scholarly journals Genetic Abnormalities, Clonal Evolution, and Cancer Stem Cells of Brain Tumors

2018 ◽  
Vol 6 (4) ◽  
pp. 85 ◽  
Author(s):  
Ugo Testa ◽  
Germana Castelli ◽  
Elvira Pelosi
Keyword(s):  
Brain Tumors ◽  
Clonal Evolution ◽  
Pediatric Brain Tumors ◽  
Genetic Alterations ◽  
World Health ◽  
Driver Mutations ◽  
Low Grade ◽  
High Grade ◽  
Genetic Profiling ◽  
Health Organization

Brain tumors are highly heterogeneous and have been classified by the World Health Organization in various histological and molecular subtypes. Gliomas have been classified as ranging from low-grade astrocytomas and oligodendrogliomas to high-grade astrocytomas or glioblastomas. These tumors are characterized by a peculiar pattern of genetic alterations. Pediatric high-grade gliomas are histologically indistinguishable from adult glioblastomas, but they are considered distinct from adult glioblastomas because they possess a different spectrum of driver mutations (genes encoding histones H3.3 and H3.1). Medulloblastomas, the most frequent pediatric brain tumors, are considered to be of embryonic derivation and are currently subdivided into distinct subgroups depending on histological features and genetic profiling. There is emerging evidence that brain tumors are maintained by a special neural or glial stem cell-like population that self-renews and gives rise to differentiated progeny. In many instances, the prognosis of the majority of brain tumors remains negative and there is hope that the new acquisition of information on the molecular and cellular bases of these tumors will be translated in the development of new, more active treatments.

scholarly journals Comparison of Diffusion and Perfusion Techniques in Differentiating High Versus Low Grade Pediatric Brain Tumors

2020 ◽  
Vol 3 ◽  
Author(s):  
Eric Chen ◽  
Chang Ho ◽  
Benjamin Gray ◽  
Jason Parker ◽  
Emily Diller ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Tumor Grade ◽  
Pediatric Brain Tumors ◽  
Solid Cancer ◽  
Low Grade ◽  
Dynamic Susceptibility ◽  
High Grade ◽  
Dynamic Contrast Enhancement ◽  
Significant Difference ◽  
Pediatric Brain

Background/Objective: Brain tumors are the most common solid cancer in children and cause significant mortality and morbidity. We compare the effectiveness of different parameters in predicting tumor grade between dynamic contrast enhancement (DCE), intravoxel incoherent motion (IVIM), dynamic susceptibility contrast (DSC) perfusion and diffusion weighted imaging (DWI).    Methods: A retrospective blinded review of pediatric brain tumors with DCE, IVIM, DWI, and DSC was performed. Parametric maps were registered to T2 weighted images. Volumetric regions of interest (ROI) were manually segmented from solid tumor components for each patient by a neuroradiologist (CH), neuroradiology fellow (BG), and medical student (EC). Resulting mean values for parameters from DCE (Ktrans, Kep, Ve, Vp,), IVIM (D, D*, f), DSC (rCBV) and DWI (ADC) were compared using Student’s t-test for high- and low-grade tumor groups based on WHO grading from pathology. For significant parameters, receiver operating characteristic (ROC) analysis with area under curve (AUC) was performed.     Results: 20 subjects were included with 9 low grade and 11 high grade tumors. Significant differences between low versus high grade were demonstrated for D (10−3 mm2/s) (1.4±0.4 vs 0.9±0.2, p=0.01), f (0.04±0.02 vs 0.07±0.02, p=0.02), ADC (10−3 mm2/s) (1.4±0.4 vs 0.9±0.3, p=0.009) and rCBV (2.2±0.9 vs 4.7±2.1, p=0.003). No significant difference was found for D* or any DCE parameter. AUC from ROC was similar for all significant parameters [D (0.81, p=0.003); f (0.80, p=0.003); ADC (0.83, p=0.001); rCBV (0.83, p=0.0005)].    Conclusion: D and f parameters from IVIM can significantly differentiate high versus low grade pediatric brain tumors similar to ADC and rCBV. Conversely, no DCE parameter was significant.    Scientific Implications: The results will assist the selection of MRI sequences that best predict tumor grade, as well as guide tumor biopsy for the most aggressive tumor portions. Further study of these techniques may correlate with molecular profiling and predict outcome. 

scholarly journals From first symptoms to diagnosis: Initial clinical presentation of primary brain tumors

