amplification of MDM2, a gene that encodes an inhibitor of p53. Similarly, while secondary glioblastomas have increased signaling through the PDGF-A receptor, primary glioblastomas often have amplified, mutated epidermal growth factor receptor (EGFR) genes, which encode aberrant forms of EGFR known as EGFRvIII. Both types of mutations lead to increased receptor tyrosine kinase activity and the activation of the RAS and PI-3 kinase pathways, whichstimulate the growth and survival of tumor cells ( Chapter 7 ). Based on whole genome sequencing, it is estimated that combinations of mutations that activate RAS and PI-3 kinase and inactivate p53 and RB are present in 80% to 90% of primary glioblastomas
I- Slow growing astrocytomas, benign, and associated with long-term survival. Individuals with very slow growing tumors where complete surgical removal is possible may experience total remission.II-Consist of relatively slow-growing astrocytomas, usually considered benign that sometimes evolve into more malignant or as highergrade tumors. They are prevalent in younger people who are often present with seizures. III-It is often related to seizures, neurologic deficits, headaches, or changes in mental status. The standard initial treatment is to remove as much of the tumor as possible without worsening neurologic deficitsIV-Most malignant primary brain tumor. Growand spread to other parts of the brain quickly; they can become very large before producing symptom, which often begin abruptly
progression from lower to higher grades is associated with a concomitant lower incidence of seizures and a higher incidence of focal neurologic deficits.
All grades of infiltrative astrocytomas exhibit immunoreactivity for glial fibrillary acidic protein, S100, and vimentinPrognostic significance has been attached to the labeling index by the MIB1 (Ki-67) antibody. Low (< 3%) labeling indices characterize the diffuse astrocytoma. The distinctive feature of anaplastic astrocytomas resides in the high mitotic index and, therefore, brisk Ki-67 labeling index that can range from 3% to 10%
Zagada, Timothy M.
• 34 year old male
• Has recurrent severe headache of 8 weeks
• Initially relieved by Mefenamic Acid.
• 1 day PTA, the patient noted weakness of the left upper
• Few minutes PTA, he had seizures thus consulted and
• CT Scan revealed a mass over the right cerebral
• Glioma- most common group of primary brain tumors
• Glial cells- support and protection for neurons. They are
thus known as the "supporting cells" of the nervous
Four main functions of glial cells:
1. To surround neurons and hold them in place
2. To supply nutrients and oxygen to neurons
3. To insulate one neuron from another
4. To destroy pathogens and remove dead neurons.
• Astrocyte- star-shaped glial cells in the brain and spinal cord.
• the most abundant cell of the human brain.
• many functions, including
• biochemical support of endothelial cells that form the blood–brain
• provision of nutrients to the nervous tissue
• maintenance of extracellular ion balance
• role in the repair and scarring process of the brain and spinal cord
following traumatic injuries.
• Astrocytoma- derived from an immortalized astrocyte
• The exact cause is unknown
• Astrocytomas of all grades have been associated with
cranial therapeutic irradiation
• People who have certain rare genetic conditions such as
neurofibromatosis or Li-Fraumeni syndrome
• People over the age of 65 are diagnosed with brain
cancer at a rate four times higher than younger people.
• mutations affecting p53
• overexpression of platelet-derived growth
factor α (PDGF-A) and its receptor
• Disruption of tumor suppressor genes
• RB and p16/CDKNaA
• tumor suppressor on chromosome 19q
most common in
transition to higher
Grade Astrocytoma Description
Slow growing astrocytomas, benign, and
associated with long-term survival.
Consist of relatively slow-growing astrocytomas,
usually considered benign that sometimes evolve
into more malignant or as highergrade tumors.
It is often related to seizures, neurologic deficits,
headaches, or changes in mental status.
Most malignant primary brain tumor. Grow and
spread to other parts of the brain quickly; they
can become very large before producing
symptom, which often begin abruptly
• Low grade astrocytomas
appear as greyish white areas
in the cerebral or cerebellar
hemisphere that tend to
"erase" normal structures and
enlarge the area in which they
• High grade astrocytomas such
as the glioblastoma multiforme
are multiform in their
appearance being firm to
necrotic and yellow, grey
, brown and/or hemorrhagic.
• low grade astrocytomas have
mainly oval pale nuclei with
indistinct cytoplasmic borders and
fibrillary processes with only mild
• higher the grade, the more cellular, the more pleomorphic and
the more basophilic the tumor cell nuclei become.
• Glioblastoma- very pleomorphic and basophilic nuclei are seen
as are necrosis, mitotic figures and capillary endothelial
Tumor cells collect along the edges of the necrotic regions, producing a histologic pattern referred
to as pseudo-palisading
• Astrocytomas act as progressive mass lesions of the brain
parenchyma causing progressive loss of function in the areas
• Brain irritation- seizures
• increased intracranial mass- headaches
• Brain invasion;
• Frontal lobe-gradual changes in mood and personality, paralysis
on one side of the body
• Temporal lobe-problems with coordination, speech, and memory
• Parietal lobe-problems with sensation, writing, or fine motor
• Cerebellum-problems with coordination and balance
• Occipital lobe-problems with vision, visual hallucinations
What is the current prognosis for patient
with Glioblastoma multiforme?
• Prognosis for individuals with glioblastoma is very
poor, although the use of newer chemotherapeutic agents
has provided some benefit
• With current optimal treatment, consisting of :
• Radiation therapy
• The mean length of survival after diagnosis has increased to 15
• 25% of such patients are alive after 2 years.
• Survival is substantially shorter in older patients, for those with
lower performance status, and for large unresectable lesions.