IDH-wildtype glioblastoma

IDH-Wildtype Glioblastoma: A Malignant Brain Tumor

IDH-wildtype glioblastoma is the most common and aggressive type of primary brain tumor in adults, accounting for about 90% of all glioblastomas. This cancerous growth lacks mutations in the IDH1 or IDH2 genes, which are enzymes involved in cellular metabolism.

Characteristics

• Aggressive clinical course: IDH-wildtype glioblastoma is known to have a poor prognosis and an often-aggressive clinical course.
• Histological features: This type of tumor exhibits brisk mitotic activity (rapid cell division) and microvascular proliferation or necrosis, which are hallmarks of its malignant nature.
• Genetic alterations: IDH-wildtype glioblastoma is characterized by genetic changes such as EGFR gene amplification, TERT promoter mutations, and combined gain of whole chromosome 7, loss of chromosome 10.

Diagnosis

The diagnosis of IDH-wildtype glioblastoma is typically made based on histological examination of the tumor tissue, which shows a hypercellular infiltrative lesion with variable morphology. Frozen section description may reveal brisk mitotic activity and microvascular proliferation or necrosis.

Treatment

Treatment for IDH-wildtype glioblastoma is multimodal and includes maximal safe surgical resection, fractionated radiation, chemotherapy, and tumor-treating fields. However, therapeutic breakthroughs are still lacking, and the prognosis remains poor.

References

• [1] Glioblastoma, IDH wild type is an aggressive, infiltrating, astrocytic glioma that lacks mutations in IDH1, IDH2 and histone H3 genes and is histologically defined by brisk mitotic activity and microvascular proliferation or necrosis.
• [9] GBM are now defined as diffuse, astrocytic gliomas that are IDH-wildtype and H3-wildtype, exhibiting one or more of the following histological or genetic features: microvascular proliferation, necrosis, telomerase reverse transcriptase (TERT) promoter mutation, epidermal growth factor receptor (EGFR) gene amplification, a concomitant gain of whole chromosome 7, loss of chromosome 10.
• [13] GBM are now defined as diffuse, astrocytic gliomas that are IDH-wildtype and H3-wildtype, exhibiting one or more of the following histological or genetic features: microvascular proliferation, necrosis, telomerase reverse transcriptase (TERT) promoter mutation, epidermal growth factor receptor (EGFR) gene amplification, a concomitant gain of whole chromosome 7, loss of chromosome 10.

Common symptoms of IDH-wildtype glioblastoma include:

• Headaches [1]
• Seizures [2]
• Changes in mental function, mood, personality [2]
• Muscle weakness [1]
• Visual changes [1]
• Language deficit [1]

These symptoms can be subtle and may not always be specific to the location of the tumor. It's essential to seek medical attention if you or someone you know is experiencing any of these symptoms.

Additional information:

IDH-wildtype glioblastoma is an aggressive type of brain cancer that typically affects individuals in their 60s and 70s [6]. The symptoms can be generalized or specific to the location of the tumor, making it crucial for a proper diagnosis by a medical professional.

References: [1] - Context result 1 [2] - Context result 2 [6] - Context result 6

Diagnostic Tests for IDH-wildtype Glioblastoma

IDH-wildtype glioblastoma, also known as glioblastoma without mutations in the IDH1 or IDH2 genes, is a type of aggressive brain cancer. Diagnosing this condition requires a combination of imaging tests and molecular analysis.

Imaging Tests:

• Magnetic Resonance Imaging (MRI): MRI with and without contrast is considered the gold standard diagnostic modality for evaluating glioblastoma, including IDH-wildtype cases [3][9]. This test helps identify the tumor's location, size, and extent of spread.
• Computed Tomography (CT) Scan: While not as sensitive as MRI, CT scans can also be used to evaluate glioblastoma and may be particularly useful in emergency situations or when MRI is contraindicated [4].

Molecular Analysis:

• IDH1/2 Mutation Testing: This test detects mutations in the IDH1 or IDH2 genes, which are essential for diagnosing IDH-wildtype glioblastoma. The assay only detects mutations in codons 96 through 138 of the IDH1 gene [2].
• Genomic and Transcriptomic Analysis: Advanced molecular tests can provide a comprehensive understanding of the tumor's genetic profile, including mutations in genes such as EGFR, TERT promoter, or chromosome 7/10 alterations [5][12].

Other Diagnostic Considerations:

• Histological Examination: Histopathological examination is crucial for diagnosing glioblastoma, IDH-wildtype. The presence of necrosis or microvascular proliferation is required for a histologic diagnosis of GBM [13].
• Integrated Diagnosis: An integrated diagnosis that combines imaging and molecular analysis can provide a more accurate diagnosis and help distinguish IDH-wildtype glioblastoma from other types of brain tumors.

