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Indian Journal of Pathology &... May 2022Glioblastoma is the most common malignant central nervous system (CNS) tumor in adults. Acute common clinical symptoms include headache, seizure, behavior changes, focal... (Review)
Review
Glioblastoma is the most common malignant central nervous system (CNS) tumor in adults. Acute common clinical symptoms include headache, seizure, behavior changes, focal neurological deficits, and signs of increased intracranial pressure. The classic MRI finding of glioblastoma is an irregularly shaped, rim-enhancing or ring-enhancing lesion with a central dark area of necrosis. This constellation of features correlates with microscopic findings of tumor necrosis and microvascular proliferation. Besides these common features, several well-recognized histological subtypes include giant cell glioblastoma, granular cell glioblastoma, gliosarcoma, glioblastoma with a primitive neuronal component, small cell glioblastoma, and epithelioid glioblastoma. While glioblastoma was historically classified as isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant groups, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) and the fifth edition of the WHO Classification of Tumors of the Central Nervous System clearly updated the nomenclature to reflect glioblastoma to be compatible with wildtype IDH status only. Therefore, glioblastoma is now defined as "a diffuse, astrocytic glioma that is IDH-wildtype and H3-wildtype and has one or more of the following histological or genetic features: microvascular proliferation, necrosis, Telomerase reverse transcriptase promoter mutation, Epidermal growth factor receptor gene amplification, +7/-10 chromosome copy-number changes (CNS WHO grade 4)."
Topics: Adult; Astrocytoma; Brain Neoplasms; Central Nervous System Neoplasms; Glioblastoma; Humans; Isocitrate Dehydrogenase; Mutation; Necrosis; World Health Organization
PubMed: 35562131
DOI: 10.4103/ijpm.ijpm_1109_21 -
Orphanet Journal of Rare Diseases Dec 2023The randomised double-blinded placebo-controlled EXIST-1-3 studies have showed everolimus effective with adverse effects reported as acceptable in treatment of symptoms... (Clinical Trial)
Clinical Trial
BACKGROUND
The randomised double-blinded placebo-controlled EXIST-1-3 studies have showed everolimus effective with adverse effects reported as acceptable in treatment of symptoms in patients with tuberous sclerosis complex (TSC), although evidence of outcomes in clinical practice remains limited. This study aimed to investigate, in clinical practice, the effectiveness and safety of everolimus for epilepsy, renal angiomyolipoma (rAML), and subependymal giant cell astrocytoma (SEGA) in patients with TSC.
RESULTS
The study included 64 patients with TSC (median age: 19, range 0.9-54 years) receiving everolimus treatment (Norway: n = 35; Denmark: n = 29). Among 45 patients with epilepsy, 14 (31%) were responders experiencing ≥ 50% reduction in seizure frequency in the last 3 months of treatment compared with the last 3 months before treatment. Nineteen (42%) patients changed their anti-seizure medications (ASMs). Responders were more common among patients < 18 years (46%) than among patients ≥ 18 years (14%, p = 0.03). In 29 patients with rAML, everolimus reduced (≥ 30% decrease) and stabilized (< 20% increase, ≤ 30% decrease) longest diameter of rAML in 38% and 59%, respectively, after a mean treatment duration of 37 months. SEGA volume was reduced in three patients by 71%, 43%, and 48% after 39, 34, and 82 months. Adverse effects were reported in 61 of 64 patients (95%) after a median treatment duration of 31 months (range 0-106), with oral ulceration/stomatitis (63%) and upper respiratory tract infections (38%) being the most common. The most common laboratory abnormalities were increased cholesterol (41%), anaemia (30%), and leucopoenia (25%). Grade 3-4 adverse effects were reported in 36% of cases, and life-threatening conditions were reported in two patients. Nine patients discontinued everolimus treatment.
CONCLUSIONS
Seizure reduction in this study sample was consistent with results from EXIST, but might be lower than expected, given that changes in concomitant ASMs are part of clinical practice. Seizure reduction was associated with younger age. As with EXIST, everolimus reduced or stabilised rAML size in most patients. SEGA volume was reduced in all three patients. Close follow-up is needed for this group, especially for children and patients who may not be able to report adverse effects.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Infant; Middle Aged; Young Adult; Angiomyolipoma; Antineoplastic Agents; Astrocytoma; Epilepsy; Everolimus; Kidney Neoplasms; Seizures; Tuberous Sclerosis
PubMed: 38042867
DOI: 10.1186/s13023-023-02982-1 -
Brain Pathology (Zurich, Switzerland) Jan 2021Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a...
Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a cohort of 67 patients with histologically defined PXA (n = 53, 79%) or anaplastic PXA (A-PXA, n = 14, 21%), including copy number analysis (ThermoFisher Oncoscan, n = 67), methylation profiling (Illumina EPIC array, n = 43) and targeted next generation sequencing (n = 32). The most frequent alterations were CDKN2A/B deletion (n = 63; 94%) and BRAF p.V600E (n = 51, 76.1%). In 7 BRAF p.V600 wild-type cases, alternative driver alterations were identified involving BRAF, RAF1 and NF1. Downstream phosphorylation of ERK kinase was uniformly present. Additional pathogenic alterations were rare, with TERT, ATRX and TP53 mutations identified in a small number of tumors, predominantly A-PXA. Methylation-based classification of 46 cases utilizing a comprehensive reference tumor allowed assignment to the PXA methylation class in 40 cases. A minority grouped with the methylation classes of ganglioglioma or pilocytic astrocytoma (n = 2), anaplastic pilocytic astrocytoma (n = 2) or control tissues (n = 2). In 9 cases, tissue was available from matched primary and recurrent tumors, including 8 with anaplastic transformation. At recurrence, two tumors acquired TERT promoter mutations and the majority demonstrated additional non-recurrent copy number alterations. Methylation class was preserved at recurrence. For 62 patients (92.5%), clinical follow-up data were available (median follow-up, 5.4 years). Overall survival was significantly different between PXA and A-PXA (5-year OS 80.8% vs. 47.6%; P = 0.0009) but not progression-free survival (5-year PFS 59.9% vs. 39.8%; P = 0.05). WHO grade remained a strong predictor of overall survival when limited to 38 cases defined as PXA by methylation-based classification. Our data confirm the importance of WHO grading in histologically and epigenetically defined PXA. Methylation-based classification may be helpful in cases with ambiguous morphology, but is largely confirmatory in PXA with well-defined morphology.
Topics: Adolescent; Adult; Aged; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Cohort Studies; DNA Methylation; Female; Humans; Male; Middle Aged; Neoplasm Grading; Young Adult
PubMed: 32619305
DOI: 10.1111/bpa.12874 -
Journal of Neuro-oncology May 2023Astrocytomas and oligodendrogliomas are mainly diffuse primary brain tumors harboring a diagnostic and prognostically favorable isocitrate dehydrogenase mutation. They... (Review)
Review
PURPOSE
Astrocytomas and oligodendrogliomas are mainly diffuse primary brain tumors harboring a diagnostic and prognostically favorable isocitrate dehydrogenase mutation. They are still incurable besides growing molecular knowledge and therapy options. Circumscribed astrocytomas are also discussed here, although they represent a separate entity despite similarities in the nomenclature.
METHODS
We reviewed clinical trials, preclinical approaches as well as guideline recommendations form the major scientific Neuro-Oncology organizations for astrocytomas and oligodendrogliomas according to PRISMA guidelines.
RESULTS
After histopathological diagnosis and eventually a maximal safe resection, patients with good prognostic factors may be followed by magnetic resonance imaging (MRI). If further treatment is necessary, either after diagnosis or at progression, diffuse astrocytomas and oligodendrogliomas are mainly treated with combined radiochemotherapy or maximal safe resection followed by combined radiochemotherapy according to current guidelines based on randomized trials. Circumscribed gliomas like pilocytic astrocytomas, CNS WHO grade 1, or pleomorphic xanthoastrocytomas, CNS WHO grade 2, are often treated with surgery alone. Current approaches for therapy optimization include decision of the best chemotherapy regimen. The IDH mutation presents a rational target for small molecule inhibition and immune therapy in diffuse astrocytomas and oligodendrogliomas, while the BRAF pathway is frequently mutated and treatable in circumscribed gliomas.
CONCLUSION
Despite establishment of standard treatment approaches for gliomas that include resection, radio- and chemotherapy, there is a lack of effective treatments for progressive disease. Immune- and targeted therapies are currently investigated.
