Pediatric spinal cord diffuse midline glioma, H3 K27-altered with intracranial and spinal leptomeningeal spread: A case report

Primary spinal cord high-grade gliomas, including those histologically identified as glioblastoma (GBM), are a rare entity in the pediatric population but should be considered in the differential diagnosis of intramedullary lesions. Pediatric spinal cord high-grade gliomas have an aggressive course with poor prognosis. The aim of this case report is to present a 15-year-old female adolescent with histopathologically confirmed spinal cord GBM with H3F3A K27 M mutation consistent with a diffuse midline glioma (DMG), H3 K27-altered, CNS WHO grade 4 with leptomeningeal seeding on initial presentation. As imaging features of H3 K27-altered DMGs are non-specific and may mimic more frequently encountered neoplastic diseases as well as demyelinating disorders, severe neurological deficits at presentation with short duration, rapid progression, and early leptomeningeal seeding should however raise the suspicion for a pediatric-type diffuse high-grade glioma like DMG, H3 K27-altered.

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Case Report: Five Adult Cases of H3K27-Altered Diffuse Midline Glioma in the Spinal Cord

Frontiers in Oncology ◽

10.3389/fonc.2021.701113 ◽

2021 ◽

Vol 11 ◽

Author(s):

Quanquan Gu ◽

Yajing Huang ◽

Hao Zhang ◽

Biao Jiang

Keyword(s):

Spinal Cord ◽

Case Report ◽

Aggressive Behavior ◽

Progression Free Survival ◽

Central Canal ◽

Rapid Progression ◽

High Grade ◽

First Case ◽

Diffuse Midline Glioma

BackgroundDiffuse midline glioma with H3K27-altered (DMG-H3K27a) is a novel tumor entity of the pediatric-type diffuse high-grade tumor in the latest WHO CNS 5. It mostly affects children and is only rarely found in adults. The tumor has a high level of aggressiveness, with a rapid progression and bad prognosis. In adults, the spinal cord is the most common site of DMG-H3K27a. Rare adult cases of primary DMG-H3K27a in the spinal cord were reported in this study, together with clinico-histopathologico-radiographic data.MethodsFrom January 2016 to December 2020, we conducted a retrospective study of five adults with primary DMG-H3K27a in the spinal cord, analyzing their clinical, pathohistological, and radiographic datasets from the first diagnosis to follow-up.ResultsAll five patients were diagnosed for the first time and were given full treatment. In three of the five patients, post-operative follow-up revealed tumor recurrence. The longest survival of the five patients was 45 months at the time of report submission, while the longest progression-free survival (PFS) following surgery was 20 months. Immunohistochemical studies showed the tumors featured aggressive behavior (grade 4) and were positive for the H3K27M mutation. The radiographic appearances were varied, but they were all initially mistaken as benign. DMG-H3K27a in the spinal cord was characterized by isointense/hyperintense on T1WI and isointense/hyperintense on T2WI, as well as cystic necrosis and peripheral spinal cord edema, as well as central canal enlargement and other types of enhancement.ConclusionThis is the first case report focusing on adult DMG-H3K27a of the pediatric-type diffuses high-grade gliomas in the spinal cord. In our cases, we discovered the following: 1) adults had a better prognosis with a longer PFS compared with prior pediatric reports; 2) despite aggressive behavior under the microscope, radiographic appearances of the tumors were less aggressive; and 3) adjuvant treatment, including TCM, may have played a role in the prognosis.

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Cervical Intramedullary Spinal Cord Glioblastoma in a 10 Year-Old Child. Case Report

JBNC - JORNAL BRASILEIRO DE NEUROCIRURGIA ◽

10.22290/jbnc.v30i3.1849 ◽

2019 ◽

Vol 30 (3) ◽

pp. 261-266

Author(s):

Otávio Garcia Martins ◽

Amir José dos Santos ◽

Antonio Carlos Garcia D’Almeida ◽

Samir Cezimbra dos Santos ◽

Anna Júlia Ramos Fontanari ◽

...

Keyword(s):

Spinal Cord ◽

Case Report ◽

Rare Case ◽

High Grade ◽

Pediatric Tumors ◽

Spinal Cord Tumors ◽

Intramedullary Spinal Cord ◽

High Grade Gliomas

Among all pediatric tumors in CNS, the intramedullary spinal cord tumors are less than one-third of 1% and only about 1-3% of them are high-grade gliomas. Intramedullary glioblastoma (GBM) is considered highly threatening because of its aggressiveness and, even with intense management, lesion progress and patients develop severe deficits. Authors report a very rare case of a 10-year-old patient with extensive cervical GBM with an unusual outcome.

