What's New in Grade II and Grade III Gliomas?

2018 ◽  
Vol 38 (01) ◽  
pp. 041-049
Author(s):  
Wolfgang Wick ◽  
Julie Miller
Keyword(s):  
World Health ◽  
Metabolic Enzyme ◽  
Disease Entity ◽  
Wild Type ◽  
Preclinical Models ◽  
Isocitrate Dehydrogenase 1 ◽  
Molecular Features ◽  
Grade Ii ◽  
Health Organization ◽  
Grade Iii

AbstractThe majority of World Health Organization grade II and grade III gliomas harbor heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1), and tumors with an IDH wild-type status show molecular features of a glioblastoma and simply may constitute a separate disease entity. This discovery has led to a profound shift in the way that gliomas are classified and, consequently, how treatment decisions are made. We will review the current understanding of IDH-mutant gliomagenesis and the preclinical models being used to investigate the underlying biology of these tumors and to explore new therapeutic options for these patients. We further summarize the results of recent pivotal trials addressing treatment of grade II and grade III gliomas and highlight promising IDH-mutant-specific therapies on the horizon.

Stereotactic radiation treatment for recurrent nonbenign meningiomas

2007 ◽  
Vol 106 (5) ◽  
pp. 846-854 ◽  
Author(s):  
Carlos A. Mattozo ◽  
Antonio A. F. De Salles ◽  
Ivan A. Klement ◽  
Alessandra Gorgulho ◽  
David McArthur ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Progression Free Survival ◽  
Malignant Progression ◽  
World Health ◽  
Who Grade ◽  
Stereotactic Radiation ◽  
Grade Ii ◽  
Health Organization ◽  
Grade Iii

Object The authors analyzed the results of stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for the treatment of recurrent meningiomas that were described at initial resection as showing aggressive, atypical, or malignant features (nonbenign). Methods Twenty-five patients who underwent SRS and/or SRT for nonbenign meningiomas between December 1992 and August 2004 were included. Thirteen of these patients underwent treatment for multiple primary or recurrent lesions. In all, 52 tumors were treated. All histological sections were reviewed and reclassified according to World Health Organization (WHO) 2000 guidelines as benign (Grade I), atypical (Grade II), or anaplastic (Grade III) meningiomas. The median follow-up period was 42 months. Seventeen (68%) of the cases were reclassified as follows: WHO Grade I (five cases), Grade II (11 cases), and Grade III (one case). Malignant progression occurred in eight cases (32%) during the follow-up period; these cases were considered as a separate group. The 3-year progression-free survival (PFS) rates for the Grades I, II, and III, and malignant progression groups were 100, 83, 0, and 11%, respectively (p < 0.001). In the Grade II group, the 3-year PFS rates for patients treated with SRS and SRT were 100 and 33%, respectively (p = 0.1). After initial treatment, 22 new tumors required treatment using SRS or SRT; 17 (77%) of them occurred inside the original resection cavity. Symptomatic edema developed in one patient (4%). Conclusions Stereotactic radiation treatment provided effective local control of “aggressive” Grade I and Grade II meningiomas, whereas Grade III lesions were associated with poor outcome. The outcome of cases in the malignant progression group was intermediate between that of the Grade II and Grade III groups, with the lesions showing a tendency toward malignancy.

Pathology of Spinal Ependymomas

Neurosurgery ◽  
2013 ◽  
Vol 73 (2) ◽  
pp. 247-255 ◽  
Author(s):  
Phiroz E. Tarapore ◽  
Peter Modera ◽  
Agne Naujokas ◽  
Michael C. Oh ◽  
Beejal Amin ◽  
...  
Keyword(s):  
Adjuvant Radiotherapy ◽  
Histological Grade ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
World Health ◽  
Subtotal Resection ◽  
Who Grade ◽  
Grade Ii ◽  
Health Organization ◽  
Grade Iii

