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Purpose: There is lack of comprehensive analysis evaluating the impact of clinical, molecular, imaging, and surgical data on survival of patients with gliomatosis cerebri (GC). This study aimed to investigate prognostic factors of GC in adult-type diffuse glioma patients., Methods: Retrospective chart and imaging review was performed in 99 GC patients from adult-type diffuse glioma (among 1,211 patients; 6 oligodendroglioma, 16 IDH-mutant astrocytoma, and 77 IDH-wildtype glioblastoma) from a single institution between 2005 and 2021. Predictors of overall survival (OS) of entire patients and IDH-wildtype glioblastoma patients were determined., Results: The median OS was 16.7 months (95% confidence interval [CI] 14.2-22.2) in entire patients and 14.3 months (95% CI 12.2-61.9) in IDH-wildtype glioblastoma patients. In entire patients, KPS (hazard ratio [HR] = 0.98, P = 0.004), no 1p/19q codeletion (HR = 10.75, P = 0.019), MGMTp methylation (HR = 0.54, P = 0.028), and hemorrhage (HR = 3.45, P = 0.001) were independent prognostic factors on multivariable analysis. In IDH-wildtype glioblastoma patients, KPS (HR = 2.24, P = 0.075) was the only independent prognostic factor on multivariable analysis. In subgroup of IDH-wildtype glioblastoma with CE tumors, total resection of CE tumor did not remain as a significant prognostic factor (HR = 1.13, P = 0.685)., Conclusions: The prognosis of GC patients is determined by its underlying molecular type and patient performance status. Compared with diffuse glioma without GC, aggressive surgery of CE tumor in GC patients does not improve survival., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gliomatosis Cerebri (GC) is a rare, aggressive, diffusely infiltrating cerebral tumor. Prognostic indicators and management strategies are currently poorly characterized. The National Cancer Database was queried for patients with histologically confirmed GC between 2004 and 2016. Demographic, tumor, and treatment characteristics were collected, including the Charlson/Deyo score, a comorbidity index adapted from the Charleston Comorbidity Index. Allowable values for the Charlson/Deyo score are 0 (no recorded comorbidities), 1, 2, and 3+ (most severe). Factors associated with overall survival were identified via bivariate log-rank tests and multivariate stepwise Cox proportional hazards models. The query returned 108 GC patients. The median age was 60.0 years, males were predominantly affected (63%), and most patients were white (86%). While 12% of cases achieved near/gross total resection and 27% of cases achieved partial resection, most surgeries were for biopsy (61%). Treatments included radiation therapy in 64% and chemotherapy in 63% of patients. The median overall survival was 15.1 (95% confidence interval [CI] = 11.1-24.8) months. On bivariate analysis, chemotherapy improved overall survival (p = 0.01) while radiation therapy (p = 0.07) and extent of resection (p = 0.48) did not. On multivariate analysis, older patients (hazard ratio [HR] = 1.07, CI = 1.03-1.11, p < 0.01) and Charlson/Deyo scores of ≥1 versus 0 (HR = 3.47, CI = 1.40-8.60, p < 0.01) had significantly increased mortality risk following surgery. In particular, the Charlson/Deyo score is a novel prognostic factor for GC that may guide clinical and surgical decision-making for this rare, rapidly fatal tumor. Further prospective studies are warranted to clarify the effects of chemotherapy versus radiation as treatment modalities for GC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

MN1 alteration characterizes a recently described group of neuroepithelial tumors with varied morphological features. In cIMPACT-NOW update 6, only those with astroblastoma morphology has been accepted as a newly recognized tumor type, whereas the rest of morphological variants are considered lesions sub-judice. We perform an individual patient data meta-analysis of MN1-altered neuroepithelial tumors comprising a total of 73 cases, in order to study the survival data and predictive markers for better diagnosis and management of this rare molecular entity. The 5- and 10-year progression-free survival are 38% and 0%, whereas the 5- and 10-year overall survival are 89% and 55%, respectively. Among all the morphological variants of MN1-altered tumor, astroblastoma morphology is significantly associated with an improved overall survival, emphasizing the importance of providing an integrated histologic and molecular diagnosis. Histological grading within the molecularly-defined MN1-altered astroblastoma remains controversial. In tumors with astroblastoma morphology, the odds of MN1-altered status among patients less than 15-year-old is 10.5 times that of those 15-year-old and older, and female of 9.4 times that of the male gender. Gross tumor resection appears as main treatment modality for better disease control based on observational data.

Here, we present a patient with high-grade neuroepithelial tumors with mutations in the BCL6 corepressor BCOR (HGNET-BCOR), a rare, highly malignant brain tumor with poor prognosis. The patient underwent gross total tumor resection (GTR), high-dose chemotherapy, and, after local relapse, GTR, proton radiation, and chemotherapy. After a 7.5 year-long complete remission, the tumor recurred locally, was treated by GTR, and responded to temozolomide treatment. In addition to an internal tandem duplication in BCOR common to the majority of HGNET-BCOR cases, molecular analysis revealed a second BCOR mutation in this tumor: a frame shift mutation. The combination of these mutations was associated with relatively low BCOR expression compared to other HGNET-BCOR cases., (© 2020 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.)

Astroblastoma (AB) is a rare CNS tumor demonstrating abundant astroblastomatous pseudorosettes. Its molecular features have not been comprehensively studied and its status as a tumor entity is controversial. We analyzed a cohort of 27 histologically-defined ABs using DNA methylation profiling, copy number analysis, FISH and site-directed sequencing. Most cases demonstrated mutually exclusive MN1 rearrangements (n = 10) or BRAF V600E mutations (n = 7). Two additional cases harbored RELA rearrangements. Other cases lacked these specific genetic alterations (n = 8). By DNA methylation profiling, tumors with MN1 or RELA rearrangement clustered with high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1) and RELA-fusion ependymoma, respectively. In contrast, BRAF V600E -mutant tumors grouped with pleomorphic xanthoastrocytoma (PXA). Six additional tumors clustered with either supratentorial pilocytic astrocytoma and ganglioglioma (LGG-PA/GG-ST), normal or reactive cerebrum, or with no defined DNA methylation class. While certain histologic features favored one genetic group over another, no group could be reliably distinguished by histopathology alone. Survival analysis between genetic AB subtypes was limited by sample size, but showed that MN1-rearranged AB tumors were characterized by better overall survival compared to other genetic subtypes, in fact, significantly better than BRAF V600E -mutant tumors (P = 0.013). Our data confirm that histologically-defined ABs are molecularly heterogeneous and do not represent a single entity. They rather encompass several low- to higher-grade glial tumors including neuroepithelial tumors with MN1 rearrangement, PXA-like tumors, RELA ependymomas, and possibly yet uncharacterized lesions. Genetic subtyping of tumors exhibiting AB histology, particularly determination of MN1 and BRAF V600E status, is necessary for important prognostic and possible treatment implications.

