Astrocytomas
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Overview


Astrocytomas are a type of brain tumor that are formed when astrocytes, which make up the supportive tissue of the brain, begin to metastasize and grow at an abnormal and uncontrollable rate. There are four different “grades” of astrocytomas, Grade I (Pilocytic Astrocytoma) being the most benign, and Grade IV (Glioblastoma) being the most malignant. [1] Unfortunately, Grade IV astrocytomas have only a 6% survival rate beyond 5 years, although Grade I tumors can easily be surgically removed if they are discovered before they advance to Grade II. [2] Overall, astrocytomas account for approximately 10% of all brain tumors. [3]


Functional Anatomy


Astrocytes - Astrocytes are star-shaped cells that make up the connective tissue of the entire central nervous system (CNS). They are the most numerous cell in the entire nervous system, even more numerous than neurons. These cells act as a barrier between nerves and their surrounding structures, making up the blood-brain barrier around the brain. Some of these cells function as a chemical filter to protect the CNS from damaging bacteria while others are simply defense cells against possible physical injury. The leg-like structures branching off from astrocyte cell bodies are called processes, and they project to hold together the pial surface of brain matter, blood vessels, and axons within the CNS. [4]

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Cerebellum - The cerebellum is the most posterior section of the brain, located inferior to the occipital and temporal lobes of the cerebral cortex and just superior to the brain stem. This particular region contains a very large percentage of the brain’s neurons (approximately 50%) although anatomically it is not extremely large. The cerebellum is divided into two major areas: the deep nuclei, which conduct signals from the cerebellum out of the brain to the rest of the nervous system; and the cerebellar cortex, which is made up of many sheets of tissue and fissures that encases the deep nuclei. Among the cerebellar cortex are three lobes: the anterior lobe, the posterior lobe, and the flocculonodular lobe. The deep nuclei located in the cerebellum include 1) fastigial nuclei, which receive signals from the somatosensory, auditory and visual pathways and project to the vestibular nuclei and reticular formation. [5], 2) interposed nuclei, which receive signals from spinal, proximal somatosensory, auditory and visual pathways and project to the origin of the rubrospinal tract, which assists with voluntary movements, and 3) dentate nuclei, which receive information from the pontine nucleus and the lateral hemispheres of the cortex and project to the rubrospinal tract and the ventrolateral thalamic tract.


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Cerebrum - The cerebrum is the largest part of the brain, made up of the cortex, basal ganglia, and all divisions of the thalamus. The cortex makes up the “gray matter” of the brain, which is the most external layer. The cortex is divided into two hemispheres, which are held together by the “white matter,” the corpus callosum. The cerebrum is further divided into 4 lobes: the frontal lobe, the parietal lobe, the temporal lobe, and the occipital lobe.
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Pilocytic Astrocytoma
Pilocytic Astrocytomas are the most treatable form of astrocytoma, and they do not spread beyond the cells they originated in. As can be seen in the included picture, the largest part of this type of astrocytoma is a liquid-filled sac. This sac is relatively slow-growing, although if the tumor remains undiagnosed for a long time it can become quite large. Pilocytic astrocytomas are the most common type of brain tumor that is diagnosed in teenagers and young adults. [4] This particular type of astrocytoma usually develops in the cerebellum, the region of the brain that is most commonly used in coordination of movement and posture detection. When the astrocytes in the cerebellum begin to become neoplastic (growing uncontrollably), they begin to interrupt signals coming from the vestibular, visual, and auditory system. As a result, patients begin to experience dizziness, inability to balance, and difficulty with coordinating planned movements .


Treatment of Pilocytic Astrocytomas
In general, pilocytic astrocytomas are the most easily treatable with surgery. However, in abnormal cases where the tumor is growing on a region of the brain other than the cerebellum, it may be difficult (or impossible) to completely remove the growth. These abnormal tumors usually require radiation treatment, which is not always effective. Overall, pilocytic astrocytomas are the easiest to remove surgically out of all of the grades of astrocytomas, but like any cancer, no two cases are exactly the same and individual factors may influence the treatability or effectiveness of surgery. [6]


Warning: Video contains graphic depiction of the surgical removal of a frontal pilocytic astrocytoma, which is a very rare location for this type of tumor: __https://www.youtube.com/watch?v=xjmOrTPbeQA__ 7



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Grade II Astrocytoma
Grade II astrocytomas, also known as diffuse astrocytomas, are similar to pilocytic astrocytomas, but they are metastatic and spread to surrounding tissue. [7[ These tumors most often occur in the cerebrum, although they have been documented in various other locations throughout the brain and spinal cord. [8] They are described as “well-differentiated” meaning that they look like the tissue they are growing within and although they are growing, they are doing so slowly. [9] Because this tumor usually grows in the cerebrum, which controls movements and thinking, seizures are a very common symptom. Hemiparesis, weakness on one side of the body, is also indicative of grade II astrocytoma. [10] Because the descending tracts from the cerebrum decussate, whichever side becomes weak is opposite the side of the brain that the tumor is developing in.


