Subependymal giant cell astrocytoma overview

# Overview
Subependymal giant cell astrocytoma is a benign tumor arising within the ventricles of the brain. It is almost exclusively associated with tuberous sclerosis, an autosomal dominant disorder associated with the inactivation of the tumor suppressor genes, TSC1 and/or TSC2. Subependymal giant cell astrocytoma is believed to arise from a subependymal nodule present in the ventricular wall of a patient with tuberous sclerosis. On microscopic histopathological analysis, it is characterized by pleomorphic multinuleated eosinophilic cells with abundant cytoplasm, arranged in a perivascular pseudopallisading pattern. Subependymal giant cell astrocytoma is a disease that tends to affect the pediatric, adolescent, and young adult population. Males are more commonly affected than females. According to the International Tuberous Sclerosis Complex Consensus, screening for subependymal giant cell astrocytoma by MRI is recommended every 1-3 years among patients with tuberous sclerosis, even in the absence of symptoms. If left untreated, patients with subependymal giant cell astrocytoma may progress to develop seizures, occlusion of the foramen of Monro with subsequent elevated intracranial pressure and obstructive hydrocephalus, infection, stroke, and death. Common complications of subependymal giant cell astrocytoma include obstructive hydrocephalus, intratumoral hemorrhage, and infection. Symptoms of subependymal giant cell astrocytoma include headache, seizures, vision loss, changes in speech, weakness in limbs, and sensory loss. Common physical examination findings of subependymal giant cell astrocytoma include papilledema, vision field defects, developmental delay, aphasia, sensory loss, and hemiparesis. Head CT scan and brain MRI may be helpful in the diagnosis of subependymal giant cell astrocytoma. On head CT scan, subependymal giant cell astrocytoma is characterized by an intraventricular mass near the foramen of Monro, which is iso- or slightly hypoattenuating to the grey matter. Accompanying hydrocephalus may be present. There is marked enhancement on contrast administration. On MRI, subependymal giant cell astrocytoma is characterized by hypo- to isointensity on T1-weighted imaging and hyperintensity on T2-weighted imaging. There may be marked enhancement on contrast administration. Surgical resection is the mainstay treatment of subependymal giant cell astrocytoma but in certain cases, medical therapy such as everolimus is used.

# Historical Perspective
In 2012, subependymal giant cell astrocytoma was described at the International Tuberous Sclerosis Complex Consensus Conference as a lesion located in the caudothalamic groove having a size of >1 cm in any direction or a subependymal lesion that has shown serial growth on consecutive imaging regardless of size and location.

# Classification
There is no classification system established for subependymal giant cell astrocytoma.

# Pathophysiology
Subependymal giant cell astrocytoma is almost exclusively associated with tuberous sclerosis complex, which is an autosomal dominant disorder. It is associated with inactivation of the tumor suppressor genes, TSC1 and/or TSC2. It is also believed to arise from a subependymal nodule present in the ventricular wall of a patient with tuberous sclerosis. Some of the common findings seen on microscopic pathology include pleomorphic multinuleated eosinophilic cells, streams of elongated tumor cells with abundant cytoplasm, and clustered cells arranged in a perivascular pseudopallisading pattern. On immunohistochemistry, the tumor cells are positive for glial fibrillary acidic protein, microtubule-associated protein 2, synaptophysin, S-100, neurofilament, and neuron-specific enolase.

# Causes
Subependymal giant cell astrocytoma is predominantly seen in patients with tuberous sclerosis complex which is caused by a mutation in the TSC1 and TSC2 tumor suppressor genes.

# Differentiating Subependymal Giant Cell Astrocytoma from other Diseases
Subependymal giant cell astrocytoma must be differentiated from ependymoma, meningioma, tuberculoma, intraventricular hemorrhage, glioblastoma multiforme, primary CNS lymphoma, and cerebral metastases.

# Epidemiology and Demographics
Subependymal giant cell astrocytoma is the most common central nervous system tumor in patients with tuberous sclerosis complex. Approximately 10-20% of patients with tuberous sclerosis develop subependymal giant cell astrocytoma. It is a disease that tends to commonly affect the pediatric population with males being more affected than females.

