Rare Primary Brain Tumors Research Articles

Prognostic value of Ki-67 index in adult medulloblastoma after accounting for molecular subgroup: a retrospective clinical and molecular analysis

Medulloblastoma (MB) is a rare primary brain tumor in adults. We previously evaluated that combining both clinical and molecular classification could improve current risk stratification for adult MB. In this study, we aimed to identify the prognostic value of Ki-67 index in adult MB. Ki-67 index of 51 primary adult MBs was reassessed using a computer-based image analysis (Image-Pro Plus). All patients were followed up ranging from 12months up to 15years. Gene expression profiling and immunochemistry were used to establish the molecular subgroups in adult MB. Combined risk stratification models were designed based on clinical characteristics, molecular classification and Ki-67 index, and identified by multivariable Cox proportional hazards analysis. In our cohort, the mean Ki-67 value was 30.0 ± 11.3% (range 6.56-63.55%). The average Ki-67 value was significantly higher in LC/AMB than in CMB and DNMB (P = .001). Among three molecular subgroups, Group 4-tumors had the highest average Ki-67 value compared with WNT- and SHH-tumors (P = .004). Patients with Ki-67 index large than 30% displayed poorer overall survival(OS) and progression free survival(PFS) than those with Ki-67 less than 30% (OS: P = .001; PFS: P = .006). Ki-67 index (i.e. > 30%, < 30%) was identified as an independent significant prognostic factor (OS: P = .017; PFS: P = .024) by using multivariate Cox proportional hazards model. In conclusion, Ki-67 index can be considered as a valuable independent prognostic biomarker for adult patients with MB.

Astroblastoma \u2013 a rare and challenging tumor: a case report and review of the literature

BackgroundAstroblastoma is a controversial and an extremely rare central nervous system neoplasm. Although its histogenesis has been clarified recently, controversies exist regarding its cellular origin and validity as a distinct entity. Because of its extreme rarity and because its common features are shared with other glial neoplasms, this tumor is prone to misdiagnosis and remains challenging not only in terms of diagnosis and classification but also in the subsequent management. This case report describes a new case of astroblastoma. It discusses clinical, radiologic, pathological, and therapeutic features and differential diagnosis of this rare neoplasm, with a review of the recent literature.Case presentationWe report the case of an 8-year-old Moroccan girl who presented with a 1-year history of epileptic seizure, headache, and decreased visual acuity. Cranial magnetic resonance imaging revealed a right occipito-temporal mass. A tumor resection was performed and histological examination combined with immunohistochemical study confirmed the diagnosis of low-grade astroblastoma.ConclusionsAstroblastoma is a very rare primary brain tumor. Its diagnosis is often challenging because of the astroblastic aspects that can be found in astrocytic tumors, in ependymomas, and in non-neuroepithelial tumors. Considerable confusion surrounds its histogenesis and classification. The low incidence rate makes it difficult to conduct studies to examine tumor characteristics.

Supra-Tentorial Cortical Ependymoma in an Adult: Case Report and Review of the Literature

Supratentorial cortical ependymoma is a rare primary brain tumor in adults. Only 50 cases are reported in the literature including pediatric and adult patients. We report a 30-year-old male with sensory-type seizures who was found to have a right posterior frontal cortical lesion with large cystic component. The lesion was resected completely and histopathology and immunohistochemistry examinations confirmed anaplastic ependymoma WHO grade III. The patient received radiotherapy treatment post-surgery, and he was tumor free one year after treatment.

