Adult Brainstem Gliomas With H3K27M Mutation: Radiology, Pathology, and Prognosis

Daoud, Elena V; Rajaram, Veena; Cai, Chunyu; Oberle, Robert; Martin, Gregory R.; Raisanen, Jack M.; White, Charles L.; Foong, Chan; Mickey, Bruce; Pan, Edward; Hatanpaa, Kimmo J.

doi:10.1093/jnen/nly006

Cited by 77 publications

(62 citation statements)

References 37 publications

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“…We reviewed eight articles and 187 cases (including the 23 cases in this study) of adult diffuse midline glioma. 13,[18][19][20][21][22][23][24] The prognosis was examined by the presence or absence of K27M or by histological grade in 171 or 164 cases, respectively. When the prognosis was examined based on the presence or absence of K27M mutation, cases that did not determine K27M mutation status were excluded and we reviewed 171 cases.…”

Section: Review Of Literature: H3k27m-mutant and Histological Gradementioning

confidence: 99%

Midline Glioma in Adults: Clinicopathological, Genetic, and Epigenetic Analysis

Enomoto

Aoki

Hamasaki

et al. 2020

Neurol. Med. Chir.(Tokyo)

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The histone H3K27M-mutant diffuse midline glioma is often seen in children and has a very poor prognosis regardless of its histological grade. Although it can occur in adults, few studies on adult cases have been reported. We examined adult midline glioma cases for their histological grade, presence of H3K27M mutation, and expression of related factors-enhancer of zeste homolog 2 (EZH2), H3K27me3, p16, and methylthioadenosine phosphorylase. These tumor characteristics were also evaluated for their prognostic value in adult midline glioma. High histological grade, H3K27M-mutant, high EZH2 expression, and high H3K27me3 expression was detected in 12/23 (53%), 11/23 (48%), 9/23 (39%), and 12/23 (52%) cases, respectively. Histological grade and prognosis were significantly correlated (P <0.01). The high expression of EZH2 and the low expression of H3K27me3 correlated with histological malignancy (P = 0.019 and 0.009) and prognosis (P = 0.048 and 0.047). To broaden the scope of our analysis, a review of cases reported in the literature (2014-2019) was performed. In the 171 cases, H3K27M-mutant showed poor prognosis in the young adult group (P = 0.001), whereas H3K27 status had no effect on prognosis in the older age group (P = 0.141). Histological grade was correlated with prognosis in both young adults and older groups (P <0.001, P = 0.003, respectively). We demonstrate differences in prognostic factors for diffuse gliomas in the midline region for children and adults. Importantly, the H3K27M mutation significantly influences prognosis in children, but not necessarily in adults. Contrarily, histological grading and immunostaining are important prognostic tools in adults.

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Section: Review Of Literature: H3k27m-mutant and Histological Gradementioning

confidence: 99%

Midline Glioma in Adults: Clinicopathological, Genetic, and Epigenetic Analysis

Enomoto

Aoki

Hamasaki

et al. 2020

Neurol. Med. Chir.(Tokyo)

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“…In general, H3 K27M mutation is associated with a poor outcome [22]. However, this conclusion is mainly based on studies of diffuse intrinsic pontine gliomas (DIPG) or pan-midline gliomas, while 80% of DIPG cases are H3 K27M-mutant gliomas [12,22,33].…”

Section: Introductionmentioning

confidence: 99%

The molecular characteristics of spinal cord gliomas with or without H3 K27M mutation

Chai

Zhang

Liu

et al. 2020

acta neuropathol commun

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Due to the rare incidence of spinal cord astrocytomas, their molecular features remain unclear. Here, we characterized the landscapes of mutations in H3 K27M, isocitrate dehydrogenase 1 (IDH1) R132H, BRAF V600E, and the TERT promoter in 83 diffuse spinal cord astrocytic tumors. Among these samples, thirty-five patients had the H3 K27M mutation; this mutant could be observed in histological grade II (40%), III (40%), and IV (20%) astrocytomas. IDH1 mutations were absent in 58 of 58 cases tested. The BRAF V600E mutation (7/57) was only observed in H3-wildtype astrocytomas, and was associated with a better prognosis in all histological grade II/III astrocytomas. TERT promoter mutations were observed in both H3 K27M-mutant (4/25) and-wildtype (9/33) astrocytomas, and were associated with a poor prognosis in H3-wildtype histological grade II/III astrocytomas. In the 2016 WHO classification of CNS tumors, H3 K27M-mutant diffuse midline gliomas, including spinal cord astrocytomas, are categorized as WHO grade IV. Here, we noticed that the median overall survival of histological grade II/III H3 K27M-mutant cases (n = 28) was significantly longer than that of either the total histological grade IV cases (n = 12) or the H3 K27M-mutant histological grade IV cases (n = 7). We also directly compared H3 K27M-mutant astrocytomas to H3-wildtype astrocytomas of the same histological grade. In histological grade II astrocytomas, compared to H3-wildtype cases (n = 37), H3 K27M-mutant patients (n = 14) had showed a significantly higher Ki-67-positive rate and poorer survival rate. However, no significant differences in these parameters were observed in histological grade III and IV astrocytoma patients. In conclusion, these findings indicate that spinal cord astrocytomas are considerably different from hemispheric and brainstem astrocytomas in terms of their molecular profiles, and that the histological grade cannot be ignored when assessing the prognosis of H3 K27M-mutant spinal cord astrocytomas.

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“…For example, Yi et al reported on 25 spinal tumours with H3K27 mutation; however, only 15 of these were grade IV gliomas by histological grade 20. Despite an often lower histological grade, tumours that harbour the H3K27 mutation are clinically aggressive and often behave as high-grade gliomas regardless of histology 21 22…”

Section: Discussionmentioning

confidence: 99%

Prolonged survival in a patient with a cervical spine H3K27M-mutant diffuse midline glioma

et al. 2019

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We report a case of prolonged survival in a patient with known cervical intramedullary H3K27M-mutant diffuse midline glioma. A 39-year-old man presented for evaluation with several months of progressive upper extremity pain and weakness. MRI of the cervical spine revealed an intramedullary ring-enhancing lesion centred at C3-C4. Following subtotal surgical resection, a diagnosis of glioblastoma (GBM) was confirmed. Subsequent testing at a later date revealed an H3K27M mutation. He was initially treated with radiation and concomitant and adjuvant temozolomide. He had multiply recurrent disease and was treated with various regimens, including the histone deacetylase inhibitor valproic acid. The patient passed away 31 months (~2.5 years) after diagnosis. Our case is one of few reported adult spinal cord GBMs possessing the H3K27M mutation, and one with the longest reported overall survival in the literature to date.

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Adult Brainstem Gliomas With H3K27M Mutation: Radiology, Pathology, and Prognosis

Cited by 77 publications

References 37 publications

Midline Glioma in Adults: Clinicopathological, Genetic, and Epigenetic Analysis

Midline Glioma in Adults: Clinicopathological, Genetic, and Epigenetic Analysis

The molecular characteristics of spinal cord gliomas with or without H3 K27M mutation

Prolonged survival in a patient with a cervical spine H3K27M-mutant diffuse midline glioma

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