Topics: Humans; Oligodendroglioma; Astrocytoma; Glioma; Magnetic Resonance Imaging; Mutation
PubMed: 36566461
DOI: 10.1007/s11060-022-04216-z -
CNS Oncology 2015
Topics: Astrocytoma; Brain Neoplasms; Humans; Wnt Signaling Pathway
PubMed: 26497968
DOI: 10.2217/cns.15.24 -
Acta Neuropathologica Jun 2015Pilocytic astrocytomas (PAs) were recognized as a discrete clinical entity over 70 years ago. They are relatively benign (WHO grade I) and have, as a group, a 10-year... (Review)
Review
Pilocytic astrocytomas (PAs) were recognized as a discrete clinical entity over 70 years ago. They are relatively benign (WHO grade I) and have, as a group, a 10-year survival of over 90%. Many require merely surgical removal and only very infrequently do they progress to more malignant gliomas. While most show classical morphology, they may present a spectrum of morphological patterns, and there are difficult cases that show similarities to other gliomas, some of which are malignant and require aggressive treatment. Until recently, almost nothing was known about the molecular mechanisms involved in their development. The use of high-throughput sequencing techniques interrogating the whole genome has shown that single abnormalities of the mitogen-activating protein kinase (MAPK) pathway are exclusively found in almost all cases, indicating that PA represents a one-pathway disease. The most common mechanism is a tandem duplication of a ≈2 Mb-fragment of #7q, giving rise to a fusion between two genes, resulting in a transforming fusion protein, consisting of the N-terminus of KIAA1549 and the kinase domain of BRAF. Additional infrequent fusion partners have been identified, along with other abnormalities of the MAP-K pathway, affecting tyrosine kinase growth factor receptors at the cell surface (e.g., FGFR1) as well as BRAF V600E, KRAS, and NF1 mutations among others. However, while the KIAA1549-BRAF fusion occurs in all areas, the incidence of the various other mutations identified differs in PAs that develop in different regions of the brain. Unfortunately, from a diagnostic standpoint, almost all mutations found have been reported in other brain tumor types, although some retain considerable utility. These molecular abnormalities will be reviewed, and the difficulties in their potential use in supporting a diagnosis of PA, when the histopathological findings are equivocal or in the choice of individualized therapy, will be discussed.
Topics: Astrocytoma; Central Nervous System Neoplasms; Genetic Predisposition to Disease; Humans; Models, Molecular; Molecular Biology; Neuroimaging
PubMed: 25792358
DOI: 10.1007/s00401-015-1410-7 -
Cirugia Y Cirujanos 2017Pilocytic astrocytoma is a rare tumour, usually occurring in paediatric ages, and mainly located in the posterior fossa. It can cause hydrocephalus and intracranial... (Review)
Review
BACKGROUND
Pilocytic astrocytoma is a rare tumour, usually occurring in paediatric ages, and mainly located in the posterior fossa. It can cause hydrocephalus and intracranial hypertension and, less frequently, seizures, or a focal neurological deficit. The main imaging study by magnetic resonance imaging, which shows a tumour with solid and cystic components without peri-lesional swelling. The election treatment is surgical, and the patient is considered cured if a total resection is accomplished.
CLINICAL CASE
The case is presented of 22-year-old female patient with a supratentorial pilocytic astrocytoma and epilepsy. Histopathology reported a low grade glial proliferation, with an extensive fibrillar matrix, small cells without atypia, extensive calcifications and piloid areas consisting of bipolar fusiform cells, and some Rosenthal fibres. There were also spongiotic areas consisting of multipolar cells and associated microcysts. The final report was a pilocytic astrocytoma.
CONCLUSIONS
Pilocytic astrocytoma is more frequent in paediatric patients and in the posterior fossa. The case presented is of a young female adult with supratentorial location, making it a special case. The surgery achieved a total resection. The long-term prognosis is good, but it is necessary to perform a follow-up, particularly in adult patients because of a higher risk of recurrence.
Topics: Anticonvulsants; Astrocytoma; Cholecystitis, Acute; Craniotomy; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Neuroimaging; Piracetam; Remission Induction; Seizures; Supratentorial Neoplasms; Young Adult
PubMed: 27417707
DOI: 10.1016/j.circir.2016.05.009 -
Current Oncology (Toronto, Ont.) Feb 2023Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO...
PURPOSE
Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO classification of tumors of the central nervous system (CNS WHO), 5th edition, rates PXAs as grade 2 and grade 3. The histological grading was based on mitotic activity (≥2.5 mitoses/mm). This study specifically evaluates the clinical, morphological, and, especially, the molecular characteristics of grade 2 and 3 PXAs.
METHODS
Between 2003 and 2021, we characterized 53 tumors with histologically defined grade 2 PXA (n = 36, 68%) and grade 3 PXA (n = 17, 32%).
RESULTS
Compared with grade 2 PXA, grade 3 PXA has a deeper location and no superiority in the temporal lobe and is more likely to be accompanied by peritumoral edema. In histomorphology, epithelioid cells and necrosis were more likely to occur in grade 3 PXA. Molecular analysis found that the promoter mutation was more prevalent in grade 3 PXA than in grade 2 PXA (35% vs. 3%; = 0.0005) and all mutation sites were C228T. The cases without mutation or with necrosis in grade 3 PXA had a poor prognosis ( = 0.01).
CONCLUSION
These data define PXA as a heterogeneous astrocytoma. Grade 2 and grade 3 PXAs have different clinical and histological characteristics as well as distinct molecular profiles. promoter mutations may be a significant genetic event associated with anaplastic progression. Necrosis and mutation play an important role in the prognosis of grade 3 PXA.
