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Hematology/oncology Clinics of North... Feb 2022Isocitrate dehydrogenase (IDH) 1 and 2 mutations represent essential components for the diagnosis of diffuse astrocytic tumors and oligodendroglioma. IDH wild-type glial... (Review)
Review
Isocitrate dehydrogenase (IDH) 1 and 2 mutations represent essential components for the diagnosis of diffuse astrocytic tumors and oligodendroglioma. IDH wild-type glial tumors include a wide spectrum of tumors with differences in prognosis and recommended therapeutic approaches. Tumors characterized as molecular glioblastoma in the World Health Organization 2021 classification should be treated according to the glioblastoma therapeutic principles and included in glioblastoma trials. Improving on existing treatments options including targeted and immunotherapy approaches is imperative for most patients with IDH wild-type glial tumors, and enrollment in clinical trials is encouraged.
Topics: Brain Neoplasms; Glioblastoma; Glioma; Humans; Isocitrate Dehydrogenase; Oligodendroglioma
PubMed: 34756799
DOI: 10.1016/j.hoc.2021.08.007 -
Journal of Ayub Medical College,... 2023Granular cell astrocytoma (GCA) is a rare glial neoplasm composed of abundant granular cytoplasm gives immunoreactivity for GFAP and S100 stains. We report a case of GCA...
Granular cell astrocytoma (GCA) is a rare glial neoplasm composed of abundant granular cytoplasm gives immunoreactivity for GFAP and S100 stains. We report a case of GCA in a 64 years old male presented with history of fits, right sided weakness and loss of consciousness. The microscopy showed sheets of large cells with abundant eosinophilic granular cytoplasm. No high-grade features were seen. Its differential diagnosis includes most of the benign histiocytic conditions. Granular cell astrocytoma has an aggressive clinical course and its survival rate is less than 1 year. That's why early correct diagnosis is very essential.
Topics: Humans; Male; Middle Aged; Coloring Agents; Diagnosis, Differential; Microscopy; Staining and Labeling; Astrocytoma
PubMed: 36849399
DOI: 10.55519/JAMC-01-10493 -
Brain Pathology (Zurich, Switzerland) Sep 2023Fusions involving CRAF (RAF1) are infrequent oncogenic drivers in pediatric low-grade gliomas, rarely identified in tumors bearing features of pilocytic astrocytoma, and...
Fusions involving CRAF (RAF1) are infrequent oncogenic drivers in pediatric low-grade gliomas, rarely identified in tumors bearing features of pilocytic astrocytoma, and involving a limited number of known fusion partners. We describe recurrent TRAK1::RAF1 fusions, previously unreported in brain tumors, in three pediatric patients with low-grade glial-glioneuronal tumors. We present the associated clinical, histopathologic and molecular features. Patients were all female, aged 8 years, 15 months, and 10 months at diagnosis. All tumors were located in the cerebral hemispheres and predominantly cortical, with leptomeningeal involvement in 2/3 patients. Similar to previously described activating RAF1 fusions, the breakpoints in RAF1 all occurred 5' of the kinase domain, while the breakpoints in the 3' partner preserved the N-terminal kinesin-interacting domain and coiled-coil motifs of TRAK1. Two of the three cases demonstrated methylation profiles (v12.5) compatible with desmoplastic infantile ganglioglioma (DIG)/desmoplastic infantile astrocytoma (DIA) and have remained clinically stable and without disease progression/recurrence after resection. The remaining tumor was non-classifiable; with focal recurrence 14 months after initial resection; the patient remains symptom free and without further recurrence/progression (5 months post re-resection and 19 months from initial diagnosis). Our report expands the landscape of oncogenic RAF1 fusions in pediatric gliomas, which will help to further refine tumor classification and guide management of patients with these alterations.
Topics: Child; Female; Humans; Adaptor Proteins, Vesicular Transport; Astrocytoma; Brain Neoplasms; Ganglioglioma; Glioma; Oncogene Fusion
PubMed: 37399073
DOI: 10.1111/bpa.13185 -
International Journal of Molecular... Nov 2020Astrocytomas and, in particular, their most severe form, glioblastoma, are the most aggressive primary brain tumors and those with the poorest vital prognosis. Standard... (Review)
Review
Astrocytomas and, in particular, their most severe form, glioblastoma, are the most aggressive primary brain tumors and those with the poorest vital prognosis. Standard treatment only slightly improves patient survival. Therefore, new therapies are needed. Very few risk factors have been clearly identified but many epidemiological studies have reported a higher incidence in men than women with a sex ratio of 1:4. Based on these observations, it has been proposed that the neurosteroids and especially the estrogens found in higher concentrations in women's brains could, in part, explain this difference. Estrogens can bind to nuclear or membrane receptors and potentially stimulate many different interconnected signaling pathways. The study of these receptors is even more complex since many isoforms are produced from each estrogen receptor encoding gene through alternative promoter usage or splicing, with each of them potentially having a specific role in the cell. The purpose of this review is to discuss recent data supporting the involvement of steroids during gliomagenesis and to focus on the potential neuroprotective role as well as the mechanisms of action of estrogens in gliomas.
