40. Glial central nervous system tumors

General

The majority of CNS tumors are brain metastases; these are three times as common as all primary CNS tumors combined. The most common primary sites of brain metastases are breast and lung tumors, melanoma, renal cell cancer and colorectal cancer. The most common primary CNS tumors in adulthood are glioblastomas, meningiomas and vestibular schwannomas while for childhood pilocytic astrocytomas, meningiomas and medulloblastomas are most frequent.

Tumors of the CNS have certain unique characteristics that sets them apart from tumors elsewhere in the body:

  • These tumors don’t have detectable premalignant or in situ stages
  • Even low-grade tumors may cause severe symptoms due to the closed nature of the skull
  • The anatomical site of the neoplasm can influence the outcome independent of the histological subtype due to local effects
  • Even the most malignant primary CNS tumors very rarely metastases outside the CNS
  • The grading system used for CNS tumors is different than normal, as seen below.

Primary tumors of the CNS are usually solitary masses, while brain metastases are often multifocal. The only known predisposing factor to brain tumors is ionizing radiation to the head.

While primary brain tumors rarely metastasise outside the CNS they can disseminate with the CSF and reach the lower regions of the spinal cord. These metastases are called drop metastases.

The symptoms of CNS tumor vary depending on the type and location, but typical symptoms include:

  • Progressive headache as the tumor grows
  • Focal neurological symptoms
    • Aphasia
    • Deafness
    • Visual abnormalities
  • Vomiting – due to increased intracranial pressure
  • Sudden onset epilepsy

CNS tumors are classified like this:

  • Neuroepithelial tumors – develop from neuroepithelium
    • Gliomas – develop from glial cells
      • Diffuse astrocytic and oligodendroglial tumors
      • Other astrocytic tumors
      • Ependymal tumors
    • Neuronal and mixed neuronal-glial tumors – develop from neurons, potentially also from glial cells
    • Choroid plexus tumors – develop from the choroid plexus
    • Embryonal tumors – develop from embryonal cells
  • Meningeal tumors – develop from the meninges
  • Other primary tumors
    • Mesenchymal tumors – develop from the mesenchyme
    • Lymphomas – lymphomas that develop in the CNS
    • Cranial and paraspinal tumors – develop from cranial nerves
    • Tumors of the sellar region – develop from the pituitary
    • Tumors of the pineal region – develop from the pineal gland
  • Metastases
Grading

The process of grading CNS tumors is different than normally. In tumors other than in the CNS, the differentiation of the specific tumor of the specific patient determines the grade of the tumor. Two patients can have the same neoplasm but with different degree of differentiation and therefore different gradings. A colorectal carcinoma can be either low-grade or high-grade, depending on the degree of differentiation.

For CNS tumors, the grading is different. The classification system used is made by the WHO and is based on the histological characteristics like atypia, mitosis, endothelial proliferation and necrosis. The grade of the tumor doesn’t depend on the degree of differentiation of the specific case of tumor but rather on the histological type. The histological type of the tumor corresponds to a certain grade. The table below shows the grading system for all CNS tumors that are mentioned in the lecture:

Histological type WHO grade
Astrocytic tumors
Pilocytic astrocytoma Grade I
Diffuse astrocytoma Grade II
Pleiomorphic xanthoastrocytoma Grade II
Anaplastic astrocytoma Grade III
Glioblastoma (multiforme) Grave IV
Oligodendrogliomas
Oligodendroglioma Grade II
Anaplastic oligodendroglioma Grade III
Ependymal tumors
Myxopapillary ependymoma Grade I
Ependymoma Grade II
Anaplastic ependymoma Grade III
Neuronal and neuronal-glial tumors
Dysembryoplastic neuroepithelial tumor Grade I
Gangliocytoma/ganglioglioma Grade I
Central neurocytoma Grade II
Embryonal tumors
Medulloblastoma Grade IV
Atypical teratoid/rhabdoid tumor Grade IV
CNS primary neuroectodermal tumor (PNET) Grade IV
Tumors of the sellar region
Pituicytoma Grade I
Choroid plexus tumors
Choroid plexus papilloma Grade I
Atypical choroid plexus papilloma Grade II
Choroid plexus carcinoma Grade III
Meningiomas
Meningioma Grade I
Atypical meningioma Grade II
Anaplastic meningioma Grade III
Other
Schwannoma Grade I
Hemangioblastoma Grade I
Primary CNS lymphoma Not applicable