Background/aim: Secondary leptomeningeal gliomatosis (LG) is a rare and severe progression pattern of glioma. Our objective was to evaluate the characteristics and outcome of patients with LG., Patients and Methods: We retrospectively reviewed 31 patients diagnosed with secondary LG. At the time of LG diagnosis, the median age of patients was 45 years. The histological grade was IV in 20 patients and II to III in 11 patients. As a first-line of therapy for LG, 22 patients received an oncological treatment: i) BCNU-temozolomide (TMZ) (n=15), ii) other type of chemotherapy (n=7), and iii) no treatment (supportive care) (n=9)., Results: Following LG diagnosis, the median progression-free survival (PFS) and overall survival (OS) were 1.8 months [95% confidence interval (CI)=0.9-2.7] and 2.1 months (95%CI=1.3-3), respectively. The univariate analyses showed an improved OS with age of less than 45 years (p<0.001), a prolonged interval from the initial glioma diagnosis (IGD) to LG diagnosis (p=0.003), BCNU-TMZ as the preferred first-line treatment for LG out of the three options (p=0.008), and Karnofsky performance status (KPS) ≥70 (p=0.012). Prolonged interval from IGD to LG diagnosis (HR=5.839) and BCNU-TMZ as the chosen first-line treatment for LG (HR=6.635) remained significant in the multivariate analyses as well. Among the 22 treated patients, the median OS was significantly higher (p=0.008) with the BCNU-TMZ treatment (5.7 months; 95%CI=4.2-7.1), compared to other types of treatment offered (2 months; 95%CI=1.1-2.9)., Conclusion: The time interval from the IGD to the LG diagnosis is a potential prognostic factor for LG. BCNU-TMZ may be a therapeutic option in the present setting., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Gliomatosis cerebri (GC) is a fatal diffusely infiltrating glioma. Because of its rarity, only scarce evidence is available regarding outcome predictors and the proper management of GC., Methods: Reported studies of patients with histologically confirmed GC were systematically reviewed and individual patient-level data (n = 523) extracted. Multivariable Cox proportional hazard models were fit for overall survival (OS) and progression-free survival (PFS)., Results: The median OS and PFS were 13 and 10 months, with 5-year rates of 18% and 13%, respectively. Age ≥65 years at diagnosis (hazard ratio for OS [HR OS ], 2.32; 95% confidence interval [CI], 1.62-3.31), high-grade tumor (HR PFS for grade III, 1.57; 95% CI, 1.02-2.40; HR PFS for grade IV, 1.74; 95% CI, [0.98-3.10), GC type II (HR OS , 1.49; 95% CI, 1.12-1.98; HR PFS , 1.56; 95% CI, 1.04-2.34), more central nervous system (CNS) regions involved (HR OS , 1.09; 95% CI, 1.01-1.18), focal neurological deficits (HR OS , 1.41; 95% CI, 1.07-1.86), cerebellar symptoms (HR PFS , 2.20; 95% CI, 1.42-3.39), more symptoms at presentation (HR OS , 1.21; 95% CI, 1.05-1.40), Karnofsky performance scale score <70 (HR OS , 3.58; 95% CI, 1.73-7.39; HR PFS , 4.48; 95% CI, 1.39-14.4), magnetic resonance imaging contrast enhancement (HR OS , 1.48; 95% CI, 1.12-1.96; HR PFS , 1.74; 95% CI, 1.18-2.55), symmetric bilateral CNS invasion (HR OS , 1.42; 95% CI, 1.03-1.96), and high proliferation index (Ki-67 >5%; HR OS , 2.32; 95% CI, 1.11-4.86) were independent predictors of poor outcomes. In contrast, seizure occurrence (HR OS , 0.77; 95% CI, 0.60-1.00; HR PFS , 0.68; 95% CI, 0.47-0.95), isocitrate dehydrogenase 1 mutation (HR OS , 0.16; 95% CI, 0.05-0.49), and O6-methylguanine-DNA-methyltransferase promoter methylation (HR OS , 0.23; 95% CI, 0.09-0.59) were associated with prolonged survival. Chemotherapy and surgical resection were associated with improved outcomes, but radiotherapy, whether monotherapy or combined with chemotherapy, was not superior to chemotherapy alone., Conclusions: In the largest study to date on GC, we have identified clinical, imaging, and molecular outcome predictors that are similar to other gliomas and highlight the beneficial effect of chemotherapy and surgical resection, when feasible, on outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: To evaluate the use of chemotherapy and radiation, and their outcomes for patients with astroblastoma., Patients & Methods: This is a retrospective review of patients extracted from the National Cancer Database. We investigated overall survival (OS) using Kaplan-Meier curves. Cox proportional hazards models were used to correlate OS with risk variables and treatments., Results: OS at 5 years was 79.5%. Patients with high-grade tumors were more likely to receive chemotherapy and radiation. Patients with high-grade astroblastoma who did not receive adjuvant radiation had poor survival., Conclusion: Patients with astroblastoma should be treated with curative intent. Radiation is likely beneficial in high-grade astroblastoma. The exact role of radiation and chemotherapy following surgical resection warrant further investigation.