Topics: Animals; Astrocytoma; Disease Progression; Female; Hormones; Humans; Male; Models, Biological; Receptors, Steroid; Sex Characteristics
PubMed: 33266110
DOI: 10.3390/ijms21239114 -
BMJ Case Reports Mar 2016
Topics: Adult; Astrocytoma; Brain Neoplasms; Confusion; Female; Humans; Neoplasm Recurrence, Local; Paresis; Temporal Lobe
PubMed: 27033282
DOI: 10.1136/bcr-2015-213013 -
Neurology India 2022Intraventricular pilocytic astrocytomas are a rare occurrence, accounting for approximately 4% -15.6% of all pilocytic astrocytomas .The aim of the study was to describe...
BACKGROUND
Intraventricular pilocytic astrocytomas are a rare occurrence, accounting for approximately 4% -15.6% of all pilocytic astrocytomas .The aim of the study was to describe the radiology, surgical management and outcome in 15 patients with histopathologically proven intraventricular pilocytic astrocytoma(IVPA).
OBJECTIVE
To study the clinical presentation radiology and operative challenges in rare intra ventricular pilocytic astrocytomas.
MATERIALS AND METHODS
Between January 2010 and August 2018, 15 patients with histopathologically proven IVPA were identified. The radiological images were obtained from PACS. Patient and surgical details were obtained from the computerized discharge summary, OT records and operative notes, whereas follow up was obtained from the record section.
RESULTS
Headache with progressive loss of vision was the most common presentation. Duration of symptoms varied from 4 months to 2 years (mean 9. 88 months). Except one patient, all patients with preoperative CT scan revealed calcifications in the lesion, with extensive calcification in 3 patients. All the tumors were predominantly hypointense on T1WI and iso to hyperintense on T2WI. Lesion in all patients showed heterogenous contrast enhancement on post gadolinium images. Mean blood loss in the series was 1969 ml (range 250 ml- 4500 ml).There was one death in this series due to meningitis and septic shock.
CONCLUSION
IVPAs are rare tumors and are difficult to diagnose in the preoperative period based on the radiologic profile alone. These tumors can be extremely vascular with potential for massive blood loss. These tumors can be associated with extensive calcification and the calcified tumors have less bleeding as expected.
Topics: Astrocytoma; Brain Neoplasms; Calcinosis; Gadolinium; Humans; Tomography, X-Ray Computed
PubMed: 36076645
DOI: 10.4103/0028-3886.355185 -
Neuro-oncology Apr 2023Unresectable hypothalamic/optic pathway pilocytic astrocytoma (PA) often progresses despite multiple therapies. Identifying clinical and molecular characteristics of...
BACKGROUND
Unresectable hypothalamic/optic pathway pilocytic astrocytoma (PA) often progresses despite multiple therapies. Identifying clinical and molecular characteristics of progressive tumors may aid in prognostication and treatment.
METHODS
We collected 72 unresectable, non-neurofibromatosis type 1-associated hypothalamic/optic pathway PA to identify clinical and biologic factors associated with tumor progression. Tumors that progressed after therapy, metastasized, or resulted in death were categorized into Cohort B; those that did not meet these criteria were categorized into Cohort A. DNA methylation and transcriptome analyses were performed on treatment-naïve tumors, and the findings were validated by immunohistochemistry (IHC).
RESULTS
The median follow-up of the entire cohort was 12.3 years. Cohort B was associated with male sex (M:F = 2.6:1), younger age at diagnosis (median 3.2 years vs 6.7 years, P = .005), and high incidence of KIAA1549-BRAF fusion (81.5% vs 38.5%, P = .0032). Cohort B demonstrated decreased CpG methylation and increased RNA expression in mitochondrial genes and genes downstream of E2F and NKX2.3. Transcriptome analysis identified transcription factor TBX3 and protein kinase PIM1 as common downstream targets of E2F and NKX2.3. IHC confirmed increased expression of TBX3 and PIM1 in Cohort B tumors. Gene enrichment analysis identified enrichment of MYC targets and MAPK, PI3K/AKT/mTOR, and p53 pathways, as well as pathways related to mitochondrial function.
CONCLUSIONS
We identified risk factors associated with progressive PA. Our results support the model in which the p53-PIM1-MYC axis and TBX3 act alongside MAPK and PI3K/AKT/mTOR pathways to promote tumor progression, highlighting potential new targets for combination therapy and refining disease prognostication.
Topics: Humans; Male; Child, Preschool; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Tumor Suppressor Protein p53; Astrocytoma; TOR Serine-Threonine Kinases; Brain Neoplasms; Proto-Oncogene Proteins B-raf
PubMed: 36260562
DOI: 10.1093/neuonc/noac241 -
Cureus Aug 2022Glioma can be classified according to its infiltrative capacity into circumscribed and "diffuse"/infiltrative glioma. Pilocytic astrocytoma is typically grouped under...