Outcomes and Prognostic Factors in Pediatric Oligodendroglioma: A Population-Based Study

Background/Aims: Pediatric oligodendroglioma (pODG) is a rare primary brain tumor that remains poorly understood. Demographics, outcomes, and prognostic factors were analyzed in 346 pODG cases from the Surveillance, Epidemiology, and End Results database. Methods: Gender, race, age, tumor location, tumor size, tumor grade, extent of resection, and use of radiotherapy were evaluated with respect to overall survival (OS) by univariate and multivariate analysis. These factors were assessed in the pediatric cohort and 5,753 adult oligodendroglioma cases for comparison. Results: The mean OS in pODG was 199.6 months. Five- and 10-year survival rates were 85 and 81%. pODG arose less frequently in the frontal lobe than adult tumors (53 vs. 22%) but was more common in the temporal lobe (32 vs. 18%) and extracortical regions (19 vs. 5%, p < 0.0001). pODG presented with smaller size (55 vs. 24%, p < 0.0001) and lower grade (72 vs. 54%, p < 0.0001) than adult tumors. Tumor location, size, grade, use of radiotherapy, and extent of resection were significant prognostic factors. Size and grade were much stronger prognostic factors in children than adults. While children with oligodendroglioma survive much longer than adults on the whole, there was no difference in outcome between children with high-grade tumors and adults with high-grade tumors. Conclusion: pODG differs significantly from adult oligodendroglioma along a number of demographic and tumor factors at a population level, and key prognostic factors influence survival differently in pODG than in adult disease.

ACTR-36. GLIOMATOSIS CEREBRI; CLINICAL COURSE AND TREATMENT OUTCOMES IN SINGLE INSTITUTION

Gliomatosis cerebri (GC) reported by Nevin in 1938 is a mysterious and rare primary brain tumor. GC is defined as a diffuse infiltration of neoplastic glial cell at least three lobes in the World Health Organization (WHO) classification and can be categorized with two patterns. Type1 is typical infiltration and has no tumor mass, type2 has tumor mass spreading to CNS involvement. Prognosis of GC is dismal and there is no standard therapeutic regimen for them. Here, we report clinical course in gliomatosis patients at Tokyo Women’s Medical University in Japan. Fourteen GC patients at Tokyo Women’s Medical University were diagnosed by operation or stereotactic biopsy and treated between October 2003 and April 2015. Using retrospective chart review, we analyzed patient demographics, clinical outcome and duration of therapy were estimated using the Kaplan-Meier estimate. GC patients were 10 males and 4 females. The median age was 50 years (range 18–73). Median Overall Survival (mOS),median Progression Free Survival(mPFS) was 30.5 months, 12.5 months and poor OS(grade II, III, IV:38.5,30,8months; P<0.001)and PFS (18.5,17,5months; P<0.001) was related with higher grade. Among Radiation Therapy group(RT),ChemoTherapy group (CT) and Radiation Chemo Therapy group(CRT), CT was related with better prognosis (OS CT, RT, CRT:43, 34, 17months; P<0.05),PFS (24, 12, 8months; P=0.053). Higher histologic grade was associated with poor prognosis. Although radiation therapy was effective in most reported literatures, radiation alone was not effective. Chemotherapy suggested it was possible to be better prognosis.

Genomic characterization of recurrent high-grade astroblastoma

Astroblastomas are rare primary brain tumors, diagnosed based on histologic features. Not currently assigned a WHO grade, they typically display indolent behavior, with occasional variants taking a more aggressive course. We characterized the immunohistochemical characteristics, copy number (high-resolution array comparative genomic hybridization, OncoCopy) and mutational profile (targeted next-generation exome sequencing, OncoPanel) of a cohort of seven biopsies from four patients to identify recurrent genomic events that may help distinguish astroblastomas from other more common high-grade gliomas. We found that tumor histology was variable across patients and between primary and recurrent tumor samples. No common molecular features were identified among the four tumors. Mutations commonly observed in astrocytic tumors (IDH1/2, TP53, ATRX, and PTEN) or ependymoma were not identified. However one case with rapid clinical progression displayed mutations more commonly associated with GBM (NF1(N1054H/K63)*, PIK3CA(R38H) and ERG(A403T)). Conversely, another case, originally classified as glioblastoma with nine-year survival before recurrence, lacked a GBM mutational profile. Other mutations frequently seen in lower grade gliomas (BCOR, BCORL1, ERBB3, MYB, ATM) were also present in several tumors. Copy number changes were variable across tumors. Our findings indicate that astroblastomas have variable growth patterns and morphologic features, posing significant challenges to accurate classification in the absence of diagnostically specific copy number alterations and molecular features. Their histopathologic overlap with glioblastoma will likely confound the observation of long-term GBM "survivors". Further genomic profiling is needed to determine whether these tumors represent a distinct entity and to guide management strategies.