AbstractBACKGROUND:Ependymomas constitute approximately 40% of primary intraspinal tumors. Current World Health Organization (WHO) grading may not correlate with observed progression-free survival (PFS).OBJECTIVE:This retrospective study of prospectively collected data examines whether PFS is influenced by the histological grade or by the extent of resection. It also analyzes the usage and effectiveness of postoperative adjuvant radiotherapy.METHODS:We reviewed 134 consecutive patients with ependymomas of all grades. Pathology slides were re-reviewed and the histological grades were confirmed by a single neuropathologist. Postoperative residual or recurrence was evaluated with follow-up magnetic resonance imaging.RESULTS:There were 85 male and 49 female patients, ranging from 10 to 79 (median 41) years of age. Thirty patients had WHO grade I tumors, 101 had grade II tumors, and 3 had grade III tumors. Kaplan-Meier analysis of PFS demonstrated a mean duration of 6 years for grade I, 14.9 years for grade II, and 3.7 years for grade III (P &lt; .001). In grade II ependymomas, mean PFS was 11.2 years with subtotal resection and 17.8 years with gross total resection (P &lt; .01). PFS of patients who underwent subtotal resection was not significantly changed by adjuvant radiotherapy (P &lt; .36).CONCLUSION:Patients with grade II ependymoma have significantly longer PFS than patients with grade I ependymoma. The extent of resection did not affect PFS in grade I ependymoma but it did in grade II. Contrary to its higher grade, WHO grade II ependymoma carries a better prognosis than WHO grade I ependymoma.

The Ki-67 labeling index as a prognostic factor in Grade II oligoastrocytomas

2005 ◽  
Vol 102 (6) ◽  
pp. 1033-1039 ◽  
Author(s):  
Mark E. Shaffrey ◽  
Elana Farace ◽  
David Schiff ◽  
James M. Larner ◽  
Melike Mut ◽  
...  
Keyword(s):  
Labeling Index ◽  
World Health ◽  
Ki 67 ◽  
Content Type ◽  
Prognostic Utility ◽  
Grade Ii ◽  
Health Organization ◽  
The University ◽  
Grade Iii ◽  
Fine Print

Object. This study was conducted to determine whether proliferative tumor activity, as assessed using the Ki-67 immunohistochemical labeling index (LI), has prognostic utility for patients with Grade II oligoastrocytomas. Methods. The study period spans the years 1988 to 2000. In a retrospective analysis, the authors selected cases with biopsy-proven diagnoses of Grade II oligoastrocytomas on initial presentation. The authors added new patients to this group and followed all patients prospectively at the University of Virginia Neuro-Oncology Center. Twenty-three adult patients were followed for at least 1 year (median 40.3 months). Eleven patients with Grade II tumors and initial Ki-67 LIs less than 10% had a significantly longer median time to tumor progression (TTP, 51.8 months compared with 9.9 months) and a longer median survival (93.1 months compared with 16.1 months) than 12 patients with initial Ki-67 LIs of 10% or greater. Twelve patients with Grade III oligoastrocytomas had a mean TTP that was similar to the TTP of patients with Grade II tumors and high Ki-67 LIs (mean 4 months compared with 9.9 months) and duration of survival (13.3 months compared with 16.1 months). Conclusions. Patients with a Grade II oligoastrocytoma and a Ki-67 LI of 10% or greater have a much shorter TTP and potentially a poorer disease prognosis than expected—more similar to patients with a Grade III oligoastrocytoma. These results indicate that in the future a measure of proliferative activity should be taken into consideration along with the World Health Organization grading criteria for oligoastrocytomas.

scholarly journals PATH-61. IMMUNOHISTOCHEMICAL PHENOTYPING AND SURVIVAL ANALYSIS OF WHO GRADE II-IV GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi157-vi157
Author(s):  
Nora Poulos ◽  
Srikar Sattiraju ◽  
Charles Opalak ◽  
Mikhail Dozmorov ◽  
Jason Harrison ◽  
...  
Keyword(s):  
Overall Survival ◽  
Wilms Tumor ◽  
Positive Staining ◽  
High Grade ◽  
Wild Type ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Clinical Prognosis ◽  
Grade Ii ◽  
Grade Iii