Background: The complete and safe resection of pediatric cervicothoracic tumors, mostly represented by neurogenic tumors, remains a surgical challenge because of the complex anatomy of this region. The transmanubrial osteomuscular-sparing approach (TOSA) is an alternative to isolated or combined cervical and thoracic approaches enabling the control of supra-aortic vessels and nerves through the thoracic inlet., Methods: We retrospectively reviewed the tumor characteristics, completeness of resection, morbidity, and long-term outcome of patients with cervicothoracic tumors removed by TOSA between 2000 and 2012 in our institution., Results: Thirteen patients (7 males, 6 females) underwent surgery at a median age of 72 months (4-188) for neuroblastoma (n = 6), ganglioneuroblastoma (n = 3), rhabdoid tumor (n = 1), melanotic schwannoma (n = 1), chordoma (n = 1), and malignant peripheral nerve sheath tumor in one patient with type 1 neurofibromatosis. The median duration of the procedure was 215 minutes (110-315). Two children presented with postoperative chylothorax that resolved spontaneously. The median duration of hospitalization was 7 days (4-22). At a median follow-up of 39 months (2-159), four patients had died of metastatic relapse (n = 2), locoregional progression (n = 1), and chemotoxicity (n = 1). The patient with melanotic schwannoma was lost to follow-up after a local relapse at 5 months. Long-term morbidity revealed homolateral Claude-Bernard Horner sign and upper limb vasomotor dysfunction in disease-free patients due to mandatory resection of the stellate ganglia., Conclusions: TOSA is a valuable surgical approach for all cervicothoracic tumors with acceptable long-term morbidity when compared with its complexity. We can therefore recommend TOSA for tumors involving the thoracic inlet., (© 2017 Wiley Periodicals, Inc.)

Background: Astroblastoma (AB) is a rare tumor with significant dilemma regarding diagnostic criteria, behavior, and optimum treatment., Materials and Methods: We searched PubMed, Google Search, and Cochrane Library for eligible studies with the following search words: astroblastoma, high-grade astroblastoma, and anaplastic astroblastoma till July 1, 2016, published in English language and collected data regarding age, sex, site of disease, pathological grade, treatment received, and survival., Results: Data of 152 patients were retrieved from 63 publications. Median age was 16 years (range 0-71). Females were affected twice more frequently than male (70.3 vs. 29.7%). Tumors were most commonly located in the frontal (39%) followed by parietal lobe (26.7%). Fifty-two and 25% of the patients had headache and seizure at presentation, 76.3% of the patients underwent a gross total resection, 41 out of 89 had a high-grade tumor, and 56 patients received adjuvant radiation with a median dose of 54 Gy (range 20-72). Adjuvant chemotherapy was used in 23 patients. Temozolomide was the most common drug used in 30% of the patients. A combination of cisplatin, etoposide with vincristine, or ifosfamide was used in 17%. Median follow-up duration was 37 months (range 1-238). Median progression-free survival and OS were 36 and 184 months, respectively. Patients with a higher-grade tumor had significantly worse OS with HR 5.260 and p = 0.001. Forty patients experienced local progression. Sixty-five percent patients underwent surgery while 50% underwent radiation as salvage., Conclusion: AB has two distinct grades with higher-grade tumors having significantly poor survival. Maximal safe surgery followed by adjuvant radiation and temozolomide should be advocated for these tumors.

Objective: We used the SEER (Surveillance Epidemiology and End Results) database (1999-2010) to analyze the clinical practice patterns and overall survival in patients with gliomatosis cerebri (GC), or glioma involving 3 or more lobes of the cerebrum., Methods: We identified 111 patients (age ≥18 years) with clinically or microscopically diagnosed GC in the SEER database. Analyses were performed to determine clinical practice patterns for these patients and whether these practices were associated with survival., Results: Fifty-eight percent of the 111 patients with GC received microscopic confirmation of their diagnosis. Of the remaining patients, 40% were diagnosed via imaging or laboratory tests, and 2% had unknown methods of diagnosis. Seven percent of patients who did not have microscopic confirmation of their diagnosis received radiation therapy. Radiation therapy and surgery were not associated with survival. The only variable significantly associated with overall survival was age at diagnosis. Patients aged 18-50 years showed improved survival relative to patients aged >50 years (median survival, 11 and 6 months, respectively; P = 0.03). For patients aged >50 years, improved overall survival was observed in the post-temozolomide era (2005-2010) relative to those treated in the pre-temozolomide era (1999-2004) (median survival, 9 and 4 months, respectively; P = 0.005)., Conclusions: In the SEER database, ∼40% of the patients with glioma with imaging findings of GC do not receive microscopic confirmation of their diagnosis. We propose that tissue confirmation is warranted in patients with GC, because genomic analysis of these specimens may provide insights that will contribute to meaningful therapeutic intervention., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Gliomatosis cerebri is a rare diffusely infiltrating malignant glial neoplasm. Presenting symptoms include seizures, neurologic deficits, and frequently symptoms related to increased intracranial pressure (ICP). Surgical intervention, including brain biopsy, may induce worsening of these neurologic symptoms. We reviewed our database to identify prognostic and risk factors for perioperative deterioration specifically associated with elevated ICP., Methods: Between 2006 and 2014, 78 patients were treated for gliomatosis cerebri. Ten patients required perioperative emergent treatment for elevated ICP. The clinical course and outcome of these 10 patients (study group) were characterized and compared with the remaining 68 patients., Results: The study group patients developed life-threatening symptoms of increased ICP and required urgent decompressive craniectomy (n = 5 urgent decompressive craniectomy after biopsy, n = 2 urgent decompressive craniectomy on admission) or aggressive medical therapy (n = 3). Demographic and clinical variables were similar in both groups. In patients with severe symptoms of increased ICP, enhancing tumor volume was significantly greater than in asymptomatic patients. Radiologic evidence of obliteration of the basal cisterns and herniation was more common in symptomatic patients. The proliferation index in the biopsy specimens of tumors was also significantly higher in patients with symptomatic ICP elevation., Conclusions: Clinical symptoms and radiologic appearance suggestive of elevated ICP at presentation, volume of contrast enhancement, and high Ki-67 proliferation index may predict the need for aggressive rapid treatment to control ICP in a small but significant subset of patients with GC. Further studies are needed to clarify the biologic basis for the unusual clinical course in these tumors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Incidence of neuroepithelial Primary Brain Tumors (nPBT) varies, ranging from 7.3 to 11.6 cases/100,000/year across Europe. We present incidence and survival of nPBT in the Emilia-Romagna region (ER), Italy. This study is the largest in Southern Europe. Specialists in neurosurgery, neurology, neuroradiology, oncology, radiotherapy, genetics, and pathology of ER notified all suspected nPBT adult cases residing in ER (4,337,966 inhabitants) observed during 2009. Furthermore, through ICD-9 discharge codes, we identified and reviewed all possible cases. Neuroepithelial PBT diagnosis was based on histological or radiological findings. We included 400 incident nPBT cases, of which 102 (25%) were retrospectively identified. These latter were significantly older. The standardized incidence was 10.5/100,000/year (95% CI 9.4-11.5), higher for men. It was 9.2/100,000/year (95% CI 8.3-10.2) for astrocytic tumors, 0.6/100,000/year (95% CI 0.4-0.9) for oligodendroglial tumors, and 7.1 (95% CI 6.3-8.0) for glioblastoma (GBM). Among GBM patients, median survival was 249 days if prospectively identified vs. 132 days when identified through ICD-9 codes (p < 0.0001). The incidence of nPBT in the ER region is among the highest in the literature. Older patients were more likely to escape an active surveillance system. This should be considered when comparing incidence rates across studies, giving the increasing number of elderly people in the general population.