2020 ◽  
Vol 4 (2) ◽  
pp. 2514183X2096836
Author(s):  
B Alther ◽  
V Mylius ◽  
M Weller ◽  
AR Gantenbein
Keyword(s):  
Brain Tumors ◽  
Clinical Presentation ◽  
Personality Change ◽  
University Hospital ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Primary Brain Tumors ◽  
Presenting Symptoms ◽  
Time To Diagnosis

Background: Despite modern imaging methods, a long symptom-to-diagnosis interval can be observed in patients with primary brain tumors. Objective: The study evaluated the initial and subsequent clinical presentation of patients with brain tumors in the context of time to diagnosis, localization, histology, and tumor grading. Methods: In this retrospective analysis of 85 consecutive patients with primary brain tumors, we assessed the presenting symptoms and signs. The analyses were based on entries from medical records at the Department of Neurology of Zurich University Hospital between 2005 and 2010. Results: A total of 54 men and 31 women with a mean age at diagnosis of 48 years were included. 60% of the patients present with a malignant tumor (World Health Organization grading III–IV), 24.7% with a benign tumor (I–II), and 15.3% were not classified. The interval between symptom onset and diagnosis varied from 1 day to 96 months (median: 39 days). High-grade tumors (III–IV) were diagnosed significantly earlier than low-grade tumors (II) after the first symptoms occurred (median: 26 vs. 138 days; z = −3.847, p < 0.001). Conclusions: Symptoms with a short symptom-to-diagnosis interval such as nausea/vomiting, seizures, as well as of personality change are assumed to contribute to a faster diagnosis in high-grade tumors. Visual disturbances and headaches, although occurring relatively seldom, did not contribute to a decrease in time to diagnosis and should therefore be considered for further diagnostic workup.

Correlation of Ki-67 and p53 With the New World Health Organization/International Society of Urological Pathology Classification System for Urothelial Neoplasia

2001 ◽  
Vol 125 (5) ◽  
pp. 646-651 ◽  
Author(s):  
Stephen J. Cina ◽  
Kristen J. Lancaster-Weiss ◽  
Kristen Lecksell ◽  
Jonathan I. Epstein
Keyword(s):  
Papillary Carcinoma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Papillary Lesions ◽  
Flat Lesions ◽  
Papillary Hyperplasia ◽  
Health Organization ◽  
Papillary Neoplasm

Abstract Objective.—The present study examines p53 and Ki-67 staining patterns of the diagnostic entities included within the new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms. Design.—We retrospectively studied 151 bladder biopsies from 81 patients with the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12); low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB-1). Two hundred cells from each lesion were visually counted, and the percentage of positive cells was tabulated without knowledge of the WHO/ISUP diagnosis. Results.—In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder, 29% of the benign urothelial cells were p53 positive. In papillary lesions, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high-grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary neoplasm of LMP. Conclusions.—An increased proliferative index as demonstrated by immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma but may be seen in benign-appearing urothelium, suggesting a “field effect” with occult molecular aberration.

scholarly journals Do Intratumoral And Peritumoral Apparent Diffusion Coefficient (ADC) Values Have A Role In The Diagnosis Of Pediatric Brain Tumors?

2020 ◽  
Author(s):  
Güleç Mert Doğan ◽  
Ahmet Sığırcı ◽  
Sevgi Taşolar ◽  
Aslınur Cengiz ◽  
Hilal Er Ulubaba ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Brain Tumors ◽  
Magnetic Resonance Image ◽  
Pediatric Patients ◽  
Pediatric Brain Tumors ◽  
Low Grade ◽  
High Grade ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Pediatric Brain

INTRODUCTION: The motion of water particles within biological tissues, which is called random Brownian motion, is detected at the microscopic level by Diffusion-Weighted Imaging (DWI) sequence of Magnetic Resonance Image technique. The Apparent Diffusion Coefficient (ADC) calculated on DWI has been used for tumor diagnosis and grading. The purpose of this study was to evaluate of ADC values in the differential diagnosis of supratentorial and infratentorial pediatric brain tumors and to reveal the difference of peritumoral ADC measurements of pediatric patients from adult patients. METHODS: All of the 56 pediatric patients included in this retrospective study had lesions >1 cm in diameter on magnetic resonance image and all of the diagnosies were confirmed by histopathology. Intratumoral and peritumoral ADC values and ratios were measured in diffusion weighted Magnetic Resonance Image. RESULTS: The 58.9% (n=33) of these tumors were supratentorial and 41.1% (n=23) were infratentorial. ADC values and ADC ratios were significantly lower in high-grade tumors than low-grade tumors (p<0.05). Peritumoral ADC values in high-grade tumors were lower than low grade tumors (p<0.05). The cut-off value of the ADC ratio between these two groups was 1 and the ADC cut-off value was 1.1*10-3 mm2/s. DISCUSSION AND CONCLUSION: In the differentiation of low and high-grade pediatric brain tumors, cut-off values of 1.1*10_3mm2/s for ADC Value and 1.0 for ADC Ratio may be useful. Although, peritumoral ADC values differ in children compared to the adult group, both intratumoral and peritumoral ADC values can help for grading pediatric brain tumors.

