Glioblastoma
Neurosurgery Service, Alicante University General Hospital, Spain.
Definition
While glioblastoma was historically classified as isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant groups, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) and the World Health Organization Classification of Tumors of the Central Nervous System 2021 clearly updated the nomenclature to reflect glioblastoma to be compatible with wildtype IDH status only. Therefore, glioblastoma is now defined as “a diffuse, astrocytic glioma that is IDH-wildtype and H3-wildtype and has one or more of the following histological or genetic features: microvascular proliferation, necrosis, TERT promoter mutation, Epidermal growth factor receptor gene amplification, +7/-10 chromosome copy-number changes (CNS WHO grade 4) 1).
History
see Glioblastoma History.
Epidemiology
see Glioblastoma epidemiology.
Prior malignancies in patients harboring glioblastoma
Patients who develop Glioblastoma following a prior malignancy constitute ~8% of patients with Glioblastoma. Despite significant molecular differences these two cohorts appear to have a similar overall prognosis and clinical course. Thus, whether or not a patient harbors a malignancy prior to diagnosis of Glioblastoma should not exclude him or her from aggressive treatment or for consideration of novel investigational therapies 2).
Classification
Glioblastoma cell lines
Glioblastoma stem-like cells
Glioblastoma biology
Pathogenesis
Pathophysiology
Molecular pathways in the development of glioblastoma
Genome-wide profiling studies have shown remarkable genomic diversity among glioblastomas.
Molecular studies have helped identify at least 3 different pathways in the development of glioblastomas.
● 1st pathway: dysregulation of growth factor signaling through amplification and mutational activation of receptor tyrosine kinase (RTK) genes. RTKs are transmembrane proteins that act as receptors for an epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) & platelet-derived growth factor (PDGF). They can also act as receptors for cytokines, hormones, and other signaling pathways
● 2nd pathway: activation of the Phosphoinositide 3 kinase (PI3K)/AKT/mTOR, which is an intracellular signaling pathway that is essential in regulating cell survival
● 3rd pathway: inactivation of the p53 and retinoblastoma (Rb) tumor suppressor pathways
Risk factors
Glioblastomas are intrinsic brain tumors thought to originate from a neuroglial stem or progenitor cells. More than 90% of glioblastomas are isocitrate dehydrogenase (IDH)-wildtype tumors. Incidence increases with age, males are more often affected. Beyond rare instances of genetic predisposition and irradiation exposure, there are no known glioblastoma risk factors.
Biomarkers
Microcirculation patterns
Vessels with different microcirculation patterns are required for glioblastoma (Glioblastoma) growth. However, details of the microcirculation patterns in Glioblastoma remain unclear.
Mei et al. examined the microcirculation patterns of Glioblastoma and analyzed their roles in patient prognosis together with two well-known GMB prognosis factors (O6 -methylguanine DNA methyltransferase [MGMT] promoter methylation status and isocitrate dehydrogenase [IDH] mutations).
Eighty Glioblastoma clinical specimens were collected from patients diagnosed between January 2000 and December 2012. The microcirculation patterns, including endothelium-dependent vessels (EDVs), extracellular matrix-dependent vessels (ECMDVs), Glioblastoma cell-derived vessels (GDVs), and mosaic vessels (MVs), were evaluated by immunohistochemistry (IHC) and immunofluorescence (IF) staining in both Glioblastoma clinical specimens and xenograft tissues. Vascular density assessments and three-dimensional reconstruction were performed. MGMT promoter methylation status was determined by methylation-specific PCR, and IDH1/2 mutations were detected by Sanger sequencing. The relationship between the microcirculation patterns and the patient prognosis was analyzed by the Kaplan-Meier method.
All 4 microcirculation patterns were observed in both Glioblastoma clinical specimens and xenograft tissues. EDVs was detected in all tissue samples, while the other three patterns were observed in a small number of tissue samples (ECMDVs in 27.5%, GDVs in 43.8%, and MVs in 52.5% tissue samples). GDV-positive patients had a median survival of 9.56 months versus 13.60 months for GDV-negative patients (P = 0.015). In MGMT promoter-methylated cohort, GDV-positive patients had a median survival of 6.76 months versus 14.23 months for GDV-negative patients (P = 0.022).
GDVs might be a negative predictor for the survival of Glioblastoma patients, even in those with MGMT promoter methylation 3).
Pathology
Genetics
Growth
see Glioblastoma growth.
Radioresistance
Clinical Features
It generally presents with epilepsy, cognitive decline, headache, dysphasia, or progressive hemiparesis. 4).
