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Cureus Feb 2021Pilocytic spinal cord astrocytomas make up 21% of intramedullary tumors. Only 20% of those tumors are associated with syringomyelia. To our knowledge, this is the first...
Pilocytic spinal cord astrocytomas make up 21% of intramedullary tumors. Only 20% of those tumors are associated with syringomyelia. To our knowledge, this is the first report of an adult presenting with multiple spinal pilocytic astrocytomas associated with syringomyelia. We report a case of a 27-year-old woman who had neck and arm pain for months. She underwent cervical magnetic resonance imaging (MRI) that demonstrated a syrinx from C2 and extending to C6. A coronal view of the MRI showed multiple mural nodules. Total excision of multicentric nodules within a cyst was performed with an uneventful intraoperative and postoperative period and the patient was discharged home with moderate right-hand numbness.
PubMed: 33747654
DOI: 10.7759/cureus.13353 -
Journal of Veterinary Diagnostic... Jul 2019Gliomas are common primary central nervous system neoplasms of dogs and cats, but atypical glioma subtypes are rare. Herein we report an angiocentric astrocytoma in a...
Gliomas are common primary central nervous system neoplasms of dogs and cats, but atypical glioma subtypes are rare. Herein we report an angiocentric astrocytoma in a 15-y-old spayed female domestic shorthaired cat that was euthanized after therapy-resistant seizures. Gross anatomic changes consisted of swelling of the rostral leptomeninges over the olfactory bulbs and rostral telencephalon. Histologically, polygonal-to-elongate atypical neoplastic cells were arranged along perivascular spaces within these areas. Neoplastic cells were positive for glial fibrillary acidic protein, S100 protein, and vimentin. Ultrastructurally, round-to-elongate neoplastic cells emitting long processes with aggregates of intermediary filaments expanded and occupied the spaces between the vascular basement membrane and the glia limitans; nuclei had marginal and central heterochromatin. Tight junctions connected the plasma membrane of neighboring cells. The cell morphology, immunohistochemistry, and ultrastructural findings were consistent with an astrocytoma; the exclusive perivascular arrangement of neoplastic cells with no parenchymal mass warranted the diagnosis of angiocentric astrocytoma.
Topics: Animals; Astrocytoma; Brain; Brain Neoplasms; Cat Diseases; Cats; Female; Glial Fibrillary Acidic Protein; S100 Proteins; Seizures; Vimentin
PubMed: 31018782
DOI: 10.1177/1040638719847239 -
Diagnostics (Basel, Switzerland) Jul 2022Pilocytic astrocytoma with a predominant oligodendrocyte-like component can be difficult to distinguish from oligodendroglioma, dysembryoplastic neuroepithelial tumors...
Pilocytic astrocytoma with a predominant oligodendrocyte-like component can be difficult to distinguish from oligodendroglioma, dysembryoplastic neuroepithelial tumors (DNTs), central neurocytoma, and ependymoma (clear cell phenotype). The utility of GFAP immunostaining in this context is not well discussed. All cases with a diagnosis of pilocytic astrocytoma were retrieved from the pathological archives along with the following information: age, sex, and pathological description. The GFAP immunostaining was scored as score 1 (<25%), score 2 (25−50%), score 3 (50−75%), and score 4 (>75%). The comparison group included oligodendrogliomas, DNTs, ependymomas, and central neurocytomas. All 26 cases (16 males and 10 females) of pilocytic astrocytoma showed strong and diffuse (score 4) GFAP immunostaining in the neoplastic cells of both the solid fibrillary and oligodendrocyte-like components. The staining pattern in the neoplastic round cells in the oligodendrocyte-like areas was perinuclear cytoplasmic with no processes. In the comparison group, GFAP immunostaining was mostly restricted to the reactive astrocytes in the background. Focal areas of the neoplastic cells showed scores of 1−3 in the neoplastic cells, but the staining pattern was different from those in pilocytic astrocytoma. In the setting of tumors with predominant oligodendrocyte-like areas, the GFAP immunostaining score and pattern help distinguish pilocytic astrocytoma from its mimickers.
PubMed: 35885538
DOI: 10.3390/diagnostics12071632 -
Eye (London, England) Apr 2023To use multimodal imaging techniques to characterise features of retinal astrocytomas (RA) which would aid practitioners distinguish them from other causes of...
