Tumor Types > Astrocytomas
Glial Neoplasms comprise the majority of primary intracranial tumors and affect about 14,000 Americans annually. Glial tumors are divided into a classification scheme based on cell type - usually based on the supposed cell of origin. Thus, astrocytomas are derived from astrocytes, Oligodendrogliomas derived from oligodendroglial cells and mixed gliomas (or oligoastrocytomas) are derived from both astrocytes and oligodendroglial elements.
The following discussion concerns astrocytomas only and is presented in hopes that it will provide some insight into the classification and treatment of these tumors.
Types
In general astrocytic tumors are classified according to histologic grade. There is some confusion among pathologists on the proper system for tumor grading. This can result in confusion for physicians, research protocols and most especially, for patients. Below an attempt is made to clarify the classification issue as it is extremely important for understanding the tumor and its prognosis.
The astrocytoma is derived from a normal supporting cell in the brain called the astrocyte. In a patient with one of these tumors, the cells in the astrocytoma tumor are no longer normal. The degree of this abnormality is used to determine the tumor's grade, and the tumor's grade determines the prognosis of the tumor. Astrocytomas are graded from 1 to 4, with grade 1 being the slowest growing and grade 4 being the most rapidly growing and malignant lesions. The following descriptions refer to the appearance of the tumor under the pathologist's microscope.
Grade 1: In these tumors, astrocytic tumor cells are often normal in appearance but there are more of them than typically seen in microscopic examinations of brain tissue. The only symptom usually exhibited with Grade 1 astrocytomas is the onset epileptic seizures - due to the tumor's irritating presence to surrounding brain tissue. Since they are well tolerated by the brain, these astrocytic tumors can become quite large. However, a point is reached when the mass effect of the tumor and the mass of the brain combine within the non-yielding skull cavity, with a resultant rise in pressure inside the skull. This can cause headaches, paralysis, personality change, coma and death. The prognosis for Grade 1 astrocytomas is generally good, though surgery to reduce mass effect is sometimes required. Patients with Grade 1 astrocytomas have been known to live 30 years or more following diagnosis. Radiation therapy is probably not appropriate in these tumors.
Pilocytic astrocytomas: These benign astrocytomas tend to occur in children and young adults, and are histologically circumscribed. Despite the fact that many are located in the thalamus and other important subcortical locations, they can be completely resected by computer assisted stereotactic technique with excellent postoperative results. These lesions exhibit prominent enhancement on CT or on MR imaging with gadolinium. The histologic borders are usually defined accurately by the contrast enhancement.
Grade 2: In Grade 2 tumors, the tumor cells are slightly abnormal in appearance as well as increased in number. The variations in appearance of these cells is referred to as pleomorphism. There should be no mitotic figures (indications that the cells are dividing) and no necrosis (dead tissue). In general, these tumors are made up of isolated tumor cells within functioning brain tissue. On imaging, studies these lesions show hypodensity on CT and prolongation of T1 and T2. Very rarely do they exhibit contrast enhancement.
Removal of the tumor is, in fact, removal of "sick" brain tissue. Thus, these tumors are only biopsied unless located in unimportant brain tissue - in which case they can be removed. In addition, these lesions (tumors) rarely produce paralysis.
There remains some debate on the place for radiation therapy and chemotherapy in these tumors. However, recent studies have shown that 5 year survival in Grade 2 astrocytomas without treatment is about 34% -- with treatment (radiation therapy): about 70%. Therefore most centers recommend radiation therapy after a Grade 2 astrocytoma is diagnosed by biopsy or some other surgical procedure.
Grade 3: Tumors of Grade 3 and Grade 4 astrocytomas are frequently referred to as malignant astrocytomas. They exhibit contrast enhancement on imaging studies. Frequently, the contrast enhancing mass is surrounded by a zone of hypodensity on CT and prolonged T1 and T2 on MRI. This zone is often termed "edema" and it is edematous brain parenchyma infiltrated by isolated tumor cells.
In another classification scheme these are referred to as anaplastic astrocytomas . In Grade 3 tumors, cells are abnormal in appearance with some showing evidence of mitosis. Mitosis is the cellular process by which cells divide; where one cell becomes two. Mitoses are readily apparent to the pathologist as the surgical specimen is reviewed under the microscope. Some of the cells in the tumor infiltrate into brain tissue - similar to the picture seen with Grade 1 and Grade 2 astrocytomas; other cells stay put and continue to divide and destroy the brain parenchyma in which they reside as joined cells of a mass of solid tumor tissue. When the tumor tissue is formed in important brain areas, the brain tissue in that area is destroyed by the evolving tumor tissue mass, and neurological deficits corresponding to that area are exhibited. For example, a Grade 3 astrocytoma forming in the central area of the brain, with formation of solid tumor tissue in the motor area, produces weakness and paralysis on the opposite side of the patient's body (contralateral control of brain-body hemispheres).
Treatment for Grade 3 astrocytomas involves establishing the diagnosis by surgery or stereotactic biopsy, and following up with radiation therapy and chemotherapy. The average survival of patients with Grade 3 astrocytomas is 18 months with treatment.
Grade 4: Grade 4 astrocytomas, frequently referred to as glioblastomas or glioblastoma multiforme, are the most malignant variety of these tumors. They are made up of cells which infiltrate brain tissue with a region - in some cases, multiple regions - of solid tumor tissue within the zone of infiltrated brain tissue. Mitoses are frequently noted by the pathologist as the surgical specimen is examined. In addition, regions of necrosis (dead tissue) are also noted where the tumor has grown so fast that parts of it has outpaced its blood supply. These tumors induce the formation of new but abnormal blood vessels. The identification of these blood vessels are also important in establishing the diagnosis. The CT and MRI demonstrate a contrast enhancing mass with a hypodense center (corresponding to necrosis), surrounded by a zone of hypodensity on CT and prolonged T1 and T2 on MRI (corresponding to infiltrated parenchyma).
The Grade 4 astrocytoma has the worst prognosis of all: 17 weeks average (mean)survival after diagnosis without treatment; 30 weeks average survival with biopsy followed by radiation therapy; 37 weeks average survival following surgical removal of most of the tumor tissue component of the tumor and radiation therapy; and 51 weeks average survival following stereotactic volumetric resection of the tumor tissue component and radiation therapy.
The prognosis for any patient with a malignant astrocytoma (Grade 3 or 4) is also very dependent upon age (older people do not live as long as young patients) and performance status (patients who are neurologically normal and independent live longer than patients who have a neurological deficit). Chemotherapy has been shown to add several weeks to survival. Radiation implants(brachytherapy) have also been shown to increase survival but more than half of these patients require another operation to remove dead tissue resulting from the radiation.