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Table of Contents
CASE REPORT
Year : 2022  |  Volume : 5  |  Issue : 3  |  Page : 107-109

WHO grade III diffuse astrocytic glioma in a 35-year-old male


Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China

Date of Submission08-Sep-2022
Date of Decision15-Sep-2022
Date of Acceptance17-Sep-2022
Date of Web Publication13-Oct-2022

Correspondence Address:
Dr. Ping Liang
Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/glioma.glioma_26_22

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  Abstract 


Gliomas are tumors that originate from glial cells and the most common neoplasms in the central nervous system. The World Health Organization (WHO) has classified glioma into four grades, I to IV, with multidisciplinary therapies required for the management of high-grade gliomas (grades III and IV). Molecular pathology has become increasingly critical in guiding the treatment and predicting the prognosis of patients with gliomas. A 35-year-old man diagnosed with WHO grade III diffuse astrocytic glioma initially underwent surgical resection, followed by immunohistochemical and molecular diagnosis. The patient was administered adjuvant radiotherapy and chemotherapy based on the molecular characteristics of the tumor. Long term follow-up showed a relatively satisfactory therapeutic response. Molecular classification may help guide decisions on the comprehensive treatment of patients with WHO grade III diffuse astrocytic glioma. This study was approved by the Ethics Committee of Zhongda Hospital of Southeast University, China (approval No. 20211015001, approval date: October 15, 2021).

Keywords: Case report, glioma, IDH1 mutation, O (6)-methylguanine-DNA methyltransferase promoter methylation, World Health Organization grade III


How to cite this article:
Du R, Liu H, Yi G, Cheng H, Liang P. WHO grade III diffuse astrocytic glioma in a 35-year-old male. Glioma 2022;5:107-9

How to cite this URL:
Du R, Liu H, Yi G, Cheng H, Liang P. WHO grade III diffuse astrocytic glioma in a 35-year-old male. Glioma [serial online] 2022 [cited 2022 Dec 8];5:107-9. Available from: http://www.jglioma.com/text.asp?2022/5/3/107/358555




  Introduction Top


Gliomas, the most prevalent type of brain tumor, have been classified by the World Health Organization (WHO) into four grades, grades I to IV, with grades III and IV considered high-grade glioma. Surgical resection is the standard of care, with most patients having high-grade gliomas administered adjuvant radiotherapy and/or chemotherapy.[1] The treatment of high-grade glioma remains challenging due to the relative paucity of effective therapeutic regimens, the high risk of tumor recurrence, and poor patient prognosis.[2] The introduction of genetic characterization has enabled molecular analysis to provide critical information, including the ability to better predict patient prognosis and determine optimal treatment regimens.[3] Mutations in the isocitrate dehydrogenase 1 (IDH1) gene have been detected frequently in primary glioma tissue, and predict a favorable prognosis with prolonged patient survival.[4] In addition, promoter methylation and expression silencing of the O (6)-methylguanine-DNA methyltransferase (MGMT) gene, which encodes a DNA repair enzyme that antagonizes alkylating chemotherapeutic agents, has been shown to predict a favorable outcome in glioma patients.[5] The present report describes a 35-year-old man who was diagnosed with a WHO grade III diffuse astrocytic glioma and was managed by initial surgery, followed by adjuvant radiochemotherapy guided by the molecular characteristics of the tumor.


  Case Report Top


A 35-year-old man was admitted to our hospital with progressive headache for a year. Magnetic resonance imaging (MRI) showed a heterogeneous mass with hemorrhage in the right frontal and temporal lobes. The mass was surrounded by areas of edema, and a shift of the midline structures to the left was also observed. The mass was significantly enhanced with contrast, suggesting high-grade glioma [Figure 1]. The tumor was totally resected due to its having relatively clear boundaries with normal brain tissue. Immunohistochemical analysis diagnosed the tumor as a WHO grade III diffuse astrocytic glioma, with Ki67 of 20%, an IDH1 mutation, high methylation of the MGMT promoter, and loss of ATRX. Molecular pathological report confirmed that the tumor had IDH1R132H, ATRXE351Rfs*2, and TP53C135W mutations and MYC amplification. Following surgery, the patient received radiation therapy and concomitant chemotherapy based on the molecular identity of the tumor. MRI at 3 months showed no evidence of recurrence, whereas MRI at 6 months showed an abnormal gadolinium-enhanced lesion [Figure 2]. Although the patient did not experience any neurological symptoms, long-term follow-up is required for the confirmation and management of the recurrent tumor.
Figure 1: Preoperative and postoperative gadolinium-enhanced T1-weighted magnetic resonance images. Preoperative sagittal (A), axial (B), and coronal (C) images showing the tumor (arrows). Postoperative sagittal (D), axial (E), and coronal (F) images following tumor resection

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Figure 2: Follow-up gadolinium-enhanced T1-weighted magnetic resonance images. Sagittal (A), axial (B), and coronal (C) images at 3 months. Sagittal (D), axial (E), and coronal (F) images at 6 months, showing tumor relapse (arrows). Sagittal (G), axial (H), and coronal (I) images at 9 months, showing tumor recurrence (arrows)

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Informed consent was obtained from the patient. This study was approved by the Ethics Committee of Zhongda Hospital of Southeast University, China (approval No. 20211015001, approval date: October 15, 2021).