Generally, we can say that the following characteristics apply for each grade:

  • Grade I
    • Benign
    • Slow growing
    • Cells almost normal
    • Rarely recurs after treatment
    • Good prognosis
  • Grade II
    • “Semi-malignant”
    • Atypia of cells
  • Grade III
    • Malignant
    • Fast growing
    • Anaplastic cells
    • High recurrence
    • Poor prognosis
  • Grade IV
    • Most malignant
    • Fastest growing
    • Microvascular proliferation
    • Necrosis and haemorrhage often present
    • Worst prognosis

Basically, the higher grade, the faster the growth, the more atypia is present, the recurrence after treatment increases and the prognosis becomes worse. However, as noted earlier even grade I tumors can arise in areas where they are impossible to resect or treat completely, effectively giving them a poor prognosis. Tumors localized next to the basal ganglia and internal capsule have particularly poor prognosis.

The presence of certain molecular markers, like IDH, are also important in determining the prognosis of CNS tumors.

Glial cells are non-neuronal cells in the nervous system that include the oligodendrocytes, astrocytes, ependymal cells and microglia. All CNS tumors that originate from these cells are glial CNS tumors or gliomas and will be discussed in this topic. This includes the astrocytic, oligodendroglial and ependymal tumors. All non-glial CNS tumors will be discussed in the next topic.

Gliomas

Gliomas originate from glial cells of the CNS and are classified like the following:

  • Diffuse astrocytic and oligodendroglial tumors
    • Diffuse astrocytoma – grade II
    • Anaplastic astrocytoma – grade III
    • Glioblastoma (multiforme) – grade IV
    • Oligodendroglioma – grade II
    • Anaplastic oligodendroglioma – grade III
  • Other astrocytic tumors
    • Pilocytic astrocytoma – grade I
    • Pleomorphic xanthoastrocytoma – grade II
  • Ependymal tumors
    • Myxopapillary ependymoma – grade I
    • Ependymoma – grade II
    • Anaplastic ependymoma – grade III

The diffuse tumors are highly infiltrative and form diffuse masses, while the ependymal tumors tend to form solid masses.

The diagnosis of gliomas is based on molecular studies, the grade (the degree of atypia, necrosis, mitosis and so on) and the histological tissue characteristics. Certain molecular abnormalities are present in certain gliomas. Mutation of IDH1 or IDH2 is very common in grade II and III gliomas. Codeletion 1p19q, meaning the combined loss of the short arm of chromosome 1 and long arm of chromosome 19, is another important genetic marker. It is characteristic in oligodendrogliomas and glioblastomas. TP53 deletion is also common in certain gliomas.

Pilocytic astrocytoma, a grade I glioma, is most common in children. They’re most commonly located in the cerebellum and optic pathways. The tumor often produces a cyst next to it.

Diffuse astrocytoma, a grade II glioma, is most common in adults between 30 and 40. They’re most commonly located in the frontal or temporal lobes. They’re usually poorly defined and infiltrative.

Anaplastic astrocytoma, a grade III glioma, is most common in adults between 40 and 50. Like the diffuse astrocytoma, they’re most commonly located in the frontal or temporal lobes and are poorly defined and infiltrative. Anaplastic astrocytoma shows severe atypia/anaplastic cells, increased mitotic activity, but no necrosis.

Glioblastoma (multiforme), a grade IV glioma, is most common in adults between 50 and 70 and the most common primary CNS tumor overall. It commonly affects the cerebral hemispheres bilaterally, forming a characteristic “butterfly” pattern. The histological characteristics are similar to those of anaplastic astrocytoma, just with the addition of pseudopalisading necrosis and microvascular proliferation. The average survival is less than one year.

Oligodendroglioma, a grade II glioma, is most common in adults between 40 and 50. It frequently occurs in the frontal or temporal lobes and presents with seizures. The prognosis is good but even better if codeletion 1p19q is present.

Anaplastic oligodendroglioma, a grade III glioma, is most common in adults between 40 and 50. It is more aggressive than the non-anaplastic oligodendroglioma.

Ependymomas range from grade I to grade III and develop from the ependyma that lines the ventricular system, including the central canal of the spinal cord. In children they usually occur near the fourth ventricle (causing hydrocephalus) while in adults they usually occur in the spinal cord. Ependymomas are associated with the condition neurofibromatosis type II. The tumor cells form elongated structures called rosettes and pseudorosettes.


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