Study of central nervous system tumours in the neurosurgery department of Batna (eastern Algeria)

Spontaneous rodent nervous system tumors, in comparison to those of man, are less well differentiated. Among the central nervous system (CNS) tumors, the "embryonic" forms (medulloblastoma, pineoblastoma) occur both in rodents and humans, whereas the human "adult" forms (gliomas, ependymomas, meningiomas) have fewer counterparts in rodents. In general, the incidence of spontaneous CNS tumors is higher in rats (>1%) than in mice (>0.001%). A characteristic rat CNS tumor is the granular cell tumor. Usually it is associated with the meninges, and most meningeal tumors in rats seem to be totally or at least partly composed of granular cells, which have eosinophilic granular cytoplasm, are periodic acid-Schiff reaction (PAS)-positive, and contain lysosomes. Such tumors are frequently found on the cerebellar surface or at the brain basis. Rat astrocytomas are diffuse, frequently multifocal, and they invade perivascular spaces and meninges. The neoplastic cells with round to oval nuclei and indistinct cytoplasm grow around preexisting neurons, producing satellitosis. In large tumors, there are necrotic areas surrounded by palisading cells. Extensive damage of brain tissue is associated with the presence of scavenger cells that react positively with histiocytic/macrophage markers. The neoplastic astrocytes do not stain positively for glial fibrillary acidic protein; they probably represent an immature phenotype. In contrast to neoplastic oligodendroglia, they bind the lectin RCA-1. Astrocytomas are frequently located in the brain stem, especially the basal ganglia. Rat oligodendroglial tumors are well circumscribed and frequently grow in the walls of brain ventricles. Their cells have water-clear cytoplasm and round, dark-staining nuclei. Atypical vascular endothelial proliferation occurs, especially at the tumor periphery. Occasionally in the oligodendrogliomas, primitive glial elements with large nuclei occur in the form of cell groups that form rows and circles. Primitive neuroectodermal tumors of rats, such as pineal tumors or medulloblastomas, appear to have features similar to those found in man. In mice, the meningeal tumors are mostly devoid of granular cells and the astrocytomas are similar to those occurring in rats, whereas spontaneous oligodendrogliomas are observed extremely rarely. Tumorlike lesions, such as lipomatous hamartomas or epidermoid cysts, are occasionally encountered in the mouse CNS. It is suggested that we classify rodent CNS lesions as "low grade" and "high grade" rather than as "benign" and "malignant." The size of CNS tumors is generally related to their malignancy. Tumors of the peripheral nervous system are schwannomas and neurofibromas or neurofibrosarcomas consisting of Schwann cells, fibroblasts, and perineural cells. Well-differentiated schwannomas are characterized by S-100 positivity and the presence of basement membrane. They show either Antoni A pattern with fusiform palisading cells or Antoni B pattern, which is sparsely cellular and has a clear matrix. The rat develops specific forms of schwannomas in the areas of the submandibular salivary gland, the external ear, the orbit, and the endocardium. Spontaneous ganglioneuromas occur in the rat adrenal medulla or thyroid gland. Compared to experimentally induced neoplasms, the spontaneous tumors of the rodent nervous system are poor and impractical models of human disease, although they may serve as general indicators of the carcinogenic potential of tested chemicals.

The occurrence of cancer among parents, siblings, and offspring of 725 children with central nervous system (CNS) tumors was compared with occurrence of cancer among such relatives of 360 birth certificate controls, using the Connecticut Tumor Registry. 84 (12%) of the children with CNS tumors (cases), none of whom had neurofibromatosis, and 42 controls (12%) had at least one first-degree relative with cancer. However, certain types of cancer were much more frequent among relatives of cases. There were 9 CNS tumors and 3 other nervous system tumors among relatives of cases, but no nervous system tumors among relatives of controls. Leukemia occurred in 6 relatives of cases but in no relatives of controls. Disproportionately many patients with cancer of the bladder, ovaries, and uterus were similarly found among relatives of cases. 12 siblings of cases developed cancer before age 20, while only 1 sibling of a control did. In each of 3 families, 3 siblings developed various cancers, confirming previously reported associations of CNS tumors, leukemia, and colonic cancer. Children with more malignant tumors (eg, medulloblastoma) were more likely to have a relative with a CNS tumor than children with better-differentiated tumors (eg, astrocytoma). These data suggest that there is a familial occurrence of CNS tumors, and that the occurrence of a CNS tumor in a child may be associated with an increased incidence of CNS tumors, leukemia, and childhood tumors in general among his relatives.

