A case of diffuse midline glioma, H3 K27M mutant mimicking a hemispheric malignant glioma in an elderly patient

Fujioka, Yutaka; Hata, Nobuhiro; Hatae, Ryusuke; Suzuki, Satoshi; Sangatsuda, Yuhei; Nakahara, Yukiko; Mizoguchi, Masahiro; Iihara, Koji

doi:10.1111/neup.12609

Cited by 6 publications

(4 citation statements)

References 20 publications

(34 reference statements)

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“…Moreover, the frequency of elderly patients with DMG, H3 K27M-mut is notable [28,29]. We recently described an elderly patient with the DMG, H3 K27M-mut that mimicked a hemispheric malignant glioma [30]. Taken together, the H3 status of an adult hemispheric diffuse glioma affecting the midline should be confirmed even in elderly patients.…”

Section: Discussionmentioning

confidence: 89%

Molecular diagnosis of diffuse glioma using a chip-based digital PCR system to analyze IDH, TERT, and H3 mutations in the cerebrospinal fluid

et al. 2021

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Purpose Conventional genetic analyzers require surgically obtained tumor tissues to confirm the molecular diagnosis of diffuse glioma. Recent technical breakthroughs have enabled increased utilization of cell-free tumor DNA (ctDNA) in body fluids as a reliable resource for molecular diagnosis in various cancers. Here, we tested the application of a chip-based digital PCR system for the less invasive diagnosis (i.e., liquid biopsy) of diffuse glioma using the cerebrospinal fluid (CSF). Methods CSF samples from 34 patients with diffuse glioma were collected from the surgical field during craniotomy. Preoperative lumbar CSF collection was also performed in 11 patients. Extracted ctDNA was used to analyze diagnostic point mutations in IDH1 R132H, TERT promoter (C228T and C250T), and H3F3A (K27M) on the QuantStudio® 3D Digital PCR System. These results were compared with their corresponding tumor DNA samples. Results We detected either of the diagnostic mutations in tumor DNA samples from 28 of 34 patients. Among them, we achieved precise molecular diagnoses using intracranial CSF in 20 (71%). Univariate analyses revealed that the World Health Organization (WHO) grade (p = 0.0034), radiographic enhancement (p = 0.0006), and Mib1 index (p = 0.01) were significant predictors of precise CSF-based molecular diagnosis. We precisely diagnosed WHO grade III or IV diffuse gliomas using lumbar CSF obtained from 6 (87%) of 7 patients with tumors harboring any mutation. Conclusion We established a novel, non-invasive molecular diagnostic method using a chip-based digital PCR system targeting ctDNA derived from CSF with high sensitivity and specificity, especially for high-grade gliomas.

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Section: Discussionmentioning

confidence: 89%

Molecular diagnosis of diffuse glioma using a chip-based digital PCR system to analyze IDH, TERT, and H3 mutations in the cerebrospinal fluid

et al. 2021

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“…However, paediatric-type diffuse gliomas may also occur in adults, especially young adults. For example, many cases of “diffuse midline glioma, H3 K27-altered” have been reported in young adults ( 15 , 16 ), and cases have even been reported in patients over 60 years of age ( 17 , 18 ). Paediatric-type diffuse gliomas are IDH wt by definition ( 2 ), thus some of the entities are a consideration in adult patients with an IDH wt glioma, in particular H3 K27-altered and H3 G34-mutant gliomas (which demonstrate different changes in the H3 histone).…”

Section: Key Changes In the 2021 Who Classificationmentioning

confidence: 99%

“…Conversely, a glioma demonstrating H3 K27-alteration but no involvement of midline structures cannot be diagnosed as this entity ( 2 , 33 ). It is worthwhile noting that more disseminated tumours with a component of midline involvement may also harbour this molecular change ( 18 ), and such a pattern may not be apparent without close attention to the imaging. Beyond this, however, no features have yet been identified which can confidently suggest or exclude this genotype ( 16 ).…”

Section: Opportunitiesmentioning

confidence: 99%

Radiogenomics of adult intracranial gliomas after the 2021 World Health Organisation classification: a review of changes, challenges and opportunities

