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Journal of Child Neurology Oct 2020Pilocytic astrocytomas are the primary tumors most frequently found in children and adolescents, accounting for approximately 15.6% of all brain tumors and 5.4% of all... (Review)
Review
Pilocytic astrocytomas are the primary tumors most frequently found in children and adolescents, accounting for approximately 15.6% of all brain tumors and 5.4% of all gliomas. They are mostly found in infratentorial structures such as the cerebellum and in midline cerebral structures such as the optic nerve, hypothalamus, and brain stem. The present study aimed to list the main characteristics about this tumor, to better understand the diagnosis and treatment of these patients, and was conducted on search of the published studies available in NCBI, PubMed, MEDLINE, Scielo, and Google Scholar. It was possible to define the main histologic findings observed in these cases, such as mitoses, necrosis, and Rosenthal fibers. We described the locations usually most affected by tumor development, and this was associated with the most frequent clinical features. The comparison between the molecular diagnostic methods showed great use of fluorescent in situ hybridization, polymerase chain reaction (PCR), and reverse transcriptase-PCR, important techniques for the detection of mutation and fusion, characteristic molecular alterations in pilocytic astrocytomas.
Topics: Astrocytoma; Brain Neoplasms; Humans; In Situ Hybridization, Fluorescence; Polymerase Chain Reaction
PubMed: 32691644
DOI: 10.1177/0883073820937225 -
Acta Neuropathologica Aug 2018Tumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular...
Tumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular proliferation and palisading necrosis) have often been designated anaplastic pilocytic astrocytomas. The status of these tumors as a separate entity has not yet been conclusively demonstrated and molecular features have only been partially characterized. We performed DNA methylation profiling of 102 histologically defined anaplastic pilocytic astrocytomas. T-distributed stochastic neighbor-embedding (t-SNE) and hierarchical clustering analysis of these 102 cases against 158 reference cases from 12 glioma reference classes revealed that a subset of 83 of these tumors share a common DNA methylation profile that is distinct from the reference classes. These 83 tumors were thus denominated DNA methylation class anaplastic astrocytoma with piloid features (MC AAP). The 19 remaining tumors were distributed amongst the reference classes, with additional testing confirming the molecular diagnosis in most cases. Median age of patients with MC AAP was 41.5 years. The most frequent localization was the posterior fossa (74%). Deletions of CDKN2A/B (66/83, 80%), MAPK pathway gene alterations (49/65, 75%, most frequently affecting NF1, followed by BRAF and FGFR1) and mutations of ATRX or loss of ATRX expression (33/74, 45%) were the most common molecular alterations. All tumors were IDH1/2 wildtype. The MGMT promoter was methylated in 38/83 tumors (45%). Outcome analysis confirmed an unfavorable clinical course in comparison to PA, but better than IDH wildtype glioblastoma. In conclusion, we show that a subset of histologically defined anaplastic pilocytic astrocytomas forms a separate DNA methylation cluster, harbors recurrent alterations in MAPK pathway genes in combination with alterations of CDKN2A/B and ATRX, affects patients who are on average older than those diagnosed with PA and has an intermediate clinical outcome.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Cyclin-Dependent Kinase Inhibitor p16; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Histones; Humans; Infant; Isocitrate Dehydrogenase; Kaplan-Meier Estimate; Male; Middle Aged; Mitogen-Activated Protein Kinase Kinases; Mutation; Retrospective Studies; Signal Transduction; Tumor Suppressor Proteins; X-linked Nuclear Protein; Young Adult
PubMed: 29564591
DOI: 10.1007/s00401-018-1837-8 -
CNS Oncology Jul 2016Anaplastic astrocytoma (AA) is a diffusely infiltrating, malignant, astrocytic, primary brain tumor. AA is currently defined by histology although future classification... (Review)
Review
Anaplastic astrocytoma (AA) is a diffusely infiltrating, malignant, astrocytic, primary brain tumor. AA is currently defined by histology although future classification schemes will include molecular alterations. AA can be separated into subgroups, which share similar molecular profiles, age at diagnosis and median survival, based on 1p/19q co-deletion status and IDH mutation status. AA with co-deletion of chromosomes 1p and 19q and IDH mutation have the best prognosis. AA with IDH mutation and no 1p/19q co-deletion have intermediate prognosis and AA with wild-type IDH have the worst prognosis and share many molecular alterations with glioblastoma. Treatment of noncodeleted AA based on preliminary results from the CATNON clinical trial consists of maximal safe resection followed by radiotherapy with post-radiotherapy temozolomide (TMZ) chemotherapy. The role of concurrent TMZ and whether IDH1 subgroups benefit from TMZ is currently being evaluated in the recently completed randomized, prospective Phase III clinical trial, CATNON.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Chromosome Deletion; Chromosomes, Human, Pair 1; Humans; Isocitrate Dehydrogenase; Mutation
PubMed: 27230974
DOI: 10.2217/cns-2016-0002 -
Acta Neuropathologica Jul 2018According to the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO), IDH-mutant astrocytic gliomas comprised WHO grade...
