Clinical, radiological, histological and molecular characteristics of paediatric epithelioid glioblastoma

Broniscer, Alberto; Tatevossian, Ruth; Sabin, Noah D.; Klimo, Paul; Dalton, James; Lee, Ryan P.; Gajjar, Amar; Ellison, David W.

doi:10.1111/nan.12093

Cited by 100 publications

(98 citation statements)

References 36 publications

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“…It is usually seen within the first three decades of life and the majority of cases are primary (ie, no previously established lower grade precursor). The course of eGBM is an aggressive one and is often complicated by early recurrence, intratumoral hemorrhage and leptomeningeal spread (2). Nevertheless, surprisingly long survival times have been reported in a subset (1,8) as was found also in a subset of our own patients.…”

Section: Discussionmentioning

confidence: 87%

“…Only case reports and a few small series have been previously reported (2,8). It is usually seen within the first three decades of life and the majority of cases are primary (ie, no previously established lower grade precursor).…”

Section: Discussionmentioning

confidence: 94%

“…While one study makes a distinction between eGBM and rhabdoid GBM based on the focal loss of INI1 immunoreactivity in rhabdoid areas (9), there is considerable overlap and others use these terms interchangeably (11,17,27). The diagnosis of eGBM is often challenging and only a few small series have been reported in the adult and pediatric populations (2,8,19). Excluding other CNS tumors with epithelioid features is critical and it has been noted that a subset of anaplastic pleomorphic xanthoastrocytomas (PXAs) have similar pathologic features (7,14) and even some overlapping molecular findings (5,8).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Epithelioid Glioblastomas and Anaplastic Epithelioid Pleomorphic Xanthoastrocytomas—Same Entity or First Cousins?

et al. 2015

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Epithelioid glioblastoma (eGBM) and pleomorphic xanthoastrocytoma (PXA) with anaplastically transformed foci (ePXA) show overlapping features. Eleven eGBMs and 5 ePXAs were reviewed and studied immunohistochemically. Fluorescence in situ hybridization for EGFR amplification, PTEN deletion and ODZ3 deletion was also performed, with Ilumina 450 methylome analysis obtained in five cases. The average age for eGBM was 30.9 (range 2-79) years, including five pediatric cases and a M : F ratio of 4.5. The ePXA patients had a M : F ratio of 4 and averaged 21.2 (range 10-38) years in age, including two pediatric cases. Six eGBMs and two ePXAs recurred (median recurrence interval of 12 and 3.3 months, respectively). All tumors were composed of solid sheets of loosely cohesive, "melanoma-like" cells with only limited infiltration. ePXAs showed lower grade foci with classic features of PXA. Both tumor types showed focal expression of epithelial and glial markers, retained INI1 and BRG1 expression, occasional CD34 positivity, and lack of mutant IDH1 (R132H) immunoreactivity. BRAF V600E mutation was present in four eGBMs and four ePXAs. ODZ3 deletion was detected in seven eGBMs and two ePXAs. EGFR amplification was absent. Methylome analysis showed that one ePXA and one eGBM clustered with PXAs, one eGBM clustered with low-grade gliomas, and two eGBMs clustered with pediatric-type glioblastomas. Common histologic, immunohistochemical, molecular and clinical features found in eGBM and ePXA suggest that they are closely related or the same entity. If the latter is true, the nomenclature and WHO grading remains to be resolved.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Epithelioid Glioblastomas and Anaplastic Epithelioid Pleomorphic Xanthoastrocytomas—Same Entity or First Cousins?

et al. 2015

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“…Dual-color FISH was performed as previously described to assess copy number abnormalities in PDGFRA [4]. …”

Section: Methodsmentioning

confidence: 99%

Gliomatosis cerebri in children shares molecular characteristics with other pediatric gliomas

