Primary glioblastoma of the cauda equina with molecular and histopathological characterization: Case report (original) (raw)
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Case comparison and literature review of glioblastoma: A tale of two tumors
Surgical Neurology International, 2014
Background: Diagnosis of glioblastoma multiforme (GBM) includes a heterogeneous group of tumors. We describe two cases with histopathologically and molecularly similar tumors, but very different outcomes. We attempt to illustrate the need for improved prognostic markers for GBM. Case Description: Two patients with similar molecular profiles were retrospectively identified. The following markers were assessed: O 6 -methylguanine DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) 1 and 2 status, epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) status, Ki-67, p53, and 1p/19q status. Each patient was assigned a Karnofsky performance score at presentation. Case 1 (62-year-old male) was a right temporal lobe glioblastoma with a molecular profile of amplified EGFR, normal PTEN, no IDH1/2 mutation, 28.7% MGMT promoter methylation, 5-20% Ki-67, 1p deletion, and 19q intact. The patient underwent resection followed by radiation therapy and 2 years of chemotherapy, and was asymptomatic and tumor free 5 years post diagnosis. Tumor eventually recurred and the patient expired 72 months after initial diagnosis. Case 2 (63-year-old male) was a right frontal white matter mass consistent with glioblastoma with a molecular profile of amplified EGFR, absent PTEN, no IDH1/2 mutation, 9.9% MGMT promoter methylation, 5-10% Ki-67, and 1p/19q status inconclusive. A radical subtotal resection was performed; however, 2 weeks later symptoms had returned. Subsequent imaging revealed a tumor larger than at diagnosis. The patient expired 3 months after initial diagnosis. Conclusion: The need for formulating more robust means to classify GBM tumor subtypes is paramount. Standard histopathologic and molecular analyses are costly and did not provide either of these patients with a realistic appraisal of their prognosis. Individualized whole genome testing similar to that being reported for medulloblastoma and other tumors may be preferable to the array of tests as currently utilized.
Oncology Letters
Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence.
A clinicopathological and molecular analysis of glioblastoma multiforme with long-term survival
Journal of Clinical …, 2011
The median survival time of patients with glioblastoma multiforme (GBM) is 12 months, and only 3-5% of patients survive longer than 3 years. We performed histomorphological and detailed molecular analyses of seven long-term survivors of GBM to identify any prognostic factors that potentially contribute to survival. Morphology and immunohistochemistry for p53, phosphatase and tensin homologue (PTEN) and epidermal growth factor receptor (EGFR) protein expression were investigated. EGFR amplification and 1p/19q deletion were assessed by fluorescent in situ hybridization. The O6-methylguanine-DNA methyltransferase (MGMT) gene methylation status was evaluated by performing methylation-specific polymerase chain reaction assays. All tumors were classical GBMs and no significant oligodendroglial differentiation was noted. The majority showed EGFR amplification (4/7), PTEN protein expression (6/7) and MGMT promoter methylation (5/6). Immunopositivity for p53 was noted in three of seven patients. Deletion of chromosome 1p/19q, either isolated or combined, was not identified in any of the se patients. All patients were treated by gross total resection followed by radiotherapy; six patients received additional temozolomide treatment. A relatively young age of onset (48 years), with a high MGMT promoter methylation and PTEN protein expression were favorable factors for long-term survival. The presence of EGFR amplification indicates that more than a single factor determines survival in GBM.
Diagnostics
Glioblastoma (GBM) is regarded as an aggressive brain tumor that rarely develops extracranial metastases. Despite well-investigated molecular alterations in GBM, there is a limited understanding of these associated with the metastatic potential. We herein present a case report of a 43-year-old woman with frontal GBM with primitive neuronal component who underwent gross total resection followed by chemoradiation. Five months after surgery, the patient was diagnosed with an intraspinal GBM metastasis. Next-generation sequencing analysis of both the primary and metastatic GBM tissues was performed using the Illumina TruSight Tumor 170 assay. The number of single nucleotide variants observed in the metastatic sample was more than two times higher. Mutations in TP53, PTEN, and RB1 found in the primary and metastatic tissue samples indicated the mesenchymal molecular GBM subtype. Among others, there were two inactivating mutations (Arg1026Ile, Trp1831Ter) detected in the NF1 gene, two nov...
The median survival time of patients with glioblastoma multiforme (GBM) is 12 months, and only 3–5% of patients survive longer than 3 years. We performed histomorphological and detailed molecular analyses of seven long-term survivors of GBM to identify any prognostic factors that potentially contribute to survival. Morphology and immunohistochemistry for p53, phosphatase and tensin homologue (PTEN) and epidermal growth factor receptor (EGFR) protein expression were investigated. EGFR amplification and 1p/19q deletion were assessed by fluorescent in situ hybridization. The O6-methylguanine–DNA methyltransferase (MGMT) gene methylation status was evaluated by performing methylation-specific polymerase chain reaction assays. All tumors were classical GBMs and no significant oligodendroglial differentiation was noted. The majority showed EGFR amplification (4/7), PTEN protein expression (6/7) and MGMT promoter methylation (5/6). Immunopositivity for p53 was noted in three of seven patients. Deletion of chromosome 1p/19q, either isolated or combined, was not identified in any of the se patients. All patients were treated by gross total resection followed by radiotherapy; six patients received additional temozolomide treatment. A relatively young age of onset (48 years), with a high MGMT promoter meth-ylation and PTEN protein expression were favorable factors for long-term survival. The presence of EGFR amplification indicates that more than a single factor determines survival in GBM.