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COT-21 EFFECT OF BEVACIZUMAB FOR PEDIATRIC HIGH GRADE GLIOMA

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.201 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii44-ii44

Author(s):

Yoshihiro Tsukamoto ◽

Manabu Natsumeda ◽

Masayasu Okada ◽

Takeyoshi Eda ◽

Junichi Yoshimura ◽

...

Keyword(s):

Tumor Progression ◽

Therapeutic Agent ◽

High Grade Glioma ◽

Wound Complication ◽

Symptomatic Improvement ◽

Diffuse Intrinsic Pontine Glioma ◽

Rapid Progression ◽

High Grade ◽

Diffuse Midline Glioma ◽

Pediatric High Grade Glioma

Abstract INTRODUCTION Bevacizumab (BEV) therapy has been used for pediatric high grade glioma,however the evidence and effectiveness are not understood yet. METHODS We report 7 cases (age 2 to 10 years old) of pediatric high grade glioma treated with BEV. One case is thalamic diffuse midline glioma H3K27 mutant (DMGH3K27M),one case is brain stem DMGH3K27M,one case is cerebellar high grade glioma,and 4 cases are diffuse intrinsic pontine glioma (DIPG) diagnosed clinically without biopsy. 5 cases were treated with BEV when diagnosed as recurrence after chemo-radiotherapy. One case was treated for rapid tumor progression during radiotherapy. One case was started on BEV therapy with radiation and concomitant temozolomide therapy. RESULT The number of times of BEV was 2 to 13 times (median 7 times). The period of BEV was 1 to 9 months (median 4 months). One case which was treated with BEV at rapid progression during radiation showed good response on imaging and improvement of symptoms. 4 of 5 cases who were treated at recurrence clinically showed mild symptomatic improvement. One case treated with BEV and radiotherapy initially was not evaluated. The adverse effects of BEV included wound complication of tracheostomy and rash. CONCLUSION BEV showed good response for rapid progression during radiotherapy,and mild response for recurrence cases. BEV is thought to be an effective therapeutic agent for pediatric HGG at recurrence and rapid tumor progression during radiotherapy.

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The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors

Neurosurgery ◽

10.1227/neu.0000000000001020 ◽

2015 ◽

Vol 78 (3) ◽

pp. 401-411 ◽

Cited By ~ 60

Author(s):

Mohammed Jaber ◽

Johannes Wölfer ◽

Christian Ewelt ◽

Markus Holling ◽

Martin Hasselblatt ◽

...

Keyword(s):

Aminolevulinic Acid ◽

Methylation Status ◽

Imaging Features ◽

High Grade ◽

Ki 67 ◽

Who Grade ◽

Fet Pet ◽

Grade Ii ◽

Grade Iii ◽

Mib 1

Abstract BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.

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Pilomyxoid astrocytoma of the cervical spinal cord in a child with rapid progression into glioblastoma: case report and literature review

Child s Nervous System ◽

10.1007/s00381-010-1171-5 ◽

2010 ◽

Vol 27 (2) ◽

pp. 313-321 ◽

Cited By ~ 14

Author(s):

Dimitrios Paraskevopoulos ◽

Ioannis Patsalas ◽

Georgios Karkavelas ◽

Nikolaos Foroglou ◽

Ioannis Magras ◽

...

Keyword(s):

Spinal Cord ◽

Case Report ◽

Literature Review ◽

Cervical Spinal Cord ◽

Rapid Progression ◽

Pilomyxoid Astrocytoma

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Potential CanonicalWntPathway Activation in High-Grade Astrocytomas

The Scientific World JOURNAL ◽

10.1100/2012/697313 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 14

Author(s):

Rebecca Schüle ◽

Christine Dictus ◽

Benito Campos ◽

Feng Wan ◽

Jörg Felsberg ◽

...