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Treatment of Grade II Astrocytoma
Grade II astrocytomas are harder to treat than pilocytic tumors because they have tiny extensions that grow into surrounding brain tissue, and since they are well-differentiated, neurosurgeons cannot always tell the difference between cancerous tissue and normal tissue. In some cases, grade II astrocytomas are removable by surgery, but in others it is not. Once an inoperable grade II astrocytoma is diagnosed, patients can proceed with radiation and chemotherapy. Sometimes these two forms of treatment are combined, in a very aggressive treatment plan, but usually radiation is the first choice. Patients who go untreated for this grade of astrocytoma usually only survive for about 5 years, but when it is treated (but not surgically removed entirely) the survival rate rises slightly. [11] Although this is considered a low-grade brain tumor, if left untreated the prognosis is not good.




Anaplastic Astrocytoma
Anaplastic astrocytomas are considered high-grade tumors, and they are very malignant. Malignancy is determined by how fast a tumor grows into the tissue surrounding it, and unfortunately anaplastic astrocytomas grow very rapidly, at least when compared to low-grade astrocytomas. Very often they are the remnants of a low-grade tumor that was unsuccessfully operated on. When surgery of a grade II astrocytoma was incomplete and cancerous tissue was left, it can then develop into a grade III (anaplastic) tumor. This grade of astrocytoma is considered quite rare, and its exact cause is unknown at this point. Scientists speculate that it may be caused due to environmental factors, genetic mutations, or even high stress levels. [12] Symptoms of this grade of astrocytoma vary depending on its location, but some very common symptoms are headaches due to increased pressure in the brain, vomiting, lethargy, or personality changes. Anaplastic astrocytomas do not have a “normal” location in the brain where they grow, unlike pilocytic and grade II tumors, so they may appear in various forms and areas.


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Treatment of Anaplastic Astrocytoma
Anaplastic Astrocytomas are often treated in a similar manner to diffuse astrocytomas. Surgery is the first thing that most doctors will attempt, but unfortunately the high rate of tumor growth in this grade makes it very difficult to guarantee a completely successful removal. If surgery is incomplete, radiation and then chemotherapy are used to reduce the size of the tumor and possibly alleviate some of the more severe symptoms. The prognosis for children diagnosed with anaplastic astrocytoma is 25% for 5 years. This statistic is slightly lower for adults.



Glioblastoma

Glioblastoma (Grade IV) multiforme is the most malignant type of astrocytoma. Unfortunately, this particular grade of tumor makes up 50% of all diagnosed astrocytomas. It is made up of varying cell types, which makes it very difficult to treat. These cells begin to grow uncontrollably due to a mutation in the life cycle of the cell, but in glioblastomas these cells often die off. Unfortunately, the cells only die after they have spread to various locations around their origination site, and, although they are no longer growing, they remain anchored to the surrounding tissue. Due to glioblastoma’s rapid rate of growth and the variability of cell types involved, the average survival time for a patient is under one year. Only about 3% of those diagnosed with glioblastoma live more than five years. [13] Although this grade can appear in any age group, most people diagnosed with glioblastoma are around 64 years old. [14]


Treatment of Glioblastoma Multiforme

Like most other forms of cancer, glioblastoma multiforme is usually initially confronted with surgery, depending on which region of the brain it is located in. If surgery fails, radiation and chemotherapy are the next steps. Chemotherapy is the more aggressive form of treatment, and is not usually used by itself. Because of the variability of cells within glioblastoma multiforme, cell-specific treatments may not be entirely effective. If one type of cell is destroyed, the other cells within the tumor simply take over the available space. Biological therapy is a new form of treatment that is not being used widely, but has been used in some cases on glioblastoma multiforme cases. This treatment targets particular phases of the cell growth cycle, which is sometimes enough to trigger a cease in tumor growth and malignancy. Although there are many ways of treating some of the symptoms of glioblastoma multiforme, the tumor itself is very difficult to remove, and the survival rate for this grade of astrocytoma is horrifyingly low.