Lasocki¹,

Roberts-Thomson²,

Gaillard³

2023

Quant Imaging Med Surg

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The classification of diffuse gliomas has undergone substantial changes over the last decade, starting with the 2016 World Health Organisation (WHO) classification, which introduced the importance of molecular markers for glioma diagnosis, in particular isocitrate dehydrogenase (IDH) status and 1p/19codeletion. This has spurred research into the correlation of imaging features with the key molecular markers, known as "radiogenomics" or "imaging genomics". Radiogenomics has a variety of possible benefits, including supplementing immunohistochemistry to refine the histological diagnosis and overcoming some of the limitations of the histological assessment. The recent 2021 WHO classification has introduced a variety of changes and continues the trend of increasing the importance of molecular markers in the diagnosis. Key changes include a formal distinction between adult-and paediatric-type diffuse gliomas, the addition of new diagnostic entities, refinements to the nomenclature for IDH-mutant (IDH mut ) and IDH-wildtype (IDH wt ) gliomas, a shift to grading within tumour types, and the addition of molecular markers as a determinant of tumour grade in addition to phenotype. These changes provide both challenges and opportunities for the field of radiogenomics, which are discussed in this review. This includes implications for the interpretation of research performed prior to the 2021 classification, based on the shift to first classifying gliomas based on genotype ahead of grade, as well as opportunities for future research and priorities for clinical integration.

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“…Nevertheless, these tumors can occasionally be larger. For example, out of 66 H3 K27Mmutant adult gliomas reported by Qiu et al, eight demonstrated cerebral hemispheric infiltration together with thalamic and/or brainstem involvement [22], and cases of extensive H3 K27M-mutant gliomas in older patients have been reported [33,36].…”

Section: Tumor Margins and Extentmentioning

confidence: 99%

Imaging features associated with H3 K27-altered and H3 G34-mutant gliomas: a narrative systematic review

et al. 2022

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Background Advances in molecular diagnostics accomplished the discovery of two malignant glioma entities harboring alterations in the H3 histone: diffuse midline glioma, H3 K27-altered and diffuse hemispheric glioma, H3 G34-mutant. Radiogenomics research, which aims to correlate tumor imaging features with genotypes, has not comprehensively examined histone-altered gliomas (HAG). The aim of this research was to synthesize the current published data on imaging features associated with HAG. Methods A systematic search was performed in March 2022 using PubMed and the Cochrane Library, identifying studies on the imaging features associated with H3 K27-altered and/or H3 G34-mutant gliomas. Results Forty-seven studies fulfilled the inclusion criteria, the majority on H3 K27-altered gliomas. Just under half (21/47) were case reports or short series, the remainder being diagnostic accuracy studies. Despite heterogeneous methodology, some themes emerged. In particular, enhancement of H3 K27M-altered gliomas is variable and can be less than expected given their highly malignant behavior. Low apparent diffusion coefficient values have been suggested as a biomarker of H3 K27-alteration, but high values do not exclude this genotype. Promising correlations between high relative cerebral blood volume values and H3 K27-alteration require further validation. Limited data on H3 G34-mutant gliomas suggest some morphologic overlap with 1p/19q-codeleted oligodendrogliomas. Conclusions The existing data are limited, especially for H3 G34-mutant gliomas and artificial intelligence techniques. Current evidence indicates that imaging-based predictions of HAG are insufficient to replace histological assessment. In particular, H3 K27-altered gliomas should be considered when occurring in typical midline locations irrespective of enhancement characteristics.

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A case of diffuse midline glioma, H3 K27M mutant mimicking a hemispheric malignant glioma in an elderly patient

Cited by 6 publications

References 20 publications

Molecular diagnosis of diffuse glioma using a chip-based digital PCR system to analyze IDH, TERT, and H3 mutations in the cerebrospinal fluid

Molecular diagnosis of diffuse glioma using a chip-based digital PCR system to analyze IDH, TERT, and H3 mutations in the cerebrospinal fluid

Radiogenomics of adult intracranial gliomas after the 2021 World Health Organisation classification: a review of changes, challenges and opportunities

Imaging features associated with H3 K27-altered and H3 G34-mutant gliomas: a narrative systematic review

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