Background: Primary leptomeningeal gliomatosis (PLG) is a poorly recognized tumor of the central nervous system., Objective: To describe the histopathological, immunohistochemical, and molecular features of PLG., Methods: Results of our multicentric retrospective study of 6 PLG cases (3 pediatric and 3 adult) were compared with literature data., Results: The mean age was 54.7 years for adults and 8.7 years for children, with 3 males and 3 females. Clinical symptoms were nonspecific. Cerebrospinal fluid analyses showed a high protein level often associated with pleocytosis but without neoplastic cells. On neuroimaging, diffuse leptomeningeal enhancement and hydrocephalus were observed, except in 1 case. PLG was mostly misinterpreted as infectious or tumoral meningitis. The first biopsy was negative in 50% of cases. Histopathologically, PLG cases corresponded to 1 oligodendroglioma without 1p19q codeletion and 5 astrocytomas without expression of p53. No immunostaining for IDH1R132H and no mutations of IDH1/2 and H3F3A genes were found. Overall survival was highly variable (2-82 months) but seems to be increased in children treated with chemotherapy., Conclusion: This study shows the difficulties of PLG diagnosis. The challenge is to achieve an early biopsy to establish a diagnosis and to begin a treatment, but the prognosis remains poor. PLG seems to have a different molecular and immunohistochemical pattern compared with intraparenchymal malignant gliomas.

Purpose: To evaluate the efficacy of radiotherapy and factors affecting the prognosis of gliomatosis cerebri., Methods: Twenty-eight patients with pathologically confirmed gliomatosis cerebri underwent radiotherapy between August 1988 and September 2003. The median age of the patients was 39 years (range 18-67). Performance status was good (ECOG score ≤2) in 23 patients (82 %). The extent of radiotherapy was partial brain in 17 patients, whole brain in 2 patients, and whole brain followed by partial brain in 9 patients. The median radiation dose was 55.8 Gy (range 46.8-70.4). The median duration of follow-up was 136 months for survivors (range 39-191)., Results: The median overall and progression-free survival times of all patients were 20 and 11 months, respectively. When initial response to radiotherapy was grouped as improved, stationary, and aggravated, the median overall survival times in patients with improved, stationary, and aggravated responses were 76, 20, and 7 months, respectively (p = 0.0129). However, radiation parameters such as dose and irradiation volume had no impact on overall survival. On multivariate analysis, both performance status and initial response to radiotherapy were significant prognostic factors affecting overall survival (p = 0.0249 and 0.0065, respectively)., Conclusions: This study showed that gliomatosis cerebri could be effectively treated with radiotherapy and that initial response to radiotherapy was a significant prognostic factor affecting the survival.

Background: The patterns of lobar involvement, optimal treatment, and disease course among patients with gliomatosis cerebri (GC) have not been fully characterized. The current study evaluates the clinical presentations and outcomes for patients with GC treated with radiation therapy (RT) at our institution., Methods: A total of 26 patients (25 with follow-up) with GC were diagnosed and treated between January 2004 and June 2012. Inclusion criteria consisted of brain magnetic resonance imaging and neuroradiology confirmation of contiguous involvement of ≥ 3 lobes/lobar equivalents with preservation of neural architecture. Patients were treated with either partial-brain RT to involved tumor (25 patients) or whole-brain RT (1 patient). The median RT dose was 54.0 Gray. The median follow-up was 17.3 months., Results: The median age of the patients at the time of diagnosis was 57 years. Twenty-one patients (81%) and 5 patients (19%) had 3 to 6 and ≥ 7 involved lobes/lobar equivalents, respectively. The median progression-free survival and overall survival were 7.4 months and 14.9 months, respectively. Fifteen patients experienced radiographic disease progression after partial-brain RT, 14 of whom (93%) developed infield disease recurrence. On univariate analysis, higher tumor grade and type II GC (with focal mass) were associated with a poorer progression-free survival. The extent of lobar involvement and chemotherapy were not associated with overall survival., Conclusions: Even with partial-brain RT, nearly all disease recurrences were infield and clinical outcomes were similar to previous GC series, thereby suggesting that whole-brain RT is not necessary for this patient population. A greater number of involved lobes did not correlate with inferior outcomes. Further studies are necessary to establish more uniform and optimal treatments for this rare disease., (© 2014 American Cancer Society.)

