The World Health Organization (WHO) classifies astrocytomas, a type of brain tumor, on a scale from grade 1 (least malignant) to grade 4 (most malignant). This grading is determined by examining the tumor cells under a microscope, considering factors such as the abnormality of the cells (atypia), their rate of growth (mitosis), and the presence of newly formed blood vessels within the tumor (vascular proliferation). Additionally, the tumor’s genetic features, analyzed through DNA analysis of the tumor cells, contribute to this classification. In general, aside from grade 1 tumors, which are more common in the pediatric population, astrocytomas predominantly affect individuals over the age of 40. Notably, as age increases, the likelihood of the astrocytoma being of a higher grade also rises.
Grade 1
- Pilocytic Astrocytoma is a well circumscribed tumor and grows slowly. Most common in the cerebellum, i.e. the part of the brain located in the back of the head, just above the neck. It does not invade into the surrounding brain, thus when resected completely it is considered cured, and it does not require either chemotherapy or radiotherapy.
- Pleomorphic Xantoastrocytoma most frequently originates in the temporal lobes and is commonly associated with seizures. Its cells can have many different shapes (pleomorphic), but usually do not show evidence of proliferation. Surgery is usually curative.
- Subependymal Giant Cell Astrocytoma (SEGA) is most common in the younger population, usually in association with a familiar syndrome called tuberous sclerosis. It characteristically grows inside the ventricles, which are fluid-filled spaces deep into the brain, and can often block the normal outflow of this fluid, thus causing hydrocephalus. Surgical resection is usually curative.
Grade 2
- Diffuse Astrocytoma is an invasive tumor, so there is no clear separation from the surrounding brain, and surgery itself might not be enough for its cure (this depends on several other factors described below). The tissue appearance is only moderately different from a normal brain, but cells appear abnormal under the microscope and slightly increased in number.
Grade 3
- Anaplastic Astrocytoma is considered a more malignant evolution of a previously lower grade astrocytoma, which has acquired more aggressive features, including a higher pace of growth and more invasion into the brain. Histologically, it displays a higher degree of cellular abnormalities, and evidence of cell proliferation (mitoses), in comparison to grade 2 tumors. Surgery is never considered curative for these tumors, and needs to be followed by radiation and almost always chemotherapy.
Grade 4
- Glioblastoma (GBM) is the most malignant, aggressive and common (60%) form of astrocytomas. Histologically, it is characterized by very abnormal-appearing cells, proliferation, areas of dead tissue and formation of new vessels. GBM can present either as a malignant progression from a previously existing lower grade astrocytoma (usually in 10% of cases) or originate directly as a grade 4 tumor (90% of cases). The former scenario is most common in younger patients, while the latter is most common after age 60. Regardless of its presentation, this tumor is a highly aggressive cancer, with pronounced brain invasion and destruction and very fast progression.
Astrocytomas are, for the vast majority, sporadic tumors, meaning that they happen by chance, or at least, it is not yet known why these occur. There are only two situations with proven evidence to cause the tumor:
Hereditary syndromes (i.e. caused by inherited DNA mutations): Li-Fraumeni: due to mutation in tumor suppressor gene p53 and characterized by young onset of multiple tumors, including breast cancer, bone cancers, leukemias and astrocytomas.
Turcot: due to mutations in several tumor suppressor genes, including APC and MMR and characterized by early onset of colon cancer and astrocytomas.
Neurofibromatosis 1: due to mutation of tumor suppressor NF1, responsible for early onset of astrocytomas, peripheral nerve tumors, skin freckling and light-brown patches in the skin.
Tuberous sclerosis: is a rare genetic disorder associated with mental retardation and early onset of subependymal giant cell astrocytoma (SEGA).
Environmental: Ionizing radiations: exposure to ionizing radiations has been associated to delayed onset of astrocytomas. Individuals at particular risk are those exposed to therapeutic radiotherapy to the head and neck region during childhood (i.e. for treatment of leukemias or other brain tumors). The interval between exposure to radiation and astrocytoma onset can be as long as 20-30 years.
Warfare chemicals: There is a yet unproven suspicion that exposure to Agent Orange during the Vietnam War might be responsible for delayed onset of astrocytomas in veterans.
Cellular phones: despite some suspicions, particularly related to heavy use, there is no data supporting a causative risk for astrocytomas.
The clinical presentation of astrocytomas depends much more on their location within the brain, rather than their biologic characteristics. There are regions of the brain that can accommodate very large tumors before they become symptomatic (for example, the regions in the forehead), while there are other locations where even a small tumor can cause problems early on, like limb weakness or difficulty with speech or vision.
Generally, low grade astrocytomas tend to be of bigger size before they become symptomatic, as compared to more aggressive, higher grade astrocytomas. This is because lower grade tumors tend to displace the brain rather than destroying it, and also because they are associated with less brain swelling than malignant ones.
Common symptoms of astrocytomas are the following:
- Persistent headaches
- Headaches which are worse in the morning or cause awakening from sleep (a sign of increased intracranial pressure)
- Double or blurred vision
- Speech problems
- Decreased cognitive abilities
- Grasp or limb weakness
- New seizures
Conventional MRI: Magnetic resonance imaging (MRI) is the most important imaging study for astrocytomas. Usually, images are acquired both before and after the administration of IV contrast. As a rule of thumb, if the tumor picks up the contrast (i.e. becomes bright on images), it is an indication of a higher grade astrocytoma.
Other imaging sequences provides clues as to tumor cellularity, brain swelling and brain infiltration.
MRI spectroscopy (MRS): It is an imaging tool, based on MRI, which provides information on the chemical composition of the tumor, and works based on the fact that certain chemicals are abundant in the normal brain (for example, NAA), while others are abundant in tumors (for example, choline). The output of this imaging modality is a diagram showing the amount of each chemical in the area of the brain under analysis: If the amount of NAA is more than choline, that suggests a normal brain. The opposite raises suspicion of a tumor. This technique can be considered as a non-invasive tissue sampling, although it is not as accurate or definitive as a standard biopsy.
Functional MRI (fMRI): fMRI is a useful technique to visualize in real time which parts of the brain become activated when the patient is asked to perform a certain task (for example talking, or moving one arm or leg). This is fundamental to define the regions of the brain which, if damaged, would cause problems to the patient. Activated brain is shown as a yellow/red signal superimposed to an otherwise standard MRI. For tumors that are localized in the proximity of critical areas (speech centers, motor cortex or visual cortex) fMRI provide an important adjunct, particularly in regards to surgical planning.
Developing an astrocytoma is often unpredictable, and in most cases, there’s no specific preventive action one can take as occurrences tend to be random.
For individuals with a genetic predisposition that elevates the risk of astrocytoma, regular check-ups with the healthcare team are crucial. This monitoring allows for the early detection of signs indicating the presence of an astrocytoma. Early identification significantly improves the chances of successful intervention and treatment.