Pediatric central nervous system (CNS) tumors are the most common solid cancers and the leading cause of cancer-related morbidity and mortality in children. The global demographic and epidemiological trends indicate a significant increase in childhood and adolescent cancers, including pediatric brain tumors, in low- and middle-income countries, particularly in Sub-Saharan African countries necessitating the dire need of multidisciplinary Pediatric Neuro-Oncology (PNO) teams to improve outcomes. The primary objective of the study was to evaluate the patterns, clinical presentations, time to diagnosis (TD), and treatment provided to pediatric and adolescent patients with central nervous system tumors who were discussed at the pediatric neuro-oncology tumor board and treated by the neuro-oncology team at Tikur Anbessa Specialized Hospital in Ethiopia. This retrospective cross-sectional study was conducted in the Pediatric Hematology and Oncology (PHO) unit at Tikur Anbessa Specialized Hospital in Ethiopia. It included all pediatric patients under 15 years old with primary central nervous system (CNS) tumors from December 2021 to May 2024. The study aimed to provide an overview of the sociodemographic characteristics of the children, clinical presentation, time to diagnosis, histopathology of the tumors, and treatment modalities recommended by the PNO tumor board. A total of two hundred ten patients with pediatric CNS tumors were discussed and reviewed at the Pediatric Neuro-Oncology (PNO) Tumor Board during the study period. More than half of the patients (54.8%, n = 114) were males. The median age at diagnosis was 7 years, and nearly half of the patients (48.6%) were between 5 and 10 years old. The most common clinical presentations were headache (66.2%), vomiting (64.3%), visual symptoms (44.8%), and cerebellar symptoms (43.8%). The median time to diagnosis was 90 days (IQR 60-210), and 60% of the patients presented after three months of symptom onset of the disease. The most common pediatric CNS tumors were medulloblastoma and embryonal CNS tumors, accounting for 32.9% (n = 69), followed by astrocytic tumors; 30.0% (n = 63), craniopharyngiomas (14.0%), and ependymal tumors (11.4%). The main treatments offered by the PNO Tumor Board were a combination of surgery, radiotherapy, and systemic chemotherapy (33.8%), surgery alone (23.8%), and surgery with radiotherapy (21.4%). The PNO Tumor Board was primarily attended by pediatric hematology-oncology fellows, pediatric oncologists (90%), and neurosurgeons (86%). This study focused on analyzing the age distribution, clinical presentation, time to diagnosis, burden, and patterns of pediatric primary CNS tumors at the largest tertiary referral center in Ethiopia. It is imperative to prioritize educating healthcare professionals about the symptoms and signs of CNS tumors in children, promoting early diagnosis, facilitating timely referrals, and enhancing the effectiveness of the PNO tumor board. These measures should be considered essential aspects of care for children with CNS tumors.