scholarly journals Expression of Ki-67 in Low-Grade and High-Grade Astrocytomas

2018 ◽  
Vol 27 (3) ◽  
pp. 225-230
Author(s):  
Cléciton Braga Tavares ◽  
Francisca Das Chagas Sheyla Almeida Gomes Braga ◽  
Emerson Brandão Sousa ◽  
José Nazareno Pearce de Oliveira Brito
Keyword(s):  
Survival Time ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Exclusion Criteria ◽  
World Health Organization Classification ◽  
Ki 67 ◽  
Mesh Terms ◽  
Health Organization ◽  
Selection Of

Objective. This review aims to carry out a survey on the importance of Ki67 in the astrocytomas study. Methods. A search in the electronic database of Medline via PubMed and using MESH terms was carried out. Articles were published between January 2005 and December 2015. All studies were analyzed by two experienced researchers, using inclusion and exclusion criteria for the selection of studies. Results. Five studies showed an association between cell proliferation and survival time. Four articles mentioned as cut-off point for survival a Ki67 of 10% and a fifth article a Ki67 of 14.3. A study showed an association between therapeutic failure and Ki67. Four studies have made the association between Ki67 and World Health Organization classification. Conclusion. High levels of Ki67 are associated to high grade astrocytomas and lower survival time.

Low-Grade Papillary Urothelial Carcinoma of the Urinary Bladder: A Clinicopathologic Analysis of a Post–World Health Organization/International Society of Urological Pathology Classification Cohort From a Single Academic Center

2010 ◽  
Vol 134 (8) ◽  
pp. 1160-1163
Author(s):  
Hiroshi Miyamoto ◽  
Fadi Brimo ◽  
Luciana Schultz ◽  
Huihui Ye ◽  
Jeremy S. Miller ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
World Health Organization ◽  
International Society ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
The Mean ◽  
Papillary Urothelial Carcinoma ◽  
Health Organization ◽  
Grade Progression

Abstract Context.—Few large cohort studies have addressed outcome in patients with noninvasive low-grade papillary urothelial carcinoma (LG-UrCa) following implementation of the 2004 World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification. Objective.—To evaluate our cohort of LG-UrCa cases classified according to 2004 WHO/ISUP to reassess outcome and interobserver agreement. Design.—Files were searched for all patients diagnosed with LG-UrCa between 1998 and 2008. All sections were reevaluated for accuracy of classification. Results.—A total of 112 cases initially diagnosed as LG-UrCa were identified. Of those, 8 of 55 cases (15%) initially diagnosed by nonurologic pathologists were reclassified as high-grade papillary urothelial carcinoma and were excluded. The mean length of follow-up was 40.1 months (range, 2–113 months). Tumor recurrence was encountered in 56 of 104 patients (53.8%), including 37 (35.6%) with LG-UrCa or lower-grade tumors and 19 (18.3%) with high-grade papillary urothelial carcinoma. Of the 19 patients demonstrating grade progression, 7 (37%) also developed stage progression (invasive carcinoma, n  =  5; metastatic carcinoma, n  =  2). Seven patients eventually underwent radical cystectomy. None of the 104 patients died of bladder cancer. The mean number of recurrence episodes was 3.11. The mean durations of time to first recurrence and time to grade progression were 13.9 months and 25.1 months, respectively. The mean size of initial tumors was 1.73 cm. There was no significant correlation between tumor size, patient age, sex, or smoking history and the likelihood for recurrence or grade progression. A significantly higher rate of recurrence was seen in patients with multiple tumors at initial diagnosis (P  =  .04). Conclusions.—A tendency to underdiagnose high-grade papillary urothelial carcinoma continues to exist. More than half (53.8%) of patients with LG-UrCa developed recurrence, with an 18.3% incidence of grade progression and a 6.7% incidence of stage progression. Patients with multiple initial tumors had significantly higher risk of developing recurrence.

