A Case of Diffuse Multicentric Metachronous Astrocytoma of Temporoinsular and Intramedullary Location

2021 ◽  
pp. 1-4
Author(s):  
Jorge Linares Torres ◽  
Jorge Linares Torres ◽  
Guillermo Ibanez Botella ◽  
Antonio Selfa Rodriguez ◽  
Laura Cerro Larrazabal ◽  
...  
Keyword(s):  
Histopathological Study ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
High Grade ◽  
Musical Ability ◽  
Wild Type ◽  
Isocitrate Dehydrogenase 1 ◽  
Intramedullary Lesion ◽  
Multicentric Gliomas ◽  
Chronological Time

Multiple gliomas are rare glial tumors with a histology that is typically consistent with high-grade gliomas. A distinction is made between multifocal and multicentric gliomas according to criteria of anatomical continuity, as well as between synchronous and metachronous gliomas according to chronological time of onset. We present the case of a professional saxophonist with a left temporoinsular lesion who underwent awake craniotomy with monitoring of verbal and musical ability as well as primary sensory and motor cortices. Histopathological study revealed an isocitrate dehydrogenase 1 (IDH)-mutant diffuse astrocytoma. After 4 years of complete oncological remission, the patient developed impaired proprioception in all four extremities. An intramedullary lesion was detected at the level of C4 consistent with an IDH wild-type diffuse astrocytoma. We highlight the singularity of this case as it involved two low-grade glial lesions, separated in time (metachronous) and location (multicentric), as well as genetic differences between both lesions (IDH mutant and wild type).

scholarly journals Molecular Landscape for Malignant Transformation in Diffuse Astrocytoma

2021 ◽  
Author(s):  
Thara Tunthanathip ◽  
Surasak Sangkhathat ◽  
Kanet Kanjanapradit
Keyword(s):  
Malignant Transformation ◽  
Extent Of Resection ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Continuous Variables ◽  
Isocitrate Dehydrogenase 1 ◽  
Molecular Alteration ◽  
Exact Test ◽  
Molecular Abnormalities ◽  
Biological Variables

Abstract Background Malignant transformation (MT) of low-grade gliomas changes dramatically the natural history to poor prognosis. Currently, factors associated with MT of gliomas have been inconclusive, in particular, diffuse astrocytoma (DA). Objective The present study aims to explore the molecular abnormalities related to MT in the same patients with different MT stages. Methods Twelve specimens from five DA patients with MT were genotyped using next-generation sequencing (NGS) to identify somatic variants in different stages of MT. We used cross-tabulated categorical biological variables and compared the mean of continuous variables to assess for association with MT. Results Ten samples succussed to perform NGS from one male and four females, with ages ranging from 28 to 58 years. The extent of resection was commonly a partial resection following postoperative temozolomide with radiotherapy in 25% of cases. For molecular findings, poly-T-nucleotide insertion in isocitrate dehydrogenase 1 (IDH1) was significantly related to MT as a dose–response relationship (Mann–Whitney's U test, p = 0.02). Also, mutations of KMT2C and GGT1 were frequently found in the present cohort, but those did not significantly differ between the two groups using Fisher's exact test. Conclusion In summary, we have identified a novel relationship between poly-T insertion polymorphisms that established the pathogenesis of MT in DA. A further study should be performed to confirm the molecular alteration with more patients.

scholarly journals Inhibitor potency varies widely among tumor-relevant human isocitrate dehydrogenase 1 mutants

2018 ◽  
Vol 475 (20) ◽  
pp. 3221-3238 ◽  
Author(s):  
Diego Avellaneda Matteo ◽  
Grace A. Wells ◽  
Lucas A. Luna ◽  
Adam J. Grunseth ◽  
Olga Zagnitko ◽  
...  
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Resistance Mutation ◽  
Poor Response ◽  
Fold Increase ◽  
Structural Features ◽  
Low Grade ◽  
Wild Type ◽  
Isocitrate Dehydrogenase 1 ◽  
Dynamics Simulations ◽  
Mutant Idh1