Food processing and risk of central nervous system tumours: A preliminary case–control analysis from the MEditerranean DIet in relation to CancEr of brAin (MEDICEA) study

The aims of this study are the following: first, to analyze incidence, trends, and survival of nervous system tumors in children under the age of 15 in the Region of Murcia, Spain, during the years 1998-2009 and second, to evaluate if certain environmental exposures may be involved in the etiology of childhood nervous system tumors. The study was performed on the spatial and temporo-spatial distribution of the observed cases. The Environment and Pediatric Cancer in the Region of Murcia is an ongoing research project aimed at carefully collecting pediatric environmental history (PEH) and to use geographical information systems to map the incidence and to analyze the geographical distribution of pediatric cancer incidence in our region. Between 1998 and 2009, 125 patients were diagnosed with nervous system tumors. The spatial and temporal space clusters were evaluated using Kulldorff's statistics. Address at diagnosis was the main feature evaluated. The incidence (cases/million children) for central nervous system (CNS) tumors was 34.2, that for sympathetic nervous system tumors was 10.9, and that for retinoblastoma was 1.9. There was evidence of space clustering for medulloblastoma and space-time clustering for all tumors, CNS tumors, astrocytoma, and neuroblastoma. The incidence and survival for each type and subtype of nervous system tumors were within the reported values for the European region. There is evidence that spatial and spatial-temporal distribution in these cases is not random. The development of a careful PEH in these patients will help to reinforce geographical information system studies and to ascertain the importance of associated risk factors.

Insulin-like growth factor-II (IGF-II) is the major IGF in human cerebrospinal fluid (CSF), whereas IGF-I is only detectable in trace amounts. The major IGFBPs in CSF are IGFBP-2 and IGFBP-4. Normally, IGFBP-3 is a minor component in CSF of healthy subjects, but may be increased in pathological states. We investigated IGF-I, IGF-II, and IGFBP-3 levels by specific RIAs in CSF from patients with central nervous system (CNS) tumor or leukemia and compared them with values in patients with meningitis. Further, as proteolysis of IGFBP-3 is part of the modulation of IGF activity, IGFBP-3 fragmentation was quantified by densitometric analysis of [125I]IGFBP-3 protease assays. We examined CSFs of 23 children with malignant CNS tumors, 18 children with leukemia, and 13 children with meningitis. The CSF from 38 children who received lumbar punctures to exclude meningitis was used to define the normal range for IGF-I, IGF-II, IGFBP-3, and IGFBP-3 protease activity in CSF. CNS tumor and leukemia patients had normal levels of IGF-I and IGF-II in CSF, whereas the IGF-II concentration in CSF of meningitis patients was elevated (P < 0.0001). Only 2 of 13 (15%) meningitis patients had elevation of CSF IGFBP-3 concentrations, despite high numbers of inflammatory cells. By comparison, elevated IGFBP-3 concentrations were found in the CSF of 16 of 23 (70%) CNS tumor patients and 6 of 7 (86%) CNS tumor patients with microscopically detectable malignant cells in CSF. Twelve of 13 (92%) patients with medulloblastoma or ependymoma and all 7 medulloblastoma/ependymoma patients with malignant cells in CSF had elevated IGFBP-3 concentrations. The IGFBP-3 protease activity in CSF was elevated in 15 of 16 (94%) patients with CNS tumors of high grade histological malignancy. Five of 6 patients (83%) with acute leukemia and microscopically detectable malignant cells in CSF at the time of diagnosis showed elevated IGFBP-3 concentrations, with normalization after chemotherapy. Leukemia patients without malignant cells in CSF had normal IGFBP-3 concentrations. We conclude that in CSF of children with highly malignant CNS tumor or CNS leukemia, IGFBP-3 is elevated. This phenomenon could be caused by disruption of the blood-CSF barrier and entry of IGFBP-3 from serum, although this appears unlikely, especially for CNS leukemia. More likely possibilities are 1) local production of IGFBP-3 by CNS tumor tissue and secretion into the CSF, or 2) local production of IGFBP-3 by malignant cells within the CSF.