Treatment and survival of supratentorial and posterior fossa ependymomas in adults

Ependymoma is a rare primary brain or spinal cord tumor that arises from the ependyma, a tissue of the central nervous system. This study analyzed a large cohort of adult supratentorial and posterior fossa ependymoma tumors in order to elucidate factors associated with overall survival. We utilized the USA National Cancer Database to study adult World Health Organization grade II/III supratentorial and posterior fossa ependymoma patients treated between 1998 and 2011. Overall survival was estimated by the Kaplan–Meier method and factors associated with survival were determined using a multivariate Cox proportional hazards model. Among 1318 patients, 1055 (80.0%) had grade II and 263 (20.0%) anaplastic tumors located in the posterior fossa (64.3%) and supratentorial region (35.7%). Overall average age was 44.3years, 48.0% of patients were female, 86.5% were Caucasian, and 36.8% underwent near/gross total surgical resection. Radiotherapy was given to 662 patients (50.8%) and 75 (5.9%) received chemotherapy. Older age at diagnosis (hazard ratio [HR] 1.51, p<0.0001), high tumor grade (HR 1.82, p=0.005), and large tumor size (HR 1.66, p=0.008) were associated with poor survival. Females compared to males (HR 0.67, p=0.03) and patients with posterior fossa tumors versus supratentorial (HR 0.64, p=0.04) had a survival advantage. Our study showed that older patients, with supratentorial tumors, and high histological grade had an increased risk of mortality. A survival benefit was captured in females and patients with posterior fossa tumors. Adjuvant radiotherapy and chemotherapy did not confer a survival benefit among all patients, even after stratification by tumor grade or anatomical location.

Somatic Mutations Detected in Plasma Cell-Free DNA By Targeted Sequencing: Assessment of Liquid Biopsy in Primary Central Nervous System Lymphoma