Abstract INTRODUCTION Specific genetic mutations are linked to clinical prognosis in gliomas. There has been increasing demand to understand the association between tissue biomarker expression and survival. Using patient-derived samples, WHO grade II-IV gliomas were evaluated by the protein-staining pattern of molecular markers of interest across tumor grade, and the association between their expression and survival was investigated. METHODS Tissue microarrays (TMA) containing duplicate 1 mm cores were generated from 78 gliomas (WHO grade II-IV) using an automated TMA system. Immunohistochemistry was performed per the manufactures recommendation to evaluate expression of: Wilms tumor 1 (WT1), platelet endothelial cell adhesion molecule (CD31), adhesion G protein-coupled receptor E5 (CD97), complement decay-accelerating factor (CD55), hypoxia inducible factor 1 subunit alpha (HIF1α), EGF-like module-containing mucin-like hormone receptor-like 3 (EMR3), integrin, and isocitrate dehydrogenase 1 (IDH1). Samples with moderate (+1) or intense (+2) staining to WT1, CD31, CD97, CD55, or HIF1α, or any staining to EMR3 or IDH1 mutation, were considered positive. RESULTS Of the 78 tumor samples, there were 11 (14%) WHO grade II, 22 (28%) grade III, and 45 (59%) grade IV gliomas. Across grade III gliomas, anaplastic astrocytomas had significantly higher positive WT1 (p=0.04), CD31 (p=0.002) and IDH1 wild-type (p< 0.0001) staining. High-grade (III & IV) gliomas had significantly higher positive staining for WT1 (p=0.013), CD31 (0.024), integrin (p=0.021), and IDH1 wild type (p=0.044). In all gliomas, positive staining for WT1 (p< 0.0001), CD31 (p=0.009), CD97 (p=0.024), EMR3 (p=0.036), and IDH1 wild type (p=0.0006) were associated with worse overall survival. After adjusting for patient age, positive staining for WT1 (p=0.003) was associated with worse overall survival. CONCLUSION Using immunohistochemistry, unique biomarker staining patterns were identified for WHO grade III anaplastic astrocytomas and for high-grade gliomas. Irrespective of grade, staining for WT1, CD97, CD31, EMR3, and IDH1 wild-type were associated with worse overall survival.

scholarly journals Pleomorphic Xanthoastrocytoma with Oligodendroglioma-Like Areas with Negative 1p19q Co-Deletion

2021 ◽  
Author(s):  
Deepa Goel ◽  
Shobhna Sharma ◽  
Aditya Gupta
Keyword(s):  
Collision Tumor ◽  
Pleomorphic Xanthoastrocytoma ◽  
The Other ◽  
World Health ◽  
Molecular Testing ◽  
Isocitrate Dehydrogenase 1 ◽  
Mixed Glioma ◽  
Molecular Features ◽  
Diffuse Gliomas ◽  
Health Organization

AbstractThe most common mixed glioma encountered in routine surgical practice is oligoastrocytoma (OA); however, its is currently considered a vanishing entity. The 2016 classification of the World Health Organization (WHO) discourages the diagnosis of tumors as mixed glioma. The recommendations are that diffuse gliomas, including those with mixed or ambiguous histological features, should be subjected to molecular testing. Dual-genotype OAs are not yet a distinct entity or variant in the classification. We report a case of mixed glioma: a pleomorphic xanthoastrocytoma (PXA) mixed with an oligodendroglioma. The immunohistochemistry (IHC) pattern of isocitrate dehydrogenase 1 (IDH1) negativity with retained nuclear expression of the alpha-thalassemia x-linked intellectual disability syndrome (ATRX) protein, and 1p19q co-deletion negativity in both the components enabled its identification as a mixed glioma rather than a collision tumor. To the best of our knowledge, the case herein presented is the fourth case of PXA with oligodendroglioma. Out of the other three reported cases, only one was of a collision tumor with a dual genotype, and the other two showed similar molecular signatures in both components. The present article discusses the histological, immunohistochemical and molecular features of the aforementioned case.