Background: Central nervous system (CNS) tumors are the most common solid tumors in children and remain a significant contributor to death by disease in this population. While there is evidence that pediatric CNS tumors arise in early-life, limited knowledge is available on the role of maternal and perinatal factors in the etiology of these malignancies, which hampers prevention efforts. Therefore, we investigated the association between these early-life factors and risk of CNS tumors in children using data from Texas Cancer Registry, which is one of the world's largest and most diverse cancer registries, which may lead to the identification of modifiable risk factors. Methods: Information on pediatric CNS tumor cases (N=1950) for the period 1995-2011 was obtained from the Texas Cancer Registry. Birth certificate controls were frequency-matched on year of birth at a ratio of 10:1 for the same period. Variables evaluated were obtained from birth records and included maternal race/ethnicity, maternal age, maternal education, maternal nativity, maternal residency (urban vs rural), residency on Mexican border, plurality and birth order of child, size for gestational age, term of birth, and mode of delivery. Unconditional logistic regression was used to generate an adjusted odds ratio (OR) and 95% confidence interval (CI) testing the association between each factor and CNS tumors overall, as well as astrocytoma (N=978) and ependymoma (N=157) subtypes individually. Results: Hispanic and non-Hispanic black mothers were less likely to have children who developed CNS tumors compared to non-Hispanic white mothers (OR: 0.88 [95%CI: 0.79-0.98]; OR: 0.78 [95%CI: 0.66-0.91], respectively). Conversely, infants born large for gestational age (OR: 1.26 [95%CI: 1.08-1.48]) as well as those delivered pre-term (&amp;lt;37 weeks) (OR: 1.18 [95%CI: 1.03-1.36]) showed an increased risk of CNS tumors compared to the respective reference groups. Compared to women with spontaneous vaginal delivery, those with vaginal forceps or vacuum delivery were more likely to have children that developed CNS tumors (OR: 1.35 [95%CI: 1.12-1.62]). This was also true for cesarean delivery, but the confidence interval included the null (OR: 1.10 [95%CI: 0.99-1.22]). Effect estimates for pre-term birth as well as vaginal forceps or vacuum delivery were stronger for astrocytomas. An increased risk of ependymoma subtype was found for offspring of native-born Mexican mothers compared to mothers born in the United States (OR: 1.67 [95%CI: 1.03-2.71]), while a decreased risk of this subtype was detected for children of mothers with education greater than high school (OR: 0.54 [95%CI: 0.35-0.82]). Conclusions: Overall, several maternal and perinatal factors were associated with pediatric CNS tumors, indicating the important role of these characteristics in the etiology of these clinically significant malignancies. Citation Format: Maral Adel Fahmideh, Erin C. Peckham-Gregory, Jeremy M. Schraw, Murali Chintagumpala, Stephen C. Mack, Philip J. Lupo, Michael E. Scheurer. Evaluating the role of early-life factors on the risk of pediatric central nervous system tumors: A registry-linkage study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4656.

Central nervous system (CNS) tumors originate from neuroectodermal cells and cause a significant burden of neurological and systemic disease in humans. CNS tumors exhibit diverse biological behaviors, ranging from benign, slow-growing masses to highly aggressive, infiltrative malignancies. We found activation of integrated stress response (ISR) in tumor cells. ISR is the final common pathway activated in response to a range of cellular stressors. ISR activation suppresses global protein translation except ATF4, leading to apoptosis in normal cells. Tumors can evade ISR activation to support proliferation, making ISR targetable. The relevance of ISR activation in the context of CNS tumors is unknown. ISR activation was analyzed with single cell transcriptomes (scRNAseq) and single cell ATAC seq (scATACseq) of pituitary adenomas (PA), schwannomas (SCH), and ependymomas (EPN) tumors from our patients. Analysis was supplemented with publicly available datasets including scRNAseq from medulloblastomas (MB) and meningiomas (MG), and corresponding human normal tissue datasets. ISR activity scores were significantly (p&amp;lt;0.05) higher in PA, EPN and MG tumor cells compared to their normal counterparts. Global functional enrichment analysis between tumor and normal cells revealed upregulation of translation, protein folding, and ER stress-related pathways. ATF4 target genes ATF6, and XBP1 were upregulated in tumor cells. These genes mediate ER stress resolution and drive the expression of HSPA5 (BiP), a molecular chaperone. HSPA5 itself was upregulated in tumor cells as well. scATACseq revealed increased promoter accesibility in several ISR-regulated genes including HSPA5, XBP1, and DDIT3 suggesting broad epigenetic reprogramming that allows ISR escape. Our findings suggests that ISR activation in some CNS tumors (PA, EPN, and MG) may play a critical role in tumor adaptation by enhancing protein homeostasis and stress resilience. These findings highlight the ISR escape as a tumor adaptation mechanism and potential therapeutic target in CNS tumors like PA, EPN, and MG.

