Gemistocytic astrocytoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]

Synonyms and keywords: Gemistocytic astrocytomas; Diffuse astrocytoma; Low grade astrocytoma

Overview

Fibrillary astrocytoma is the most common type of diffuse low grade astrocytoma. According to the WHO classification of tumors of the central nervous system, it is classified as a WHO grade II tumor. Unlike the other variants of diffuse low grade gliomas (e.g. gemistocytic astrocytoma; protoplasmic astrocytoma; oligoastrocytoma) or the focal low grade gliomas (e.g. pilocytic astrocytoma; subependymal giant cell astrocytoma), fibrillary astrocytomas are often merely referred to as a low grade glioma.

Pathophysiology

Pathogenesis

• Fibrillary astrocytoma arises from the neoplastic astrocytes, a type of glial cell found in the central nervous system.
• Fibrillary astrocytoma is predominantly composed of a tumor matrix rich with neuroglial fibrils, which give the tumor its name and firm consistency.
• As the alternative name of "diffuse astrocytoma" implies, the outline of the tumor is not clearly visible in scans, because the borders of the neoplasm tend to send out tiny microscopic fibrillary tentacles that spread into the surrounding brain tissue. These tentacles intermingle with healthy brain cells, making complete surgical removal difficult. However, they are low grade tumors, with a slow rate of growth, so that patients commonly survive longer than those with otherwise similar types of brain tumor, such as glioblastoma multiforme.

Gross Pathology

• On gross pathology, fibrillary astrocytoma is characterized by:

• Mass with ill-defined borders
• Firm in consistency
• Loss of normal gray-white matter junction
• Less vascular

Microscopic Pathology

• On microscopic histopathological analysis, fibrillary astrocytoma is characterized by:

• Neoplastic fibrillary astrocytes embedded in the tumor matrix
• Low cellular density
• Mild nuclear atypia (enlarged, irregular contour, hyperchromasia, and coarsened nuclear chromatin pattern)
• Mucinous fluid containing microcystic spaces
• No mitoses, microvascular proliferation, and necrosis

Immunohistochemistry

• Fibrillary astrocytoma is demonstrated by positivity to tumor marker such as GFAP.

Differentiating Fibrillary Astrocytoma from other Diseases

• Fibrillary astrocytoma must be differentiated from:

• Gemistocytic astrocytoma
• Protoplasmic astrocytoma
• Oligoastrocytoma
• Stroke
• Cerebritis
• Encephalitis (herpes simplex encephalitis)
• Anaplastic astrocytoma
• Oligodendroglioma
• Angiocentric glioma

Epidemiology and Demographics

Prevalence

• Fibrillary astrocytoma constitutes approximately 10-15% of all astrocytic brain tumors.

Age

• Fibrillary astrocytoma is a rare disease that tends to affect the young adult population.
• The median age at diagnosis is 35 years.

Gender

• Males are more commonly affected with fibrillary astrocytoma than females. The male to female ratio is approximately 1.5 to 1.

Natural History, Complications and Prognosis

Natural History

• If left untreated, patients with fibrillary astrocytoma may progress to develop seizures, focal neurological deficits, and hydrocephalus.

Complications

• Common complications of fibrillary astrocytoma include:

• Hydrocephalus
• Side-effects of neurosurgery

Prognosis

• The 5-year survival rate of patients with fibrillary astrocytoma is approximately 45%.
• Complete surgical excision of fibrillary astrocytoma is associated with a good prognosis.

Symptoms

• Symptoms of fibrillary astrocytoma include:

• Headaches (earliest symptom)
• Seizures (most common symptom)
• Changes in mood
• Hemiparesis
• Changes in personality
• Changes in vision
• Speech difficulties

CT

• Head CT scan is helpful in the diagnosis of fibrillary astrocytoma. On CT scan, fibrillary astrocytoma is characterized by:

• Isodense or hypodense mass
• Positive mass effect
• No enhancement
• Calcification in 10-20% (more common in mixed tumors relating to an oligodendroglial components, i.e. oligoastrocytoma)
• Cystic or fluid attenuation components (more common in gemistocytic astrocytoma and protoplasmic astrocytoma)

MRI

• Brain MRI is helpful in the diagnosis of fibrillary astrocytoma. On MRI, fibrillary astrocytoma is characterized by:

MRI component	Findings
T1	Isointense to hypointense compared to white matter
T2	Hyperintense compared to white matter
T1 with contrast	Little or no enhancement

Biopsy

• Biopsy of fibrillary astrocytoma tumor mass, taken through a needle during a simple surgical procedure, helps to confirm the diagnosis.

Other Diagnostic Studies

Magnetic Resonance Spectroscopy

• MR spectroscopy may be helpful in the diagnosis of fibrillary astrocytoma, which demonstrates elevated choline:creatine ratio.

Magnetic Resonance Perfusion

• MR perfusion may be helpful in the diagnosis of fibrillary astrocytoma, which demonstrates no elevation of relative cerebral blood volume (rCBV).

Electroencephalogram

• Electroencephalogram (EEG) is performed in cases of fibrillary astrocytoma to record the continuous electrical activity of the brain and locate the seizure activity.

Treatment

The treatment options for fibrillary astrocytoma include:

Treatment of fibrillary astrocytoma

Surgery

Radiotherapy

Radiosurgery

Chemotherapy

Surgery

• The treatment of fibrillary astrocytoma depends on the clinical presentation, tumor size, and location.
• The infiltrating growth of microscopic tentacles in fibrillary astrocytoma makes complete surgical removal difficult or impossible, without injuring brain tissue needed for normal neurological function. However, surgery can still reduce or control tumor size.

Radiotherapy

• Standard radiotherapy for fibrillary astrocytoma requires from ten to thirty sessions, depending on the sub-type of the tumor, and may sometimes be performed after surgical resection to improve outcomes and survival rates.

Radiosurgery

• Radiosurgery uses computer modelling to focus minimal radiation doses at the exact location of the tumor, while minimizing the dose to the surrounding healthy brain tissue.
• Radiosurgery may be a used as a complementary treatment post-surgery, or it may represent the primary treatment technique.

Chemotherapy

• Chemotherapy may have a role in treating recurrent/de-differentiated fibrillary astrocytomas.
• Although chemotherapy for fibrillary astrocytoma improves overall survival, it is effective only in about 20% of the cases.