Keyword(s):

Direct Sequencing ◽

Luciferase Reporter ◽

High Grade ◽

Luciferase Reporter Gene ◽

Protein Truncation Test ◽

Who Grade ◽

Transcriptional Cofactors ◽

Pathway Activation ◽

Gene Assay ◽

High Grade Gliomas

Aberrantwntpathway activation through cytoplasmic stabilization ofβ-catenin is crucial for the development of various human malignancies. In gliomagenesis, the role of canonical (i.e.,β-catenin-dependent) signalling is largely unknown. Here, we studied canonicalwntpathway activation in 15 short-term cultures from high-grade gliomas and potential pathomechanisms leading to cytoplasmicβ-catenin accumulation. Furthermore, we assessed the prognostic relevance ofβ-catenin expression in a tissue microarray comprising 283 astrocytomas. Expression ofβ-catenin, its transcriptional cofactors TCF-1 and TCF-4 as well as GSK-3βand APC, constituents of theβ-catenin degradation complex was confirmed by RT-PCR in all cultures. A cytoplasmicβ-catenin pool was detectable in 13/15 cultures leading to some transcriptional activity assessed by luciferase reporter gene assay in 8/13. Unlike other malignancies, characteristic mutations ofβ-catenin and APC leading to cytoplasmic stabilization ofβ-catenin were excluded by direct sequencing or protein truncation test. In patient tissues,β-catenin expression was directly and its degradation product's (β-catenin-P654) expression was inversely correlated with WHO grade. Increasedβ-catenin expression and lowβ-catenin-P654 expression were associated with shorter survival. Altogether, we report on potential canonicalwntpathway activation in high-grade gliomas and demonstrate thatβ-catenin expression in astrocytomas is associated with increased malignancy and adverse outcome.

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Unusual Presentation of a High Grade Spinal Cord Glioma: Case Report

Journal of Pain Management & Medicine ◽

10.35248/2684-1320.17.3.129 ◽

2017 ◽

Vol 03 (02) ◽

Author(s):

Neto S ◽

Silva A ◽

Rosa N ◽

Neto da Piedade EM

Keyword(s):

Spinal Cord ◽

Case Report ◽

Unusual Presentation ◽

High Grade ◽

Spinal Cord Glioma ◽

Glioma Case

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Diffuse midline glioma of the cervical spinal cord with H3 K27M genotype phenotypically mimicking anaplastic ganglioglioma: a case report and review of the literature

Brain Tumor Pathology ◽

10.1007/s10014-020-00365-z ◽

2020 ◽

Vol 37 (3) ◽

pp. 89-94

Author(s):

Theo F. J. Kraus ◽

Lukas Machegger ◽

Johannes Pöppe ◽

Barbara Zellinger ◽

Eva Dovjak ◽

...

Keyword(s):

Spinal Cord ◽

Case Report ◽

Cervical Spinal Cord ◽

Review Of The Literature ◽

Diffuse Midline Glioma

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DNA hydroxymethylation in high-grade gliomas

Journal of Neurological Surgery Part A Central European Neurosurgery ◽

10.1055/a-1713-7699 ◽

2021 ◽

Author(s):

Angelika Stapińska-Syniec ◽

Marta Grabiec ◽

Marcin Rylski ◽

Albert Acewicz ◽

Michał Sobstyl

Keyword(s):

Regulation Of Gene Expression ◽

Epigenetic Mechanism ◽

High Grade ◽

Who Grade ◽

Dna Hydroxymethylation ◽

Current State ◽

Survival Estimation ◽

High Grade Gliomas ◽

Tet Enzymes

Background and Study Aims Since the new WHO classification of nervous system tumors (2016 revised 4th edition) has been released, gliomas are classified depending on molecular and genetic markers in connection with histopathology, instead of histopathology itself as it was in the previous classification. Over the last years, epigenetic analysis has taken on increased importance in the diagnosis and treatment of different cancers. Multiple studies confirmed that DNA methylation and hydroxymethylation play an important role in the regulation of gene expression during carcinogenesis. In this review, we aim to present the current state of knowledge on DNA hydroxymethylation in human high-grade gliomas (WHO grade III and IV). Results The correlation of DNA hydroxymethylation and survival in glioblastoma patients was evaluated by different studies. The majority of them showed that the expression of 5-hydroxymethylcytosine (5-hmC) and Ten-eleven translocation (TET) enzymes were significantly reduced, sometimes almost undetectable in high-grade gliomas in comparison with the control brain. A decreased level of 5-hmC was associated with poor survival in patients, but high expression of the TET3 enzyme was related to a better prognosis for GBM patients. This points to the relevance of DNA hydroxymethylation in molecular diagnostics of human gliomas, including survival estimation or differentiating patients in terms of response to the treatment. Conclusion Future studies may shed some more light on this epigenetic mechanism involved in the pathogenesis of human high-grade gliomas and help to develop new targeted therapies.

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