A rare case of BRAF V600E‐mutated epithelioid glioblastoma with a sarcomatous component

Ishikawa, Ryou; Kadota, Kyuichi; Hayashi, Toshitetsu; Kimura, Nachino; Inoue, Koh; Ibuki, Emi; Kagawa, Seiko; Kushida, Yoshio; Okada, Masaki; Miyake, Keisuke; Tamiya, Takashi; Nobusawa, Sumihito; Hirato, Junko; Haba, Reiji

doi:10.1111/pin.12896

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…Epithelioid glioblastomas are characterized by larger cells with epithelioid morphology. They may be found together with other glioma histology including low-grade astrocytoma ( 3 , 4 ) and pleomorphic xanthoastrocytoma ( 5 ), and gliosarcoma ( 6 ). In our patient, the histopathology consists of distinct regions of typical glioblastoma features and atypical epithelioid morphologies.…”

Section: Discussionmentioning

confidence: 99%

“…However, epithelioid glioblastoma is still an outlier that is difficult to categorize based on the new WHO classification scheme. It often coexists with glioblastoma or other types of diffuse glioma ( 3 – 6 ). More importantly, over half of the cases harbor a BRAF V600E mutation making them potentially treatable with V600E-directed targeted therapy ( 4 , 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

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Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection

Mondia

Kritselis²,

Donahue³

et al. 2023

Front. Neurol.

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PurposeEpithelioid glioblastoma is an unusual histologic variant of malignant glioma. The present study investigates both the genomic and transcriptomic determinants that may promote the development of this tumor.MethodsWhole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on an epithelioid glioblastoma, along with a specific bioinformatic pipeline to generate electronic karyotyping and investigate the tumor immune microenvironment. Microdissected sections containing typical glioblastoma features and epithelioid morphology were analyzed separately using the same methodologies.ResultsAn epithelioid glioblastoma, with immunopositivity for GFAP, Olig-2, and ATRX but negative for IDH-1 and p53, was identified. The tumor cell content from microdissection was estimated to be 85–90% for both histologic tumor components. WES revealed that both glioma and epithelioid sections contained identical point mutations in PTEN, RB1, TERT promoter, and TP53. Electronic karyotype analysis also revealed similar chromosomal copy number alterations, but the epithelioid component showed additional abnormalities that were not found in the glioblastoma component. The tumor immune microenvironments were strikingly different and WTS revealed high levels of transcripts from myeloid cells as well as M1 and M2 macrophages in the glioma section, while transcripts from CD4+ lymphocytes and NK cells predominated in the epithelioid section.ConclusionEpithelioid glioblastoma may be genomically more unstable and oncogenically more advanced, harboring an increased number of mutations and karyotype abnormalities, compared to typical glioblastomas. The tumor immune microenvironment is also different.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection

Mondia

Kritselis²,

Donahue³

et al. 2023

Front. Neurol.

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“…A thorough PubMed search was performed using the English keywords “epithelioid glioblastoma,” “ BRAF mutation and glioblastoma/malignant glioma,” and “ BRAF mutant glioblastoma/malignant glioma.” A total of 211 patients providing information about the tumor BRAF mutation status were compiled, this figure including 134 well-described individual reports, 6,10,12‐14,16‐47 in addition to 77 patients generally described in two clinical series. 4,11 The cases that had been published more than one time were only included once in the cohort.…”

Section: Literature Review Of E-gbm Tumors Providing Braf Mutation An...mentioning

confidence: 99%

“…Given the promising role that BRAF mutations might play in designing future adjuvant therapies for this as yet not well-characterized glioblastoma subtype, we have also systematically reviewed the individual E-GMB cases and series published to date with such molecular information, totaling 211 patients (Table 1). 4,6,10‐14,16‐47 This cohort comprises the largest series ever analyzed of E-GBM providing the BRAF mutation status. The influence that this mutation has on patient outcomes along with the epidemiology, tumor topography, and treatment strategy were investigated.…”

Section: Introductionmentioning

confidence: 99%

The Significance of BRAF Mutation in the Epithelioid Glioblastoma Subtype: A Systematic Literature Review and a Case Report with a Unique Intraventricular Topography

