Case 11 High Grade glioma

Figure 11-1: MRI brain of the patient: A coronal with contrast, B sagittal with contrast, C T2 axial image, D axial with contrast.

Clinical presentation

• Male patient 37 years old with history of progressive weakness with recurrent attacks of parasthesia.
• Recurrent attacks of GTCs 1 month ago.
• Left side weakness grade 4/5.

• Q1: Describe MRI finding?
• The MRI reveals a right deep frontal non-homogeneous lesion compressing and invading the corpus callosum, with surrounding edema extending into the adjacent parietal lobe.

• Q2: What is the differential diagnosis of ring enhancing lesion?
• (MAGIC DR) mnemonic. M – Metastasis A – Abscess G – Glioblastoma multiforme I – Infarct (subacute phase) C – Contusion D – Demyelinating disease (eg. tumefactive MS) R – Radiation necrosis.
• Malignant astrocytoma, metastases, abscess including toxoplasmosis, lymphomas, resolving hematoma, cysticercosis cyst, trauma and infarction.
• Abscess

Ring enhancement is typically thinner than that seen in glioblastoma multiforme (GBM), with a T2 hypointense rim and typical diffusion restriction. Magnetic resonance spectroscopy (MRS) may show metabolites such as succinate and amino acids.

• Metastasis

Typically, there are multiple lesions at gray-white junctions. The lesions are more often round than infiltrating. The primary tumor is often known, although a single lesion may be indistinguishable.

• Primary CNS lymphoma

Periventricular enhancing mass, often crossing the corpus callosum, typically appears isointense or hypointense on T2-weighted images.

• Q3: What is the new WHO classification of adult-type diffuse glioma?
• The recent WHO classification 5^th edition classifies it into:

Astrocytoma, IDH mutant

astrocytoma, IDH-mutant, grade 2

astrocytoma, IDH-mutant, grade 3

astrocytoma, IDH-mutant, grade 4

Oligodendroglioma, IDH-mutant & 1p/19q codeleted

oligodendroglioma, IDH-mutant & 1p/19q codeleted, grade 2

oligodendroglioma, IDH-mutant & 1p/19q codeleted, grade 3

Glioblastoma, IDH-wildtype 4

giant cell glioblastoma G 4

gliosarcoma G 4

epithelioid glioblastoma G 4

• Q4: Does age have any prognostic factor in glioblastoma?

Yes, GBM occur in 2 forms and two age group:

• Denovo type, occur in old age with bad prognosis.
• 2ndry type, occur in younger age as a result of differentiation of low-grade type, with better prognosis.

• Q5: How does high grade glioma appear in angiography?
• Tumour blush with early draining vein.

• Q6: When do you consider Metastatic work up in a suspected case of high-grade glioma?

In the following situations:

• Multiple brain lesions.
• History of cancer.
• Single ring enhancing lesion at gray-white interface.
• Posterior fossa cerebellar lesion in adults.

• Q7: What is the pathological basis of the different patterns of enhancement in different grades of glioma?
• The principle involves the degree of destruction of the blood-brain barrier; the greater the destruction, the more pronounced the enhancement. In grade 2, there is no enhancement; in grade 3, there is patchy enhancement; in grade 4, there is solid enhancement; and in glioblastoma multiforme (GBM), there is necrosis with irregular ring enhancement due to rapid growth.

• Q8: What is the general role of surgery in high grade glioma?
• Maximal gross safe resection, when possible, followed by chemotherapy with radiation.

• Q9: What is the advantage of surgery and gross total resection?
• It helps in:

1. Obtain generous tissue for diagnosis.
2. Reduce tumour burden which facilitates adjuvant therapy.
3. Reduce mass effect and improve function.
4. Decrease ICP and decrease oedema.
5. Reduce seizure frequency.
6. Decrease the risk of wounded glioma (hemorrhage and oedema).
7. Increase time to tumour progression and increase median survival.

• Q10: What is the relative contraindication for surgery (meaning consideration for a biopsy)?
• It includes the following:

1. Extensive dominant lobe high grade glioma
2. Elderly, patient older than 75 years.
3. KPS less than 70
4. Patient with poor medical condition
5. Multicentric glioma
6. Lesions with bilateral involvement (butterfly glioma), except surgery are indicated to decrease ICP and risk of herniation.