Clinical Case Reports, 2021
We here report the unusual case of a 60-year-old woman with an intramedullary mixed malignant tumor comprising of glioblastoma and schwannoma, who underwent resection and adjuvant chemoradiation and relapsed with grade 3 ependymoma after one year. After secondary resection, she received PCV chemotherapy and has remained disease-free after 3 years. Intramedullary spinal cord tumors (IMSCT) are responsible for a rare but remarkable cause of neurological morbidity and mortality. Primary intramedullary spinal glioblastoma multiform (GBM) is a very rare IMSCT that accounts for only 1%-5% of all GBMs and only 1.5% of all spinal cord tumors. 1 Young males are more commonly affected by this disease, and the most frequently involved sites are cervical and thoracic spinal regions. 2 Due to the low incidence of primary spinal cord GBM, reports are necessarily limited to single-case studies and small-number case series. It is, therefore, not surprising that little is known about the clinical characteristics and treatment protocols of this debilitating malignancy. 3 Spinal intramedullary GBM frequently affects the cervical and thoracic regions of the spinal cord. 2 Back pain which may be diffuse or radicular is the most common presenting symptom. Also, numbness and weakness of the extremities are the other frequent presenting symptoms. 4 Currently, the standard treatment for newly diagnosed GBM consists of surgical resection to the extent feasible, followed by concurrent chemoradiotherapy with temozolomide (TMZ) and adjuvant temozolomide chemotherapy. 5 Glioblastomas containing a methylated O-methylguanine-DNA methyltransferase (MGMT) promoter are associated with significantly greater long-term benefit from temozolomide and alkylating chemotherapy drugs than patients with an unmethylated MGMT promoter. Methylation of the MGMT promoter is correlated with improved response to radiotherapy as well. 6,7 In conventionally fractionated radiation therapy, the tolerance dose for the spinal cord has been reported to be 50 Gy
Acta Neuropathologica, 2012
Glioblastoma (GBM) is a morphologically heterogeneous tumor type with a median survival of only 15 months in clinical trial populations. However, survival varies greatly among patients. As part of a central pathology review, we addressed the question if patients with GBM displaying distinct morphologic features respond differently to combined chemo-radiotherapy with temozolomide. Morphologic features were systematically recorded for 360 cases with particular focus on the presence of an oligodendroglioma-like component and respective correlations with outcome and relevant molecular markers. GBM with an oligodendroglioma-like component (GBM-O) represented 15% of all confirmed GBM (52/339) and was not associated with a more favorable outcome. GBM-O encompassed a pathogenetically heterogeneous group, significantly enriched for IDH1 mutations (19 vs. 3%, p = 0.003) and EGFR amplifications (71 vs. 48%, p = 0.04) compared with other GBM, while co-deletion of 1p/19q was found in only one case and the MGMT methylation frequency was alike (47 vs. 46%). Expression profiles classified most of the GBM-O into two subtypes, 36% (5/14 evaluable) as proneural and 43% as This work is dedicated to the memory of the late Dr. Robert-Charles Janzer who suddenly died in 2010. RCJ outlined the morphological analysis and coordinated central pathology review of this study.
Case Report - Glioblastoma multiforme with long term survival
2005
Glioblastoma multiforme (GBM) Patients generally have a dismal prognosis, with median survival of 10-12 months. GBM with long-term survival (LTS) of ≥ 5 years is rare, and no definite markers indicating better prognosis have been identified till date. The present study was undertaken to evaluate GBMs with LTS in order to identify additional correlates associated with favourable outcome. The cases were evaluated for relevant clinicopathological data, proliferation index and expression of tumortumour suppressor gene (p53), cyclin-dependant kinase-inhibitors (p27 and p16) and epidermal growth factor receptor (EGFR) proteins. Six cases of GBM with LTS with an average survival of 9 years (range 5-15 years) were identified. All were young patients with mean age of 27 years (range 8-45 years). Histology of three cases was consistent with conventional GBM, while two showed prominent oligodendroglial component admixed with GBM areas. One was a giant cell GBM, which progressed to gliosarcoma on recurrence. The mean MIB-1LI was 12% (range 6-20%). p53 was immunopositive in 4 out of 5 cases. EGFR and p27 were immunonegative in all, whereas p16 was immunonegative in 3 out of 5 cases. Currently, in the absence of specific molecular and genetic markers, GBM in young patients should be meticulously evaluated for foci of oligodendroglial component and/or giant cell elements, in addition to proliferative index and p53 expression, since these probably have prognostic connotations, as evident in this study. The role of p16 and p27 however needs better definition with study of more number of cases.