Background and Purpose: In 2007, the WHO classification of brain tumors was extended by three new entities of glioneuronal tumors: papillary glioneuronal tumor (PGNT), rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) and glioneuronal tumor with neuropil-like islands (GNTNI). Focusing on clinical characteristics and outcome, the authors performed a comprehensive individual patient data (IPD) meta-analysis of the cases reported in literature until December 2012., Methods: PubMed, Embase and Web of Science were searched for peer-reviewed articles reporting on PGNT, RGNT, and GNTNI using predefined keywords., Results: 95 publications reported on 182 patients (PGNT, 71; GNTNI, 26; RGNT, 85). Median age at diagnosis was 23 years (range 4-75) for PGNT, 27 years (range 6-79) for RGNT, and 40 years (range 2-65) for GNTNI. Ninety-seven percent of PGNT and 69% of GNTNI were located in the supratentorial region, 23% of GNTNI were in the spinal cord, and 80% of RGNT were localized in the posterior fossa. Complete resection was reported in 52 PGNT (73%), 36 RGNT (42%), and 7 GNTNI (27%) patients. Eight PGNT, 3 RGNT, and 12 GNTNI patients were treated with chemo- and/or radiotherapy as the primary postoperative treatment. Follow-up data were available for 132 cases. After a median follow-up time of 1.5 years (range 0.2-25) across all patients, 1.5-year progression-free survival rates were 52±12% for GNTNI, 86±5% for PGNT, and 100% for RGNT. The 1.5-year overall-survival were 95±5%, 98±2%, and 100%, respectively., Conclusions: The clinical understanding of the three new entities of glioneuronal tumors, PGNT, RGNT and GNTNI, is currently emerging. The present meta-analysis will hopefully contribute to a delineation of their diagnostic, therapeutic, and prognostic profiles. However, the available data do not provide a solid basis to define the optimum treatment approach. Hence, a central register should be established.

Object: Maximized tumor resection and minimized surgical morbidity are extremely important in the treatment of children with malignant neuroepithelial tumors. However, the indications for repeat surgery for these tumors remain unclear. The present study investigated the clinical significance and limitations of repeat resection for these tumors., Methods: This study included 61 consecutive pediatric patients with malignant neuroepithelial tumor, histologically diagnosed as WHO Grades III and IV. All patients were initially treated between January 1997 and March 2011 and had follow-up of more than 2 years. The number of surgeries, presence of leptomeningeal dissemination, survival, WHO grade, and Eastern Cooperative Oncology Group performance status before and after surgery were retrospectively reviewed., Results: Repeat resections were performed for 21 patients (34.4%). Eastern Cooperative Oncology Group performance status was not aggravated by surgery, even after multiple operations. The 5-year survival rates of patients who received single and repeat surgery were 58.6% and 38.7%, respectively (p = 0.12). The mean interval between initial surgery and leptomeningeal dissemination detection was 331 ± 108 days in the single-surgery group and 549 ± 122 days in the repeat-surgery group (p = 0.19). The median survival time after leptomeningeal dissemination was 580 days in the single-surgery group and 890 days in the repeat-surgery group (p = 0.74)., Conclusions: Repeat resection with minimized surgical morbidity is an effective method to achieve better local control of pediatric malignant neuroepithelial tumors. Leptomeningeal dissemination was a leading cause of death, but repeat surgery did not increase the frequency of death.

Gliomatosis cerebri is a rare diffusely infiltrating primary neoplastic glial process of the brain. Our objective is to review clinical presentation, management, and outcome in a large single institution series of gliomatosis cerebri patients. 54 consecutive gliomatosis cerebri cases presenting to Mayo Clinic Rochester between 1991 and 2008 were retrospectively reviewed. Inclusion criteria included involvement of at least three cerebral lobes, lack of a single discrete mass and pathological confirmation of diffuse glioma. Median overall survival (OS) was 18.5 months. Age, gender, presenting symptoms, and contrast enhancement did not correlate significantly with survival, though there was a trend toward decreased overall survival in patients above the median age of 46 years. Karnofsky performance score <70 was associated with poor OS (median 9.5 vs. 20.5 months, p = 0.02). Higher histologic grade was associated with poor progression-free survival (PFS; median for WHO grades II, III, and IV: 21.5, 6.5, and 4 months; p = 0.03) and OS (median 34, 15.5, and 8.5 months; p < 0.05). Radiation therapy was strongly associated with better prognosis (PFS 16.5 vs. 4.5 months, p < 0.01; OS 27.5 vs. 6.5, p < 0.01), but chemotherapy was not. Gliomatosis cerebri patients have a poor prognosis. Lower KPS upon presentation and higher histologic grade predict decreased survival. Surgery's role is limited beyond biopsy for diagnostic purposes. Radiotherapy appears beneficial, although selection bias could be present in this retrospective study. Chemotherapy's value is not as clear but this must be interpreted with caution given variable treatment regimens in this series.

The prognostic significance of IDH1 mutations has been demonstrated in gliomas. It is unclear whether IDH1 mutation is also a prognostic factor in gliomatosis cerebri (GC). Primary GCs can be grouped into type 1 GCs, which have the classical diffuse growth pattern without mass formation, and type 2 GCs, which form neoplastic masses in addition to classic diffuse lesions. In this study, the prognostic relevance of IDH1/2 mutations in 74 GCs (43 type 1 and 31 type 2) was evaluated. We detected 33 (44.6%) IDH1 mutations, including R132H and R132S, by bidirectional Sanger sequencing. No mutations were detected in IDH2. The percentage of 2-year overall survival for wild-type IDH1 patients was 46 vs. 72% for patients with IDH1-mutated tumors. Mutations of IDH1 were strongly correlated with both increased overall survival (OS) and progression-free survival (PFS) in patients with type 2 GCs, and IDH1 mutations were also an independent prognostic factor predicting increased OS and PFS in type 2 GC patients in multivariate analysis. However, IDH1 mutations did not correlate with survival outcomes in patients with type 1 GCs. Finally, the subgroup of GC, which has IDH1 wild-type and additional solid component showed the worst prognosis., (© 2011 The Authors; Brain Pathology © 2011 International Society of Neuropathology.)