OBJECTIVES
To use multimodal imaging techniques to characterise features of retinal astrocytomas (RA) which would aid practitioners distinguish them from other causes of non-pigmented fundal lesions.
METHODS
Retrospective analysis of notes and imaging of 17 patients diagnosed with RA at a single centre between January 2012 and June 2021 was conducted. Demographics, examination findings and imaging including colour fundus photography, optical coherence tomography (OCT), infra-red (IR) and ultrasound (US) were analysed. These were compared to differential diagnoses, including retinoblastomas, amelanotic choroidal melanomas, choroidal metastases and idiopathic scleromas.
RESULTS
Fourteen patients (82%; 14/17) had idiopathic RA and three (18%; 3/17) were associated with tuberous sclerosis. Mean age at presentation was 43 years. Twelve patients (71%; 12/17) were asymptomatic. Thirteen (76%; 13/17) had better than 6/12 vision, with 41% (7/17) better than 6/6. All lesions were creamy-white. There were two distinct appearances, seven (39%; 7/18) were poorly-defined translucent retinal elevations and eleven (61%; 11/18) were well-defined solid opaque retinal masses. Six (33%; 6/18) displayed clustered, calcified spherules giving them the pathognomonic 'mulberry-like' appearance. On OCT, all appeared as dome-shaped retinal thickening with disruption of the inner retinal layers and nine (60%; 9/15) had intra-retinal cystic spaces giving a 'moth-eaten' appearance. Mean basal diameter and thickness on OCT was 2.93 mm and 0.86 mm, respectively. High internal reflectivity on US was noted in 92% (11/12).
CONCLUSIONS
RAs display characteristic clinical, demographic and imaging features which can aid differentiating them from other non-pigmented fundal lesions. We advise using multiple imaging modalities when diagnosing these lesions.
Topics: Humans; Retrospective Studies; Retina; Hamartoma; Tomography, Optical Coherence; Retinal Neoplasms; Astrocytoma; Fluorescein Angiography
PubMed: 36224356
DOI: 10.1038/s41433-022-02275-0 -
BMC Cancer Dec 2022Juvenile Pilocytic Astrocytomas (JPAs) are one of the most common pediatric brain tumors, and they are driven by aberrant activation of the mitogen-activated protein...
BACKGROUND
Juvenile Pilocytic Astrocytomas (JPAs) are one of the most common pediatric brain tumors, and they are driven by aberrant activation of the mitogen-activated protein kinase (MAPK) signaling pathway. RAF-fusions are the most common genetic alterations identified in JPAs, with the prototypical KIAA1549-BRAF fusion leading to loss of BRAF's auto-inhibitory domain and subsequent constitutive kinase activation. JPAs are highly vascular and show pervasive immune infiltration, which can lead to low tumor cell purity in clinical samples. This can result in gene fusions that are difficult to detect with conventional omics approaches including RNA-Seq.
METHODS
To this effect, we applied RNA-Seq as well as linked-read whole-genome sequencing and in situ Hi-C as new approaches to detect and characterize low-frequency gene fusions at the genomic, transcriptomic and spatial level.
RESULTS
Integration of these datasets allowed the identification and detailed characterization of two novel BRAF fusion partners, PTPRZ1 and TOP2B, in addition to the canonical fusion with partner KIAA1549. Additionally, our Hi-C datasets enabled investigations of 3D genome architecture in JPAs which showed a high level of correlation in 3D compartment annotations between JPAs compared to other pediatric tumors, and high similarity to normal adult astrocytes. We detected interactions between BRAF and its fusion partners exclusively in tumor samples containing BRAF fusions.
CONCLUSIONS
We demonstrate the power of integrating multi-omic datasets to identify low frequency fusions and characterize the JPA genome at high resolution. We suggest that linked-reads and Hi-C could be used in clinic for the detection and characterization of JPAs.
Topics: Child; Adult; Humans; Multiomics; Proto-Oncogene Proteins B-raf; Oncogene Proteins, Fusion; Astrocytoma; Brain Neoplasms; Receptor-Like Protein Tyrosine Phosphatases, Class 5
PubMed: 36503484
DOI: 10.1186/s12885-022-10359-z -
Neuro-oncology May 2021The conditional reprogramming cell culture method was developed to facilitate growth of senescence-prone normal and neoplastic epithelial cells, and involves co-culture...