BackgroundPrimary Central Nervous System Lymphoma (PCNSL) are rare and aggressive primary brain tumors. Histological diagnosis can be difficult at initial stages or at relapse due to deep brain structure involvement. Finding a minimally invasive biomarker aiding the diagnosis remains an unsolved question. Plasma Cell-Free DNA (cfDNA) seems to have shown its diagnostic and prognostic value in nodal Diffuse Large B Cell Lymphomas (DLBCL) [Roschewski et al, Lancet Oncology, 2015; Kurtz et al, Blood, 2015]. Our main objective was to demonstrate that targeted sequencing of cfDNA in plasma at time of diagnosis could identify PCNSL somatic mutations.Methods30 immuno-competent patients suffering from newly diagnosed PCNSL, without any extranevraxic lesions, were enrolled from 2008 to 2014. Tumor tissues and plasma samples were collected at the time of diagnosis and frozen until use. High throughput sequencing was performed on primitive tumors using a panel of 34 genes relevant to lymphomagenesis, as previously reported [Dubois et al, Oncotarget, 2015; Bohers et al, Haematologica, 2015]. We next performed patient-specific targeted sequencing of identified somatic mutations in cfDNA. The detection sensitivity threshold was set at 1% for all SNVs, except for MYD88 L265P, which was set at 0.1%. The primary endpoint was the proportion of patients having at least one somatic mutation found in the plasma.ResultsAmong 24 available plasmas, 15 patients (63%) had at least one detected somatic mutation in cfDNA. All plasmas had detectable cfDNA (mean concentration 1.6 ng/µL). No correlation was found between tumor volume and cfDNA concentration (R squared coefficient 0.01). Regarding the whole sequenced cohort (n=30) 21 (70%) were classified as nonGC subtype, 8 (27%) as GC subtype and 1 patient (3%) as unclassifiable, according to the Hans algorithm. 29 tumors had at least one somatic mutation, mainly nonsynonymous single nucleotide variants (SNV). The NF-kB pathway was the most affected by mutations: MYD88 (n=23, 77%), PIM1 (n=11, 37%), TNFAIP3 (n=6, 20%), IRF4 (n=3, 10%), CARD11 (n=3, 10%) and PRDM1 (n=3, 10%). Among the 23 tumors harboring a MYD88 mutation, the L265P variant was the most frequent (20 patients, 67%); mean tumor variant allele frequency was 46% [min 8%, max 91%]. One tumor harbored a single MYD88 L265P mutation with no other detectable abnormality. Among patients with both available plasma and a somatic MYD88 L265P mutation in the tumor, 15 patients (88%) had an identifiable L265P variant in cfDNA, with a mean variant allele frequency of 4% [min 0.1%, max 28%]. PIM1 and TNFAIP3 SNVs were also detected in cfDNA for respectively two and one patient.The second most affected pathway was the apoptotic pathway: genes affected by mutations included GNA13 (n=7, 23%), TP53 (n=2, 7%), MYC (n=1, 3%), CDKN2A (n=2, 7%) and BCL2 (n=1, 3%). The B Cell Receptor (BCR) pathway was also affected, mainly due to mutations targeting CD79B (n=10, 33%) and ITPKB (n=3, 10%) mutations. 8 tumors (27%) harbored a dual alteration affecting MYD88 and CD79B. One tumor of the GC subtype had one EZH2 SNV (Y646H), but the mutation was not found in cfDNA.There was no significant difference in overall survival (OS) between patients with and without mutations detected in cfDNA: mean OS 27 months versus 18 months (HR 0.6; IC95% [0.2 - 1.6], p value 0.3).Tumor gene copy number variations were detected in 29/30 patients with either homo or heterozygous deletions or copy gains. CDKN2A/2B deletions were detected in 23 cases (77%).ConclusionTo our knowledge this is the first study that provides evidence that somatic mutations can be detected in cfDNA in patients suffering from PCNSL, therefore constituting a minimally invasive tool helping for diagnosis. Further studies are now required to improve prognosis and predictive values of this new promising procedure for PCNSL patient care. DisclosuresNo relevant conflicts of interest to declare.

Retrospective analysis of 104 histologically proven adult brainstem gliomas: clinical symptoms, therapeutic approaches and prognostic factors

BackgroundAdult brainstem gliomas are rare primary brain tumors (<2% of gliomas). The goal of this study was to analyze clinical, prognostic and therapeutic factors in a large series of histologically proven brainstem gliomas.MethodsBetween 1997 and 2007, 104 patients with a histologically proven brainstem glioma were retrospectively analyzed. Data about clinical course of disease, neuropathological findings and therapeutic approaches were analyzed.ResultsThe median age at diagnosis was 41 years (range 18-89 years), median KPS before any operative procedure was 80 (range 20-100) and median survival for the whole cohort was 18.8 months. Histopathological examinations revealed 16 grade I, 31 grade II, 42 grade III and 14 grade IV gliomas. Grading was not possible in 1 patient. Therapeutic concepts differed according to the histopathology of the disease. Median overall survival for grade II tumors was 26.4 months, for grade III tumors 12.9 months and for grade IV tumors 9.8 months. On multivariate analysis the relative risk to die increased with a KPS ≤ 70 by factor 6.7, with grade III/IV gliomas by the factor 1.8 and for age ≥ 40 by the factor 1.7. External beam radiation reduced the risk to die by factor 0.4.ConclusionAdult brainstem gliomas present with a wide variety of neurological symptoms and postoperative radiation remains the cornerstone of therapy with no proven benefit of adding chemotherapy. Low KPS, age ≥ 40 and higher tumor grade have a negative impact on overall survival.

