Novel insight into histological and molecular astrocytoma, IDH-mutant, Grade 4 by the updated WHO classification of central nervous system tumors

Wenlin Chen; Siying Guo; Yaning Wang; Yixin Shi; Xiaopeng Guo; Delin Liu; Yilin Li; Yuekun Wang; Hao Xing; Yu Xia; Junlin Li; Jiaming Wu; Tingyu Liang; Hai Wang; Qianshu Liu; Shanmu Jin; Tian Qu; Huanzhang Li; Tianrui Yang; Kun Zhang; Yu Wang; Wenbin Ma

doi:10.1002/cam4.6476

Novel insight into histological and molecular astrocytoma, IDH-mutant, Grade 4 by the updated WHO classification of central nervous system tumors

Cancer Med. 2023 Sep;12(18):18666-18678. doi: 10.1002/cam4.6476. Epub 2023 Sep 5.

Authors

Wenlin Chen¹, Siying Guo^{1

2}, Yaning Wang¹, Yixin Shi^{1

2}, Xiaopeng Guo^{1

3}, Delin Liu^{1

2}, Yilin Li^{1

4}, Yuekun Wang¹, Hao Xing¹, Yu Xia^{1

2}, Junlin Li^{1

2}, Jiaming Wu^{1

2}, Tingyu Liang¹, Hai Wang¹, Qianshu Liu^{1

2}, Shanmu Jin^{1

4}, Tian Qu^{1

2}, Huanzhang Li^{1

2}, Tianrui Yang^{1

2}, Kun Zhang^{1

2}, Yu Wang^{1

3}, Wenbin Ma^{1

3}

Affiliations

¹ Department of Neurosurgery, Center for Malignant Brain Tumors, National Glioma MDT Alliance, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Eight-year Medical Doctor Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ China Anti-Cancer Association Specialty Committee of Glioma, Beijing, China.
⁴ 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Background: The latest fifth edition of the World Health Organization (WHO) classification of the central nervous system (CNS) tumors (WHO CNS 5 classification) released in 2021 defined astrocytoma, IDH-mutant, Grade 4. However, the understanding of this subtype is still limited. We conducted this study to describe the features of astrocytoma, IDH-mutant, Grade 4 and explored the similarities and differences between histological and molecular subtypes.

Methods: Patients who underwent surgery from January 2011 to January 2022, classified as astrocytoma, IDH-mutant, Grade 4 were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis.

Results: Altogether 33 patients with astrocytoma, IDH-mutant, Grade 4 were selected, including 20 with histological and 13 with molecular WHO Grade 4 astrocytoma. Tumor enhancement, intratumoral-necrosis like presentation, larger peritumoral edema, and more explicit tumor margins were frequently observed in histological WHO Grade 4 astrocytoma. Additionally, molecular WHO Grade 4 astrocytoma showed a tendency for relatively longer overall survival, while a statistical significance was not reached (47 vs. 25 months, p = 0.22). TP53, CDK6, and PIK3CA alteration was commonly observed, while PIK3R1 (p = 0.033), Notch1 (p = 0.027), and Mycn (p = 0.027) alterations may affect the overall survival of molecular WHO Grade 4 astrocytomas.

Conclusions: Our study scrutinized IDH-mutant, Grade 4 astrocytoma. Therefore, further classification should be considered as the prognosis varied between histological and molecular WHO Grade 4 astrocytomas. Notably, therapies aiming at PIK3R1, Notch 1, and Mycn may be beneficial.

Keywords: 2021 WHO classification of central nervous system tumors; Grade 4; IDH-mutant; astrocytoma; glioma; molecular alteration; radiological characteristics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Astrocytoma* / genetics
Brain Neoplasms*
Central Nervous System Neoplasms* / genetics
Glioblastoma*
Humans
Isocitrate Dehydrogenase / genetics
Mutation
N-Myc Proto-Oncogene Protein
World Health Organization

Substances

N-Myc Proto-Oncogene Protein
Isocitrate Dehydrogenase