PATH-12. CLINICAL AND PATHOLOGICAL ANALYSIS OF 43 PATIENTS WITH EPITHELIOID GLIOBLASTOMA

BACKGROUND AND PURPOSE Epithelioid glioblastoma (eGBM) is a rare and aggressive subtype of glioblastoma. The clinical characteristics, pathological features and radiological findingsare still not well characterized. METHODS The clinical data of 43 patients with eGBM confirmed pathologically after surgery in Guangdong Sanjiu Brain Hospital from June 2015 to January 2021 were reviewed, and to investigate the clinical, pathological and imaging characteristics of the eGBM. RESULTS The range of patients' age was from 5 to 70 years (median 39 years). There were 24 males and 19 females. The median karnofsky performance score (KPS）at diagnosis was 70 (40-90). The most common symptom were headache (81.4%), and other common symptoms included nausea or vomiting (44.1%), limb weakness (30.2%), disturbance of consciousness (20.9%) and seizures (9.3%). Most of the tumors (97.6%) were located in the cerebral hemisphere ,except for one case located in the cerebellum,and with an average diameter of 5.3 cm (2.5-9.4 cm). There were 2 cases of intracranial metastasis and 7 cases of spinal cord metastasis in MRI. In pathologic examination, immunohistochemistry showed all the patients were IDH1 wild-type (43/43) and H3K27M wild-type(34/34). 25 (58.1%) of cases harbored BRAF mutation and 19 (44.2%) cases of MGMT positive. Most of patients were positive for GFAP, P53, Olig-2 and ATRX. CONCLUSION Epithelioid glioblastoma is more common in adults, most of which are located on the supratentorial, intracranial and spinal cord dissemination may occur. Half of patients showed BRFA mutation and maybe benefit from targeted therapy.These findings may help clinicians understand and treat epithelioid glioblastoma better.

Prevalence of BRAF V600 in primary gliomas: a systematic review

Aims Glioma is a fatal disease that causes significant years of life lost to an individual. Mutations in the driver gene BRAF, such as the V600 alteration, may contribute to gliomagenesis in adults and children through abnormal signaling causing uncontrolled cell proliferation. The use of BRAF-inhibitor drugs including Vemurafenib and Dabrafenib have shown a favorable response in 48% and 50% of melanoma patients with BRAF V600 mutations respectively. BRAF inhibitors and MEK inhibitors have shown efficacy in certain paediatric gliomas in the recurrent setting. Despite the potential benefit of BRAF inhibitors, the prevalence of BRAF V600 within primary gliomas is not fully discovered. Some studies identify the prevalence to be over 50%, while others find the prevalence to be around 1%. We performed a comprehensive systematic review to determine the prevalence of BRAF V600 within the adult and paediatric glioma population in different diagnostic groups. Method A systematic literature search was performed using Ovid MEDLINE and Embase from genesis to the 22nd October 2020. Studies were not restricted by language. Studies were eligible if patients were histologically diagnosed according to WHO guidelines as a primary glioma evaluating the prevalence of BRAF V600 and included ≥ 10 primary glioma patients. The review protocol was registered in PROSPERO (CRD42019127704). Search results were managed using Endnote. Two independent reviewers assessed the eligibility of the publications using Rayyan, conflicts were evaluated by a third reviewer. Included articles were extracted by one reviewer and confirmed by a second reviewer. Risk of bias assessments were conducted using Hoy et al’s risk of bias tool. Results were synthesized using “metaprop” in R. The meta-analysis was carried out in R which produced forest plots. Results Our cohort included 182 studies with a total of 13669 adult and paediatric glioma patients classified diagnostically according to WHO guidelines. Among 48 glioma entities, BRAF V600 was identified most commonly in epithelioid glioblastoma with a prevalence of 69% (95% confidence interval (CI): 45-89%), followed by pleomorphic xanthoastrocytoma with a prevalence of 56% (95% CI: 48-64%), anaplastic pleomorphic xanthoastrocytoma with a prevalence of 38% (95% CI: 23-54%), ganglioglioma with a prevalence of 40% (95% CI: 33-46%), and anaplastic ganglioglioma with a prevalence of 46% (95% CI: 18-76%). Other glioma entities were found to have a prevalence of BRAF V600, these include astroblastoma (24%), desmoplastic infantile astrocytoma (16%), subependymal giant cell astrocytoma (8%), dysembryoplastic neuroepithelial tumour (3%), diffuse astrocytoma (3%), and pilocytic astrocytoma (3%). Conclusion To our knowledge, this is the largest systematic review examining the prevalence of BRAF V600 in adult and paediatric glioma classified according to diagnostic WHO criteria. However, there were some limitations in this review. The sample sizes of some studies were very small, and the method of mutational analysis for BRAF V600 varied between papers. We found BRAF V600 in a significant prevalence of epithelioid glioblastoma, pleomorphic xanthoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, ganglioglioma, and anaplastic ganglioglioma. Of interest, BRAF V600 mutation was found in a lower prevalence of astroblastoma, desmoplastic infantile astrocytoma, subependymal giant cell astrocytoma, dysembryoplastic neuroepithelial tumour, diffuse astrocytoma, and pilocytic astrocytoma. Consideration of assessment of BRAF V600 mutation may enable further treatment options with BRAF and/or MEK inhibitors in these particular diagnostic entities.