et al. 2016

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Gliomatosis cerebri (GC), a rare and deadly CNS neoplasm characterized by involvement of at least three cerebral lobes, predominantly affects adults. While a few small series have reported its occurrence in children, little is known about the molecular characteristics of pediatric GC. We reviewed clinical, radiological, and histological features of pediatric patients with primary GC treated at our institution over 15 years. Targeted sequencing of mutational hotspots in H3F3A, IDH1/2, and BRAF, and genome-wide analysis of DNA methylation and copy number abnormalities was performed in available tumors. Thirty-two patients [23 (72 %) with type 1 and 9 (28 %) with type 2 GC] were identified. Median age at diagnosis was 10.2 years (range 1.5–19.1). A median of 4 cerebral lobes (range 3–8) was affected at diagnosis. In addition, symmetrical bithalamic involvement was observed in 9 (28 %) patients. Twenty-two patients (69 %) had an anaplastic astrocytoma. Despite aggressive therapy, only two patients younger than 3 years at diagnosis are long-term survivors. Clustering analysis of methylation array data from 18 cases classified tumors as IDH (n = 3, 17 %), G34 (n = 4, 22 %), mesenchymal (n 3, 17= %), and RTK I ‘PDGFRA’ (n = 8, 44 %). No tumors were classified as K27 subgroup. PDGFRA was the most commonly amplified oncogene in 4 of 22 tumors (18 %). H3F3A p.G34 occurred in all cases classified as G34. Two of 3 cases in the IDH subgroup had IDH1 p.R132H. No H3F3A p.K27 M, IDH2 p.R172, or BRAF p.V600E mutations were observed. There was a trend towards improved survival in the IDH subgroup (P = 0.056). Patients with bithalamic involvement had worse outcomes (P = 0.019). Despite some overlap, the molecular features of pediatric GC are distinct from its adult counterpart. Like in adults, the similarity of genetic and epigenetic characteristics with other infiltrative high-grade gliomas suggests that pediatric GC does not represent a distinct molecular entity.

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“…Despite aggressive multimodality treatments, including cytoreductive surgery, radiotherapy (RT) and systemic chemotherapy, GB recurs and it is invariably fatal. Additional therapeutic strategies are urgently required to elicit prolong tumor control and patient survival (1).…”

Section: Introductionmentioning

confidence: 99%

Rapid regression of glioblastoma following carmustine wafer implantation: A case report

Fukai¹,

Nishibayashi²,

Uematsu³

et al. 2016

Molecular and Clinical Oncology

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Abstract. Carmustine wafers, which are locally delivered chemotherapy in the form of biodegradable implants, confer a survival benefit to patients with glioblastoma (GB) following surgical resection. While the adverse events of this method, including gas retention and perifocal edema, have been extensively investigated, the immediate efficacy of the implant has rarely been reported. To the best of our knowledge, this is the first reported case of GB in which the tumor rapidly regressed after partial surgical removal followed by implantation of carmustine wafers. A 77-year-old woman presented with motor aphasia and right hemiparesis. Neuroimaging revealed a tumor located in the left frontal lobe of the brain. The tumor was partially removed under 5-aminolevulinic acid fluorescence guidance and 8 carmustine wafers were implanted in the resection cavity. The histopathological findings suggested the diagnosis of GB. Genetic and immunohistochemical analyses revealed O 6 -methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and low MGMT protein expression, respectively, in the tumor cells. One month after the operation, when adjuvant temozolomide chemotherapy was planned, computed tomography and magnetic resonance imaging revealed a marked regression of the residual tumor and perifocal edema. The patient's symptoms and signs had improved. As adjuvant temozolomide without radiation was therapeutically beneficial, the tumor gradually regressed and the patient has remained progression-free for >12 months after the operation. Therefore, adjuvant local chemotherapy with carmustine wafer implants was able to induce rapid regression of GB. IntroductionGlioblastoma (GB), a frequent type of malignant glioma, is the most common primary brain tumor and is associated with a poor prognosis. Despite aggressive multimodality treatments, including cytoreductive surgery, radiotherapy (RT) and systemic chemotherapy, GB recurs and it is invariably fatal. Additional therapeutic strategies are urgently required to elicit prolong tumor control and patient survival (1).A carmustine (bis-chloroethylnitrosourea, BCNU; an alkylating agent of the nitrosourea family) wafer (Gliadel ® ; Eisai Inc., Tokyo, Japan) is a controlled-release preparation of BCNU that is implanted into the brain (2). Carmustine wafers, lined along the wall of the resection cavity following tumor removal, exert antitumor effects on the residual tumor as adjuvant local chemotherapy. This implant has been shown to enhance the overall survival of patients with malignant gliomas in controlled clinical trials in the United States and Europe (3). A prospective, multicenter phase-I/II study on Japanese patients was recently performed and the application of carmustine wafers has been covered by Japanese public health insurance since 2012 (2).Through local application, an increased concentration of carmustine may be delivered to the tumor bed over a period of ≥3 weeks, during which, local reactions caused by this chemotherapeutic may occur (4). Previous studies hav...

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Clinical, radiological, histological and molecular characteristics of paediatric epithelioid glioblastoma

Cited by 100 publications

References 36 publications

Epithelioid Glioblastomas and Anaplastic Epithelioid Pleomorphic Xanthoastrocytomas—Same Entity or First Cousins?

Epithelioid Glioblastomas and Anaplastic Epithelioid Pleomorphic Xanthoastrocytomas—Same Entity or First Cousins?

Gliomatosis cerebri in children shares molecular characteristics with other pediatric gliomas

Rapid regression of glioblastoma following carmustine wafer implantation: A case report

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