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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 -
BMC Medical Imaging May 2022The accurate grading of IDH-mutant astrocytoma is essential to make therapeutic strategies and assess the prognosis of patients. The purpose of this study was to...
BACKGROUND
The accurate grading of IDH-mutant astrocytoma is essential to make therapeutic strategies and assess the prognosis of patients. The purpose of this study was to investigate the usefulness of DWI, SWI and DSC-PWI in grading IDH-mutant astrocytoma.
METHODS
One hundred and seven patients with IDH-mutant astrocytoma who underwent DWI, SWI and DSC-PWI were retrospectively reviewed. Minimum apparent diffusion coefficient (ADC), intratumoral susceptibility signal intensity(ITSS) and maximum relative cerebral blood volume (rCBV) values were assessed. ADC, ITSS and rCBV values were compared between grade 2 vs. grade 3, grade 3 vs. grade 4 and grade 2 + 3 vs. grade 4 tumors. Logistic regression, tenfold cross-validation,and receiver operating characteristic (ROC) curve analyses were used to assess their diagnostic performances.
RESULTS
Grade 4 IDH-mutant astrocytomas showed significantly lower ADC and higher rCBV as compared to grade 3 tumors (adjusted P < 0.001). IDH-mutant grade 3 astrocytomas showed significantly lower ITSS levels as compared with grade 4 tumors (adjusted P < 0.001). ITSS levels between IDH-mutant grade 2 and grade 3 astrocytomas were significantly different (adjusted P = 0.002). Combined the ADC, ITSS and rCBV resulted in the highest AUC for differentiation grade 2 and grade 3 tumors from grade 4 tumors.
CONCLUSION
ADC rCBV and ITSS can be used for grading the IDH-mutant astrocytomas. The combination of ADC ITSS and rCBV could improve the diagnostic performance in grading of IDH-mutant astrocytoma.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Humans; Magnetic Resonance Imaging; Perfusion; Retrospective Studies
PubMed: 35644621
DOI: 10.1186/s12880-022-00832-3 -
Clinical and Translational Medicine Feb 2024Paediatric and adult astrocytomas are notably different, where clinical treatments used for adults are not as effective on children with the same form of cancer and... (Review)
Review
Paediatric and adult astrocytomas are notably different, where clinical treatments used for adults are not as effective on children with the same form of cancer and these treatments lead to adverse long-term health concerns. Integrative omics-based studies have shown the pathology and fundamental molecular characteristics differ significantly and cannot be extrapolated from the more widely studied adult disease. Recent clinical advances in our understanding of paediatric astrocytomas, with the aid of next-generation sequencing and epigenome-wide profiling, have led to the identification of key canonical mutations that vary based on the tumour location and age of onset. These driver mutations, in particular the identification of the recurrent histone H3 mutations in high-grade tumours, have confirmed the important role epigenetic dysregulations play in cancer progression. This review summarises the current updates of the classification, epidemiology, pathogenesis and clinical management of paediatric astrocytoma based on their grades and the ongoing clinical trials. It also provides novel insights on genetic and epigenetic alterations as diagnostic biomarkers, highlighting the potential of targeting these pathways as therapeutics for this devastating childhood cancer.
Topics: Adult; Humans; Child; Brain Neoplasms; Astrocytoma; Histones; Epigenesis, Genetic; Epigenomics
PubMed: 38299304
DOI: 10.1002/ctm2.1560 -
Folia Neuropathologica 2016Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a... (Review)
Review
Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome - neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection. However, the behaviour and prognosis might also be related to tumour histology and location. Pilomyxoid astrocytoma (PMA) represents a variant of classical PA with more invasive growth and increased risk of recurrences and dissemination. Typically, PAs exhibit distinct histology with biphasic architecture of loose, microcystic and compact, fibrillary areas. However, some tumours arise in an uncommon location and display heterogeneous histopathological appearance. The morphological pattern of PA can mimic some other glial neoplasms, including oligodendroglioma, pleomorphic xanthoastrocytoma, ependymoma or diffuse astrocytoma. Not infrequently, the advanced degenerative changes, including vascular fibrosis, and recent and old haemorrhages, may mimic vascular pathology. Sometimes, the neoplastic piloid tissue can resemble reactive gliosis, related to long-standing non neoplastic lesions. Not infrequently, PA exhibits histological features typical for anaplasia, including necrosis, mitoses and glomeruloid vascular proliferation that can suggest a diffuse high-grade glioma. However, even those PAs that lack distinct histological features of anaplasia can behave unpredictably, in a more aggressive manner, with leptomeningeal spreading. Genetic alterations resulting in aberrant signalling of the mitogen-activated protein kinase (MAPK) pathway have been considered to underlie the development of PAs. The most commonly identified KIAA1549-BRAF fusion is important for appropriate tumour molecular diagnosis. In this paper we summarize the clinicopathological presentation of PAs, with emphasis on their heterogeneous morphology, based on our own experience in the field of surgical neuropathology and the literature data. Diagnosis of pilocytic tumours requires careful analysis of clinical, histopathological and molecular features to avoid misinterpretation of these benign neoplastic lesions.