Seizures as the presenting symptom of glioblastoma predicted longer survival in adults younger than 60 years. The IDH1 R132H mutation and p53 overexpression (>40%) were associated with seizures at presentation. Seizures showed no relationship with the tumor size or proliferation parameters 5).
Diagnosis
Differential diagnosis
Scores
Treatment
Outcome
Diet
Complications
Case series
Case reports
Case report from the HGUA
A 26-year-old woman with a history of smoking, childhood hiccup spasms, nephritic colics, and a diagnosis of fibromyalgia since adolescence. The patient experienced persistent right-sided hemibody sensory disturbance, including dysesthesias, hypoesthesia, and hyperalgesia, over the past 6 months. Initial evaluation revealed a left hemispheric lesion on neuroimaging, prompting differential diagnoses of neoplasia, venous infarction, and demyelinating lesion. The patient was admitted to the Neurology department for further evaluation. Brain MRI findings indicated a low-grade glial primary neoplasia, primarily located in the frontal region with extension to the left parietal and temporal regions. She subsequently underwent a craniotomy and probable subtotal resection of the left frontal lesion using (MNIO). The histological examination confirmed the diagnosis of glioblastoma. Follow-up MRI revealed a significant increase in the size of the lesion. Further evaluation and monitoring are recommended to assess disease progression and guide treatment decisions.
Introduction: Glioblastoma is a malignant primary brain tumor that arises from glial cells, commonly exhibiting aggressive behavior and poor prognosis. Its occurrence in young adults, like our patient, is relatively uncommon. The combination of persistent hemibody sensory disturbances and the identification of a left hemispheric lesion on neuroimaging necessitated further investigations to establish an accurate diagnosis and determine appropriate management.
Case Presentation: A 26-year-old woman with a history of smoking and childhood hiccup spasms, nephritic colics, and fibromyalgia since adolescence presented with a new onset of persistent right-sided hemibody sensory disturbances. These symptoms included abnormal sensations (dysesthesias), reduced sensitivity to touch or pain (hypoesthesia), and increased sensitivity to pain (hyperalgesia). The patient sought medical attention due to the progressive and distressing nature of her symptoms.
Clinical Course: The patient was initially evaluated in a private clinic, and a brain MRI was performed, revealing a left hemispheric lesion. Given the atypical presentation and location of the lesion, a comprehensive differential diagnosis was considered, including neoplasia, venous infarction, and demyelinating lesion. As a result, she was referred to the Neurology department of our institution for further evaluation.
Investigations: Brain MRI with contrast showed a low-grade glial primary neoplasia, predominantly located in the frontal region with extension into the left parietal and temporal regions. Given the patient's young age and the lesion's atypical appearance, the possibility of glioblastoma was considered.
Treatment and Outcome: In consideration of the patient's clinical presentation and MRI findings, she underwent a craniotomy for the removal of the left frontal lesion. The procedure was performed using Minimally Non-Invasive Surgery (MNIO) techniques and was completed without any notable complications.
Histopathology: Histological examination of the resected tissue confirmed the diagnosis of glioblastoma, a highly malignant and aggressive brain tumor.
Follow-up: Follow-up MRI revealed a marked increase in the size of the left temporal lesion, measuring 2.5 cm compared to 1.1 cm in the previous control. The lesion showed characteristics of a solid cystic mass with surrounding edema. Additionally, there was a slight increase in the sensation of cortico-subcortical frontoparietal mass effect on the left. Hyperintensity on the FLAIR sequence was associated with minimal contrast enhancement, and perfusion sequence values were inconclusive, making infiltration difficult to rule out. Further evaluations and regular follow-up visits are recommended to monitor disease progression and inform treatment decisions.
Discussion: Glioblastoma is a rare occurrence in young adults, and its diagnosis can be challenging due to atypical clinical presentations. The combination of persistent hemibody sensory disturbances and a left hemispheric lesion on neuroimaging raised suspicion for an underlying neoplastic process. The patient's history of smoking and fibromyalgia could have potential implications in the pathogenesis or management of glioblastoma, although further research is needed to explore these associations.
Conclusion: We report a rare case of glioblastoma in a 26-year-old woman presenting with persistent hemibody sensory disturbances. The identification of a left hemispheric lesion on neuroimaging prompted further evaluation, leading to the diagnosis of glioblastoma. Surgical intervention was performed using MNIO techniques, and the patient's condition is being closely monitored to guide further treatment decisions. This case underscores the importance of considering glioblastoma in the differential diagnosis of young adults presenting with neurological symptoms and focal brain lesions. Early detection and management are crucial for improving patient outcomes in such cases.