Brain Tumor Res Treat.  2022 Oct;10(4):255-264. 10.14791/btrt.2022.0035.

Clinical Features and Prognosis of Diffuse Midline Glioma: A Series of 24 Cases

• Jang SW
• Song SW
• Kim YH
• Cho YH
• Hong SH
• Kim JH
• Ra YS
• Chong S

• KMID: 2534724
• DOI: http://doi.org/10.14791/btrt.2022.0035

Abstract

Background
Diffuse midline glioma (DMG) which occurs in midline structures and characterized by harboring K27M mutation in genes encoding the histone 3 protein is classified as World Health Organization (WHO) grade IV regardless of histological findings and has a poor prognosis. Nevertheless, because of its relatively rare incidence compared with other high-grade gliomas, a comprehensive description encompassing clinical features and genomic profiles of DMG is still lacking.
Methods
In this study, we analyzed data of 24 patients who were diagnosed as DMG which was confirmed by surgical specimens in both pediatric and adult patients. We described the clinical outcomes of patients with DMG and their genomic profiles through a retrospective analysis of 24 patients with DMG.
Results
The clinical characteristics of the 24 patients with DMG were analyzed. Ten patients (41%) underwent tumor resection and 14 patients (59%) underwent tumor biopsy. The median overall survival was 10.4 months (95% confidence interval [CI], 8.4 to 12.5) and progression free survival was 3.9 months (95% CI, 2.6 to 5.2). Fifteen patients (62%) were accompanied by hydrocephalus. None of the patient, tumor, or treatment factors had any significant associated with survival. In both immunohistochemistry staining (n=24) and targeted next generation sequencing (n=15), TP53 mutation was the most common genetic mutation (25% and 46%, respectively) found in the patients except alterations in histone 3 protein.
Conclusion
Although surgical treatment of patient with DMG does not affect the overall survival prognosis, it can help improve the patient’s accompanying neurological symptoms in some limited cases. Hydrocephalus is often accompanied with DMG and treatment for hydrocephalus is often also required. Multidisciplinary therapeutic approach is needed.

Keyword

Diffuse intrinsic pontine glioma; Histone H3; Biopsy; Chemoradiotherapy; Sequence analysis; Survival

Figure

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  Fig. 1 Age distribution of the patients. Green, diffuse (from thalamus–pons–cerebellum); skyblue, basal ganglia; orange, thalamus; purple, midbrain; pink, pons; dark pink, medulla; blue, spinal cord; yellow, cerebellum.

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  Fig. 2 Kaplan-Meier survival curves. A: Overall survial curves of the whole cohort (median=10.4 months). B-F: Survival analysis between groups of patients according to tumor locations (p=0.275) (B), surgical treatments (p=0.570) (C), Ki-67 LI of the specimens (p=0.272) (D), tumor sizes and (p=0.054) (E), and adjuvant treatments (p=0.175) (F) reveals no significant differences between the groups (log-rank test). LI, labeling index, CCRT, concurrent chemoradiation therapy; RT, radiation therapy.

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  Fig. 3 Kaplan-Meier survival curves. A: Progression-free survival curves for the whole cohort (median=3.9 months). B: Analysis of progression-free survial between brainstem group and non-brainstem group shows no significant difference (log-rank test, p=0.275).

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  Fig. 4 Genomic landscape of DMG patients obtained by targeted NGS. DMG, diffuse midline glioma; NGS, next generation sequencing; SNV, single-nucleotide variant; CNV, copy number variation; INS, insertion; DEL, deletion.

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  Fig. 5 Illustrative case (Case 12). Preoperative MRI and CT images (A-C) and postoperative MRI and CT images (D-F). A 4-year-old female patient presented with left side weakness (grade 3). The day before surgery, motor weakness aggravated to grade 2 and diplopia occurred. Images revealed pontine tumor with tumor bleeding. The tumor was removed partially and the patient was diagnosed as diffuse midline glioma, H3 K27M altered. After resection, diplopia disappeared and weakness also improved to nearly normal for 9 months till progression.

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  Fig. 6 Illustrative case (Case 18). Preoperative MRI and CT images (A-C) and postoperative MRI and CT images (D-F). A 20-year-old female patient presented with progressive left side weakness (grade 3). Images reveals right thalamic mass with hydrocephalus. The tumor was removed subtotally and the patient was diagnosed as diffuse midline glioma, H3 K27M altered. Note that hydrocephalus is resolved after resection. After resection, weakness improved to grade 4 and hydrocephalus remains resolved for 4 months till progression.

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