Topics: Animals; Astrocytes; Astrocytoma; Brain Neoplasms; Glioma; Humans; Mitogen-Activated Protein Kinases; Neoplasm Recurrence, Local
PubMed: 27764513
DOI: 10.5114/fn.2016.62530 -
European Journal of Medical Genetics Jan 2020Mutations in LZTR1, already known to be causal in familial schwannomatosis type 2, have been recently involved in a small proportion of patients with autosomal dominant...
Mutations in LZTR1, already known to be causal in familial schwannomatosis type 2, have been recently involved in a small proportion of patients with autosomal dominant and autosomal recessive Noonan syndrome. LZTR1 is also a driver gene in non syndromal glioblastoma. We report a 26-year-old patient with typical Noonan syndrome, and the dominantly transmitted c.850C > T (p.(Arg284Cys)) variant in LZTR1. An oligoastrocytoma was diagnosed in the patient at the age of 22 years; recurrence of the tumor occurred at age 26, as a ganglioblastoma. The patient had been transiently treated with growth hormone between ages 15 and 17. Considering the implication of LZTR1 in sporadic tumors of the nervous system, we hypothesize that gliomas are a possible complication of LZTR1-related Noonan syndrome. This report also supports a possible link between occurrence of a cerebral tumor in Noonan syndrome and a previous treatment with growth hormone.
Topics: Adolescent; Adult; Astrocytoma; Female; Genetic Predisposition to Disease; Glioblastoma; Humans; Male; Mutation; Noonan Syndrome; Pedigree; Transcription Factors
PubMed: 30664951
DOI: 10.1016/j.ejmg.2019.01.007 -
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 -
Polish Journal of Pathology : Official... 2019In this study we assessed whether gliomas could be subdivided into different molecular subtypes by immunohistochemistry (IHC) reminiscent of those first described by...
In this study we assessed whether gliomas could be subdivided into different molecular subtypes by immunohistochemistry (IHC) reminiscent of those first described by Verhaak et al. in 2010 (classical, proneural, mesenchymal and neural). We also evaluated the prognostic significance of single molecular factors and searched for significant correlations between markers. In this study, we included 146 patients with glioblastomas (GBMs) and 26 with diffuse astrocytomas (DAs). The glioma samples were tested for PDGFRA, IDH1 R132H, CD44, p53, Ki-67, p21 and p27 expression. We found that gliomas could be subdivided into molecular subtypes by IHC. Fifty per cent of GBMs were of the proneural subtype, 18.5% of mesenchymal subtype and 31.5% were not otherwise classified. However, most of the DAs (92.3%) belonged to the proneural subtype. No prognostic role was found for the molecular subtypes, but predictive roles were noted. Both proneural and mesenchymal molecular subtypes showed a benefit from the addition of chemotherapy and radiotherapy; however, the mesenchymal subtype showed a greater response. Interestingly, the mesenchymal subtype did not receive any benefit from the addition of radiotherapy compared with palliative management and surgery alone. Regarding single molecular markers, only IDH1 R132H was found to have a prognostic role for GBMs. There was a trend towards better survival in tumours with lower PDGFRA expression (p = 0.066). In DAs, PDGFRA and Ki-67 expression had prognostic roles. The following statistically significant correlations were found in GBMs: Ki-67/p53, Ki-67/p27 and p53/PDGFRA; in DAs: p53/PDGFRA, CD44/PDGFRA, and p21/PDGFRA.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Glioma; Humans; Immunohistochemistry; Isocitrate Dehydrogenase; Mutation; Prognosis
PubMed: 32146793
DOI: 10.5114/pjp.2019.93126 -
European Review For Medical and... 2015Glioblastoma (GBM) is a very lethal form of human brain cancer, which is characterized by rapid diffuse, infiltrative growth and high level of cellular heterogeneity.... (Review)
Review
Glioblastoma (GBM) is a very lethal form of human brain cancer, which is characterized by rapid diffuse, infiltrative growth and high level of cellular heterogeneity. Such cancer patients usually survive for one year under treatment. Recently, the role of small non-coding RNA known as microRNAs (miRNA), have been suggested to be involved in the pathogenesis of glioblastoma, as miRNAs play a critical role in the tumor-forming processes. The change in expression levels of several miRNAs has been found in GBM patients within last 10 years. It is evident now that impairment of miRNA regulation is one of the key mechanisms in GBM pathogenesis. The miRNA deregulation is involved in many processes, such as cell proliferation, cell cycle regulation, apoptosis, invasion, glioma stem cell behavior, and angiogenesis. GBM is also known as Grade IV astrocytoma, a rare disease with an incidence of 2-3 cases per 100,000 people in Europe and North America, and 50% with GBM die within 1 year, while 90% within 3 years. The treatments of GBM involve chemotherapy, radiation and surgery. The median survival with standard radiation and chemotherapy with Temozolomide is 1 year and 3 months, and median survival without treatment is four and a half months. In this article, symptoms of GBM, treatments, the role of miRNAs, gene expressions, types of miRNAs, neoplasms and glioblastomas, the miRNA biogenesis pathways, deregulation of miRNAs, and care of GBM have been described.