scholarly journals PATH-05. A RETROSPECTIVE STUDY OF TREATMENT STRATEGIES AND OUTCOMES IN WHO GRADE II AND III ISOCITRATE DEHYDROGENASE (IDH) WILD-TYPE ASTROCYTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii164-ii165
Author(s):  
Ashley Aaroe ◽  
Antonio Dono ◽  
Michael Youssef ◽  
Kristin Alfaro-Munoz ◽  
Shiao-Pei Weathers ◽  
...  
Keyword(s):  
Health Science ◽  
Concurrent Chemoradiation ◽  
Diffuse Glioma ◽  
Wild Type ◽  
Science Center ◽  
Who Grade ◽  
Molecular Features ◽  
Adjuvant Temozolomide ◽  
Grade Ii ◽  
Grade Iii

Abstract BACKGROUND WHO grade II and III IDH wild-type astrocytomas behave more aggressively than their IDH mutated counterparts. A subpopulation shares molecular features with the novel entity proposed in cIMPACT-NOW Update 3 “Diffuse astrocytic glioma, IDH wild-type, with molecular features of glioblastoma (GBM), WHO IV”. METHODS We performed a retrospective analysis of clinical and molecular features, management and survival of 134 adult patients treated for grade II and III IDH wild-type astrocytoma between 06/2012 and 12/2018 at MD Anderson Cancer Center (MDACC - 112) and UT Health Science Center at Houston (UTHSC - 22). All patients had IDH1 sequenced, all but 2 had IDH2 sequenced, and 73 had further next generation sequencing. RESULTS Median age at diagnosis was 53 (interquartile range 18-83). 82 patients (61%) were male. 31 patients were histologically diagnosed with grade II astrocytoma, 102 with grade III astrocytoma, and one with diffuse glioma (insufficient tissue to render histologic grade or perform sequencing). EGFR alterations were found in 31 patients and TERT promoter mutations in 22. 84 (63%) received concurrent chemoradiation and adjuvant temozolomide (grade II, n=9; grade III, n=74; NOS, n=1). PFS overall was 12.0 months (grade II = 17.9; grade III = 10.7). OS in patients treated with concurrent chemoradiation and adjuvant temozolomide was 17.1 months versus 17.7 in patients treated with sequential radiation and temozolomide (p = NS), and 10.6 in patients treated with RT alone or surveillance (p&lt; 0.016). The highest 2-year OS was seen in grade II patients treated with concurrent chemoradiation and adjuvant temozolomide (60%). CONCLUSIONS WHO grade II and III IDHwt astrocytoma survival is similar to historical GBM cohorts. The proportion meeting molecular criteria for GBM is yet undefined. Groups who received chemotherapy may perform better than those who do not. Further analysis of MGMT methylation and other molecular factors is ongoing.

WORLD HEALTH ORGANIZATION GRADES II AND III MENINGIOMAS ARE RARE IN THE CRANIAL BASE AND SPINE

Neurosurgery ◽  
2007 ◽  
Vol 61 (6) ◽  
pp. 1194-1198 ◽  
Author(s):  
Burak Sade ◽  
Ali Chahlavi ◽  
Ajit Krishnaney ◽  
Sean Nagel ◽  
Eugene Choi ◽  
...  
Keyword(s):  
World Health Organization ◽  
Tumor Location ◽  
Cranial Base ◽  
World Health ◽  
Spinal Tumors ◽  
Who Grade ◽  
Grade Ii ◽  
Spinal Meningiomas ◽  
Health Organization ◽  
Grade Iii