Expression of Cathepsin D (Cath D) in some primary neuroepithelial brain tumors and its prognostic value were studied. The research included 65 samples of human primary neuroepithelial brain tumors. There were 50 glial tumors (10 diffuse astrocytomas (DA), 15 anaplastic astrocytomas (AA), 25 glioblastomas (GB), 15 embryonic tumors (15 medulloblastomas (MB) as well as 5 samples of normal brain tissue. Immunohistochemical method was applied to monitor diffuse positive reaction in the cytoplasm of brain tumor cells, endothelial cells and tumor stromal cells and showed diffuse positive reaction for Cath D in the cytoplasm of brain tumor cells, endothelial cells and stromal cells in all analyzed samples of DA, AA, GB and MB as well as in microglial cells, neurons and in endothelial cells in all analyzed samples of normal brain tissue. Qualitative analysis of Cath D expression in the cytoplasm of brain tumor cells and endothelial cells as well as the percentage of brain tumor cells, endothelial cells and stromal cells immunopositive for Cath D showed that there was difference between analyzed brain tumor groups, but according to statistical tests the difference was not statistically significant. Survival correlated with the percentage of stromal cells immunopositive for Cath D. Survival prognosis was influenced by the percentage of stromal cells immunopositive for Cath D and tumor grade. The obtained results singled out the percentage of stromal cells immunopositive for Cath D as an independent parameter. The results of this research on the prognostic value of Cath D in some primary brain tumors of neuroepithelial origin indicate that there is real possibility to use Cath D as an independent prognostic factor in human glioma progression and thus open up possibilities for further scientific research.

An increase in the incidence of CNS tumors has been observed in many countries in the last decades. The reality of this trend has been much debated, as it has happened during a period when computer-assisted tomography and MRI have dramatically improved the detection of these tumors. The Gironde CNS Tumor Registry provides here the first data on CNS tumor incidence and trends in France for all histological types, including benign and malignant tumors, for the period 2000-2007. Incidence rates were calculated globally and for each histological subtype. For trends, a piecewise log-linear model was used. The overall annual incidence rate was found to be 17.6/100 000. Of this rate, 7.9/100 000 were neuroepithelial tumors and 6.0/100 000 were meningiomas. An overall increase in CNS tumor incidence was observed from 2000 to 2007, with an annual percent change (APC) of +2.33%, which was explained mainly by an increase in the incidence of meningiomas over the 8-year period (APC = +5.4%), and also more recently by an increase in neuroepithelial tumors (APC = +7.45% from 2003). The overall increase was more pronounced in women and in the elderly, with an APC peaking at +24.65% in subjects 85 and over. The increase in the incidence rates we observed may have several explanations: not only improvements in registration, diagnosis, and clinical practice, but also changes in potential risk factors.

Gliomatosis cerebri (GC) constitutes a heterogeneous group of conditions involving diffuse neoplastic glial cell infiltration of the brain. Management is difficult and an obvious challenge is to identify prognostic factors. Alpha-internexin (INA) expression, which is closely related to the 1p19q codeletion, is a strong prognostic marker in oligodendroglial tumors. Similarly, the R132H isocitrate dehydrogenase 1 IDH1 mutation, which can now be detected by use of a specific antibody, predicts better outcome in gliomas. In a retrospective series of 40 GC treated with up-front chemotherapy, we analyzed IDH1(R132H) mutant protein and INA immunohistochemical expression and correlated it with outcome; 17/40 GC expressed IDH1(R132H) and 10/40 GC expressed INA. IDH1(R132H) staining was strongly related to progression-free survival (42.3 vs. 15.5 months for positive IDH1(R132H) vs. negative tumors; P < 0.0001) and overall survival (73.9 vs. 23.6 months; P < 0.0001). This effect was independent of grade, histologic subtype, and INA expression (P < 0.001). Combined expression of IDH1(R132H) and INA was strongly associated with response to chemotherapy (100% vs. 36%; P = 0.003). These data strongly suggest that INA and IDH1(R132H) mutant protein immunohistochemical analysis is of a great prognostic value in biopsied GC.

Objective: Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare neoplasm with a short survival time of a few months. There is currently no standardized therapeutic approach for PDLG. -, Material and Methods: We report on a 53-year-old male patient who presented with epileptic seizures, gait disturbance, paraparesis and sensory deficits in the dermatomes T8-10. -, Results: Magnetic resonance imaging (MRI) revealing numerous spinal and cranial gadolinium-enhancing nodules in the meninges and histopathology led us to diagnose primary diffuse leptomeningeal gliomatosis with WHO grade III astrocytic cells. Consecutively, the patient underwent craniospinal radiotherapy (30Gy) and 11 sequential cycles of temozolomide. This regimen led to partial tumor regression. Thirteen months later, spinal MRI revealed tumor progression. Second-line chemotherapy with 5 cycles of irinotecan and bevacizumab did not prevent further clinical deterioration. The patient died twenty-two months after diagnosis, being the longest survival time described thus far with respect to PDLG consisting of astrocytic tumor cells. -, Conclusions: Radiochemotherapy including temozolomide, as established standard therapy for brain malignant astrocytomas, might be valid as a basic therapeutic strategy for this PDLG subtype.

Astroblastoma is a rare tumor, and thus experience with these lesions is very limited. The prognosis and appropriate treatment is not well understood, as few individual centers have enough experience with astroblastoma to guide treatment recommendations. We performed a systematic comprehensive search of the published English language literature on patients undergoing surgery for astroblastoma to summarize what is known about these tumors, and to provide some framework for future efforts in this area. A total of 62 references met our inclusion criteria, and contained individual patient data on 116 patients with astroblastoma. Determination of overall survival rates was performed using Kaplan-Meier analysis. This analysis suggests that the distribution is bimodal, with a prominent peak in young adulthood. Astroblastomas are generally amenable to complete tumor resection, even when very large, with gross total resection (GTR) achieved in 71/85 (84%) of reported patients, including both 9cm tumors reported. Patients undergoing GTR experienced a significant improvement in survival compared to patients who underwent subtotal resection (STR) (5-year progression-free survival: GTR 83% versus [vs.] STR 55%, log rank p=0.011). Although patients receiving external beam radiotherapy or fractionated three-dimensional conformal radiotherapy (XRT) seemed to have lower survival rates, this was not statistically significant (5-year survival: GTR 94% vs. GTR+XRT 73%, log rank p=0.463). Thus, we have reported the results of a summary of the literature on astroblastomas and have accurately described outcome characteristics using a data set that would be difficult to accumulate at a single center treating this tumor., (Copyright © 2010. Published by Elsevier Ltd.)