Topics: Brain Neoplasms; Europe; Female; Glioblastoma; Humans; MicroRNAs; Middle Aged; North America; Survival Analysis
PubMed: 26004603
DOI: No ID Found -
Neuropathology and Applied Neurobiology Dec 2022Anaplastic ganglioglioma is a rare tumour, and diagnosis has been based on histological criteria. The 5th edition of the World Health Organization Classification of...
AIMS
Anaplastic ganglioglioma is a rare tumour, and diagnosis has been based on histological criteria. The 5th edition of the World Health Organization Classification of Tumours of the Central Nervous System (CNS WHO) does not list anaplastic ganglioglioma as a distinct diagnosis due to lack of molecular data in previous publications. We retrospectively compiled a cohort of 54 histologically diagnosed anaplastic gangliogliomas to explore whether the molecular profiles of these tumours represent a separate type or resolve into other entities.
METHODS
Samples were subjected to histological review, desoxyribonucleic acid (DNA) methylation profiling and next-generation sequencing. Morphological and molecular data were summarised to an integrated diagnosis.
RESULTS
The majority of tumours designated as anaplastic gangliogliomas resolved into other CNS WHO diagnoses, most commonly pleomorphic xanthoastrocytoma (16/54), glioblastoma, isocitrate dehydrogenase protein (IDH) wild type and diffuse paediatric-type high-grade glioma, H3 wild type and IDH wild type (11 and 2/54), followed by low-grade glial or glioneuronal tumours including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumour and diffuse leptomeningeal glioneuronal tumour (5/54), IDH mutant astrocytoma (4/54) and others (6/54). A subset of tumours (10/54) was not assignable to a CNS WHO diagnosis, and common molecular profiles pointing to a separate entity were not evident.
CONCLUSIONS
In summary, we show that tumours histologically diagnosed as anaplastic ganglioglioma comprise a wide spectrum of CNS WHO tumour types with different prognostic and therapeutic implications. We therefore suggest assigning this designation with caution and recommend comprehensive molecular workup.
Topics: Child; Humans; Ganglioglioma; Retrospective Studies; Glioma; Astrocytoma; Brain Neoplasms; Central Nervous System Neoplasms; Isocitrate Dehydrogenase
PubMed: 35977725
DOI: 10.1111/nan.12847 -
Medicina (Kaunas, Lithuania) Jul 2019Being the fourth leading cause of cancer-related death, glial tumors are highly diverse tumor entities characterized by important heterogeneity regarding tumor... (Review)
Review
Being the fourth leading cause of cancer-related death, glial tumors are highly diverse tumor entities characterized by important heterogeneity regarding tumor malignancy and prognosis. However, despite the identification of important alterations in the genome of the glial tumors, there remains a gap in understanding the mechanisms involved in glioma malignancy. Previous research focused on decoding the genomic alterations in these tumors, but due to intricate cellular mechanisms, the genomic findings do not correlate with the functional proteins expressed at the cellular level. The development of mass spectrometry (MS) based proteomics allowed researchers to study proteins expressed at the cellular level or in serum that may provide new insights on the proteins involved in the proliferation, invasiveness, metastasis and resistance to therapy in glial tumors. The integration of data provided by genomic and proteomic approaches into clinical practice could allow for the identification of new predictive, diagnostic and prognostic biomarkers that will improve the clinical management of patients with glial tumors. This paper aims to provide an updated review of the recent proteomic findings, possible clinical applications, and future research perspectives in diffuse astrocytic and oligodendroglial tumors, pilocytic astrocytomas, and ependymomas.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Glioma; Humans; Mass Spectrometry; Neoplasm Staging; Neoplasms; Oligodendroglioma; Prognosis; Proteomics
PubMed: 31357616
DOI: 10.3390/medicina55080412