Success at Last: A Molecular Factor That Informs Treatment

Anaplastic oligodendrogliomas are rare primary brain tumors. However, they respond more effectively to treatment and have a better prognosis than commoner varieties. About 25year ago, reports emerged that oligodendrogliomas can respond robustly and durably to chemotherapy with procarbazine, lomustine (CCNU), and vincristine (PCV). It was also discovered that co-deletion of chromosome arms 1p and 19q is more commonly observed in oligodendrogliomas (rather than astrocytomas). Early results of phase III trials confirmed that 1p/19q co-deletion was a favorable prognostic marker. Mature results now conclusively demonstrate that co-deletion also predicts longer survival from the addition of PCV chemotherapy to radiotherapy for newly diagnosed disease. However, changes in the treatment landscape, including a preference for deferred radiotherapy, the emergence of temozolomide as a better tolerated chemotherapy regimen, and the discovery of other biomarkers (e.g. IDH mutation and MGMT promoter methylation) that occurred in the interim emphasize the need for earlier, validated, and acceptable trial end points.

Pilocytic astrocytomas in adults: A retrospective study of 125 patients.

2022 Background: Pilocytic astrocytomas (PAs) are rare primary brain tumors in adults. The natural history is poorly defined with the largest published series including only 30-40 patients. To better define clinical characteristics of adult PAs, we present an analysis of adult PAs at MD Anderson Cancer Center. Methods: We conducted an IRB-approved, retrospective chart review of patients ≥18 years diagnosed with PAs from 1990-2011 at our institution. Results: We identified 125 patients with a median age of 29 (range 18-72y), female to male ratio of 1.7:1, and median follow-up of 62 months. The most common anatomic locations were brainstem 22%, cerebellum 14%, intraventricular 14%, and cortical/lobar 14% (36% other locations). 21% of cases had an initial pathologic diagnosis discordant with neuropathologic review at our institution. Comorbidities included neurofibromatosis type 1 (5 pts) and a history of asthma or autoimmune disease (14%). 38 patients had a gross total (GTR), 55 a sub-total resection (STR) and the remainder a biopsy. 62 patients were treated with radiotherapy (RT): 45 as adjuvant (adj), 17 at recurrence; 2 received RT in both adj and recurrent settings. 73 (58%) patients were stable after initial treatment (surgery +/- adj RT). Median progression free survivals (mPFS) based on upfront treatment as follows: GTR only (n=30) - not been reached, STR only (n=32) 226.6 months, GTR plus adj RT (n=8) 13.2 months, STR plus adj RT (n=23) is 52.4 months (p=0.026, logrank test for trend). At last follow-up, 77% of all patients were stable and 13% were deceased. Conclusions: This is the largest series of adult PAs reported to date. Extracerebellar location, slight female predominance, and history of allergic/autoimmune disease were associations found in this cohort. Neuropathologic review is essential to avoid misdiagnosis. A significant subset of adult PAs behave more aggressively than expected for a grade I tumor with over 40% of patients experiencing recurrence after initial treatment. Adj RT following GTR or STR did not improve PFS, and a trend towards worse PFS with adj RT was observed although these analyzed subgroups were small. These results may help provide a framework for prospective studies in this tumor type.

