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. 2019 Nov;40(11):1804-1810.
doi: 10.3174/ajnr.A6302. Epub 2019 Nov 6.

Diffusion Characteristics of Pediatric Diffuse Midline Gliomas with Histone H3-K27M Mutation Using Apparent Diffusion Coefficient Histogram Analysis

M S Aboian  1 , E Tong  2 , D A Solomon  3 , C Kline  4 , A Gautam  5 , A Vardapetyan  6 , B Tamrazi  7 , Y Li  8 , C D Jordan  8 , E Felton  4 , B Weinberg  9 , S Braunstein  10 , S Mueller  11   12   4 , S Cha  8
Affiliations

Diffusion Characteristics of Pediatric Diffuse Midline Gliomas with Histone H3-K27M Mutation Using Apparent Diffusion Coefficient Histogram Analysis

M S Aboian et al. AJNR Am J Neuroradiol. 2019 Nov.

Abstract

Background and purpose: Diffuse midline gliomas with histone H3 K27M mutation are biologically aggressive tumors with poor prognosis defined as a new diagnostic entity in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. There are no qualitative imaging differences (enhancement, border, or central necrosis) between histone H3 wildtype and H3 K27M-mutant diffuse midline gliomas. Herein, we evaluated the utility of diffusion-weighted imaging to distinguish H3 K27M-mutant from histone H3 wildtype diffuse midline gliomas.

Materials and methods: We identified 31 pediatric patients (younger than 21 years of age) with diffuse gliomas centered in midline structures that had undergone assessment for histone H3 K27M mutation. We measured ADC within these tumors using a voxel-based 3D whole-tumor measurement method.

Results: Our cohort included 18 infratentorial and 13 supratentorial diffuse gliomas centered in midline structures. Twenty-three (74%) tumors carried H3-K27M mutations. There was no difference in ADC histogram parameters (mean, median, minimum, maximum, percentiles) between mutant and wild-type tumors. Subgroup analysis based on tumor location also did not identify a difference in histogram descriptive statistics. Patients who survived <1 year after diagnosis had lower median ADC (1.10 × 10-3mm2/s; 95% CI, 0.90-1.30) compared with patients who survived >1 year (1.46 × 10-3mm2/s; 95% CI, 1.19-1.67; P < .06). Average ADC values for diffuse midline gliomas were 1.28 × 10-3mm2/s (95% CI, 1.21-1.34) and 0.86 × 10-3mm2/s (95% CI, 0.69-1.01) for hemispheric glioblastomas with P < .05.

Conclusions: Although no statistically significant difference in diffusion characteristics was found between H3-K27M mutant and H3 wildtype diffuse midline gliomas, lower diffusivity corresponds to a lower survival rate at 1 year after diagnosis. These findings can have an impact on the anticipated clinical course for this patient population and offer providers and families guidance on clinical outcomes.

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Figures

Fig 1.
Fig 1.
Histology of H3-K27M and wild-type diffuse midline gliomas. Hematoxylin and eosin (H&E) and antihistone H3-K27M immunohistochemistry of diffuse intrinsic pontine gliomas with H3-K27M mutation (A) and histone H3 wildtype (B). 400x magnification.
Fig 2.
Fig 2.
Diffusion characteristics of diffuse midline gliomas based on the presence of the H3-K27M mutation. Tumor 3D volume segmented from the FLAIR image (A) was coregistered onto the ADC map. Voxel-based histogram of tumor (B). Normal distribution curves are superimposed on the ADC histograms.
Fig 3.
Fig 3.
Voxel-based 3D whole-tumor ADC boxplots comparing histone H3-K27M and wild-type tumors without a difference in ADCmean (A), ADCmedian (B), and ADCmin (10−6mm2/s) (C).
Fig 4.
Fig 4.
ADC histogram descriptive statistics of diffuse midline gliomas. No difference in skewness, kurtosis, and variance between wildtype and histone H3-K27M mutant tumors (A). Examples of histogram parameters of ADC (10−6mm2/s) (B). Normal distribution curves are superimposed on the ADC histograms.
Fig 4.
Fig 4.
ADC histogram descriptive statistics of diffuse midline gliomas. No difference in skewness, kurtosis, and variance between wildtype and histone H3-K27M mutant tumors (A). Examples of histogram parameters of ADC (10−6mm2/s) (B). Normal distribution curves are superimposed on the ADC histograms.
Fig 5.
Fig 5.
Comparison of diffusion characteristics between diffuse midline gliomas centered within the pons (top) and hemispheric glioblastomas centered within right frontal lobe (bottom) (A). Boxplot comparison of mean and median ADC shows higher ADC (10−6mm2/s) in diffuse midline gliomas compared with hemispheric glioblastomas (B).
Fig 6.
Fig 6.
Kaplan-Meier survival curve based on histone H3-K27M mutation status (A) and ADC (10−6mm2/s) being below the 1.1 × 10−3mm2/s cutoff (B). Boxplots of ADC mean and median comparing patients with overall survival <12 months and ≥12 months (C and D).
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References

    1. Hoshide R, Jandial R. 2016 World Health Organization Classification of Central Nervous System Tumors: an era of molecular biology. World Neurosurg 2016;94:561–62 10.1016/j.wneu.2016.07.082 - DOI - PubMed
    1. Solomon DA, Wood MD, Tihan T, et al. . Diffuse midline gliomas with H3-K27M mutation: a series of 47 cases assessing the spectrum of morphologic variation and associated genetic alterations. Brain Pathol 2016;26:569–80 10.1111/bpa.12336 - DOI - PMC - PubMed
    1. Castel D, Philippe C, Calmon R, et al. . Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol 2015;130:815–27 10.1007/s00401-015-1478-0 - DOI - PMC - PubMed
    1. Korshunov A, Ryzhova M, Hovestadt V, et al. . Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers. Acta Neuropathol 2015;129:669–78 10.1007/s00401-015-1405-4 - DOI - PubMed
    1. Aboian MS, Solomon DA, Felton E, et al. . Imaging characteristics of pediatric diffuse midline gliomas with histone mutation. AJNR Am J Neuroradiol 2017;38:795–800 10.3174/ajnr.A5076 - DOI - PMC - PubMed

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