ASTROCYTOMAZagada, Timothy M.

CASE

• 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

extremity. • Few minutes PTA, he had seizures thus consulted and

subsequently admitted.

• CT Scan revealed a mass over the right cerebral hemisphere.

• 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 system

Four main functions of glial cells: 1. To surround neurons and hold them in place2. To supply nutrients and oxygen to neurons3. To insulate one neuron from another4. 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 barrier• 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

ETIOLOGY

• 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.

Etiology• 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 the low-grade astrocytomas

transition to higher grade astrocytoma

Grading

Grade Astrocytoma Description

I Pilocytic astrocytoma

Slow growing astrocytomas, benign, and associated with long-term survival.

IILow-grade (fibrillary) astrocytoma

Consist of relatively slow-growing astrocytomas, usually considered benign that sometimes evolve into more malignant or as highergrade tumors.

III Anaplastic astrocytoma

It is often related to seizures, neurologic deficits, headaches, or changes in mental status.

IV Glioblastoma multiforme (GBM)

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

MORPHOLOGY• 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 arise

• High grade astrocytomas such as the glioblastoma multiforme are multiform in their appearance being firm to necrotic and yellow, grey , brown and/or hemorrhagic.

MORPHOLOGY• low grade astrocytomas have

mainly oval pale nuclei with indistinct cytoplasmic borders and fibrillary processes with only mild pleomorphism

MORPHOLOGY• 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 proliferation.

Tumor cells collect along the edges of the necrotic regions, producing a histologic pattern referred to as pseudo-palisading

PATHOGENESIS AND CLINICAL MANIFESTATION• Astrocytomas act as progressive mass lesions of the brain

parenchyma causing progressive loss of function in the areas invaded

• 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 skills• 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 :

• Resection • Radiation therapy• Chemotherapy

• The mean length of survival after diagnosis has increased to 15 months• 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.