BACKGROUND
The conditional reprogramming cell culture method was developed to facilitate growth of senescence-prone normal and neoplastic epithelial cells, and involves co-culture with irradiated fibroblasts and the addition of a small molecule Rho kinase (ROCK) inhibitor. The aim of this study was to determine whether this approach would facilitate the culture of compact low-grade gliomas.
METHODS
We attempted to culture 4 pilocytic astrocytomas, 2 gangliogliomas, 2 myxopapillary ependymomas, 2 anaplastic gliomas, 2 difficult-to-classify low-grade neuroepithelial tumors, a desmoplastic infantile ganglioglioma, and an anaplastic pleomorphic xanthoastrocytoma using a modified conditional reprogramming cell culture approach.
RESULTS
Conditional reprogramming resulted in robust increases in growth for a majority of these tumors, with fibroblast conditioned media and ROCK inhibition both required. Switching cultures to standard serum containing media, or serum-free neurosphere conditions, with or without ROCK inhibition, resulted in decreased proliferation and induction of senescence markers. Rho kinase inhibition and conditioned media both promoted Akt and Erk1/2 activation. Several cultures, including one derived from a NF1-associated pilocytic astrocytoma (JHH-NF1-PA1) and one from a BRAF p.V600E mutant anaplastic pleomorphic xanthoastrocytoma (JHH-PXA1), exhibited growth sufficient for preclinical testing in vitro. In addition, JHH-NF1-PA1 cells survived and migrated in larval zebrafish orthotopic xenografts, while JHH-PXA1 formed orthotopic xenografts in mice histopathologically similar to the tumor from which it was derived.
CONCLUSIONS
These studies highlight the potential for the conditional reprogramming cell culture method to promote the growth of glial and glioneuronal tumors in vitro, in some cases enabling the establishment of long-term culture and in vivo models.
Topics: Animals; Astrocytoma; Brain Neoplasms; Cell Culture Techniques; Cellular Reprogramming; Glioma; Mice; Proto-Oncogene Proteins B-raf; Zebrafish
PubMed: 33258947
DOI: 10.1093/neuonc/noaa263 -
Journal of Clinical Oncology : Official... Jun 2023Children with low-grade glioma often require long-term therapy and suffer from treatment morbidity. Although targeted agents are promising, tumor targets often encompass... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Children with low-grade glioma often require long-term therapy and suffer from treatment morbidity. Although targeted agents are promising, tumor targets often encompass normal developmental pathways and long-term effects of inhibition are unknown. Lenalidomide is an immunomodulatory agent with wide-ranging properties. Phase I studies indicated greater tolerability of lenalidomide in children compared with adults and a potential dose-response effect.
PATIENTS AND METHODS
We performed a phase II trial of lenalidomide in children with pilocytic astrocytomas and optic pathway gliomas who failed initial therapy. Primary objectives included determination of objective response rate of children randomly assigned to regimen A, low-dose (20 mg/m/dose), or regimen B, high-dose (115 mg/m/dose) lenalidomide, and assessment for early progression. Secondary objectives included estimation of event-free survival, overall survival, incidence of toxic events, and assessment of plasma lenalidomide concentrations. Lenalidomide was administered once daily × 21 days of each 28-day cycle for each regimen.
RESULTS
Seventy-four eligible patients were enrolled (n = 37, each arm). The predefined activity level of interest was achieved for both arms. Four objective responses were observed in each arm, and the number of early progressors was low. Eighteen patients completed 26 cycles of therapy (regimen A, n = 12; regimen B, n = 6). The median number of cycles was 14 (range, 2-26) for regimen A and 11 for regimen B (range, 1-26). Of 74 eligible patients who received study drug, 30 required dose reduction for toxicity (regimen A, n = 6; regimen B, n = 24) and 16 discontinued because of toxicity (regimen A, n = 2; regimen B, n = 14).
CONCLUSION
Lenalidomide demonstrates a sufficient level of activity in children with low-grade glioma to warrant further exploration. Low-dose (20 mg/m/dose administered once daily × 21 days of each 28-day cycle) lenalidomide appears to have better tolerability with comparable activity.