Background and AimsPediatric central nervous system (CNS) tumors are the most common solid cancers and the leading cause of cancer-related morbidity and mortality in children. The primary objective of the study was to evaluate the patterns, age distribution, time to diagnosis (TD), and treatment provided to pediatric and adolescent patients with central nervous system tumors who were discussed at the pediatric neuro-oncology tumor board and treated at Tikur Anbessa Specialized Hospital in Ethiopia.MethodsThis retrospective cross-sectional study was conducted in the Pediatric Hematology and Oncology (PHO) unit at Tikur Anbessa Specialized Hospital, and it included all pediatric patients under 15 years old with primary central nervous system (CNS) tumors from December 2021 to May 2024.ResultsTwo hundred ten patients with pediatric CNS tumors were discussed and reviewed at the PNO Tumor Board. More than half of the patients (54.8%, n = 114) were males. The median age at diagnosis was 7 years, and nearly half of the patients (48.6%) were between 5 and 10 years old. The most common clinical presentations were headache (66.2%), vomiting (64.3%), visual symptoms (44.8%), and cerebellar symptoms (43.8%). The median time to diagnosis was 90 days (IQR 60-210), and 60% of the patients presented after three months of symptom onset of the disease. The most common pediatric CNS tumors were medulloblastoma and embryonal CNS tumors, accounting for 32.9% (n = 69), followed by astrocytic tumors. The main treatments offered by the PNO Tumor Board were a combination of surgery, radiotherapy, and systemic chemotherapy (33.8%). The PNO Tumor Board was primarily attended by pediatric hematology-oncology fellows, pediatric oncologists (90%), and neurosurgeons (86%).ConclusionIt is imperative to prioritize educating healthcare professionals about the symptoms and signs of CNS tumors in children, promoting early diagnosis, facilitating timely referrals, and enhancing the effectiveness of the PNO tumor board.