Glioma can be classified according to its infiltrative capacity into circumscribed and "diffuse"/infiltrative glioma. Pilocytic astrocytoma is typically grouped under the circumscribed astrocytic glioma in the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors. The distinction of pilocytic astrocytoma from diffuse glioma is fundamental as it could be the difference between CNS WHO grade 1 and grade 4 glioma. This study aims to determine the infiltrative nature of pilocytic astrocytoma in different brain locations. All cases diagnosed as "pilocytic astrocytoma" were retrieved from 2008 to 2021. The clinical information (age, sex, location of the tumor), pathological description, and performed immunostaining were obtained from the pathological reports. The available pathological slides were retrieved and examined for the following features: diagnosis, infiltrative vs. circumscribed tumor, and immunostaining characteristics. There were 20 males and 19 females aged 17 months to 31 years. The diagnosis of pilocytic astrocytoma was confirmed in 38/39 cases, and in one case, the diagnosis changed to a dysembryoplastic neuroepithelial tumor. Histological infiltration is defined as the presence of neoplastic cells among the nonneoplastic brain parenchyma. Twenty cases were well-circumscribed with no evidence of infiltration histologically, while 18/38 cases showed apparent infiltration into adjacent brain tissue. The infiltration was not restricted to cerebellar pilocytic astrocytoma (12/24, 50%) but was also present in 3/7 supratentorial, single brainstem, and single spinal cord cases. In conclusion, cases with typical morphological features of pilocytic astrocytoma could show areas of brain infiltration, which should not affect the certainty of the diagnosis.
PubMed: 36120224
DOI: 10.7759/cureus.27940 -
Child's Nervous System : ChNS :... Nov 2016The purpose of this review is to document the various types of astrocytoma that occur in the fetus and neonate, their locations, initial findings, pathology, and... (Review)
Review
INTRODUCTION
The purpose of this review is to document the various types of astrocytoma that occur in the fetus and neonate, their locations, initial findings, pathology, and outcome. Data are presented that show which patients are likely to survive or benefit from treatment compared with those who are unlikely to respond.
MATERIALS AND METHODS
One hundred one fetal and neonatal tumors were collected from the literature for study.
RESULTS
Macrocephaly and an intracranial mass were the most common initial findings. Overall, hydrocephalus and intracranial hemorrhage were next. Glioblastoma (GBM) was the most common neoplasm followed in order by subependymal giant cell astrocytoma (SEGA), low-grade astrocytoma, anaplastic astrocytoma, and desmoplastic infantile astrocytoma (DIA). Tumors were detected most often toward the end of the third trimester of pregnancy.
CONCLUSION
A number of patients were considered inoperable since their tumor occupied much of the intracranial cavity involving large areas of the brain. High-grade astrocytomas were more common than low-grade ones in this review. Fetuses and neonates with astrocytoma have a mixed prognosis ranging from as low as 20 % (GBM) to a high of 90 %. The overall survival was 47/101 or 46 %.
Topics: Astrocytoma; Brain Neoplasms; Female; Fetus; Humans; Infant, Newborn; Pregnancy
PubMed: 27568373
DOI: 10.1007/s00381-016-3215-y -
Neuro-oncology Aug 2023People with NF1 have an increased prevalence of central nervous system malignancy. However, little is known about the clinical course or pathologic features of...
BACKGROUND
People with NF1 have an increased prevalence of central nervous system malignancy. However, little is known about the clinical course or pathologic features of NF1-associated gliomas in adults, limiting clinical care and research.
METHODS
Adults (≥18 years) with NF1 and histologically confirmed non-optic pathway gliomas (non-OPGs) at Johns Hopkins Hospital, Memorial Sloan Kettering Cancer Center, and Washington University presenting between 1990 and 2020 were identified. Retrospective data were collated, and pathology was reviewed centrally.
RESULTS
Forty-five patients, comprising 23 females (51%), met eligibility criteria, with a median of age 37 (18-68 years) and performance status of 80% (30%-100%). Tissue was available for 35 patients. Diagnoses included infiltrating (low-grade) astrocytoma (9), glioblastoma (7), high-grade astrocytoma with piloid features (4), pilocytic astrocytoma (4), high-grade astrocytoma (3), WHO diagnosis not reached (4) and one each of gliosarcoma, ganglioglioma, embryonal tumor, and diffuse midline glioma. Seventy-one percent of tumors were midline and underwent biopsy only. All 27 tumors evaluated were IDH1-wild-type, independent of histology. In the 10 cases with molecular testing, the most common genetic variants were NF1, EGFR, ATRX, CDKN2A/B, TP53, TERT, and MSH2/3 mutation. While the treatments provided varied, the median overall survival was 24 months [2-267 months] across all ages, and 38.5 [18-109] months in individuals with grade 1-2 gliomas.
CONCLUSIONS
Non-OPGs in adults with NF1, including low-grade tumors, often have an aggressive clinical course, indicating a need to better understand the pathobiology of these NF1-associated gliomas.
Topics: Female; Humans; Adult; Neurofibromatosis 1; Retrospective Studies; Glioma; Astrocytoma; Brain Neoplasms; Disease Progression
PubMed: 36840626
DOI: 10.1093/neuonc/noad033