According to the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO), IDH-mutant astrocytic gliomas comprised WHO grade II diffuse astrocytoma, IDH-mutant (AII), WHO grade III anaplastic astrocytoma, IDH-mutant (AAIII), and WHO grade IV glioblastoma, IDH-mutant (GBM). Notably, IDH gene status has been made the major criterion for classification while the manner of grading has remained unchanged: it is based on histological criteria that arose from studies which antedated knowledge of the importance of IDH status in diffuse astrocytic tumor prognostic assessment. Several studies have now demonstrated that the anticipated differences in survival between the newly defined AII and AAIII have lost their significance. In contrast, GBM still exhibits a significantly worse outcome than its lower grade IDH-mutant counterparts. To address the problem of establishing prognostically significant grading for IDH-mutant astrocytic gliomas in the IDH era, we undertook a comprehensive study that included assessment of histological and genetic approaches to prognosis in these tumors. A discovery cohort of 211 IDH-mutant astrocytic gliomas with an extended observation was subjected to histological review, image analysis, and DNA methylation studies. Tumor group-specific methylation profiles and copy number variation (CNV) profiles were established for all gliomas. Algorithms for automated CNV analysis were developed. All tumors exhibiting 1p/19q codeletion were excluded from the series. We developed algorithms for grading, based on molecular, morphological and clinical data. Performance of these algorithms was compared with that of WHO grading. Three independent cohorts of 108, 154 and 224 IDH-mutant astrocytic gliomas were used to validate this approach. In the discovery cohort several molecular and clinical parameters were of prognostic relevance. Most relevant for overall survival (OS) was CDKN2A/B homozygous deletion. Other parameters with major influence were necrosis and the total number of CNV. Proliferation as assessed by mitotic count, which is a key parameter in 2016 CNS WHO grading, was of only minor influence. Employing the parameters most relevant for OS in our discovery set, we developed two models for grading these tumors. These models performed significantly better than WHO grading in both the discovery and the validation sets. Our novel algorithms for grading IDH-mutant astrocytic gliomas overcome the challenges caused by introduction of IDH status into the WHO classification of diffuse astrocytic tumors. We propose that these revised approaches be used for grading of these tumors and incorporated into future WHO criteria.
Topics: Adolescent; Adult; Aged; Algorithms; Astrocytoma; Brain Neoplasms; Cyclin-Dependent Kinase Inhibitor p16; Female; Gene Expression Regulation, Neoplastic; Humans; Isocitrate Dehydrogenase; Ki-67 Antigen; Male; Middle Aged; Models, Biological; Mutation; Neoplasm Grading; Neoplasm Proteins; World Health Organization; Young Adult
PubMed: 29687258
DOI: 10.1007/s00401-018-1849-4 -
Acta Neuropathologica Nov 2018EGFR amplification (EGFRamp), the combination of gain of chromosome 7 and loss of chromosome 10 (7+/10-), and TERT promoter mutation (pTERTmut) are alterations...
Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDHwt astrocytoma to glioblastoma.
EGFR amplification (EGFRamp), the combination of gain of chromosome 7 and loss of chromosome 10 (7+/10-), and TERT promoter mutation (pTERTmut) are alterations frequently observed in adult IDH-wild-type (IDHwt) glioblastoma (GBM). In the absence of endothelial proliferation and/or necrosis, these alterations currently are considered to serve as a surrogate for upgrading IDHwt diffuse or anaplastic astrocytoma to GBM. Here, we set out to determine the distribution of EGFRamp, 7+/10-, and pTERTmut by analyzing high-resolution copy-number profiles and next-generation sequencing data of primary brain tumors. In addition, we addressed the question whether combinations of partial gains on chromosome 7 and partial losses on chromosome 10 exhibited a diagnostic and prognostic value similar to that of complete 7+/10-. Several such combinations proved relevant and were combined as the 7/10 signature. Our results demonstrate that EGFRamp and the 7/10 signature are closely associated with IDHwt GBM. In contrast, pTERTmut is less specific for IDHwt GBM. We conclude that, in the absence of endothelial proliferation and/or necrosis, the detection of EGFRamp is a very strong surrogate marker for the diagnosis of GBM in IDHwt diffuse astrocytic tumors. The 7/10 signature is also a strong surrogate marker. However, care should be taken to exclude pleomorphic xanthoastrocytoma. pTERTmut is less restricted to this entity and needs companion analysis by other molecular markers to serve as a surrogate for diagnosing IDHwt GBM. A combination of any two of EGFRamp, the 7/10 signature and pTERTmut, is highly specific for IDHwt GBM and the combination of all three alterations is frequent and exclusively seen in IDHwt GBM.
Topics: Adult; Aged; Astrocytoma; Brain; Brain Neoplasms; Chromosomes, Human, Pair 10; Chromosomes, Human, Pair 7; Cohort Studies; ErbB Receptors; Female; Glioblastoma; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation
PubMed: 30187121
DOI: 10.1007/s00401-018-1905-0 -
Arkhiv Patologii 2018Gemistocytic astrocytomas (GA) are a variant of diffuse astrocytomas GII (WHO, 2016). Like all diffuse astrocytomas, GA recur with time, which is often accompanied by...
Gemistocytic astrocytomas (GA) are a variant of diffuse astrocytomas GII (WHO, 2016). Like all diffuse astrocytomas, GA recur with time, which is often accompanied by malignant degeneretion into the anaplastic astrocytoma GIII or to the secondary glioblastoma GIV. However, the progression-free survival and overall survival in patients with GA is less than in patients with diffuse astrocytomas. Given that this group of patients, according to the WHO classification (2016), is classified as GII, patients with GA usually do not receive comprehensive treatment. We have conducted a thorough analysis of research on this problem for the period from 1956 to 2017. Differences in the histological pattern, immunohistochemical and molecular-genetic profiles, survival of patients with GA and diffuse astrocytomas GII are shown there. A clinical case of a patient with transformation of a diffuse astrocytoma in GA (GIII) and then into a secondary glioblastoma is presented.
Topics: Adult; Astrocytoma; Brain Neoplasms; ErbB Receptors; Gene Expression Regulation, Neoplastic; Humans; Male; Mutation; Neoplasm Proteins
PubMed: 30059069
DOI: 10.17116/patol201880427 -
Neurosurgery Clinics of North America Jan 2019Incidence, prevalence, and survival for diffuse low-grade gliomas and diffuse anaplastic gliomas (including grade II and grade III astrocytomas and oligodendrogliomas)... (Review)
Review
Incidence, prevalence, and survival for diffuse low-grade gliomas and diffuse anaplastic gliomas (including grade II and grade III astrocytomas and oligodendrogliomas) varies by histologic type, age at diagnosis, sex, and race/ethnicity. Significant progress has been made in identifying potential risk factors for glioma, although more research is warranted. The strongest risk factors that have been identified thus far include allergies/atopic disease, ionizing radiation, and heritable genetic factors. Further analysis of large, multicenter epidemiologic studies, and well-annotated "omic" datasets, can potentially lead to further understanding of the relationship between gene and environment in the process of brain tumor development.