Mutations in isocitrate dehydrogenase 1 (IDH1) drive most low-grade gliomas and secondary glioblastomas and many chondrosarcomas and acute myeloid leukemia cases. Most tumor-relevant IDH1 mutations are deficient in the normal oxidization of isocitrate to α-ketoglutarate (αKG), but gain the neomorphic activity of reducing αKG to D-2-hydroxyglutarate (D2HG), which drives tumorigenesis. We found previously that IDH1 mutants exhibit one of two reactivities: deficient αKG and moderate D2HG production (including commonly observed R132H and R132C) or moderate αKG and high D2HG production (R132Q). Here, we identify a third type of reactivity, deficient αKG and high D2HG production (R132L). We show that R132Q IDH1 has unique structural features and distinct reactivities towards mutant IDH1 inhibitors. Biochemical and cell-based assays demonstrate that while most tumor-relevant mutations were effectively inhibited by mutant IDH1 inhibitors, R132Q IDH1 had up to a 16 300-fold increase in IC50 versus R132H IDH1. Only compounds that inhibited wild-type (WT) IDH1 were effective against R132Q. This suggests that patients with a R132Q mutation may have a poor response to mutant IDH1 therapies. Molecular dynamics simulations revealed that near the NADP+/NADPH-binding site in R132Q IDH1, a pair of α-helices switches between conformations that are more wild-type-like or more mutant-like, highlighting mechanisms for preserved WT activity. Dihedral angle changes in the dimer interface and buried surface area charges highlight possible mechanisms for loss of inhibitor affinity against R132Q. This work provides a platform for predicting a patient's therapeutic response and identifies a potential resistance mutation that may arise upon treatment with mutant IDH inhibitors.

Anatomical location differences between mutated and wild-type isocitrate dehydrogenase 1 in low-grade gliomas

2017 ◽  
Vol 127 (10) ◽  
pp. 873-880 ◽  
Author(s):  
Jinhua Yu ◽  
Zhifeng Shi ◽  
Chunhong Ji ◽  
Yuxi Lian ◽  
Yuanyuan Wang ◽  
...  
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Anatomical Location ◽  
Low Grade ◽  
Wild Type ◽  
Isocitrate Dehydrogenase 1 ◽  
Low Grade Gliomas

PET–CT for the diagnosis and treatment of primary musculoskeletal tumors in Chinese patients - experience from 255 patients in a single center

2021 ◽  
Author(s):  
Aikeremujiang Muheremu ◽  
Tianlin Wen ◽  
Xiaohui Niu
Keyword(s):  
Soft Tissue ◽  
Case Series ◽  
Soft Tissue Sarcomas ◽  
Standardized Uptake Value ◽  
Chinese Patients ◽  
Histopathological Study ◽  
Low Grade ◽  
High Grade ◽  
Musculoskeletal Tumors ◽  
Pet Ct

Objective: The current study was carried out to assess the value of positron emission tomography (PET)/CT on the diagnosis and staging of primary musculoskeletal tumors. Methods: PET–CT test results and histopathological study reports of all the patients with primary musculoskeletal tumors in our department from January 2006 to July 2015 were retrospectively reviewed. Maximum standardized uptake value (SUVmax) in these PET–CT reports were recorded and analyzed respectively for each type of sarcoma. Results: A total of 255 patients were included in the final analysis. Sensitivity of SUVmax based diagnosis was 96.6% for primary malignant osseous sarcomas and 91.2% for soft tissue sarcomas. SUVmax of high-grade osseous sarcomas (average 8.4 ± 5.5) was significantly higher (p < 0.001) than low-grade osseous sarcomas (average 3.9 ± 1.8); based on current case series, SUVmax of high-grade soft tissue sarcomas (7.5 ± 5.1) was not significantly different (p = 0.229) from that of low-grade soft tissue sarcomas (5.3 ± 3.7). Significant decrease of SUVmax value after chemotherapy was associated with favorable prognosis in patients with osteosarcoma. Conclusion: Results of the current study indicate that, the SUVmax based application of PET–CT can be a valuable supplementary method to histopathological tests regarding the diagnosis and staging of primary musculoskeletal sarcomas. Advances in knowledge: SUVmax based application of PET–CT is a highly sensitive method in diagnosis of primary osseous and soft tissue sarcomas in Chinese patients.