scholarly journals Radiohistogenomics of pediatric low-grade neuroepithelial tumors

2021 ◽  
Author(s):  
Asim K. Bag ◽  
Jason Chiang ◽  
Zoltan Patay
Keyword(s):  
Holistic Approach ◽  
Genetic Alterations ◽  
Genetic Alteration ◽  
World Health ◽  
Low Grade ◽  
Neuroepithelial Tumors ◽  
Molecular Features ◽  
Standard Clinical Practice ◽  
Imaging Characteristics ◽  
Health Organization

Abstract Purpose In addition to histology, genetic alteration is now required to classify many central nervous system (CNS) tumors according to the most recent World Health Organization CNS tumor classification scheme. Although that is still not the case for classifying pediatric low-grade neuroepithelial tumors (PLGNTs), genetic and molecular features are increasingly being used for making treatment decisions. This approach has become a standard clinical practice in many specialized pediatric cancer centers and will likely be more widely practiced in the near future. This paradigm shift in the management of PLGNTs necessitates better understanding of how genetic alterations influence histology and imaging characteristics of individual PLGNT phenotypes. Methods The complex association of genetic alterations with histology, clinical, and imaging of each phenotype of the extremely heterogeneous PLGNT family has been addressed in a holistic approach in this up-to-date review article. A new imaging stratification scheme has been proposed based on tumor morphology, location, histology, and genetics. Imaging characteristics of each PLGNT entity are also depicted in light of histology and genetics. Conclusion This article reviews the association of specific genetic alteration with location, histology, imaging, and prognosis of a specific tumor of the PLGNT family and how that information can be used for better imaging of these tumors.

scholarly journals Magnetic resonance–guided stereotactic laser ablation therapy for the treatment of pediatric brain tumors: a multiinstitutional retrospective study

2020 ◽  
Vol 26 (1) ◽  
pp. 13-21
Author(s):  
Elsa V. Arocho-Quinones ◽  
Sean M. Lew ◽  
Michael H. Handler ◽  
Zulma Tovar-Spinoza ◽  
Matthew Smyth ◽  
...  
Keyword(s):  
Laser Ablation ◽  
Brain Tumors ◽  
Adjuvant Treatment ◽  
Pediatric Brain Tumors ◽  
Tumor Location ◽  
Neurological Deficits ◽  
Low Grade ◽  
High Grade ◽  
Pediatric Brain

OBJECTIVEThis study aimed to assess the safety and efficacy of MR-guided stereotactic laser ablation (SLA) therapy in the treatment of pediatric brain tumors.METHODSData from 17 North American centers were retrospectively reviewed. Clinical, technical, and radiographic data for pediatric patients treated with SLA for a diagnosis of brain tumor from 2008 to 2016 were collected and analyzed.RESULTSA total of 86 patients (mean age 12.2 ± 4.5 years) with 76 low-grade (I or II) and 10 high-grade (III or IV) tumors were included. Tumor location included lobar (38.4%), deep (45.3%), and cerebellar (16.3%) compartments. The mean follow-up time was 24 months (median 18 months, range 3–72 months). At the last follow-up, the volume of SLA-treated tumors had decreased in 80.6% of patients with follow-up data. Patients with high-grade tumors were more likely to have an unchanged or larger tumor size after SLA treatment than those with low-grade tumors (OR 7.49, p = 0.0364). Subsequent surgery and adjuvant treatment were not required after SLA treatment in 90.4% and 86.7% of patients, respectively. Patients with high-grade tumors were more likely to receive subsequent surgery (OR 2.25, p = 0.4957) and adjuvant treatment (OR 3.77, p = 0.1711) after SLA therapy, without reaching significance. A total of 29 acute complications in 23 patients were reported and included malpositioned catheters (n = 3), intracranial hemorrhages (n = 2), transient neurological deficits (n = 11), permanent neurological deficits (n = 5), symptomatic perilesional edema (n = 2), hydrocephalus (n = 4), and death (n = 2). On long-term follow-up, 3 patients were reported to have worsened neuropsychological test results. Pre-SLA tumor volume, tumor location, number of laser trajectories, and number of lesions created did not result in a significantly increased risk of complications; however, the odds of complications increased by 14% (OR 1.14, p = 0.0159) with every 1-cm3 increase in the volume of the lesion created.CONCLUSIONSSLA is an effective, minimally invasive treatment option for pediatric brain tumors, although it is not without risks. Limiting the volume of the generated thermal lesion may help decrease the incidence of complications.

