side of cuboid cells of the CP. Moreover, this polarized expression of AQP1 was weakly detectable in the endothelial cells of choroid microvessels and, with a different pattern, in the cells lining the tubules shaped into crypts. Selective AQP1 expression on the surface of the normal human CP might explain the role of CSF production by this complex structure.

Central neurocytoma (CNC) is an uncommon benign tumor of the central nervous system (CNS) occurring in adults and is more likely to be located in the region of the foramina of Monra. Few studies have described the neuroradiological features of CNC, and most are single case reports. Our aim was to analyze the clinicopathological and neuroradiological characteristics of CNC. We retrospectively studied the preoperative CT (n=2) and MRI (n=5) of three men and two women (mean age 45 years, ranging from 30 to 63 years) with pathologically proven CNC. The tumors were primarily located in the region of the foramina of Monra. Two of them occupied the lateral ventricle, appearing to be attached to the septum pellucidum, and the other three tumors arose from the septum pellucidum and extended into the lateral ventricles. The tumors were of mixed density with cystic features and patchy or fine calcification on noncontrast CT scans, and they were of low or isointense signal on T1- and heterogeneously hyperintense signal on T2- and FLAIR weighted images. Contrast enhancement varied greatly from very slight to intense. Immunohistochemical staining showed a positive reaction for synaptophysin (Syn), neuro-specific enclase (NSE), neurofilament protein (NF) in the tumor cells and glial fibrillary acid protein (GFAP) in the fibrillar zones. CNC should be taken into consideration first if a tumor arises from the region of the foramina of Monra with CNC neuroradiological characteristics and the patient is an adult.

Aims: To gain a better insight into the biological behaviour of subependymal giant cell astrocytoma (SEGA), tumour suppressor gene protein expression and various proliferative indices were studied in these tumours and correlated with histological features and clinical outcome., Methods: We studied 23 cases of SEGA, 19 from our own Institute and four from the National Institute of Mental Health and Neurological Sciences (NIMHANS), Bangalore, India. Immunohistochemical staining for various glial and neuronal markers, proliferative markers (MIB-1, Topoisomerase II alpha PCNA) and tumour suppressor gene protein expression of p53 and retinoblastoma (Rb) were performed., Results: Nineteen cases of SEGA were collected over a period of 23 years (January 1978-December 2001), which accounted for 0.16% of all intracranial tumours and 0.51% of all gliomas reported at this centre. Ages ranged from 4 to 37 years (mean 13.2 years) with a male preponderance. Nine of the 23 cases were associated with tuberous sclerosis (TS), six at the time of diagnosis, while three developed TS during the follow-up period. Treatment consisted of surgical resection (total in nine cases and subtotal in 14 cases) followed by radiotherapy in seven cases. Except for two patients who died in the immediate post-operative period of surgical complications, the remaining patients were all alive in the follow-up period (mean 37.1 months). One patient experienced recurrence 22 years after the first surgery and a second patient after 2 years. Necrosis and/or mitoses were observed in five cases. Immunohistochemically, tumours were positive for both glial and neuronal markers. Interspersed inflammatory cells were a mixture of mast cells and lymphocytes of T immunophenotype. The MIB-1 labelling index (LI) ranged from 0 to 8% (mean 3.0%), topoisomerase II alpha (topo II alpha) LI from 0 to 9.5% (mean 2.9%) and PCNA LI from 10 to 59% (mean 32.5%). The difference in the labelling indices of tumours with and without mitoses and/or necrosis was not statistically significant. None of the tumours revealed loss of Rb gene protein expression. p53 immunopositivity was seen in 14 cases (labelling indices ranged from 1 to 7.3% with a mean of 2.4%). The correlation between the MIB-1 LI and topo II alpha LI, and topo II alpha LI and PCNA LI was significant (P<0.05) but not so with other parameters like p53 protein expression, duration of survival and morphological features such as mitoses and necrosis., Conclusions: SEGAs are rare intraventricular tumours associated with TS and express both neuronal and glial markers. They have a low proliferative potential. Mitoses and necrosis are not associated with a worse prognosis. In view of the low proliferative indices and long survival of these patients without recurrence, the role of post-operative radiotherapy is questionable. These patients should be followed up closely as many of them develop stigmata of tuberous sclerosis at a later stage.

Objective and Importance: Intracranial solitary fibrous tumors have been described previously, but intraventricular solitary fibrous tumors are extremely rare. We present what is, to our knowledge, the first reported case of solitary fibrous tumor in the third ventricle., Clinical Presentation: A 63-year-old man presented with weakness of his lower extremities and headaches. Computed tomography and magnetic resonance imaging of the brain revealed an enhancing mass in the posterior part of the third ventricle., Intervention: The tumor originated from the wall of the left internal cerebral vein and extended to the posterior part of the third ventricle. Nearly total excision was performed via an infratentorial-supracerebellar approach., Conclusion: The differential diagnosis of intracranial solitary fibrous tumors includes fibroblastic meningioma, meningeal hemangiopericytoma, neurofibroma, and schwannoma. The differential diagnosis in the present case was greatly helped by the immunohistochemical and ultrastructural findings, along with a disease-free 3.5-year follow-up. These findings are presented with reference to previous reports.