scholarly journals MDM2 overexpression does not account for stabilization of wild-type p53 protein in non-Hodgkin's lymphomas

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3239-3246 ◽  
Author(s):  
R Maestro ◽  
A Gloghini ◽  
C Doglioni ◽  
D Gasparotto ◽  
T Vukosavljevic ◽  
...  
Keyword(s):  
P53 Protein ◽  
P53 Gene ◽  
Critical Ratio ◽  
Low Grade ◽  
High Grade ◽  
Protein Overexpression ◽  
Wild Type ◽  
Donor And Acceptor ◽  
Hodgkin's Lymphomas ◽  
Mdm2 Overexpression

p53 protein overexpression is a frequent finding in non-Hodgkin's lymphomas (NHL), being detected in over 25% of the cases. Moreover, some high-grade lymphomas and a large fraction of low-grade tumors show a pattern of scattered p53 accumulation in a limited percentage of neoplastic cells. In contrast, NHLs show a low frequency of p53 gene mutations. To investigate the molecular bases of p53 protein overexpression, a large series of NHLs was analyzed for p53 gene status. The analysis of the entire coding region of the gene (exons 2–11) and corresponding donor and acceptor splicing sites indicated that a significant proportion of p53-positive tumors overexpresses a wild-type form of p53 protein (wt-p53). To assess whether wt-p53 accumulation was related to the formation of inactive complexes with endogenous proteins, MDM2 oncogene expression and amplification were analyzed. MDM2 overexpression was detected only in one third of the wt-p53-positive cases, thus excluding that MDM2 accounts tout court for the accumulation of a normal p53 protein. However, the fact that MDM2 overexpression was detected in only the p53-positive cases and the observation that MDM2-positive cells were a subpopulation of p53-positive cells suggest a link between the two phenomena. In particular, our results indicate that the accumulation of a wt form of p53 protein could promote the overexpression of the MDM2 gene product. In addition, the prevalence of MDM2 positivity in intermediate/high-grade tumors together with the concordant expression of wt-p53 and MDM2 only in the high-grade component of a ‘composite’ lymphoma suggests that perturbation in the MDM2/p53 critical ratio could play a role in lymphoma progression.

scholarly journals A Simple Panel of IDH1 and P53 in Differential Diagnosis Between Low-Grade Astrocytoma and Reactive Gliosis

2021 ◽  
Vol 14 ◽  
pp. 2632010X2098616
Author(s):  
Bita Geramizadeh ◽  
Mahsa Kohandel-Shirazi ◽  
Ahmad Soltani
Keyword(s):  
Differential Diagnosis ◽  
Isocitrate Dehydrogenase ◽  
P53 Mutation ◽  
Reactive Gliosis ◽  
World Health ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Glial Tumor ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade

Background: Reactive gliosis is a response of glial tissue to different types of injury such as brain abscess, trauma, hemorrhage, or even neoplastic process. In some circumstances, especially when the tissue biopsy is small, there may be difficulty to discriminate this reactive condition with low-grade diffuse astrocytoma (World Health Organization [WHO] grade II) by conventional hematoxylin and eosin (H&E) slides, so some immunohistochemical and molecular markers have been introduced for this differential diagnosis. One of the important aspects of updated WHO classification in 2016 has been dividing some of the glial tumor according to IDH1 (isocitrate dehydrogenase 1) mutation. Objectives: In this study, we tried to evaluate IDH1 and P53 mutation by immunohistochemistry as a simple and highly specific and sensitive method to differentiate low-grade astrocytoma and reactive gliosis. Material and methods: For 5 years (2013-2018), 50 cases of clinically documented reactive gliosis and 50 cases of low-grade astrocytoma were evaluated for the presence or absence of IDH1 and P53 mutation by immunohistochemistry. Results: Isocitrate dehydrogenase 1 was positive in 92% and 4% of the astrocytoma and reactive gliosis cases and P53 was positive in 90% and 4% of the cases with the final diagnosis of astrocytoma and reactive gliosis, respectively. Discussion and conclusion: Combination of P53 and IDH1 as an immunohistochemical panel showed specificity of 96% and sensitivity of 91% for differential diagnosis of reactive gliosis and low-grade astrocytoma. These 2 markers can be extremely helpful for this differential diagnosis.