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Glossary:
Anaplastic: The characteristic of the reversion of cells to an embryonic, immature, or undifferentiated state
Astrocyte:a large, star-shaped neuroglial cell with many branches, found in certain tissues of the nervous system
Necrosis: the death of one or more cells in the body, usually within a localized area, as from an interruption of the blood supply to that part
Nuclear Atypia: abnormal appearance of cell nuclei
Nuclear Pleomorphism: The occurrence of more than one distinct form of a cell nucelus in a single life cycle.
Neoplasm: any new and abnormal growth, specifically one in which cell multiplication is uncontrolled and progressive
Vascular Proliferation: Phenomenon that involves the development of new blood vessels.




Quiz

  1. What is the least malignant form of astrocytoma?
  2. What percentage do astrocytomas make of all brain tumors?
  3. What is neoplasm?
  4. What is another name for Grade II astrocytoma?
  5. How is malignancy determined?
  6. What are the three most common methods of treatment for astrocytomas?
  7. What percentage of glioblastoma multiforme patients live beyond 5 years?
  8. What is necrosis?
  9. Are men or women more often diagnosed with astrocytomas of any grade?





Text References
[1]__http://www.cancercenter.com/brain-cancer/types/tab/astrocytomas/?source=GGLPS01&channel=paid+search&c=paid%2520search%3AGoogle%3ANon+Brand%3AExact%3ANon+Brand%3ETop+Terms%3AExact&k_clickid=170fbb12-84e8-4df1-a118-65116b2ce052__

[2]__http://www.cancerresearchuk.org/about-cancer/type/brain-tumour/treatment/statistics-and-outlook-for-brain-tumours__

[3] American Medical Association Complete Medical Encyclopedia. New York: Random House Reference, 2003. Print.

[4] __http://www.irsa.org/astrocytoma.html__

[5] http://neuroscience.uth.tmc.edu/s3/chapter05.html

[6] Kayama, Takamasa, Teiji Tominaga, and Takashi Yoshimoto. "Management of Pilocytic Astrocytoma." Neurosurgical Review Neurosurg. Rev. 19.4 (1996): 217-20. Web.
[7] Magistretti, Pierre & Bruce Ransom. Astrocytes in Neuropsychopharmacology: The Fifth Generation of Progress. Edited by Kenneth L. Davis, Dennis Charney, Joseph T. Coyle, and Charles Nemeroff. American College of Neuropsychopharmacology. 2002.

[8] McLendon, Roger E. "Pathology of Diffuse Astrocytomas Definition and Overview." (2015): n. pag.Http://emedicine.medscape.com/article/1780914-overview. Web.

[9] __http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=46445__

[10] __http://www.abta.org/secure/resource-one-sheets/low-grade-astrocytoma.pdf__

[11] http://www.mdguidelines.com/astrocytoma

[12] https://rarediseases.org/rare-diseases/anaplastic-astrocytoma/

[13] Roche. "Glioblastoma (Cancer Affecting the Brain) A Guide for Journalists on Glioblastoma and Its Treatment." (n.d.): n. pag. Web.

[14] Central Brain Tumor Registry of the United States (CBTRUS): Primary Brain Tumours in the United States Statistical Report




Image References

[1] __http://www.brain-surgery.com/wp-content/uploads/2012/04/Grade-II-Astrocytoma.jpg__

[2]__http://www.brain-surgery.com/wp-content/uploads/2012/03/CT-Scan-of-a-Malignant-Astrocytoma.jpg__

[3] __http://library.med.utah.edu/WebPath/jpeg5/CNS136.jpg__

[4] __http://img.medicalxpress.com/newman/gfx/news/hires/2015/astrocyte.jpg__

[5]__http://antranik.org/wp-content/uploads/2011/11/the-cerebellum-coronal-section-posterior-view-of-white-and-gray-matter.jpg__

[6] __https://o.quizlet.com/fsNcicTHZ-8zhga9wnEOgg_m.jpg__

[7] __https://www.youtube.com/watch?v=xjmOrTPbeQA__ (video)

[8] __http://library.med.utah.edu/WebPath/jpeg5/CNS125.jpg__

[9] __http://img.medscapestatic.com/pi/meds/ckb/36/38436tn.jpg__

[10] __http://www.pubcan.org/images/large/0072_anaplastisches-Astrozytom_v2.jpg__

[11] __http://library.med.utah.edu/WebPath/jpeg5/CNS136.jpg__





Quiz Answers

  1. Pilocytic
  2. 10%
  3. New and abnormal cell growth with uncontrolled and progressive cell growth
  4. Diffuse
  5. Rate of uncontrolled cell growth
  6. Surgery, chemotherapy, radiation
  7. 3%
  8. Cell death
  9. Men