Adult Medulloblastoma Comprises Three Major Molecular Variants

Medulloblastoma is a rare primary brain tumor in adults, whereas it constitutes the most common malignant brain tumor in children. Integrated genomics approaches revealed at least four distinct disease variants in children. The aim of this study was to investigate molecular subtypes and their prognostic implication in a large cohort of adult medulloblastomas as the biology in this age group remains poorly understood. We combined transcriptome and DNA copy number analyses for 28 adult medulloblastomas. Statistical and bioinformatic tools were applied to discover distinct molecular variants. Clinical and molecular characteristics of each biologic subtype were validated using immunohistochemistry on a tissue microarray derived from an independent patient cohort of adult medulloblastomas (n = 103). Gene expression profiles revealed three distinct molecular variants with stable subtype separation using the 300 most varying transcripts. Distinct demographics, genetics, transcriptome, and prognosis were noted for each subtype of adult medulloblastoma. Immunohistochemistry revealed aberrant activation of the sonic hedgehog (SHH) pathway in over half of adult medulloblastomas constituting a promising molecular therapeutic target. In contrast, subtype C tumors, which comprise a robust subtype in childhood medulloblastoma are only exceptionally seen in adult cohorts. Notably, adult subtype D and Wnt/wingless tumors were associated with worse prognosis than pediatric cohorts, whereas survival for SHH tumors was similar for both age groups. The transcriptome of adult medulloblastomas differs considerably from pediatric counterparts, both in terms of tumor biology and prognostic impact. Therefore, age-specific classification is required and must be adapted for use in clinical trials of adult medulloblastoma.

Chromosome 1p and 19q evaluation in low-grade oligodendrogliomas: A descriptive study

Oligodendrogliomas are rare primary brain tumors with variable patient outcomes which are not always adequately accounted for by clinical or pathological variables. The present study evaluated the prognostic implications of chromosome 1p and 19q status in a set of 23 low grade oligodendrogliomas (OGD II), and correlated the results with patient outcome. Loss of heterozygosity (LOH) and fluorescent in situ hybridization (FISH) analyses, the most widely used standard procedures, were used. 1p and 19q deletions were found in 65 and 61% of cases, respectively, using FISH and in 78 and 72% of cases using LOH. Both deletions were found in 56 and 64% of patients using FISH and LOH, respectively. Concordance between the results from the two techniques, determined by the Kappa statistics, ranged from fair to substantial depending on whether single or combined deletions were considered. Our results showed that the molecular alterations are associated with age and tumor localization. With regard to the impact of chromosomal alterations on clinical outcome, chromosome 19q deletions detected by LOH would seem to indicate a subgroup of patients at a higher risk of relapse, although the small number of patients recruited does not permit any definitive conclusions to be drawn. Further studies are now ongoing to determine whether this methodological approach could be potentially useful in low grade oligodendrogliomas to better characterize chromosomal alterations of 1p/19q and identify subgroups of patients with a higher risk of disease recurrence.

Clinicopathological Characteristics and Outcomes of Gliosarcoma: Analysis using the Surveillance, Epidemiology, and End Results (SEER) Registry Data

Clinicopathological Characteristics and Outcomes of Gliosarcoma: Analysis using the Surveillance, Epidemiology, and End Results (SEER) Registry Data

Patterns of care and outcomes in patients with intracranial hemangiopericytomas: The Memorial Sloan-Kettering Cancer Center (MSKCC) experience

e13011 Background: Intracranial hemangiopericytomas are rare primary brain tumors with a tendency to metastasize. Available literature is restricted to small series of patients, and little is known regarding optimal clinical management and disease course, particularly in the targeted therapy era. Methods: Retrospective review of all patients with intracranial hemangiopericytoma seen at MSKCC from January 1, 1990 to December 31, 2008. Patients were included if histology was reviewed at MSKCC, and if clinical information was deemed sufficient for the analysis. Results: A total of 32 patients met inclusion criteria. The median age was 43 (range 24–68), median KPS was 80 (range 70–100), 17 were women. Disease was metastatic at presentation in only one patient. Initial treatment consisted of surgical resection in all patients (gross total resection: 14 patients, partial resection: 7, equivocal/unknown extent of surgery: 11). Adjuvant radiotherapy following surgery was given to 21 patients. The median progression-free survival was 65 months; median overall survival was 153 months and the 15-year survival was 48%. Treatment for recurrence included re-resection in 19 patients, additional radiotherapy in 17, and chemotherapy in 10. Regimens used included cytotoxic chemotherapy (6 patients) and targeted therapy (sorafenib: 3 patients; sunitinib: 3; imatinib: 2; erlotinib: 1; sirolimus: 1; bevacizumab: 1). Stable disease was the best observed response to these agents. Metastatic sites throughout disease course included lungs in 7 patients, bone in 10, liver in 3 and chest wall in 2. Immunohistochemistry and molecular analyses are ongoing and updated results will be presented. Conclusions: Hemangiopericytomas can be associated with late recurrences, even in patients completely resected and irradiated. Salvage treatment with surgery and radiotherapy seems effective, although the efficacy of chemotherapy remains to be determined. Given the slow growth rates, the meaning of stable disease while on chemotherapy is uncertain. Several patients in this series received agents targeting PDGFR or VGFR pathways, but such strategies need to be investigated further. No significant financial relationships to disclose.