Topics: Child; Humans; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Lenalidomide
PubMed: 37126770
DOI: 10.1200/JCO.22.01777 -
Scientific Reports Jan 2019Diffuse astrocytoma (including glioblastoma) is morbid with a worse prognosis than other types of glioma. Therefore, we sought to build a progression-associated score to...
Diffuse astrocytoma (including glioblastoma) is morbid with a worse prognosis than other types of glioma. Therefore, we sought to build a progression-associated score to improve malignancy and prognostic predictions for astrocytoma. The astrocytoma progression (AP) score was constructed through bioinformatics analyses of the training cohort (TCGA RNA-seq) and included 18 genes representing distinct aspects of regulation during astrocytoma progression. This classifier could successfully discriminate patients with distinct prognoses in the training and validation (REMBRANDT, GSE16011 and TCGA-GBM Microarray) cohorts (P < 0.05 in all cohorts) and in different clinicopathological subgroups. Distinct patterns of somatic mutations and copy number variation were also observed. The bioinformatics analyses suggested that genes associated with a higher AP score were significantly involved in cancer progression-related biological processes, such as the cell cycle and immune/inflammatory responses, whereas genes associated with a lower AP score were associated with relatively normal nervous system biological processes. The analyses indicated that the AP score was a robust predictor of patient survival, and its ability to predict astrocytoma malignancy was well elucidated. Therefore, this bioinformatics-based scoring system suggested that astrocytoma progression could distinguish patients with different underlying biological processes and clinical outcomes, facilitate more precise tumour grading and possibly shed light on future classification strategies and therapeutics for astrocytoma patients.
Topics: Adult; Aged; Aged, 80 and over; Astrocytoma; Computational Biology; Female; Humans; Machine Learning; Male; Microarray Analysis; Middle Aged; Neoplasm Grading; Pathology, Molecular; Prognosis; Survival Analysis; Young Adult
PubMed: 30643174
DOI: 10.1038/s41598-018-36471-4 -
Medicina Aug 2022Tuberous sclerosis complex is an autosomal dominant genetic multisystemic disorder caused primarily by mutations in one of the two tumor suppressor genes TSC1 or TSC2,...
Tuberous sclerosis complex is an autosomal dominant genetic multisystemic disorder caused primarily by mutations in one of the two tumor suppressor genes TSC1 or TSC2, resulting in increased activation of the mTOR pathway. Regarding clinical manifestations, a wide range of phenotypic variability exists, with symptoms constellations that may differ in affected organs (brain, skin, heart, eyes, kidneys, lungs), age of presentation and severity, but usually with great impact in biopsychosocial aspects of health and in quality of life. Main clinical neurological features are epilepsy (frequently, antiepileptic drug-resistant epilepsy), neuropsychiatric disorders, and subependymal giant cell astrocytomas. Recently, many therapeutic strategies have developed, including preventive treatment of epilepsy, new options for treatment of epilepsy as cannabidiol, mTOR inhibitors, ketogenic diet, and a more precise epilepsy surgery. Subependymal giant cell astrocytomas may require surgical procedures or mTOR inhibitors treatment. mTOR inhibitors may also be useful for other comorbidities. To improve quality of life of patients with tuberous sclerosis complex, it is essential to be able to deliver an integrated approach by specialized multidisciplinary teams, coordinated with primary care physicians and health professionals, that include access to treatments, attention of psychosocial aspects, and an adequate health care transition from pediatric to adult care.
Topics: Adult; Astrocytoma; Child; Epilepsy; Humans; Quality of Life; Transition to Adult Care; Tuberous Sclerosis
PubMed: 36054862
DOI: No ID Found -
Oncotarget Oct 2015Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and... (Comparative Study)
Comparative Study
Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting non-cerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2),whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor.
Topics: Adult; Age Factors; Aneuploidy; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Child; Cohort Studies; Female; Gene Expression Profiling; Humans; Male; Mutation; Neoplasm Staging; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-mdm2; RNA, Messenger; Real-Time Polymerase Chain Reaction; Receptor, Fibroblast Growth Factor, Type 1; Reverse Transcriptase Polymerase Chain Reaction; Young Adult
PubMed: 26378811
DOI: 10.18632/oncotarget.5571