Prieto,

Barrios,

Ebrat-Mancilla

et al. 2023

Int J Surg Pathol

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Epithelioid glioblastoma (E-GBM) is an exceedingly rare subtype of isocitrate dehydrogenase (IDH)-wildtype glioblastoma, first included in the WHO 2016 classification and characterized by a dominant population of epithelioid cells. Its histological and molecular defining features remain troublesome. The significance of BRAF mutations to pathological diagnosis and surgical outcome has drawn increasing attention given their promising potential for future adjuvant therapies. Herein, we describe a unique case of an E-GBM in the atrium of the left lateral ventricle and comprehensively analyze the importance of BRAF status in a cohort of 211 E-GBMs from the literature. Our patient was a 40-year-old man with occipital pain. His brain MRI revealed a large intraventricular tumor at the same location as a signal change found 10 years earlier with no additional follow-up. He underwent gross total tumor removal followed by conventional adjuvant treatment. Histopathological diagnosis was consistent with IDH-wildtype E-GBM WHO grade 4 with pleomorphic xanthoastrocytoma-like areas. BRAF p.V600 mutation was demonstrated in the tumoral genetic study. In the cohort analyzed, male patients predominated (63%), the median age was 32 years old, and the 5-year survival rate following diagnosis was 4.2%. BRAF mutations were found in 60.3% of the tumors overall, with this rate increasing to 78.3% in young adults (19-49 years, P < .001). Presence of BRAF mutations associated with tumor progression ( P = .001), the event usually leading to death ( P < .001). In conclusion, our study supports the importance of genetic BRAF p.V600 mutation analysis because its presence not only points to an E-GBM diagnosis but may also promote tumor progression.

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“…As the primary driving mutations, BRAF mutations are involved in the occurrence and development of various cancers. Nearly 60% of melanomas show BRAF mutations [ 18 ], and mutations in this gene are also found in non-Hodgkin’s lymphoma [ 19 ], CRC [ 20 , 21 ], thyroid papillary carcinoma [ 22 , 23 ], non-small-cell lung cancer [ 24 , 25 , 26 ], glioblastoma [ 27 ], and inflammatory diseases [ 28 , 29 ]. BRAF mutations, are widely believed to be associated with poor prognosis in CRC [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

High Wnt2 Expression Confers Poor Prognosis in Colorectal Cancer, and Represents a Novel Therapeutic Target in BRAF-Mutated Colorectal Cancer

Liu,

Zhang,

Wang

et al. 2023

Medicina

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Background and Objectives: We aimed to investigate the role of Wnt2 expression in colorectal cancer (CRC) prognosis and evaluate its potential as a therapeutic target in BRAF-mutated CRC. Materials and Methods: Exactly 136 samples of formalin-fixed paraffin-embedded CRC tissue specimens were obtained from patients who underwent surgical resection for CRC. The gene mutation status of the samples was detected using fluorescence PCR. Wnt2 expression was detected using immunohistochemistry. Survival curves with high Wnt2 expression and BRAF mutations were compared using the Kaplan–Meier method. A nomogram was constructed to determine the estimated overall survival probability. We also predicted the 3-year and 5-year survival rates for patients with high Wnt2 expression and BRAF mutations. In total, 50 samples of BRAF-mutated CRC were collected and detected Wnt2 expression by immunohistochemistry. The Chi-squared test was used to analyze the association between Wnt2 expression and BRAF-mutated CRC. Results: High Wnt2 expression and BRAF mutations are associated with poor prognosis of CRC. Multivariate survival analyses indicated that high Wnt2 expression and BRAF mutations are significant independent predictors of CRC prognosis. Furthermore, high Wnt2 expression was significantly associated with BRAF-mutated CRC, and Wnt2 may be a potential therapeutic target for BRAF-mutated CRC. Conclusions: High Wnt2 expression confers poor prognosis in colorectal cancer and represents a novel therapeutic target in BRAF-mutated CRC.

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A rare case of BRAF V600E‐mutated epithelioid glioblastoma with a sarcomatous component

Cited by 5 publications

References 14 publications

Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection

Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection

The Significance of BRAF Mutation in the Epithelioid Glioblastoma Subtype: A Systematic Literature Review and a Case Report with a Unique Intraventricular Topography

High Wnt2 Expression Confers Poor Prognosis in Colorectal Cancer, and Represents a Novel Therapeutic Target in BRAF-Mutated Colorectal Cancer

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