Astrocytoma

Astrocytomas are a type of neoplasm of the brain. They originate in a particular kind of glial-cells, star-shaped brain cells in the cerebrum called astrocytes. This type of tumor does not usually spread outside the brain and spinal cord and it does not usually affect other organs. Astrocytomas are the most common glioma and can occur in most parts of the brain and occasionally in the spinal cord. Within the astrocytomas, there are two broad classes recognized in literature, those with:
 * Narrow zones of infiltration (mostly invasive tumors; e.g., pilocytic astrocytoma, subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma), that often are clearly outlined on diagnostic images
 * Diffuse zones of infiltration (e.g., low-grade astrocytoma, anaplastic astrocytoma, glioblastoma), that share various features, including the ability to arise at any location in the CNS, but with a preference for the cerebral hemispheres; they occur usually in adults; and an intrinsic tendency to progress to more advanced grades.

People can develop astrocytomas at any age. The low-grade type is more often found in children or young adults, while the high-grade type are more prevalent in adults. Astrocytomas in the base of the brain are more common in young people and account for roughly 75% of neuroepithelial tumors.

Grading
Of numerous grading systems in use for the classification of tumor of the central nervous system, the World Health Organization (WHO) grading system is commonly used for astrocytoma. Established in 1993 in an effort to eliminate confusion regarding diagnoses, the WHO system established a four-tiered histologic grading guideline for astrocytomas that assigns a grade from 1 to 4, with 1 being the least aggressive and 4 being the most aggressive.

The WHO-grading scheme is based on the appearance of certain characteristics: atypia, mitosis, endothelial proliferation, and necrosis. These features reflect the malignant potential of the tumor in terms of invasion and growth rate. Tumors without any of these features are grade I, and those with one of these features (usually atypia) are grade II. Tumors with 2 criteria and tumors with 3 or 4 criteria are WHO grades III and IV, respectively. Thus, the low-grade group of astrocytomas are grades I and II.

Various types of astrocytomas are given these WHO grades:

According to the WHO data the lowest grade astrocytomas (grade I) make up only 2% of recorded astrocytomas, grade II 8%, and the higher grade anaplastic astrocytomas (grade III) 20%. The highest graded astrocytoma (grade IV GBM) is the most common primary nervous system cancer and second most frequent brain tumor after brain metastasis. Despite the low incidence of astrocytomas compared to other human cancers, mortality is significant, as the higher grades (III & IV) present high mortality rates (mainly due to late detection of the neoplasm).

Pathophysiology
Astrocytoma causes regional effects of astrocytomas by compression, invasion, and destruction of brain parenchyma, arterial and venous hypoxia, competition for nutrients, release of metabolic end products (e.g., free radicals, altered electrolytes, neurotransmitters), and release and recruitment of cellular mediators (e.g., cytokines) that disrupt normal parenchymal function. Secondary clinical sequelae may be caused by elevated intracranial pressure (ICP) attributable to direct mass effect, increased blood volume, or increased cerebrospinal fluid (CSF) volume.

Diagnosis
A Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan is necessary to characterize the extent of these tumors (size, location, consistency). CT will usually show distortion of third and lateral ventricles with displacement of anterior and middle cerebral arteries. Histologic analysis is necessary for grading diagnosis.

In the first stage of diagnosis the doctor will take a history of symptoms and perform a basic neurological exam, including an eye exam and tests of vision, balance, coordination and mental status. The doctor will then require a computerized tomography (CT) scan and magnetic resonance imaging (MRI) of the patient's brain. During a CT scan, x rays of the patient's brain are taken from many different directions. These are then combined by a computer, producing a cross-sectional image of the brain. For an MRI, the patient relaxes in a tunnel-like instrument while the brain is subjected to changes of magnetic field. An image is produced based on the behavior of the brain's water molecules in response to the magnetic fields. A special dye may be injected into a vein before these scans to provide contrast and make tumors easier to identify.

If a tumor is found, it will be necessary for a neurosurgeon to perform a biopsy on it. This simply involves the removal of a small amount of tumor tissue, which is then sent to a neuropathologist for examination and staging. The biopsy may take place before surgical removal of the tumor or the sample may be taken during surgery. Staging of the tumor sample is a method of classification that helps the doctor to determine the severity of the astrocytoma and to decide on the best treatment options. The neuropathologist stages the tumor by looking for atypical cells, the growth of new blood vessels, and for indicators of cell division called mitotic figures.

Treatment
For low grade astrocytomas, removal of the tumor will generally allow functional survival for many years. In some reports, the five-year survival has been over 90% with well resected tumors. Indeed, broad intervention of low grade conditions is a contested matter. In particular, pilocytic astrocytomas are commonly indolent bodies that may permit normal neurologic function. However, left unattended these tumors may eventually undergo neoplastic transformation. To date, complete resection of high grade astrocytomas is impossible because of the diffuse infiltration of tumor cells into normal parenchyma. Thus, high grade astrocytomas inevitably recur after initial surgery or therapy, and are usually treated similarly as the initial tumor. Despite decades of therapeutic research, curative intervention is still nonexistent for high grade astrocytomas; patient care ultimately focuses on palliative management.

In the patient guide Dr.John W. Henson, M.D., MGH Brain Tumor Center, Harvard Medical School wrote : ''Because grade 3 and 4 tumors have a tendency to grow rapidly, treatment must be started as soon after surgery as is feasible, allowing time for the surgical incision to heal. Generally, this means that patients should be undergoing either radiation therapy or chemotherapy within 2 to 4 weeks after surgery. ''...

''While therapies for high-grade gliomas are helpful, at present these treatments cannot cure these tumors. The two major reasons for this are that tumor cells infiltrate into surrounding brain and thus cannot be completely removed by the surgeon, and that most glioma cells are at least partially resistant to radiation and chemotherapy.The goals of treatment are to:''
 * remove as many tumor cells as possible (with surgery)
 * kill as many as possible of the cells left behind (with radiation and chemotherapy)
 * put remaining tumor cells into a nondividing, sleeping state for as long as possible (with radiation and chemotherapy)

''High-grade glioma cells almost always start to grow again at some point in time. Patients receive aggressive treatment in order to delay this regrowth as long as possible. Regrowth does not necessarily imply loss of control of the tumor, but it does mean that a new series of treatments should be considered because the tumor is becoming more aggressive.

Prevention
There are no precise guidelines because the exact cause of astrocytoma is not yet known.

Notable cases
Long-time U.S. Senator Ted Kennedy (D-MA) died of malignant glioma. The course of his illness suggests GBM. After his initial seizure and subsequent diagnosis in May 2008, he chose aggressive treatment and survived 15 months.

2001 World Rally Championship winner Richard Burns was diagnosed with it after suffering a blackout while traveling to the 2003 Wales Rally GB. He died on 25 November 2005, four years to the day after winning the WRC Championship

Doctors diagnosed composer George Gershwin with a glioblastoma multiforme in 1937. However, recent studies indicate that this diagnosis may have been incorrect. Some believe it may have been a Pilocytic astrocytoma.

Mo Mowlam (Secretary of State for Northern Ireland May 1997 - October 1999) - had a mild form of glioma on left frontal lobe.