Topics: Animals; Astrocytoma; Brain Neoplasms; Glioma; Humans; Molecular Epidemiology; Mutation; Oligodendroglioma
PubMed: 30470396
DOI: 10.1016/j.nec.2018.08.010 -
Current Oncology Reports Mar 2019Temozolomide is a first-line treatment for newly diagnosed glioblastoma. In this review, we will examine the use of temozolomide in other contexts for treating gliomas,... (Review)
Review
PURPOSE OF REVIEW
Temozolomide is a first-line treatment for newly diagnosed glioblastoma. In this review, we will examine the use of temozolomide in other contexts for treating gliomas, including recurrent glioblastoma, glioblastoma in the elderly, diffuse low- and high-grade gliomas, non-diffuse gliomas, diffuse intrinsic pontine glioma (DIPG), ependymoma, pilocytic astrocytoma, and pleomorphic xanthoastrocytoma.
RECENT FINDINGS
Temozolomide improved survival in older patients with glioblastoma, anaplastic gliomas regardless of 1p/19q deletion status, and progressive ependymomas. Temozolomide afforded less toxicity and comparable efficacy to radiation in high-risk low-grade gliomas and to platinum-based chemotherapy in pediatric high-grade gliomas. The success of temozolomide in promoting survival has expanded beyond glioblastoma to benefit patients with non-glioblastoma tumors. Identifying practical biomarkers for predicting temozolomide susceptibility, and establishing complementary agents for chemosensitizing tumors to temozolomide, will be key next steps for future success.
Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; Evidence-Based Practice; Glioblastoma; Humans; Temozolomide
PubMed: 30835007
DOI: 10.1007/s11912-019-0783-5 -
Handbook of Clinical Neurology 2016Pilocytic astrocytoma (PA) is the most common pediatric brain tumor in children. PAs are a distinct histologic and biologic subset of glioma that have a slow growth rate... (Review)
Review
Pilocytic astrocytoma (PA) is the most common pediatric brain tumor in children. PAs are a distinct histologic and biologic subset of glioma that have a slow growth rate and may even spontaneously regress. These tumors tend to arise in the cerebellum and chiasmatic/hypothalamic region, but can also occur in other regions of the central nervous system. Dissemination is uncommon, but may occur in newly diagnosed PAs. Alterations in the Ras/RAF/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway (Ras/ERK) have been discovered in a majority of PAs, with KIAA1549-BRAF fusions being the most commonly identified alteration. Children with neurofibromatosis 1 are predisposed to developing PAs, primarily within the optic pathway. When required, treatment consists of surgery, chemotherapy, and/or radiation, although new molecular agents targeting the Ras/ERK and related signaling pathways are promising new approaches. The 10-year survival rates are greater than 90% in pediatric patients; however, they are poorer in adults. Tumors that are amenable to complete resection (i.e., cerebellum and cortex) have the best overall survival.
Topics: Astrocytoma; Brain Neoplasms; Child; Humans
PubMed: 26948364
DOI: 10.1016/B978-0-12-802997-8.00020-7 -
Progress in Brain Research 2022GKNS has a limited role in the management of malignant gliomas. It has little or nothing to offer in primary treatment. However, there is evidence that with recurrent...
GKNS has a limited role in the management of malignant gliomas. It has little or nothing to offer in primary treatment. However, there is evidence that with recurrent tumors which are 4cm in diameter or less, in younger patients, GKNS used together with bevacizumab can prolong overall survival. Nonetheless, more research is required to determine the precise role of the technique.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Glioma; Humans; Neoplasm Recurrence, Local
PubMed: 35074084
DOI: 10.1016/bs.pbr.2021.10.035