8A. Gliomas (+ brain tumours in general)

Central nervous system tumours can be primary (originating in the CNS) or secondary (metastasis from other organ). Primary CNS malignancies account for 2% of adult malignancies, but 30% of childhood malignancies. In adults, secondary CNS tumours (metastases) are more common than primary, and CNS metastases occur in 10% of cancer patients. Metastasis is usually from lung cancer, breast cancer, or melanoma.

In children, the most common types are craniopharyngioma, medulloblastoma, and cerebellar astrocytoma. In adults the most common types are CNS metastases, meningioma, glioblastoma, and pituitary tumours. Glioblastoma is a grade IV CNS tumour with very poor prognosis.

Etiology

The majority of primary CNS tumours are idiopathic and sporadic. However, some risk factors are known:

• HIV
• Nitrosourea exposure
• Previous radiotherapy to the head
• von Hippel-Lindau syndrome
• von Recklinghausen syndrome

Pathology

In adults most CNS tumours are supratentorial. In children they are rather infratentorial.

Mass effect

According to the Monroe-Kellie doctrine, a brain tumour must decrease CSF flow and cerebral blood flow. In the beginning phase, CSF and CBF flow can decrease to compensate for the increased ICP. Eventually the compensatory mechanisms are exhausted, causing large increase in ICP.

Classification

• Neuroepithelial tumours
  • Gliomas (most common)
    • Astrocytoma
    • Ependymoma
    • Oligodendroglioma
    • Glioblastoma (grade IV)
  • Embryonal tumours
    • Primitive neuroectodermal tumor (PNET)
    • Medulloblastoma
  • Pinealomas
  • Schwannoma
  • etc.
• Non-neuroepithelial tumours
  • Meningiomas
  • Tumours of the choroid plexus
  • Germinomas
  • Primary CNS lymphomas
  • Pituitary adenomas
  • etc.

Glioma

Gliomas are tumours which originate from glial cells like astrocytes, oligodendrocytes, and ependymal cells. They’re the second most common primary brain tumours in adults (after meningioma). There are three types, based on the cell of origin:

• Astrocytoma
• Oligodendroglioma
• Ependymoma

Astrocytomas are graded like this:

• Grade I astrocytoma = pilocytic astrocytoma
• Grade II astrocytoma = diffuse astrocytoma
• Grade III astrocytoma = anaplastic astrocytoma
• Grave IV astrocytoma = glioblastoma

Higher grades have more mitosis, more atypia, worse prognosis. Glioblastoma is the most common glioma in adults. Pilocytic astrocytoma is the most common glioma in children.

Aside from general evaluation of brain tumours, for gliomas it’s important to test for IDH and 1p/19q codeletion. Tumours with IDH mutation or 1p/19q codeletion has better prognosis than wildtype.

Clinical features

Epileptic seizures in persons without known epilepsy is a typical sign of CNS tumour. Other possible symptoms include headache and vomiting which is worse in the morning, personality changes, and focal neurological symptoms.

Diagnosis and evaluation

The gold standard for diagnosis is contrast-enhanced MRI.

The majority of cases undergo biopsy and histopathology. In many of the cases the biopsy isn’t conclusive or diagnostic, in which case we might repeat biopsy, or the precise histologic type of the tumour won’t be known until surgical removal. Histopathology is repeated after surgical removal. Brainstem tumours can’t be biopsied.

Treatment

Complete surgical resection is required for cure, but debulking surgery may improve the prognosis in cases where cure isn’t possible. Surgical resection is performed in nearly all CNS tumours. Surgical resection of tumours in the brainstem is rarely possible due to the high risk of causing injury to the brainstem. CNS lymphomas are managed with chemotherapy rather than surgery.

Glucocorticoids may be used to decrease oedema around the CNS tumour, decreasing the ICP.

Radiotherapy

Most brain tumour patients receive some form of radiotherapy, often after surgery as adjuvant therapy. External beam radiotherapy is much more common than brachytherapy. Advanced techniques like 3DCRT, IMRT and radiosurgery are used to minimize damage to the brain. Radiotherapy causes brain oedema, which may lead to increased ICP. Prophylactic glucocorticoids are given to reduce this.

Radiosurgery/stereotactic radiotherapy/gamma knife/Cyber knife therapy may be used for lesions smaller than 3 cm and have results similar to neurosurgery.

Craniospinal irradiation involves simultaneous radiation of the brain and spinal cord, and is indicated for tumours which often spread to CSF, like medulloblastoma.

Whole brain radiotherapy (WBRT) involves giving radiation to the whole brain, and is indicated when there are multiple CNS metastases. This is because there are usually invisible micro-metastases in the brain.

Chemotherapy

Drugs has to penetrate the blood-brain barrier to be eligible for use against CNS tumours. Temozolomide is the most important drug for CNS tumours. BCNU (carmustine) is also used. Methotrexate is used for CNS lymphomas.

Prognosis

There are many prognostic factors which decide the prognosis of the patient.

• Tumour grade, which depends on the histological type
• Biogenetical markers of tumour
• Karnofsky Performance Status (KPS)
• Age of patient
• Comorbidities
• Presence of metastasis of CSF