• Q11: As regards this case with relation to the motor strip, what are methods help in localization and assist in maximal gross safe resection?
• We can use the following methods:

1. MRI anatomy and surrounding sulcal landmarks.
2. Functional MRI.
3. Neuro-navigator.
4. Intraoperative MRI.
5. Intraoperative mapping and brain stimulation either:
6. A wake craniotomy with mapping.
7. Under general anesthesia with SSEPs and MUPs and neuromonitoring.

Figure11-2: intraoperative skull-scalp metric points A, dotted line for sagittal suture, B, Pre-central sulcus, C, coronal suture, D, Central sulcus, E, superior frontal sulcus, F, and its arrow, referred to staphenion which is the meeting of superior temporal line and coronal suture. The dotted circle outlines the lesion on the cortex.

• Q12: What is the expected semiology of a lesion in this location?
• The lesion is in the white matter tracts serving the motor strip of the upper and lower limb with adjacent oedema in the sensory area, weakness and sensory affection will be the predominant symptoms.

• Q13: What is the stupp protocol for adjuvant therapy for high grade glioma?
• After surgery, adjuvant radiotherapy is administered for 4 weeks, followed by chemotherapy with temozolomide (an oral alkylating agent that destroys DNA) for 6 cycles, with 5 days per month for 6 months.

• Q14: What is the role of the MGMT promoter gene in the prognosis of high-grade glioma?
• MGMT is a DNA-repair enzyme that counters the effects of chemotherapy in gliomas, leading to shorter survival. The MGMT promoter gene is responsible for the production of the MGMT enzyme. High MGMT activity is associated with shorter survival. Methylation of the MGMT promoter gene leads to decreased activity of the MGMT enzyme, which improves survival outcomes.

• Q15: What are the good prognostic factors for high grade glioma?
• It includes:

1. Younger age less than 40 years.
2. Decrease activity of MGMT
3. Pre-operative KPS more than 80.
4. Site of the lesion, frontal lobe is better.
5. Extent of resection, more than 90% is better.
6. Degree of enhancement, lower enhancement is better.
7. Size of lesion, tumour less than 6cm3 is better.
8. Histological grading, lower grades are better.

• Q16: What is the Gliadel wafer?
• It is an implant loaded with chemotherapy applied to the resection cavity after tumour excision. The principle is to bypass the blood brain barrier and to increase concentration of chemotherapy. Its complications are seizure and infection.

• Q17: What is the usual site of recurrence of high-grade glioma? When to re-operate a recurrent high-grade glioma? What is the benefit of re-surgery?
• 90% of recurrence occurs at the site of same site of original tumour, and 10% occur at remote site due to spread through white matter tracts and commissures.
• Indication of re-surgery:

1. Younger age.
2. KPS more than 70.
3. Long time between initial surgery and recurrence.
4. Histological lower grade at the initial surgery.

• Re-surgery increases survival by 9 months in GBM and 22 months in grade 3.

• Q18: What is the difference between multi-centric and multi-focal glioma? What is meningeal gliomatosis? What is the goal of treatment in these gliomas?
• The term multi-centric and multi-focal glioma is used to describe multiple gliomas, with the difference that, multi-focal glioma is due to tract spread such as fronto-temporal glioma connected through uncinate fasciculus, however in multi-centric glioma, the gliomas is not connected to each other such gliomas occur in NF1 and tuberous sclerosis.
• The term meningeal gliomatosis refers to CSF distant spread of GBM (CSF Mets).
• The goal of treatment in these types is brain radiation and chemotherapy, with surgery considered only for life threatening herniation or functional deterioration due to mass effect.

• Q19: What is meant by pseudo progression?
• It is a term referred to progressive increase in contrast enhanced area on MRI following completion of Stupp protocol which mimic tumour recurrence. It usually appears within 3 months after completion of radiation in 30-60% of patients and should be considered in the differential diagnosis of tumour recurrence. It occurs due to radiation necrosis caused by endothelial injury and destruction of BBB.