Astrocytoma overview

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

Overview

Astrocytomas are primary intracranial tumors derived from astrocytes cells of the brain. They may arise in the cerebral hemispheres, in the posterior fossa, in the optic nerve, and rarely, the spinal cord. Astrocytomas are a type of neoplasm of the brain. They originate in a particular kind of glial cells, star-shaped brain cells in the cerebrum called astrocytes. This type of tumor does not usually spread outside the brain and spinal cord and it does not usually affect other organs.

Historical Perspective

Astrocytoma was the first glioma tumor to be described. It was first explained as glioma duram by Virchow in 1840 and then as spider cell glioma by T.Simon in 1874 and astroma by M von Lenhossek in 1895. Histological description of astrocytoma was first given by Bergstrand in 1932.

Classification

Astrocytoma may be classified according to its histology into 4 grades: pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma and glioblastoma multiforme.

Pathophysiology

The exact pathogenesis of astrocytoma is not completely understood but it is believed that this tumor has a close association with genetic mutations. Microscopic pathologic findings in pilocytic astrocytoma include normal cells with slow growth rate, biphasic pattern (dense fibrillar tissue within loose myxoid tissue), Calcification, Vascular hyalinization and Nested fibrotic pattern. In diffuse astrocytoma we may see atypical cells, relatively slow mitosis rate, diffusely infiltrate neuropil and poorly defined cytoplasm. In anaplastic astrocytoma we may see pleomorphic and malignant cells, High mitosis rate, hyperchromatosis and prominent small vessels. In glioblastoma multiform we may see Pleomorphic cells, Naked nuclei, Multi-focal necrosis, Pseudopalisading pattern, Scattered pyknotic nuclear debris in the center, Micro-vascular proliferation and Vascular thrombi.

Causes

The exact cause of astrocytoma is not known but it seems that Genetic mutation has a strong association with this tumor.

Differential Diagnosis

Astrocytoma must be differentiated from other space occupying CNS lesions that cause neurological symptoms such as subependymal nodule, central neurocytoma, oligodendroglioma, intraventricular meningioma, intraventricular metastasis, medulloblastoma, sarcoma, primitive neuroectodermal tumor, choroid plexus carcinoma and glioblastoma multiforme.

Epidemiology and Demographics

The incidence of astrocytoma is 0.23 per 100,000 and the number of new cases is 700 per year. In 2012, there were an estimated 148,818 people living with brain and other nervous system cancer in the United States. The number of deaths was 4.3 per 100,000 men and women per year based on 2008-2012 deaths. The low-grade type is more often found in children or young adults, while the high-grade type is more prevalent in adults. Pilocytic astrocytoma is more common in men, who account for 62% of all cases. The male-to-female ratio of diffuse astrocytoma is 1.5:1 and for anaplastic astrocytoma is 1.8:1. Astrocytoma is more common in caucasian race.

Risk Factors

Common risk factors in the development of astrocytoma include environmental factors such as: Vinyl chloride, Phenols, organic solvents, pesticides, Formaldehyde, lubricating fluids, polycyclic aromatic hydrocarbons and past radiation therapy to the brain and genetic diseases such as: Neurofibromatosis, Tuberous sclerosis, Li-Fraumeni syndrome, Nevoid basal cell carcinoma syndrome, Turcot syndrome and Melanoma-astrocytoma syndrome. Less common risk factors include: Blood group A, previous head trauma, history of meningitis, history of epilepsy.

Natural History

If left untreated, eventually 100% of patients with low grade astrocytomas will growth rapidly similar to high grade astrocytoma tumors and 100% of patients with high grade astrocytoma will become symptomatic and deteriorate. Astrocytoma being a space occupying lesion can have following complications depending on the location of the tumor: Increased intracranial pressure, cognitive dysfunction, emotional disturbances, behavioral complications, visual defects and Muscle weakness. Low-grade astrocytomas (grade I [pilocytic] and grade II) have a relatively favorable prognosis, particularly for circumscribed, grade I lesions where complete excision may be possible. High-grade astrocytomas generally carry a poor prognosis in younger patients.