Gliosarcomas in the Elderly: Analysis of 7 Cases and Clinico-Pathological Remarks

Gliosarcomas are rare malignant primary brain tumors that usually affect the fifth or sixth decades of life. The purpose of this study was to describe our experience with such lesions in elderly patients and to establish their prognosis factors. Between 1993 and 2001, 7 patients over 60 years of age were treated at our institute for cerebral gliosarcomas. All patients underwent surgery for total or at least sub-total removal of a neoplastic mass. Owing to poor clinical conditions (Karnofsky performance score = 40), one patient was not treated postoperatively. Remaining patients were treated with whole-brain radiotherapy, whereas concomitant chemotherapy (temozolomide) was administrated only to 4 patients. Histological examination showed the prevalence of sarcomatous aspects in 3 patients; the gliomatous aspect prevailed in 4 patients. Sarcomatous aspects and multimodality treatment (surgery, radiotherapy and chemotherapy) were associated with a better prognosis and showed in these elderly patients a trend similar to that of young people.

The impact of genotype on outcome in oligodendroglioma: validation of the loss of chromosome arm 1p as an important factor in clinical decision making

Oligodendrogliomas are rare primary brain tumors. They comprise approximately 5 to 33% of all glial tumors but differ from astrocytomas by being associated with a more favorable prognosis, making their correct identification important. Allelic loss of chromosome arms 1p and 19q is found in a substantial subpopulation of tumors with an oligodendroglioma phenotype. Anaplastic oligodendrogliomas with allelic loss of 1p have been associated with chemosensitivity and a longer patient survival period. Oligodendroglial neoplasms were studied using fluorescence in situ hybridization of formalin-fixed, paraffin-embedded tissue specimens; reference and target probe sets were used to map the telomeric regions of 1p and 19q. The results were correlated with the clinical characteristics of patients treated at our institution between 1993 and 2003. Data obtained in 96 patients were analyzed. This included 63 patients (65.6%) with World Health Organization (WHO) Grade II oligodendroglioma, 22 (23%) with Grade III oligodendroglioma, and 11 (11.4%) with mixed oligoastrocytoma. Analysis of 1p in patients with pure oligodendroglioma revealed a loss of 1p in 42 patients (49.4%). In 46 of these patients 19q was lost and in 70 (82.3%) there was concordance for combined loss or retention of both 1p and 19q (p < 0.0001). Patients with oligodendroglioma in whom a loss of 1p was present fared significantly better, and this outcome was unrelated to the treatment modality or WHO grade, compared with patients in whom 1p was intact (p < 0.05). To the authors' knowledge, this study includes the largest published series of WHO Grade II oligodendroglioma and 1p analysis. The results suggest that the association between long-term survival and 1p loss in oligodendroglioma is unrelated to treatment. The authors of further prospective studies may better determine the true value of the allelic loss of 1p and its implication for clinical decision making.

Pleomorphic xanthoastrocytoma: a developmental glioneuronal tumor with prominent glioproliferative changes.