scholarly journals Urothelial Tumours of the Urinary Bladder: A Histopathological Study of Cystoscopic Biopsies

2013 ◽  
Vol 52 (191) ◽  
Author(s):  
Sujan Vaidya ◽  
Mamata Lakhey ◽  
Sabira KC ◽  
Suspana Hirachand
Keyword(s):  
Urinary Bladder ◽  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Bladder Tumour ◽  
Transitional Cell ◽  
Histopathological Study ◽  
Low Grade ◽  
High Grade ◽  
Urothelial Tumours ◽  
Bladder Tumours

Introduction: Bladder tumours constitute one of the most common urological conditions. Urothelial(transitional cell) carcinoma accounts for 90% of all primary tumours of the bladder. These tumoursare an important cause of morbidity and mortality. The objective of this study was to present thehistopathological patterns of urothelial tumours and to determine the grade and stage of thesetumours.Methods: This is a 3 year descriptive study of urothelial tumours carried out in the Departmentof Pathology, Patan Academy of Health Sciences (PAHS), Lalitpur, Nepal. Data of all cystoscopicbiopsies collected during this period were analyzed.Results: Of the 83 urinary bladder tumours, 81 (97.59%) cases were urothelial (transitional cell)tumours. Transitional cell carcinoma (TCC) was the most common bladder tumour which was seenin 67 (80.72%) cases. Thirty two (47.76%) cases of TCC were low grade while 35 (52.24%) were highgrade. Forty three (64.18%) cases of TCC were superficial or in early stage (pTa and pT1) while 24(35.82%) showed muscle invasion.Conclusions: Transitional cell carcinoma was the most common bladder cancer. Most of thesetumours were high grade. A large percentage of high grade carcinomas presented with muscleinvasion. Pathological grade and muscle invasion are the most valuable prognostic predictorsof survival. The importance of including smooth muscle in the biopsy specimens needs to beemphasized._______________________________________________________________________________________Keywords: cancer; high grade; low grade; transitional tumour; urinary bladder._______________________________________________________________________________________

scholarly journals Histopathological study of upper versus lower poles of tonsil in chronic tonsillitis among pediatric age group

2019 ◽  
Vol 5 (6) ◽  
pp. 1646
Author(s):  
Sudhakar Rao M. S. ◽  
Apoorva P. ◽  
Bindu Rani K. M. ◽  
Shadakshari G.
Keyword(s):  
Pediatric Patients ◽  
Neck Surgery ◽  
Chronic Tonsillitis ◽  
Histopathological Study ◽  
Low Grade ◽  
High Grade ◽  
Age Group ◽  
Pediatric Age ◽  
Pediatric Age Group ◽  
Grade 3