Topics: Child; Young Adult; Humans; Proto-Oncogene Proteins B-raf; Astrocytoma; Mutation; Prognosis
PubMed: 36826144
DOI: 10.3390/curroncol30020183 -
Journal of Cancer Research and... 2022Malignant transformation (MT) of low-grade astrocytoma (LGA) produces a poor prognosis in benign tumors. Currently, variables linked with MT of LGA have proven...
BACKGROUND
Malignant transformation (MT) of low-grade astrocytoma (LGA) produces a poor prognosis in benign tumors. Currently, variables linked with MT of LGA have proven equivocal. The present study aims to evaluate the risk variables, indicating that LGA gradually differentiates to malignant astrocytoma.
METHODS
Retrospective cohort analysis of LGA patients was performed. Both univariate and multivariate studies were used to discover variables connected to MT using the Cox regression method. As a result, the cumulative incidence of MT for each covariate survival curve was built after the final model.
RESULTS
In the current study, 115 individuals with LGA were included in the analysis, and MT was found in 16.5% of cases. In the case of MT, 68.4% of patients progressed to glioblastoma, whereas 31.6% progressed to anaplastic astrocytoma. Significant factors included supratentorial tumor (hazard ratio (HR) 3.41, 95% CI 1.18-12.10), midline shift > 5 mm (HR 7.15, 95% CI 2.28-34.33), and non-total resection as follows: subtotal resection (HR 5.09, 95% CI 0.07-24.02), partial resection (HR 1.61, 95% CI 1.09-24.11), and biopsy (HR 2.80, 95% CI 1.18-32.52).
CONCLUSION
In individuals with LGA, MT dramatically altered the disease's natural history to a poor prognosis. The present study's analysis of the clinical features of patients indicated supratentorial LGA, a midline shift greater than 5 mm, and the degree of resection as risk factors for MT. The more extensive the resection, the greater the reduction in tumor load and MT. In addition, more molecular study is necessary to elucidate the pathophysiology of MT.
Topics: Humans; Retrospective Studies; Brain Neoplasms; Astrocytoma; Glioblastoma; Cell Transformation, Neoplastic
PubMed: 36412420
DOI: 10.4103/jcrt.JCRT_1469_20 -
Radiation Oncology (London, England) May 2022We sought to clarify the optimal follow-up, therapeutic strategy, especially the role of reirradiation, and the diagnostic impact of isocitrate dehydrogenase (IDH) 1 and...
BACKGROUND
We sought to clarify the optimal follow-up, therapeutic strategy, especially the role of reirradiation, and the diagnostic impact of isocitrate dehydrogenase (IDH) 1 and 2 mutation status in patients with radiation-induced glioma (RIG).
METHODS
We retrospectively reviewed the clinical characteristics and treatment outcomes of 11 patients with high-grade glioma who satisfied Cahan's criteria for RIG in our database during 2001-2021. IDH 1/2 mutations were analyzed by Sanger sequencing and/or pyrosequencing.
RESULTS
The RIGs included glioblastoma with IDH 1/2 wild-type (n = 7), glioblastoma not otherwise specified (n = 2), anaplastic astrocytoma with IDH1/2 wild-type (n = 1), and anaplastic astrocytoma not otherwise specified (n = 1). The median period from primary disease and RIG diagnosis was 17 years (range: 9-30 years). All patients underwent tumor removal or biopsy, 5 patients postoperatively received reirradiation combined with chemotherapy, and 6 patients were treated with chemotherapy alone. The median progression-free and survival times were 11.3 and 28.3 months. The median progression-free survival time of patients treated with reirradiation and chemotherapy (n = 5) tended to be longer than that of patients that received chemotherapy alone (n = 6) (17.0 vs 8.1 months). However, the median survival time was similar (29.6 vs 27.4 months). Local recurrence was observed in 5 patients treated with chemotherapy alone, whereas in 2 patients among 4 patients treated with reirradiation and chemotherapy. None of the patients developed radiation necrosis. In one case, the primary tumor was diffuse astrocytoma with IDH2 mutant, and the secondary tumor was glioblastoma with IDH 1/2 wild-type. Based on the difference of IDH2 mutation status, the secondary tumor with IDH 1/2 wild-type was diagnosed as a de novo tumor that was related to the previous radiation therapy.
CONCLUSIONS
RIG can occur beyond 20 years after successfully treating the primary disease using radiotherapy; thus, cancer survivors should be informed of the long-term risk of developing RIG and the need for timely neuroimaging evaluation. Reirradiation combined with chemotherapy appears to be feasible and has favorable outcomes. Determining the IDH1/2 mutational status is useful to establish RIG diagnosis when the primary tumor is glioma.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Glioma; Humans; Isocitrate Dehydrogenase; Re-Irradiation; Retrospective Studies
PubMed: 35505351
DOI: 10.1186/s13014-022-02054-x