References:

[1] UCSF Clinical Cancer Genomics Laboratory [2] This assay only detects mutations in codons 96 through 138 of the IDH1 gene. [3]

Treatment Options for IDH-Wildtype Glioblastoma

IDH-wildtype glioblastoma, a type of brain cancer, requires effective treatment to manage its progression. While surgery and radiation therapy are common approaches, drug treatments have also been explored.

• Temozolomide: This alkylating agent is used as an initial treatment for newly diagnosed IDH-wildtype glioblastoma [7]. It has shown promise in clinical trials, but its effectiveness can vary depending on individual patient factors.
• Bevacizumab: As a monoclonal antibody, bevacizumab targets vascular endothelial growth factor (VEGF), which is involved in tumor angiogenesis. Its use in IDH-wildtype glioblastoma has been investigated, but more research is needed to fully understand its benefits and limitations [7].
• Vorasidenib: Although not specifically approved for IDH-wildtype glioblastoma, vorasidenib, a targeted drug, has shown promise in treating low-grade gliomas. Its potential application in IDH-wildtype glioblastoma is an area of ongoing research [3].

Current Treatment Landscape

The standard care for IDH-mutant glioma includes surgery, radiation therapy (RT), and/or chemotherapy. However, for IDH-wildtype glioblastoma, the treatment approach may differ. The use of temozolomide and bevacizumab has been explored in clinical trials, but more research is needed to determine their effectiveness [8].

Ongoing Research

Studies are ongoing to investigate new treatments for IDH-wildtype glioblastoma. For example, a phase II trial is examining the combination of temozolomide and radiation therapy in patients with IDH wild-type historically lower-grade gliomas or glioblastoma [5]. Additionally, zotiraciclib has been investigated as a potential treatment for recurrent gliomas containing an IDH1 or IDH2 mutation [4].

References: [3] FDA approval of vorasidenib for low-grade gliomas. [4] Investigation of zotiraciclib in recurrent gliomas with IDH mutations. [5] Phase II trial of temozolomide and radiation therapy in IDH wild-type glioblastoma. [7] Use of bevacizumab and temozolomide in newly diagnosed glioblastoma. [8] Standard care for IDH-mutant glioma.

Differential Diagnosis of IDH-wildtype Glioblastoma

IDH-wildtype glioblastoma is a type of brain cancer that does not have mutations in the isocitrate dehydrogenase (IDH) genes. When it comes to differential diagnosis, several conditions can be considered:

• Primary CNS lymphoma: This is a rare and aggressive form of non-Hodgkin lymphoma that affects the central nervous system. It can present with similar imaging characteristics as glioblastoma.
• Cerebral abscess: A cerebral abscess is a collection of pus in the brain, usually caused by bacterial or fungal infections. It can mimic the appearance of glioblastoma on imaging studies.
• Cavernous malformation: This is a rare vascular anomaly that can cause seizures and other neurological symptoms. It may be mistaken for glioblastoma due to its similar appearance on MRI scans.
• Encephalitis: Encephalitis is an inflammation of the brain, usually caused by viral infections. It can present with similar clinical and imaging features as glioblastoma.
• Intracranial hemorrhage: This refers to bleeding in the brain, which can be caused by various factors such as trauma, hypertension, or blood clotting disorders. It may be mistaken for glioblastoma due to its similar appearance on imaging studies.
• Radiation necrosis: This is a complication of radiation therapy that can cause tissue death and scarring in the brain. It may be confused with glioblastoma due to its similar appearance on MRI scans.
• Toxoplasmosis: Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii, which can affect the brain and cause symptoms such as seizures and cognitive impairment.

These conditions should be considered in the differential diagnosis of IDH-wildtype glioblastoma, especially when imaging studies are inconclusive or suggest a different diagnosis. A thorough clinical evaluation and further diagnostic testing may be necessary to confirm the correct diagnosis.

References:

• [3] Structural magnetic resonance imaging (MRI) with gadolinium remains the gold standard diagnostic modality for GBM evaluation.
• [4] Primary CNS lymphoma, cerebral abscess, cavernous malformation, encephalitis, intracranial hemorrhage, radiation necrosis, and toxoplasmosis are all potential differential diagnoses for IDH-wildtype glioblastoma.
• [7] Glioblastoma, IDH wildtype. Related Content. Differential Diagnosis. Other primary brain tumors – low grade gliomas; Metastatic lesions; Demyelinating disease...
• [8] GBM with IDH mutations are clinically and genetically distinct from GBM with wild-type IDH genes.
• [9] Diffuse gliomas that are IDH-wildtype and have molecular features of GBM can now be classified as the latter, even when histological high-grade features are present.