# Risk factors
The most potent risk factor in the development of subependymal giant cell astrocytoma is tuberous sclerosis.

# Screening
According to the International Tuberous Sclerosis Complex Consensus, screening for subependymal giant cell astrocytoma by MRI is recommended every 1-3 years among patients with tuberous sclerosis, even in the abscence of symptoms.

# Natural History, Complications and Prognosis
Subependymal giant cell astrocytoma is generally located in the caudothalamic groove adjacent to the foramen of Monro and it presents commonly in the first two decades of life. It can lead to a few complications such as obstructive hydrocephalus, intratumoral hemorrhage, and death. Although the prognosis may be poor, patients who undergo surgical resection and those below the age of 18 have a better prognosis.

# Diagnosis

## Diagnostic Study of Choice
There is no single diagnostic study of choice for the diagnosis of subependymal giant cell astrocytoma, but subependymal giant cell astrocytoma can be diagnosed based on contrast enhanced MRI and CT scan.

## History and Symptoms
Patients with subependymal giant cell astrocytoma may have a positive history of tuberous sclerosis, seizures, and personality changes. Some common symptoms that may be present include headaches, nausea, vomiting, and cognitive decline.

## Physical examination
Common physical examination findings in patients with subependymal giant cell astrocytoma include hypomelanotic macules, retinal hamartomas, sensory deficits, and muscle weakness. Because subependymal giant cell astrocytoma is predominantly seen in people with tuberous sclerosis, the examination findings listed are those seen in tuberous sclerosis patients.

## Laboratory Findings
There are no diagnostic lab findings associated with subependymal giant cell astrocytoma.

## CT
Head CT scan may be helpful in the diagnosis of subependymal giant cell astrocytoma. On head CT, some of the findings that are suggestive of subependymal giant cell astrocytoma include a heterogenous mass with uniform post contrast enhancement, enlargement of the ventricles, and iso- or slightly hypoattenuating to grey matter.

## MRI
Brain MRI may be helpful in the diagnosis of subependymal giant cell astrocytoma. On MRI, some of the findings suggestive of subependymal giant cell astrocytoma include T1 isointense and hypointense signal enhancement, T2 isointense and hyperintense signal enhancement, and enlargement of ventricles.

## Ultrasound
There are no ultrasound findings associated with subependymal giant cell astrocytoma.

## Other Imaging Findings
There are no other imaging findings associated with subependymal giant cell astrocytoma.

## Other Diagnostic Studies
There are no other diagnostic studies associated with subependymal giant cell astrocytoma.

# Treatment

## Medical Therapy
The mainstay therapy for subependymal giant cell astrocytoma is surgery, but medical therapy is preferred in some cases. Mammalian target of rapamycin (mTOR) inhibitors, everolimus and rapamycin, are the medications used. They are capable of reducing the size of the tumor and in some cases, the tumors grow back after upon cessation of use. The most common side effects associated with the use of mTOR inhibitors are stomatitis and upper respiratory tract infections.

## Interventions
The mainstay of treatment for subependymal giant cell astrocytoma is surgery with medical therapy used in some cases.

## Surgery
Surgery is the first line therapy for subependymal giant cell astrocytoma. It is preferably indicated in cases such as tumor growth, acute hydrocephalus, and worsened seizure burden. The tumors that have invaded neighboring structures, those located bilaterally, and growing residual tumors are difficult to treat surgically. Medical therapy is favored in these cases. Some of the complications of surgical resection include transient memory loss, infection, and death. Gamma knife radiosurgery may also be used to treat subependymal giant cell astrocytoma with the risk of causing radiation-induced secondary tumor.

## Primary Prevention
There is no established method for prevention of subependymal giant cell astrocytoma.

## Secondary Prevention
Effective measures for the secondary prevention of subependymal giant cell astrocytoma include brain imaging, preferably magnetic resonance imaging with and without contrast, which should be performed every 1 to 3 years until the age of 25 years in every patient with tuberous sclerosis.