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

Abstract

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
• astrocytoma
• glioma
• Grade 4
• IDH‐mutant
• molecular alteration