Recent development in stem cell biology has indicated a new possible approach for the treatment of neurological diseases. However, in spite of tremendous hope generated, we are still on the way to understand if the use of stem cells to repair mature brain and spinal cord is a reliable possibility. In particular, we know very little on the in situ regulation of adult neural stem, and this also negatively impact on cell transplant possibilities. In this chapter we will discuss issues concerning the role and function of stem cells in neurological diseases, with regard to the impact of features of degenerating neurons and glial cells on in situ stem cells. Stem cell location and biology in the adult brain, brain host reaction to transplantation, neural stem cell reaction to experimental injuries and possibilities for exogenous regulation are the main topics discussed.

The literature to date on the treatment of CNC reflects an evolution of clinical practice in neurooncology. The advent of sophisticated tools, such as MRS and molecular pathology, has facilitated more efficient diagnosis of CNC. Decreased morbidity associated with surgical intervention has resulted in better outcomes in patients undergoing resection of CNC. Prospective monitoring of treated patients with MRI coupled with judicious use of radiosurgery will likely further decrease treatment-related morbidity.

High levels of tissue-like plasminogen activator in cerebrospinal fluid reported in a patient with an intracerebral haemorrhage associated to cerebral metastasis of malignant melanoma could support the hypothesis of cerebral haemorrhage induced by tPA tumoral synthesis.

Our study of germ cell tumors (GCT) of the central nervous system (CNS) investigated the relationship between tumor histology and patient serum titers of human chorionic gonadotropin (HGC) and alpha-fetoprotein (AFP). Thirty-five patients were enrolled. Their serum titers of HCG (mlU/ml) and/or AFP (ng/ml) before initial treatment were available, as were tumor specimens obtained before the administration of adjuvant therapy. They were divided into three groups, depending on whether HCG alone (group H), AFP alone (group A), or both HCG and AFP (group HA) were detected. Each group was subdivided into three groups: patients in group I had H, A, and/or HA titers below 9.9; patients in group II/III had titers from 10.0 to 999; and those in group IV had titers of 1000 or more. Serial sections of tissue specimens were repeatedly stained, mainly with hematoxylin and eosin (H-E) stain, HCG immunostain, and AFP immunostain. There were seven patients in the H-I group and five in H-II/III. Of these 12 patients, 11 had germinomas (G) and one had an embryonal carcinoma (EC). Five patients were included in group A: one was classified as A-II/III and had a germinoma, and the remaining four patients were in A-IV and had yolk sac tumors (YST) or mixed GCT consisting mainly of YST or EC (MXGCT-YST, EC). The HA group consisted of 18 patients. Three were classified as HA-I and had germinomas; nine HA-II/III patients had T or MXGCT-T; and six HA-IV patients had choriocarcinoma (CC), YST, MXGCT-CC, or MXGCT-YST. Throughout the study, the situations for the elevated serum titers could be elucidated in only four cases (three in group A-IV and one in group HA-IV). These results led to the conclusion that serologic evaluation is superior to morphologic evaluation in diagnosing marker-producing GCTs. From a diagnostic perspective, the role of surgery is to verify the HCG- and AFP-immunonegative tissue in patients with G, T, and EC.

Objective: Few molecular targets are both consistently and selectively expressed in a majority of central nervous system (CNS) neoplasms. Receptor tyrosine kinases have been implicated in brain tumor oncogenesis. We previously isolated one such receptor, discoidin domain receptor-1 (DDR1), from high-grade pediatric brain tumors. Here, we analyze the cellular origin and distribution of DDR1 expression in human brain tumors and its expression in tumor cells relative to surrounding brain., Methods: By use of a digoxigenin-labeled DDR1 riboprobe, we investigated the expression of DDR1 messenger ribonucleic acid in a prospective series of 30 resected human primary and metastatic brain neoplasms, nonneoplastic human brain, and mouse embryonic brain, as well as a mouse glioblastoma model, by in situ hybridization., Results: All the high-grade primary brain and metastatic brain tumors showed unequivocal, intense DDR1 expression within the majority of tumor cells, whereas expression was not observed in hyperplastic tumor blood vessels, normal brain blood vessels, inflammatory cells, or in the normal brain tissue that surrounded the tumor. Receptor expression was limited to tumor cells located within solid tumor tissue. Overall, 27 of 29 resected CNS tumors exhibited tumor cell-specific DDR1 expression, whereas one specimen composed of isolated glioblastoma cells within invaded brain parenchyma showed no detectable staining for this receptor. DDR1 was also expressed preferentially in the ventricular zone (a region of highly proliferating precursor cells) of mice at embryonic Day 15.5., Conclusion: We found that DDR1 is consistently expressed in all high-grade brain neoplasms studied and is selective for tumor cells in the specimens analyzed. The expression of DDR1 by tumor cells of CNS neoplasms and by primitive cells of the embryonic ventricular zone suggests that DDR1 is a potentially useful marker of tumor cells within the CNS.