scholarly journals Clinicopathological Significance of Nestin Expression as a Diagnostic and Prognostic Marker in Brain Gliomas, Independent of IDH Mutation

2021 ◽  
Author(s):  
Chang Gok Woo
Keyword(s):  
Poor Prognosis ◽  
Tissue Microarrays ◽  
Adult Brain ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Nestin Expression ◽  
High Grade Gliomas ◽  
Health Organization ◽  
Brain Gliomas

Abstract Background: Nestin, a type VI intermediate filament, is expressed in neuroepithelial cells during embryogenesis and has been expressed in various human tumors. Recent studies have reported that expression is associated with poor prognosis in brain tumors, but the results are inconclusive. In this study, we evaluated usefulness of Nestin expression using immunohistochemistry as a diagnostic and prognostic biomarker for IDH mutation and the new World Health Organization (WHO) classification.Methods: To investigate Nestin expression, immunohistochemistry was performed on 92 adult brain gliomas using tissue microarrays. We further analyzed the clinical characteristics and survival outcomes according to Nestin expression and examined its correlation with another glioma biomarker, IDH mutation.Results: Sixty patients (65.2%) were Nestin-positive (weak and strong). Nestin expression and intensity were significantly correlated with age, location, diagnosis, and IDH mutations. Old age and high-grade gliomas showed a higher frequency and stronger intensity of Nestin expression than those of young age and with low-grade gliomas (p<0.001). Gliomas with IDH mutations that are located in the frontal lobe showed no expression or had weak positivity. Multivariate analysis demonstrated that Nestin expression (weak, hazard ratio [HR] 5.39, p=0.036; strong, HR 8.43, p=0.007) and IDH wildtype (HR 7.63; p=.001) were significant independent prognostic factors. Moreover, patients with tumors expressing Nestin showed shorter survival (p<0.001).Conclusions: Nestin expression exhibits high intensity in high-grade gliomas and is a useful diagnostic marker. High expression and level of Nestin were significantly correlated with worse survival and was considered a significant marker of poor prognosis in new WHO classification, independent of IDH mutation.

Year 1 in the Molecular Era of Pediatric Brain Tumor Diagnosis: Application of Universal Clinical Targeted Sequencing in an Unselected Cohort of Children

2018 ◽  
pp. 1-13
Author(s):  
Bonnie L. Cole ◽  
Christina M. Lockwood ◽  
Shannon Stasi ◽  
Jeffrey Stevens ◽  
Amy Lee ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Clinical Laboratory ◽  
Pediatric Brain Tumors ◽  
Genetic Alterations ◽  
Targeted Sequencing ◽  
Low Grade ◽  
Clinical Tool ◽  
Pilot Studies ◽  
Pediatric Brain

Purpose Next-generation sequencing is gaining acceptance as a clinical tool to aid diagnosis and guide treatment of pediatric cancer. Prior pilot studies have evaluated the feasibility and utility of clinical genomic profiling in a subset of selected patients with brain tumors. Here, we report an unselected prospective cohort study to evaluate the clinical use of universal targeted sequencing in pediatric patients with brain tumors. Methods We applied a universal sequencing protocol for all tumors of the CNS undergoing diagnostic workup at Seattle Children’s Hospital during the study period of November 2015 to November 2016. All tumors were sequenced using the UW-OncoPlex platform, which is a multiplexed targeted deep gene sequencing panel that detects genetic alterations in 262 cancer-related genes performed in a College of American Pathologists–accredited Clinical Laboratory Improvements Amendments–certified laboratory. Results Eighty-eight patients underwent diagnostic evaluation during the study period, of which 85 tumors (95%) yielded sufficient DNA for sequencing, including 59 newly diagnosed and 26 relapsed. Clinically relevant genetic alterations were identified in 68 of 85 patients (80%). Of these, 57 (67%) had disease-defining or disease-modifying mutations, 44 (52%) had potentially targetable mutations, and 31 (36%) had mutations requiring germline follow-up. As of the last follow-up, seven patients had been prescribed targeted agents on the basis of sequencing results, and nine had confirmed deleterious germline mutations. Conclusion Clinically validated molecular profiling of pediatric brain tumors aids diagnosis and treatment of patients with a variety of high- and low-grade primary and relapsed pediatric brain tumors.

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