What is the recommended diagnostic and treatment plan for a 25‑year‑old woman with a 5 × 4 × 3 cm left basal‑ganglia glioma compressing the thalamus and extending toward the midline and ventricle, presenting with chronic headache?

Management of Large Basal Ganglia Glioma in a Young Adult

This 25-year-old woman requires urgent neurosurgical referral for tissue diagnosis via stereotactic biopsy (given the deep, eloquent location) followed by molecular profiling to guide treatment, with immediate consideration of corticosteroids for symptomatic relief of mass effect. 1

Immediate Diagnostic Workup

Imaging Confirmation

• Contrast-enhanced MRI with gadolinium is the mandatory first-line imaging modality to fully characterize this lesion, if not already completed with appropriate sequences 1
• Advanced imaging with perfusion MRI or amino acid PET (O-(2-[18F]-fluoroethyl)-l-tyrosine or [11C-methyl]-l-methionine) can identify metabolic hotspots for targeted biopsy planning, particularly valuable for deep-seated lesions 1

Preoperative Symptom Management

• Corticosteroids should be administered immediately to reduce tumor-associated edema causing the chronic headaches, unless primary CNS lymphoma is suspected 1
• Assess for seizure history; if present, initiate anticonvulsant therapy, but do not use prophylactic anticonvulsants as they do not reduce first-seizure risk 1

Tissue Acquisition Strategy

Surgical Approach for This Location

Given the 5×4×3 cm size in the left basal ganglia with thalamic compression and midline extension, stereotactic biopsy is the appropriate initial surgical approach rather than attempted resection 1. The basal ganglia location makes this an eloquent, high-risk area where aggressive resection would likely cause devastating motor and cognitive deficits.

• Frame-based or frameless stereotactic biopsy carries low morbidity risk with high diagnostic accuracy 1
• Multiple serial samples along the biopsy trajectory are essential to avoid sampling bias 1
• 5-aminolevulinic acid fluorescence can optimize tissue sampling during stereotactic procedures 1

Critical Molecular Testing Required

The following molecular markers must be obtained from biopsy tissue to guide all subsequent treatment decisions 1:

• IDH mutation status (IDH1/IDH2) - most critical prognostic and therapeutic marker
• 1p/19q codeletion status - distinguishes oligodendroglioma from astrocytoma
• MGMT promoter methylation - predicts chemotherapy benefit
• ATRX expression and CDKN2A/B status for further classification
• TERT promoter mutation and EGFR amplification if IDH wild-type

Treatment Algorithm Based on Molecular Diagnosis

If IDH-Mutant Astrocytoma (Most Likely in 25-Year-Old)

For WHO Grade 2 IDH-mutant astrocytoma requiring treatment:

• Involved-field radiotherapy (approximately 50-54 Gy) followed by PCV chemotherapy (procarbazine, lomustine, vincristine) based on RTOG 9802 trial 1

For WHO Grade 3 IDH-mutant astrocytoma:

• Involved-field radiotherapy (60 Gy in 2 Gy fractions) followed by maintenance temozolomide (150-200 mg/m² for 5 days every 28 days, typically 12 cycles) based on CATNON trial 1

For WHO Grade 4 IDH-mutant astrocytoma:

• Treat similarly to Grade 3, with consideration of more aggressive glioblastoma protocols 1

If IDH-Mutant, 1p/19q-Codeleted Oligodendroglioma

For WHO Grade 2 or 3:

• Radiotherapy followed by PCV polychemotherapy based on EORTC 26951 and RTOG 9402 trials 1
• This subtype has significantly better prognosis and chemotherapy responsiveness 1

If IDH Wild-Type Glioblastoma (Less Likely at Age 25)

Standard treatment would be:

• Concurrent temozolomide (75 mg/m² daily throughout radiotherapy) with focal radiotherapy (60 Gy in 30 fractions), followed by adjuvant temozolomide (150-200 mg/m² days 1-5 of 28-day cycles for 6 cycles) 1
• MGMT promoter methylation status strongly predicts benefit from temozolomide 1

Multidisciplinary Team Requirement

Management must occur at a high-volume specialist center with a dedicated neuro-oncology tumor board including 1:

• Neurosurgeons experienced in stereotactic procedures
• Neuroradiologists
• Neuropathologists with molecular diagnostic capabilities
• Radiation oncologists
• Medical/neuro-oncologists

Surveillance Protocol Post-Treatment

• MRI surveillance every 3-6 months with neurological examination 1, 2
• Baseline MRI 3-4 weeks post-radiotherapy to establish new reference for monitoring 1
• Beware of pseudoprogression 4-8 weeks after radiotherapy completion; apparent progression should be confirmed with repeat MRI 4 weeks later before changing treatment 1, 2

Critical Prognostic Considerations

Favorable factors for this patient 1:

• Age <50 years (she is 25)
• Molecular profile will be determinative (IDH-mutant tumors have significantly better prognosis than IDH wild-type)

Concerning factors:

• Large size (5×4×3 cm) with mass effect
• Deep location limiting resection options
• Midline extension suggests potential for bilateral involvement

Common Pitfalls to Avoid

• Never proceed with treatment without tissue diagnosis and molecular profiling - the molecular subtype completely changes management 1
• Do not attempt aggressive resection in the basal ganglia - the morbidity would be catastrophic and biopsy provides adequate tissue for molecular testing 1
• Do not misinterpret pseudoprogression as true progression in the first 2-3 months post-radiotherapy 1, 2
• Monitor for venous thromboembolism - glioma patients have high thrombotic risk 2, 3
• Taper corticosteroids as quickly as safely possible to avoid myopathy, hyperglycemia, infections, and psychiatric complications 2