History and Symptoms

A positive history of Vinyl chloride, Phenols, organic solvents, pesticides, Formaldehyde, lubricating fluids, polycyclic aromatic hydrocarbons, past radiation therapy to the brain, Genetic disorders, blood group A, previous head trauma, Meningitis, Epilepsy, Headache, limb parasthesia or weakness, difficulty swallowing, Nausea, Diplopia, Lethargy, personality changes and Blurred vision is suggestive of astrocytoma. The most common symptoms of astrocytoma include morning headache or headache that goes away after vomiting, Nausea and vomiting, Vision, hearing, and speech problems, loss of balance and trouble walking, worsening handwriting or slow speech, Weakness or change in feeling on one side of the body, unusual sleepiness, Change in personality or behavior, Increase in the size of the head (in infants), Seizures, decreased memory, attention, and motor abilities, but unaffected intelligence, language, and academic skills. Less common symptoms of astrocytoma include Weight loss or weight gain for no known reason and more or less energy than usual.

Physical Examination

Common physical examination findings of astrocytoma include gait disturbances, Tachycardia or bradycardia, Orthostatic hypotension, reduced hearing acuity, nystagmus, abnormal extra-ocular movement, nonreactive pupils, papilledema, blurry vision, head tilt, Altered mental status, Clonus , Hyperreflexia, Muscle rigidity, proximal/distal muscle weakness unilaterally or bilaterally, cranial nerve involvement , unilateral/bilateral sensory loss in the upper/lower extremity, positive Trendelenburg's sign, unilateral/bilateral tremor and Dysmetria.

Laboratory Findings

There are no diagnostic lab findings associated with astrocytoma.

Electrocardiogram

Frontal astrocytomas can disturb autonomic pathways and cause prolonged QT syndrome.

X Ray

There are no characteristic x-ray findings associated with astrocytomas.

Echocardiography/Ultrasound

There are no echocardiography/ultrasound findings associated with astrocytoma.

CT

CT scan may be helpful in the diagnosis of astrocytoma. Findings on CT scan suggestive of astrocytoma include: Poorly demarcated mass, low density and no inhancement inside the tumor In low grade astrocytoma, poorly demarcated mass, low density and there are partial enhancement inside the tumor mas In high grade astrocytoma.

MRI

Findings on MRI suggestive of astrocytoma in Low grade astrocytoma (pilocytic and diffuse astrocytoma) include Decreased resonance in comparison to surrounding brain tissue in T1 and Increased resonance in comparison to surrounding brain tissue in T2. In anaplastic astrocytoma we have Hypointense T1, Hyperintense T2 and some contrast enhancement and edema. In glioblastoma multiform we have irregular ring-nodular enhancing lesions and central necrosis surrounding vasogenic edema.

Other Imaging Findings

PET/SPECT may be helpful in the differentiation of astrocytoma grading. Finding on PET/SPECT suggestive of low grade astrocytoma is hypometabolic mass and finding on PET/SPECT suggestive of high grade astrocytoma is hypermetabolic mass.

Other Diagnostic Studies

Biopsy is helpful in the diagnosis of astrocytomas. Findings suggestive diagnostic of astrocytoma include normal cells with slow growth rate, biphasic pattern (dense fibrillar tissue within loose myxoid tissue), Calcification, Vascular hyalinization and Nested fibrotic pattern in pilocytic astrocytoma, atypical cells, relatively slow mitosis rate, diffusely infiltrate neuropil and poorly defined cytoplasm in diffuse astrocytoma, pleomorphic and malignant cells, High mitosis rate, hyperchromatosis and prominent small vessels in anaplastic astrocytoma, Pleomorphic cells, Naked nuclei, Multi-focal necrosis, Pseudopalisading pattern, Scattered pyknotic nuclear debris in the center, Micro-vascular proliferation and Vascular thrombi in glioblastoma multiform.

Medical Therapy

The mainstay of treatment for low grade astrocytoma is wait and see approach, radiation therapy and chemotherapy. Treatment for anaplastic astrocytoma is radiotherapy with adjunctive chemotherapy, radiotherapy alone and chemotherapy alone. Treatment for glioblastoma multiform is chemotherapy and radiotherapy, Bevacizumab, alternating electric fields and Carmustine polymer wafers.

Surgery

Surgical intervention is the mainstay of treatment for astrocytomas. Extensive resection is preferred over partial resection. The relative contraindications of brain surgery are: Advanced age, sever cardiopulmonary dysfunction, inaccessible lesions and sever systemic illness such as sepsis.

Primary Prevention

Effective measures for the primary prevention of astrocytoma include eliminating environmental risk factors from happening such as: Exposure to Vinyl chloride, Phenols, Organic solvents, Pesticides, Formaldehyde, Lubricating fluids, Polycyclic aromatic hydrocarbons and Previous radiation to the brain.

Secondary Prevention

There are no established measures for the secondary prevention of astrocytoma.