What is the most likely diagnosis and appropriate management for an adult patient with a 5 × 4.1 × 3.1 cm heterogeneous lesion in the left basal ganglia and thalamus showing hemorrhagic components, irregular ring enhancement, elevated choline on magnetic resonance spectroscopy, and a 0.5 cm rightward midline shift?

Management of Suspected High-Grade Glioma (Glioblastoma)

This patient requires urgent neurosurgical consultation for maximal safe resection followed by histopathological diagnosis with molecular profiling, as the imaging features—hemorrhagic components with blooming on SWI, irregular ring enhancement, elevated choline-to-creatinine ratio (5:1), and 0.5 cm midline shift—are highly characteristic of glioblastoma. 1

Immediate Priorities

Neurosurgical Referral and Monitoring

• Transfer immediately to a specialized neurosurgical center for evaluation and surgical planning, as this is a standard recommendation for all suspected high-grade gliomas 2
• Admit to a neuromonitoring-capable unit given the 0.5 cm midline shift, which indicates significant mass effect and risk of herniation 1
• Monitor closely for signs of neurological deterioration including altered consciousness, pupillary changes, posturing, progressive headache, or vomiting 1
• Do not perform lumbar puncture due to the mass effect and risk of precipitating herniation 1

Corticosteroid Management

• Initiate corticosteroids to reduce perilesional edema and mass effect, though prophylactic use should not be routine 2
• The minimal perilesional edema noted on imaging does not preclude corticosteroid use when mass effect is present 1

Surgical Management

Maximal Safe Resection

• The primary surgical goal is maximal safe resection (gross total resection when feasible), as this improves overall survival and serves as an independent prognostic factor 1, 3
• Optimal resection should be attempted except in patients with high physiological age, multiple comorbidities, poor performance status, or lesions in highly functional regions 2
• The deep basal ganglia and thalamic location presents surgical challenges, but biopsy at minimum is mandatory for tissue diagnosis 2

Tissue Acquisition Requirements

• Obtain adequate tissue for both histopathological diagnosis AND molecular profiling (IDH mutation status, MGMT promoter methylation, 1p/19q codeletion status) 2, 1, 4
• The surgeon must ensure samples are representative of the lesion, particularly from contrast-enhancing areas, to avoid misclassification as lower grade 2
• Samples should be processed immediately by pathology for multiple purposes: formalin fixation for histology, frozen tissue for molecular studies, and smear preparations for rapid diagnosis 2

Post-Operative Imaging

• Obtain MRI within 24-48 hours (ideally within 72 hours) post-operatively with and without contrast to establish baseline residual disease before treatment-related changes appear 2, 1
• This baseline imaging is critical for distinguishing true progression from pseudoprogression during subsequent treatment 5

Histopathological Diagnosis

WHO Classification and Grading

• Use the WHO classification system as the standard for diagnosis and histoprognostic grading 2
• The imaging features strongly suggest WHO grade IV (glioblastoma): irregular ring enhancement, hemorrhagic components, elevated choline, reduced NAA, and mass effect 2, 1

Molecular Profiling (Essential)

• Test for IDH1/IDH2 mutations: IDH wild-type glioblastomas (the vast majority) have worse prognosis than IDH-mutant tumors 4
• Assess MGMT promoter methylation status: This predicts benefit from temozolomide chemotherapy and guides treatment decisions, especially in elderly patients 4
• Consider testing for 1p/19q codeletion if oligodendroglial features are present, though this is less likely given the imaging characteristics 2
• Immunohistochemistry (GFAP, Ki67) can provide additional diagnostic and prognostic information 2

Adjuvant Treatment

Standard Chemoradiotherapy Protocol

• Initiate treatment within 2-6 weeks (ideally within one month) after surgical resection 2, 1
• Standard therapy consists of external-beam radiotherapy to 60 Gy (1.8-2 Gy per fraction, 5 days per week) with concurrent temozolomide, followed by adjuvant temozolomide 2, 1, 3
• This combination improved 2-year survival from 10.9% to 27.2% and 5-year survival from 1.9% to 9.8% compared to radiotherapy alone (HR 0.6, P<0.001) 3

Radiation Planning

• The clinical tumor volume (CTV) should include a 20 mm safety margin beyond the gross tumor volume (GTV) in all three dimensions, though this can be reduced based on grade, histology, and location 2
• Use noncoplanar focused multiple beams (3-5 beams) to minimize dose to non-diseased brain 2
• The T2/FLAIR abnormality often defines radiation portals, as tumor cells infiltrate this region 2

Chemotherapy Considerations

• For glioblastoma, temozolomide is standard; nitrosourea-based chemotherapy is an option 2
• MGMT promoter methylation status guides chemotherapy decisions and predicts benefit from alkylating agents 4
• Patients should be enrolled in clinical trials when available 2

Surveillance and Follow-Up

Imaging Schedule

• Perform brain MRI every 2-3 months during the first year post-treatment, then every 3-6 months indefinitely 1
• Use identical imaging protocols (T1 pre- and post-contrast, T2, FLAIR, DWI, gradient-echo/SWI) to allow accurate longitudinal comparison 1
• MRI is preferable to CT for follow-up of disease progression 2

Interpretation Challenges

• Clinical or radiological deterioration within 2 months after radiotherapy should not automatically be considered treatment failure—this may represent pseudoprogression 2
• Pseudoprogression occurs due to blood-brain barrier disruption from treatment rather than true tumor growth 5, 6
• Advanced imaging techniques (perfusion MRI, diffusion MRI, MR spectroscopy, PET) may help distinguish pseudoprogression from true progression, though no definitive method exists 5, 6

Critical Pitfalls to Avoid

Diagnostic Pitfalls

• Do not delay neurosurgical consultation—the midline shift indicates high risk of herniation requiring prompt intervention 1
• Do not rely solely on imaging for diagnosis; histological confirmation is mandatory because neuroimaging is insufficiently specific 2
• Basal ganglia infarction can rarely mimic glioblastoma with ring enhancement and mass effect, but the hemorrhagic components, spectroscopy findings (NAA:choline 1:6, choline:creatinine 5:1), and clinical context make glioblastoma far more likely 7
• The minimal perilesional edema relative to tumor size can occur in infiltrative high-grade gliomas and should not falsely reassure 1

Treatment Pitfalls

• Do not start adjuvant therapy without molecular profiling results, as MGMT status influences treatment decisions 4
• Do not use prophylactic anticoagulation routinely, but implement thromboembolism surveillance and prevention with low-molecular-weight heparin and compression stockings perioperatively 2
• Therapeutic anticoagulation can be prescribed 4-5 days post-surgery for thromboembolic complications without undue hemorrhagic risk 2

Monitoring Pitfalls

• Do not interpret increased enhancement on early post-treatment imaging as definitive progression without considering pseudoprogression 2, 5
• Do not use contrast enhancement alone to assess treatment response—incorporate T2/FLAIR changes, clinical status, and corticosteroid requirements 5

Prognosis

• Glioblastoma is the most lethal primary brain tumor with median survival of 14-16 months using standard treatment 3, 4
• Five-year survival is approximately 9.8% with combined temozolomide and radiotherapy versus 1.9% with radiotherapy alone 3
• Important prognostic factors include histologic diagnosis, age, performance status, extent of resection, and molecular markers (IDH status, MGMT methylation) 2, 4
• Most patients ultimately die from progressive disease despite treatment 3