Pleomorphic Xanthoastrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma, and Epithelioid Glioblastoma: Case Series with Clinical Characteristics, Molecular Features and Progression Relationship

Background: Pleomorphic xanthoastrocytoma (PXA), anaplastic pleomorphic xanthoastrocytoma (A-PXA), and epithelioid glioblastoma (E-GBM) show overlapping features. However, little is known about their clinical characteristics, molecular features and relationship with progression. Methods: Fourteen patients diagnosed at Nanfang Hospital from 2016 to 2019 were enrolled, including eleven PXA patients, two A-PXA patients, and one E-GBM patient. All tumour tissue samples of the fourteen patients were examined by immunohistochemical staining (MGMT, VEGF, BRAF-V600E, etc.). The recurrent tumour tissue of the patient with E-GBM arising from A-PXA was screened to detect 11 glioma markers (MGMT, BRAF-V600E, etc.) and chromosome 1p/19q by next-generation sequencing (NGS).Results: The mean age of 13 patients with PXA or A-PXA was 25.4 years; twelve of these patients had tumours at supratentorial regions. VEGF positivity was detected in the tumour samples of 13 patients, MGMT positivity in 10 patients, and BRAF-V600E positivity in 7 patients. For the tumour sample of the E-GBM patient who survived for up to 10 years after the fourth resection, BRAF V600E was wild type in the sample obtained from the first surgery, while it was mutant in the second, third, and fourth surgeries. In contrast, the promoter status of MGMT in the four surgeries was unmethylated. The NGS results showed that the mutation frequencies of BRAF V600E in the second, third and fourth surgeries were 14.06%, 9.13% and 48.29%, respectively.Conclusions: Collectively, the results suggest that patients with A-PXA may relapse multiple times and eventually progress to E-GBM with the BRAF-V600E mutation.

Pleomorphic Xanthoastrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma, and Epithelioid Glioblastoma: Case Series with Clinical Characteristics, Molecular Features and Progression Relationship

Background: Pleomorphic xanthoastrocytoma (PXA), anaplastic pleomorphic xanthoastrocytoma (A-PXA), and epithelioid glioblastoma (E-GBM) show overlapping features. However, little is known about their clinical characteristics, molecular features and relationship with progression. Methods: Fourteen patients diagnosed at Nanfang Hospital from 2016 to 2019 were enrolled, including eleven PXA patients, two A-PXA patients, and one E-GBM patient. All tumour tissue samples of the fourteen patients were examined by immunohistochemical staining (MGMT, VEGF, BRAF-V600E, etc.). The recurrent tumour tissue of the patient with E-GBM arising from A-PXA was screened to detect 11 glioma markers (MGMT, BRAF-V600E, etc.) and chromosome 1p/19q by next-generation sequencing (NGS).Results: The mean age of 13 patients with PXA or A-PXA was 25.4 years; twelve of these patients had tumours at supratentorial regions. VEGF positivity was detected in the tumour samples of 13 patients, MGMT positivity in 10 patients, and BRAF-V600E positivity in 7 patients. For the tumour sample of the E-GBM patient who survived for up to 10 years after the fourth resection, BRAF V600E was wild type in the sample obtained from the first surgery, while it was mutant in the second, third, and fourth surgeries. In contrast, the promoter status of MGMT in the four surgeries was unmethylated. The NGS results showed that the mutation frequencies of BRAF V600E in the second, third and fourth surgeries were 14.06%, 9.13% and 48.29%, respectively.Conclusions: Collectively, the results suggest that patients with A-PXA may relapse multiple times and eventually progress to E-GBM with the BRAF-V600E mutation.