IDH-wildtype glioma [Neurosurgery Wiki]

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====== IDH-wildtype glioma ======
 is a subtype of gliomas defined by the absence of mutations in the isocitrate dehydrogenase (IDH) genes (IDH1 and IDH2). This subtype typically represents a more aggressive clinical entity compared to its IDH-mutant counterpart. Below are key aspects of IDH-wildtype gliomas:

Classification and Diagnostic Criteria
IDH-wildtype gliomas fall under the 2021 WHO Classification of CNS Tumors.
A glioma with an IDH-wildtype genotype and histological features of astrocytoma is classified as glioblastoma, IDH-wildtype if it shows:
Necrosis and/or microvascular proliferation.
TERT promoter mutation, EGFR amplification, or a chromosome 7 gain/10q loss (7+/10q−), which are molecular hallmarks of glioblastoma.
Epidemiology
Typically occurs in older adults, peaking around 50–60 years of age.
Represents a significant portion of high-grade gliomas.
Molecular Features
Lacks IDH1/IDH2 mutations, which distinguishes it from IDH-mutant gliomas.
Common molecular alterations include:
TERT promoter mutations.
EGFR amplification.
Chromosome 7 gain/10q loss.
PTEN mutations and alterations in the PI3K/AKT pathway.
These tumors often show homozygous deletion of CDKN2A/B, a marker of poor prognosis.
Prognosis
IDH-wildtype gliomas have a poorer prognosis than IDH-mutant gliomas.
The median survival depends on the grade and specific molecular alterations but is typically shorter due to their aggressive behavior.
Imaging
Often presents as non-enhancing lesions that progress to ring-enhancing masses as the tumor becomes more aggressive.
Associated with significant edema and mass effect.
Clinical Presentation
Symptoms vary depending on the tumor location but commonly include:
Headache.
Seizures.
Neurological deficits (e.g., hemiparesis, visual disturbances).
Treatment
Standard of care includes:
Maximal safe resection.
Radiotherapy (often combined with concurrent and adjuvant temozolomide chemotherapy, especially in glioblastoma).
Targeted therapies are being explored in clinical trials, particularly against EGFR, TERT, and other actionable mutations.
Research and Future Directions
Exploration of immunotherapy (e.g., immune checkpoint inhibitors) and vaccine-based approaches.
Liquid biopsy markers (e.g., circulating tumor DNA) for early detection and monitoring.
Understanding resistance mechanisms to temozolomide and radiotherapy.