Pleomorphic xanthoastrocytoma (PXA) is a rare primary brain tumor, which usually involves the superficial cortex in children and young adults. Although PXA is considered an astrocytic tumor, recent studies suggest the presence of neuronal differentiation and an origin from multipotential precursor cells. To clarify the clinicopathological characteristics, which have not been well established due to the rarity of this tumor, eight cases of histologically proven PXA were retrospectively analyzed, paying special attention to immunohistochemical findings and associated cortical dysplasia. Three males and five females of median age 17 years (range, 11-24 years) were enrolled in the study. All patients presented with epilepsy. Tumor sites included the temporal (n = 5), frontal (n = 2), and temporoparietal (n = 1) lobes. 18F-FDG PET (positron emission tomography) showed hypometabolism of PXA. Immunohistochemical study was performed in six cases using various antibodies for glial and neuronal markers. Gross total resection of the PXA was achieved in all cases. The follow-up period ranged from 7 to 14 years except for two recent cases. All patients are doing well with neither radiological nor clinical evidence of recurrence. The surgical treatment rendered all patients seizure free. The three temporal lobe PXAs were associated with cortical dysplasia. In one tumor, clusters of dysmorphic ganglion cells were found. All examined PXAs demonstrated immunoreactivity for both neuronal and glial markers in the various tumor cells. The immunohistochemical studies undertaken as a part of this study support the proposed astrocytic and neuronal differentiation of PXA, and indicate that PXA is probably a developmental neuroglial tumor with prominent glioproliferative changes associated with focal cortical dysplasia. Cortical dysplasia may be a cause of persistent epilepsy even after complete surgical excision of PXA.

Gliomatosis cerebri: treatment results with radiotherapy alone.

Gliomatosis cerebri (GC) is a rare primary brain tumor characterized by proliferation of neoplastic glial cells that typically involve multiple brain areas, with preservation of brain structures and sparing of neurons. The optimal therapeutic strategy is not well established. The impact of radiotherapy on survival in patients with GC remains undefined. Between 1980 and 2001, 12 patients with GC were identified, representing less than 1% of all patients with primary brain neoplasms treated at the Cleveland Clinic. All 12 patients had brain biopsies between March 1986 and July 2001 (seven males, five females, with a median age of 53 years [range, 13-85 years]). Median Karnofsky performance status at the time of presentation was 70 (range, 40-90). Eight patients had low-grade gliomas and four patients had anaplastic astrocytomas. Eight patients received radiation treatment to the brain as the only treatment, and four received neither radiation nor chemotherapy. The median dose of megavoltage radiation was 55.4 Gy (range, 45-61.2 Gy). Of the eight patients who received brain radiotherapy, the clinical and radiologic follow-up findings improved in three patients, stabilized in three patients, and worsened in two patients. Median follow-up was 10.3 months (range, 1-55 months). The median survival for the eight patients who received brain radiotherapy was 11.4 months. The one- and two-year survival rates were 45% and 30%, respectively. Two of the eight patients who received radiotherapy were alive at the time of writing. The four patients who did not receive radiotherapy died of the disease at 0.6, 1.0, 1.9, and 2.4 months after diagnosis. Gliomatosis cerebri is associated with poor survival. Although brain radiotherapy controlled or stabilized disease progression in most patients, the overall survival after brain radiotherapy alone was not satisfactory. More aggressive therapy may be needed.

MR Imaging Findings of Gliosarcoma: Report of Three Cases

Gliosarcoma is a rare primary brain tumor composed of neoplastic glial cells and a sareomatous spindle-cell element. We report three cases of gliosarcoma, and describe their MR findings, which in many respects are very similar to those of malignant astrocytomas. Gliosarcomas are, however, more peripherally located, abutting and/or invading the dura mater, and at T2-weighted imaging their signal intensity is lower than is usually the case with malignant astrocyomas. Despite its rarity, the possibility of gliosarcoma should be considered when MR findings of this nature are apparent.