Unlabelled: Gliomatosis cerebri (GC) is a rare disease, defined as a diffuse neoplastic glial cell infiltration of the brain. Diagnosis and management of GC are difficult., Method: The authors report a literature review and their experience based on three patients, two male, and one female, all younger than 10 years, who were treated for GC., Results: Our series of three patients were combined for the purposes of survival assessment together with the 22 patients from the literature review yielding 25 evaluable patients with diagnosis of GC. We compared the patients treated (16) with chemo, RT, or both combined, with untreated patients (7) to evaluate the median survival. Even though, as expected, the number is too small to show a statistically significant increase of survival (p = 0.08 log rank test), we still demonstrated a slight increase in survival in the group of patients treated (26.6 vs 14.8 months). We also compared the overall survival according to treatment. The comparison between the group of five patients treated with radiotherapy only, ten treated with chemotherapy with TMZ and ten with chemo and RT combined, showed a slight increase in mean survival, although not statistically significant, in the second and third groups (p = 0.6 log rank test)., Conclusion: The optimal treatment in children under 10 years with GC is still obscure and absolutely not clear because total surgical resection is impossible to perform for the diffuse nature of the disease; CHT with TMZ seems to be the best treatment for children because it demonstrates a little reduction of the extension tumoral mass, but the responsivity of this treatment is extremely variable from case to case.

To characterize a population of pediatric high-grade astrocytoma (HGA) patients by confirming the proportion with a correct diagnosis, and determine prognostic factors for survival in a subset diagnosed with uniform pathologic criteria. Sixty-three children diagnosed with HGA were treated at the Johns Hopkins Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all available histologic samples (n = 48). Log-rank analysis was used to compare survival by patient, tumor, and treatment factors. Median follow-up was 16 months for all patients and 155 months (minimum 54 months) for surviving patients. Median survival for all patients (n = 63) was 14 months with 10 long-term survivors (survival >48 months). At initial diagnosis, 27 patients were grade III (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available for review, including seven of ten long-term surviving patients. Four patients had non-HGA pathology, all of whom were long term survivors. The remaining 44 patients with confirmed HGG had a median survival of 14 months and prognostic analysis was confined to these patients. On multivariate analysis, five factors were associated with inferior survival: performance status (Lansky) <80% (13 vs. 15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16 months), resection less than gross total (13 vs. 22 months), and radiotherapy dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five adverse factors (n = 27), median survival and proportion of long-term survivors were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0-1 adverse factors (n = 17). In an historical cohort of children with HGA, the potential for long term survival was confined to the subset with less than two of the following adverse prognostic factors: low performance status, bilaterality, parietal lobe site, less than gross total resection, and radiotherapy dose <50 Gy. Pathologic misdiagnosis should be suspected in patients who are long term survivors of a pediatric high grade astrocytoma.

Background: In gliomatosis cerebri (GC), defined as a diffuse neoplastic glial cell infiltration of the brain, upfront chemotherapy is often proposed as an alternative to radiotherapy. GC invades both white matter and gray matter in varying proportions, as reflected by the gray matter index (GMI), i.e., the estimated percentage of gray matter involvement., Methods: The GMI was estimated in 71 patients with GC (42 men and 29 women; median age, 47 years) treated with upfront chemotherapy (7 PCV, 64 temozolomide)., Results: Median GMI was 30%. Patients were separated into 2 groups according to this median GMI. Compared to the 33 patients with GMI >30% (group B), the 38 patients from group A (defined as GMI

Astroblastoma is one of the rarest tumors of the central nervous system (CNS), and its classification, histogenesis, diagnosis and therapeutic management are still being debated. The typical histopathological appearance is the perivascular, astroblastic pseudorosette, which is however present in other CNS tumors. To clarify the clinical, radiological, histopathological, prognostic and therapeutic characteristics, which have been treated only recently and are not well established yet due to the rarity of this tumor, six cases of histologically proven astroblastoma were retrospectively analyzed in light of more pertinent literature and paying special attention to therapeutic remarks. Between 1996 and 2005, six patients with cerebral astroblastoma were surgically treated at the Department of Neurosciences-Neurosurgery of Sapienza University in Rome. In three cases the lesion was termed low-grade astroblastoma, and high grade in the other three, according to current standard parameters. Median age of the six patients was 36 years. The time to diagnosis ranged from 1 week to 18 months. The radiological and anatomopathological features of this lesion are described. Surgical removal was total in four cases and subtotal in two. All patients received radiotherapy: two also had chemotherapy with temozolomide (TMZ). The three patients with low-grade astroblastoma are still alive today after a follow-up of 2, 5 and 19 years, respectively. Of the three patients with high-grade lesions, one is still alive after a 7-year follow-up, while the other two survived for 17 months (progression time 15 months) and 35 months (progression-reoperation time 23 months), respectively. Conclusions radical surgical resection is the treatment of choice for astroblastomas. Radiotherapy may play an adjuvant role in the treatment of high-grade lesions. The role of chemotherapy is still very debatable. We propose an aggressive standardized treatment for those lesions that meet anaplastic criteria, owing to their postulated glial origin and the propensity to have aggressive courses, and we advocate the use of a safe adjuvant chemotherapeutic regimen with TMZ, used concomitantly and subsequently to radiotherapy, especially for the high-grade astroblastoma cases. Multicenter studies, taking into account molecular biological findings, are necessary to define a common therapeutic strategy for astroblastomas.

Background: Gliomatosis cerebri (GC) is a rare and typically fatal glial neoplasm of the central nervous system. In this report, the authors describe the largest cohort of children to date with GC and explore relations between potential prognostic factors, treatment, and survival., Methods: Imaging, pathologic, and outcome data were reviewed from 13 patients who were diagnosed with GC and were treated at the Children's Hospital of Philadelphia (CHOP) between 1982 and 2005. All patients had GC confirmed by biopsy. Twelve patients received cranial irradiation, and 8 of those patients received adjuvant chemotherapy. A single patient age 1 year received chemotherapy alone. A review of the literature identified 51 pediatric patients with GC., Results: The progression-free survival rate in this study was 13% (range, 1.5-43 months), and the overall survival (OS) rate was 64% (range, 6.5-67 months) at 2 years. OS was significantly shorter for patients who presented in the first decade of life (P = .04). The time to progression was prolonged significantly for patients who had no evidence of tumor enhancement on imaging studies (P = .03). When survival data from patients reported in the literature were combined with the CHOP cohort, treatment prolonged OS significantly (P = .003)., Conclusions: The outcome of pediatric patients with GC was extremely poor; however, the current results indicated that treatment may prolong OS. Age < 10 years and contrast enhancement on magnetic resonance imaging studies at diagnosis may be risk factors for shorter survival in pediatric patients with GC., ((c) 2006 American Cancer Society.)