Abstract OBJECTIVE This study was undertaken to assess a possible relationship between the tumor location and the incidence of World Health Organization (WHO) Grades II and III meningiomas. METHODS A retrospective review of 794 consecutive patients who underwent meningioma resection between January 1991 and March 2004 was conducted. Among these, 47 patients (5.9%) with WHO Grade II meningiomas and 16 patients (2%) with Grade III meningiomas were further analyzed. Tumor location was assessed using preoperative magnetic resonance imaging scans and/or operative reports. Histological grading was done according to the WHO 2000 Classification scheme. RESULTS WHO Grade II tumors were found in eight out of 289 (2.8%) cranial base meningiomas and in zero spinal meningiomas, compared with 39 out of 429 (9.1%) non-cranial base meningiomas. Grade III histology was encountered in two (0.7%) cranial base tumors and in one out of 76 (1.3%) spinal tumors, compared with 13 (3%) non-cranial base tumors. The combined incidence of Grades II and III meningiomas was significantly lower in the cranial base (3.5%) and spinal (1.3%) locations compared with non-cranial base locations (12.1%) (P &lt; 0.001). CONCLUSION WHO Grades II and III meningiomas occur far less frequently in the cranial base and spinal locations. Tumors arising from these locations may have different mechanisms of tumorigenesis and/or progression compared with meningiomas arising from other (non-cranial base) regions.

scholarly journals Pre-operative Neurocognitive Function Was More Susceptible to Decline in Isocitrate Dehydrogenase Wild-Type Subgroups of Lower-Grade Glioma Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Zhe Zhang ◽  
Zeping Jin ◽  
Xiaojie Yang ◽  
Liang Zhang ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Working Memory ◽  
Isocitrate Dehydrogenase ◽  
Neurocognitive Function ◽  
World Health ◽  
Lower Grade ◽  
Wild Type ◽  
Molecular Subgroups ◽  
Lower Grade Glioma ◽  
Grade Ii ◽  
Grade Iii

Background: Neuropsychological deficits frequently occur in diffuse lower-grade glioma (DLGG) patients, but their relationship with molecular subgroups based on the 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) is unclear.Methods: All patients enrolled for this study were divided into different subgroups according to the molecular-integrated 2016 CNS WHO and morphology-centric 2007 CNS WHO to compare their neurocognitive function (NCF) dysfunction. Univariate and multivariate analyses were used to assess the independent factors for NCF decline. The performance of NCF changes for discrimination of IDH and 1p19q status was evaluated by receiver operating characteristic (ROC).Results: There was no significant difference in the clinical characteristics among the molecular and morphologic subgroups. In the molecular subgroups, significant differences in NCF alterations were found in terms of attention function, working memory and executive function in grade II glioma patients; in addition to these changes in NCF, memory function and abstract thinking were also significantly different in grade III glioma patients. The pairwise comparison further confirmed that patients with astrocytoma (A)/anaplastic astrocytoma (AA) with isocitrate dehydrogenase wild-type (IDHwt) glioma were more susceptible to severe cognitive decline in terms of the NCF performance described above. For the morphologic subgroups, only working memory was significantly different in grade III glioma patients. The distribution proportion was significantly different among each subgroup of DLGG (grade II, P = 0.001; grade III, P = 0.002). The proportion of extensive NCF decline (≥5 tests) was 4, 12, and 50% in the IDH mutant oligodendroglioma (IDHm-O), IDHm-A, and IDHwt-A subgroups, and this proportion was 33, 60, and 93% in the IDHm-AO, IDHm-AA, and IDHwt-AA subgroups, respectively. In multivariate regression analysis, molecular types were independent factors for NCF alterations after adjusted the factors of tumor and demographics (p &lt; 0.05). ROC curves suggested combined NCF tests model showed an advantage in the differentiation of IDH status.Conclusions: NCF alteration is closely related to molecular-integrated subgroups with varying degrees and frequencies in DLGG. Patients with IDHwt gliomas are more susceptible to suffer from severe and extensive NCF decline than other subgroups.

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