Tumors, Central Nervous System; Epidemiology of

Background Accumulating data show cardiovascular disease (CVD) is a major cause of death in many cancer patients supporting cardio-oncology epidemiology and clinical studies. Although rare, patients diagnosed with brain and central nervous system (CNS) tumours have significant morbidity and mortality. Whether CVD is a major cause of death and if this differs by malignancy has not been comprehensively assessed. Methods We aimed to examine the risk of CVD mortality in patients diagnosed with malignant and non-malignant CNS tumours using cancer registry data in the UK and US. Analyses were conducted using Wales Cancer Registry, UK (Secure Anonymised Information Linkage, SAIL) for 8,743 patients diagnosed from 2000-2015 (54.9% of which died); and the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) for 188,526 patients diagnosed from 2005-2015 (40.0% of which died). Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated for CVD cause of death (heart disease, cerebrovascular disease, hypertension, atherosclerosis, and aortic aneurysm/dissection) and adjusted for age, sex and calendar year compared to all Welsh and US residents. SMRs were stratified by tumour types (malignant and non-malignant tumours) and main histologic types (glioma and meningioma). Results CVD is the second major cause of death for CNS tumour patients in SAIL and SEER (9.5% &amp; 12.1%, respectively). Patients with malignant and non-malignant CNS tumours had excess CVD mortality compared with the general population (SAIL SMR=2.64, 95% CI=2.39-2.90, SEER SMR=1.38, 95% CI=1.35-1.42). Patients were more likely to die of CVD compared to the general population regardless of whether they were diagnosed with non-malignant meningiomas subtypes (SAIL SMR=3.13, 95%CI=2.73-3.57; SEER SMR=1.36, 95%CI=1.32-1.40) or malignant gliomas (SAIL SMR=2.08, 95%CI=1.46-2.88; SEER SMR=2.21, 95%CI=2.05-2.38). Patients diagnosed younger than 50 years of age had excess risk from CVD mortality compared to general population than those diagnosed at older ages (SAIL SMR=4.58, 95%CI=2.38-7.84, SEER SMR 2.03-95%CI=1.79-2.03). Patients had greater risk of CVD mortality within the first year after CNS tumour diagnosis in both SAIL and SEER (SMR=2.98, 95% CI=2.39-3.66 &amp; SMR=2.14 95%CI=2.03-2.25, respectively). Conclusion CVD mortality is high among patients diagnosed with CNS tumours compared to general population. Cross national datasets for different histologic types of CNS tumours could help define high risk groups that may be targeted for future prevention and clinical studies to clarify the aetiology of CVD among CNS cancer patients. Citation Format: KAI JIN, Paul Brennan, Michael Poon, Cathie Sudlow, Jonine FIGUEROA. High cardiovascular disease mortality after central nervous system tumor diagnosis: Evidence from UK and USA population-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB084.

Background Central nervous system (CNS) tumors are the leading cause of cancer-related deaths in children aged 0–14 years. Despite significant efforts, targeted therapies based on identified pathways have not improved survival rates. Research has shown that the gut microbiota (GM) can influence brain tumor cell proliferation, suggesting that the microbiota–gut–brain axis plays a role in CNS cancer. Our study aims to assess whether the GM composition in pediatric CNS tumors exhibits specific characteristics. Methods The study included 18 pediatric patients, 9 diagnosed with CNS tumors (CNS tumors group) and 9 with other tumor types (extra-CNS tumors group). Microbial DNA was extracted from stool samples, and 16S DNA libraries were generated and sequenced. GM composition was analyzed using amplicon sequence variant (ASV) tables. Results Alpha-diversity analysis, represented by the number of observed features, was lower in the CNS tumors group (P = .0054), while Pielou’s evenness index was similar between groups. LEfSe analysis revealed a significantly reduced abundance of the Firmicutes phylum in CNS tumors group, along with other taxa within this phylum, such as the Clostridia class, Clostridiales order, and Lachnospiraceae family, compared to extra-CNS tumors group. Further analysis using sPLS-DA showed a distinct pattern in GM composition in the CNS tumors group, with lower levels of several taxa, particularly the Firmicutes phylum, Lachnospiraceae family, Clostridiales order, Clostridia class, Ruminococcaceae and Coriobacteriaceae families, and Blautia genus. Conclusions Pediatric patients with CNS tumors have a distinct GM composition. The reduction of specific beneficial microbial taxa may contribute to tumor growth through the microbiota–gut–brain axis.

With the improvement of treatments, a growing number of survivors with childhood or adolescent central nervous system (CNS) tumor are parenting their own children. We aimed to explore the risk of somatic diseases among children of these survivors compared to population controls. Children of survivors with CNS tumor below age of 20 were identified between 1973 and 2014 by combining the several Swedish registers. Five children without parental CNS tumor were matched randomly to generate the population comparisons. Relative risk (RR) and absolute excess risk (AER) were calculated for overall somatic diseases, and hazard ratio (HR) was calculated for specific type of somatic diseases. A total of 2231 somatic disease diagnoses were identified in children of survivors with a cumulative incidence rate of 94.77 per 1000 person‐years, whereas the rate was 92.79 in matched comparisons thus resulting in an overall RR of 1.02 (95% CI = 0.98‐1.07) and AER of 1.98 (95% CI = −2.06, 6.13). Specifically, five of 1364 children of survivors had CNS tumor with an incidence rate of 0.21 per 1000 person‐year, whereas the rate was 0.04 in children of matched children, generating a HR of 4.91 (95% CI = 1.42‐16.96). Children of male survivors were at a statistically increased risk of malignancy, as well as infectious and parasitic diseases. In conclusion, no significantly higher risk of overall somatic diseases was found in children of survivors with CNS tumor before the age of 20, but children with a paternal diagnosis of CNS tumor had significantly increased risk of malignancies and infectious and parasitic diseases.