<p class="abstract"><strong>Background:</strong> To compare the histopathological findings between upper and lower poles of tonsil in pediatric age group keeping in view the local and distant effects of chronic tonsillitis.</p><p class="abstract"><strong>Methods:</strong> Three relevant parameters, grade of inflammation (GOI), activity of inflammation and hyperplasia were histopathologically examined in the tonsils of n=60 pediatric patients with chronic tonsillitis who underwent tonsillectomy in Department of Otorhinolaryngology and Head and Neck Surgery, VIMS, Ballari, Karnataka, India. These parameters were analyzed and were subjected for statistical analysis.  </p><p class="abstract"><strong>Results:</strong> In our study, among 60 patients, n=32 (54.2%) were female and n=28 (45.8%) were male. Those aging 5-10 years were n=34 (57.6%) and 11-15 years were n=26 (42.4%). The tonsillar enlargement of grade 3 were present in n=46 patients (77.7%), n= 12 patients (20%) had grade 2 and n=2 patients (1.3%) had grade 4.</p><p class="abstract"><strong>Conclusions:</strong> The GOI and hyperplasia parameters in our study have highly significant association statistically (p&lt;0.01) in histopathology of upper poles when compared with lower poles both sides. Further, the activity of inflammation when analyzed was more in upper pole when compared with lower poles both sides, However this parameter in left side upper and lower poles of tonsil was not statistically significant . Among the 60 cases studied, in all the cases, the GOI was of high grade and activity of inflammation and hyperplasia was low grade. Chronic tonsillitis and histopathology of chronically infected tonsils becomes an important step in the management of the disease.</p>

scholarly journals ACTR-66. A PHASE 1, OPEN-LABEL, PERIOPERATIVE STUDY OF IVOSIDENIB (AG-120) AND VORASIDENIB (AG-881) IN RECURRENT IDH1 MUTANT, LOW-GRADE GLIOMA: UPDATED RESULTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi28-vi29 ◽  
Author(s):  
Ingo Mellinghoff ◽  
Timothy Cloughesy ◽  
Patrick Wen ◽  
Jennie Taylor ◽  
Elizabeth Maher ◽  
...  
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Phase 1 ◽  
Low Grade ◽  
Wild Type ◽  
Open Label ◽  
Isocitrate Dehydrogenase 1 ◽  
Drug Concentrations ◽  
Reference Samples ◽  
Ongoing Phase ◽  
Orthotopic Glioma

Abstract BACKGROUND Ivosidenib (AG-120, IVO) is a first-in-class oral inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), and vorasidenib (AG-881, VOR) is an oral, potent, brain-penetrant inhibitor of mIDH1/2. Both have been evaluated in glioma patients in ongoing phase 1 studies. In orthotopic glioma models, IVO and VOR reduced 2-hydroxyglutarate (2-HG) levels by 85% and 98%, respectively, despite different brain-to-plasma ratios (< 0.04 vs 1.33). METHODS Patients with recurrent, nonenhancing, WHO-2016 grade 2/3, mIDH1-R132H oligodendroglioma or astrocytoma undergoing craniotomy were randomized 2:2:1 to IVO 500mg QD, VOR 50mg QD, or no treatment (cohort 1), or 1:1 to IVO 250mg BID or VOR 10mg QD (cohort 2), for 4 weeks preoperatively. Postoperatively, patients continued receiving IVO or VOR (control patients were randomized 1:1 to IVO or VOR). Tumors were assessed for mIDH1 status, cellularity, and 2-HG and drug concentrations. Treated subjects were compared with controls and mIDH1/wild-type banked reference samples. Primary endpoint: tumor 2-HG concentration following IVO or VOR. RESULTS As of March 1, 2019, 27 patients (18 men; 25/2 grade 2/3) were randomized preoperatively in cohort 1 (IVO 10, VOR 12, untreated 5): 27 received drug (IVO 13, VOR 14); 1 discontinued VOR postoperatively due to disease progression. Of 26 tumors analyzed, 22 were evaluable. Mean brain-to-plasma ratios: 0.13 IVO, 1.59 VOR. Relative to untreated samples, IVO and VOR reduced tumor 2-HG by 92.0% (95% CI 73.2, 97.4) and 92.5% (95% CI 78.1, 97.7), respectively. Common (≥ 4 patients) TEAEs (all cohort 1 patients, all grades): diarrhea (37.0%), constipation, hypocalcemia, and nausea (each 18.5%), anemia, hyperglycemia, pruritus, headache, and fatigue (each 14.8%). Cohort 2 has completed accrual, with analyses ongoing. CONCLUSIONS In cohort 1 of this phase 1 perioperative study, IVO and VOR demonstrated brain penetrance and lowered 2-HG compared with controls. Updated data from both cohorts will be presented.

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.

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