  Discussion Top


High-grade gliomas are aggressive primary tumors of the central nervous system with high recurrence rate and poor prognosis, even after multimodal therapeutic approaches that include surgery, radiation and chemotherapy.[6] Glioma subclassification is increasingly significant in clinical practice. Novel biomarkers can be used to clarify prognostic assessments and treatment recommendations for patients. The 2021 WHO classification of central nervous system tumors also includes multiple genetic features as guidelines for tumor subtyping.[7] The WHO grade III diffuse astrocytic glioma in the present patient was found to be positive for IDH1 and ATRX mutations and for MGMT promoter methylation, indicating better responses to treatment. Although this patient received radiotherapy and temozolomide chemotherapy after total surgical resection, a 6-month postoperative MRI scan showed an abnormality, with the gadolinium-enhanced lesion becoming larger at 9 months. It is unclear, however, whether this lesion is a recurrent tumor, indicating the need for regular follow-up.

In addition to IDH1 mutations and MGMT promoter methylation, several other molecular markers are indicative of patient prognosis and response to treatment. For example, chromosome 1p/19q co-deletion has been validated as a strong prognostic marker in grades II and III gliomas, with this co-deletion being associated with longer overall survival in patients treated with radiation and/or chemotherapy.[8] Telomerase reverse transcriptase, encoded by TERT, is essential for glioma cells to maintain telomeres and proliferative potential, with the prognostic effect of TERT promoter mutations being dependent on the context of MGMT promoter methylation.[9] Novel technologies like single cell-sequencing have the potential to uncover specific biomarkers that may provide insight into the malignant features and mechanisms of treatment resistance in high-grade gliomas.[10]


  Conclusion Top


The present study describes a patient with a WHO grade III glioma who showed indications of tumor recurrence after surgical resection and sequential radio/chemotherapy. Molecular diagnosis is critical for determining treatment regimens in patients with high-grade glioma. Additional studies are required to personalize treatment of patients with high-grade glioma and improve their overall prognosis.

Acknowledgments

Nil.

Financial support and sponsorship

Nil.

Institutional review board statement

This study was approved by the Ethics Committee of Zhongda Hospital of Southeast University, China (approval No. 20211015001) on October 15, 2021.

Declaration of patient consent

The author certifies that he has obtained the appropriate patient consent form. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wang Y, Jiang T. Understanding high grade glioma: Molecular mechanism, therapy and comprehensive management. Cancer Lett 2013;331:139-46.  Back to cited text no. 1
    
2.
Stupp R, Brada M, van den Bent MJ, Tonn JC, Pentheroudakis G, ESMO Guidelines Working Group. High-grade glioma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014;25 Suppl 3:i93-101.  Back to cited text no. 2
    
3.
Reifenberger G, Wirsching HG, Knobbe-Thomsen CB, Weller M. Advances in the molecular genetics of gliomas – Implications for classification and therapy. Nat Rev Clin Oncol 2017;14:434-52.  Back to cited text no. 3
    
4.
Han S, Liu Y, Cai SJ, Qian M, Ding J, Larion M, et al. IDH mutation in glioma: Molecular mechanisms and potential therapeutic targets. Br J Cancer 2020;122:1580-9.  Back to cited text no. 4
    
5.
Weller M, Stupp R, Reifenberger G, Brandes AA, van den Bent MJ, Wick W, et al. MGMT promoter methylation in malignant gliomas: Ready for personalized medicine? Nat Rev Neurol 2010;6:39-51.  Back to cited text no. 5
    
6.
Uhm JH, Porter AB. Treatment of glioma in the 21st century: An exciting decade of postsurgical treatment advances in the molecular era. Mayo Clin Proc 2017;92:995-1004.  Back to cited text no. 6
    
7.
Miller KD, Ostrom QT, Kruchko C, Patil N, Tihan T, Cioffi G, et al. Brain and other central nervous system tumor statistics, 2021. CA Cancer J Clin 2021;71:381-406.  Back to cited text no. 7
    
8.
Otani R, Uzuka T, Higuchi F, Matsuda H, Nomura M, Tanaka S, et al. IDH-mutated astrocytomas with 19q-loss constitute a subgroup that confers better prognosis. Cancer Sci 2018;109:2327-35.  Back to cited text no. 8
    
9.
Vuong HG, Nguyen TQ, Ngo TN, Nguyen HC, Fung KM, Dunn IF. The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: A meta-analysis. BMC Cancer 2020;20:897.  Back to cited text no. 9
    
10.
Tirosh I, Suvà ML. Dissecting human gliomas by single-cell RNA sequencing. Neuro Oncol 2018;20:37-43.  Back to cited text no. 10
    


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  [Figure 1], [Figure 2]



 

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