Introduction: Gliomatosis cerebri (GC) is defined as a diffuse neoplastic glial cell infiltration of the brain involving more than two cerebral lobes and, occasionally, the infratentorial structures or the spinal cord. The tumor may appear de novo (primary GC) or result from the spreading of a focal glioma (secondary GC). Diagnosis and management of GC are difficult. Because of the diffuse nature of gliomatosis cerebri (GC), surgery is not suitable and large field radiotherapy carries the risk of severe toxicity., State of Art: The analysis of current literature shows that the male population (58 percent) is younger, has a higher incidence of oligodendroglial GC and better prognosis than the female population. Survival (median=14.5 months) is also better for young patients, with high performance status, low-grade gliomatosis, and oligodendroglial subtype. Initial chemotherapy results in nearly 30 percent clinical or radiological improvement. In this setting, temozolomide is well tolerated and appears to be a valuable alternative to procarbazine-CCNU-vincristine, especially for slow-growing, low-grade GC., Perspective: Genotyping could be helpful to predict the response to chemotherapy in GC patients.

Objective: Gliomatosis cerebri is an enigmatic diffuse brain neoplasm whose prognosis is grim. We reviewed data for patients with gliomatosis who were treated at the University of California, San Francisco, during a 10-year period. Our focus was on presentation, radiological and pathological features, and outcomes., Methods: We reviewed hospital and clinic records and magnetic resonance imaging scans for 22 patients with gliomatosis. The diagnosis was based on magnetic resonance imaging findings and tissue confirmation for all patients. Seven patients also underwent magnetic resonance spectroscopy. Eleven patients were male (50%), and the median age at presentation was 49 years (range, 7-79 yr)., Results: Kaplan-Meier analysis demonstrated median lengths of survival as follows: no treatment, 1 month (n = 4); radiotherapy alone, 28 months (95% confidence interval, 5-51 mo; n = 13); radiotherapy followed by chemotherapy, two patients, alive at 28 and 104 months; radiotherapy and chemotherapy simultaneously, three patients, one alive at 18 months and the others dead at 7 and 9 months. There was no significant difference between radiotherapy alone and radiotherapy combined with chemotherapy (P = 0.69). Karnofsky Performance Scale scores of >/=70 and grade were both significantly related to length of survival in univariate analyses (P < 0.05); these correlations were confirmed in the multivariate analysis, although the small numbers of patients and deaths precluded reliable interpretation., Conclusion: Although the small number of patients in our study and its retrospective nature preclude definitive conclusions regarding the utility of treatment, our findings suggest that biopsies are useful not only for diagnosis but also for prediction of the length of survival.

The goal of this study was to describe the demographic, histologic, and prognostic features of children with low-grade neuroepithelial tumors (LGN) of the CNS presenting with leptomeningeal metastases (LM) at diagnosis. We identified 528 newly diagnosed LGN children, 13 (3%) of whom had LM at diagnosis. LM was defined by neuroimaging, clinical evidence, and/or biopsy. The charts were reviewed and patients contacted to validate the demographic data, treatment, and clinical status. The distribution of LM patients by primary tumor site was diencephalon, 5; cerebrum, 2; spinal cord, 3; brainstem, 2; and cerebellum, 1. Six of 8 patients with LM had durable objective responses to chemotherapy. The 5-year progression-free survival of patients with LM at diagnosis was 17%, compared to 85% (95% CI, 80%-91%) for those with localized LGN who had a gross total resection and 51% (95% CI, 44%-52%) for those with localized LGN who had less aggressive surgery ( P < 0.0001). Only 1 of these 13 LM patients died. The 5-year overall survival of the localized LGN group with a gross total resection was 97% (95% CI, 92%-99.9%), and that of the localized LGN group with less aggressive surgery was 88% (95% CI, 84%-95%) ( P = 0.004). The 3% frequency of LM at diagnosis is likely an underestimate since patients with newly diagnosed LGN were not routinely staged. We suggest that staging be considered in the following circumstances: diencephalic primary site, unexplained hydrocephalus, clinical features suggestive of LM, and before adjuvant therapy is initiated. The prognosis for children with LM at diagnosis is favorable, and its identification alters therapeutic strategies.

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright 2002 American Cancer Society.)

Gliomatosis cerebri is a rare, diffusely growing neuroepithelial tumor characterized by extensive brain infiltration involving more than two cerebral lobes. Among 13 patients with gliomatosis cerebri (median age, 46 years), biopsies showed features of diffuse astrocytoma (n = 4), oligoastrocytoma (n = 1), anaplastic astrocytoma (n = 5), anaplastic oligoastrocytoma (n = 1), or glioblastoma (n = 2). Molecular genetic investigation showed TP53 mutations in three of seven tumors and both PTEN mutation and epidermal growth factor receptor overexpression in one tumor. Amplification of CDK4 or MDM2 or homozygous deletion of CDKN2A was not detected. Three of 10 patients receiving radiotherapy showed a partial response (one patient) or had stable disease (two patients) lasting for more than 1 year. Four of six patients treated with procarbazine, carmustine, vincristine chemotherapy demonstrated partial remission (one patient), minor response (two patients), or stable disease (one patient). Median survival time from diagnosis was 14 months (range, 4-91+ months). Infratentorial involvement was associated with shorter survival. We conclude that (1) the molecular genetic alterations in gliomatosis cerebri resemble those in diffuse astrocytomas; (2) the prognosis of gliomatosis cerebri is variable but for at least 50% of patients as poor as for glioblastoma; and (3) some patients respond to radiotherapy and/or procarbazine, carmustine, vincristine chemotherapy.