BackgroundMolecular signatures are being increasingly incorporated into cancer classification systems. DNA methylation-based central nervous system (CNS) tumor classification is being recognized as having the potential to aid in cases of difficult histopathological diagnoses. Here, we present our institutional clinical experience in integrating a DNA-methylation-based classifier into clinical practice and report its impact on CNS tumor patient diagnosis and treatment.MethodsProspective case review was undertaken at CNS tumor board discussions over a 3-year period and 55 tumors with a diagnosis that was not certain to two senior neuropathologists were recommended for methylation profiling based on diagnostic needs. Tumor classification, calibrated scores, and copy number variant (CNV) plots were obtained for all 55 cases. These results were integrated with histopathological findings to reach a final diagnosis. We retrospectively reviewed each patient's clinical course to determine final neuro-pathology diagnoses and the impact of methylation profiling on their clinical management, with a focus on changes that were made to treatment decisions.ResultsFollowing methylation profiling, 46 of the 55 (84%) challenging cases received a clinically relevant diagnostic alteration, with two-thirds having a change in the histopathological diagnosis and the other one-third obtaining clinically important molecular diagnostic or subtyping alterations. WHO grading changed by 27% with two-thirds receiving a higher grade. Patient care was directly changed in 15% of all cases with major changes in clinical decision-making being made for these patients to avoid unnecessary or insufficient treatment.ConclusionsThe integration of methylation-based CNS tumor classification into diagnostics has a substantial clinical benefit for patients with challenging CNS tumors while also avoiding unnecessary health care costs. The clinical impact shown here may prompt the expanded use of DNA methylation profiling for CNS tumor diagnostics within prominent neuro-oncology centers globally.

Received June 26, 2001; accepted August 21, 2001. Primary brain and other central nervous system (CNS) tumors are the most common solid tumors that occur during childhood, with an annual U.S. rate of approximately 3.0 cases per 100,000 persons aged 19 years or younger. Incidence rates of pediatric CNS malignancies were essentially unchanging during the 1990s; past concerns about trends that indicated increasing rates in the 1980s appears to be largely explainable by diagnostic and ascertainment improvements that occurred during that time period. The prevalence of persons alive with a previous diagnosis of a CNS malignancy is estimated by the National Cancer Institute to be 35 per 100,000 males and 29 per 100,000 females. Because nonmalignant CNS tumors (such as meningiomas) are not included in this statistic, the actual prevalence of CNS tumor survivors in the U.S. is substantially higher than the National Cancer Institute estimates. As treatment improves, more children are surviving cancer into adulthood. Survival rates for those with pediatric CNS tumors differ substantially by histology, site, and age at diagnosis. Overall, the 5-year survival probability for children with a CNS malignancy diagnosed between 1985 and 1994 was 67%. Pediatric patients generally have a better prognosis than adults with CNS tumors, although the morbidity from these tumors and their treatment can be substantial. As more children with CNS tumors survive and require treatment in primary care settings, it is increasingly important for health care providers to recognize long-term complications of these tumors and their treatments. The purpose of this article is to provide a concise review of the long-term effects of pediatric CNS tumors and their treatment. We hope this review will aid providers in managing CNS survivors’ existing problems and in anticipating problems that survivors may face.