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

# Overview
Gemistocytic astrocytoma is a histologic subtype of low grade astrocytoma, with a poorer prognosis than other matched WHO grade II astrocytic tumors. Gemistocytic astrocytoma is characterized by a significant gemistocytes population, which are large astrocytes with their cytoplasm filled with eosinophilic material displacing the nucleus eccentrically.

# Historical Perspective
- Gemistocytic astrocyte was first described by Franz Nissl in the 20th century.

# Classification
Gemistocytic astrocytoma is a subtype of astrocytoma and is included in the classification of astrocytoma. For more information about the classification of astrocytoma, click here.

# Pathophysiology
- Gemistocytic astrocytoma is characterized by a significant gemistocyte population, which are large astrocytes with their cytoplasm filled with eosinophilic material displacing the nucleus eccentrically.
- It is important to note that other gliomas can have occasional gemistocytes, without being designated a gemistocytic astrocytoma. A cut off of 20% of the tumor cells being gemistocytes is used before designating it as a gemistocytic astrocytoma.
- Other CNS tumors and conditions that have gemistocytes or gemistocyte-like cells include:
- Oligodendroglioma with "minigemistocytes"
- Ependymoma
- Subependymal giant cell astrocytoma
- Astroblastoma
- Reactive gliosis in inflammation, infection, or demyelinating disease
- Toxic/metabolic leukoencephalopathy
- On gross pathology, gemistocytic astrocytoma is characterized by:
- Gray-tan mass
- Well-defined borders
- Soft texture
- Cystic architecture
- Gemistocytic astrocytoma is almost always supratentorial and usually located in the frontal lobes.
- Infiltrative tumor with gemistocytes, characterized by ample eosinophilic glassy cytoplasm and eccentric nuclei with frequent prominent nucleoli.
- Background is coarse fibrillary; perivascular lymphocyte cuffing is common.
- On microscopic histopathological analysis, gemistocytic astrocytoma is characterized by:
- Neoplastic fibrillary astrocytes embedded in the tumor matrix
- Gemistocytes > 20% of the tumor cells
- Large, plump astrocytes
- Abundant eosinophilic cytoplasm
- Eccentric nuclei
- Low cellular density
- Mild nuclear atypia (enlarged, irregular contour, hyperchromasia, and coarsened nuclear chromatin pattern)
- Mucinous fluid containing microcystic spaces
- Perivascular lymphocytic infiltrate
- Absence of mitoses, microvascular proliferation, and necrosis
- GFAP (tumor marker) is positive in gemistocytic astrocytoma.

# Differentiating Gemistocytic Astrocytoma from Other Diseases
- It is important to note that other gliomas (e.g. fibrillary astrocytoma and oligodendrogliomas) can have occasional gemistocytes, without being designated a gemistocytic astrocytoma.
- A cut off of 20% of the tumor cells being gemistocytes, is used before designating a lesion to be gemistocytic astrocytoma.
- Gemistocytic astrocytoma must be differentiated from:
- Fibrillary astrocytoma
- Protoplasmic astrocytoma
- Oligoastrocytoma
- Stroke
- Cerebritis
- Herpes simplex encephalitis
- Anaplastic astrocytoma
- Oligodendroglioma
- Angiocentric glioma

# Epidemiology and Demographics
- Gemistocytic astrocytoma is a rare disease that tends to affects children and young adults.
- The mean age at diagnosis is 35 years.
- Males are more commonly affected than females. The male to female ratio is approximately 1.5 to 1.
- Gemistocytic astrocytoma makes up approximately 10% of all WHO grade II diffuse astrocytomas. 

# Risk Factors
- There are no specific risk factors for gemistocytic astrocytoma.
- For more information on risk factors for astrocytoma, click here.

# Screening
There is insufficient evidence to recommend routine screening for gemcistocytic astrocytoma.

# Natural History, Complications, and Prognosis
- If left untreated, patients with gemistocytic astrocytoma may progress to develop seizures, focal neurological deficits, hydrocephalus, or malignant transformation to anaplastic astrocytoma or glioblastoma multiforme.
- Gemistocytic astrocytoma is a slow growing tumor, but it behaves in an aggressive manner.
- Common complications of gemistocytic astrocytoma include:
- Hydrocephalus
- Malignant transformation to anaplastic astrocytoma or glioblastoma multiforme.
- Gemistocytic astrocytoma has a poorer prognosis than the other matched WHO grade II (low-grade) astrocytic tumors (fibrillary astrocytoma, protoplasmic astrocytoma, and oligoastrocytoma).
- Gemistocytic astrocytoma has been associated with an early progression and less favorable outcome; however, it remains to be determined whether the prognosis of IDH-mutant gemistocytic astrocytoma differs significantly from that of IDH-mutant diffuse astrocytoma.
- The 5-year survival rate of patients with gemistocytic astrocytoma is approximately 30%.
- The median survival time with treatment is only 2.5 years.
- The authors conclude that the presence of at least 20% gemistocytes in a glial neoplasm is a poor prognostic sign, irrespective of the pathological background.
- It is proposed that gemistocytic astrocytomas be classified with anaplastic astrocytomas and treated accordingly.
- A poor prognostic factor for gemistocytic astrocytoma is the presence of at least 20% gemistocytes in a glial neoplasm irrespective of its pathological background.
- Favorable prognostic factors for gemistocytic astrocytoma include:
- Age < 50 years
- Occurrence of seizures as the initial symptom
- Pre-operative symptoms lasting more than 6 months

# Diagnosis

## Diagnostic Study of Choice
- The diagnosis of gemistocytic astrocytoma is based on the imaging findings.
- MRI and CT scan of the brain is the preferred diagnostic approach.

## History and Symptoms
- When evaluating a patient for gemistocytic astrocytoma, you should take a detailed history of the presenting symptoms (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review.
- There are no specific factors in the patients history that are pathognomonic for low-grade glioma.
- The history, however, should alert the clinician to the presence of a neurological disorder and the need for an imaging study.
- Characteristically, low-grade gliomas present with headache, focal deficit and/or, most notably seizures.
- Symptoms of gemistocytic astrocytoma include:
- Headaches
- Seizures
- Changes in mood
- Hemiparesis
- Changes in personality
- Changes in vision
- Speech difficulties

## Physical Examination
There are no specific physical examination findings associated with gemistocytic astrocytoma.

## Laboratory Findings
There are no specific laboratory findings associated with gemistocytic astrocytoma.

## Electrocardiogram
There are no ECG findings associated with gemistocytic astrocytoma.

## X-ray
There are no x-ray findings associated with gemistocytic astrocytoma.

## Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with gemistocytic astrocytoma.

## CT scan
- Head CT scan is helpful in the diagnosis of gemistocytic astrocytoma. On CT scan, gemistocytic astrocytoma is characterized by:
- Iso-dense or hypo-dense mass
- Positive mass effect
- Wispy enhancement (most low-grade astrocytomas are without any enhancement)
- In fact, presence of enhancement would suggest more aggressive tumors
- Calcification in 10 - 20% (more common in mixed tumors relating to an oligodendroglial components, i.e. oligoastrocytoma)
- Cystic or fluid attenuation components

## MRI
- Brain MRI is helpful in the diagnosis of gemistocytic astrocytoma.
- On MRI, gemistocytic astrocytoma is characterized by:

## Other Imaging Findings

### Magnetic Resonance Spectroscopy
- MR spectroscopy may be helpful in the diagnosis of gemistocytic astrocytoma.
- Findings on MR spectroscopy include:
- Elevated choline peak, low N-Acetylaspartate peak, elevated choline:creatine ratio
- Elevated myo-inositol (mI) and mI/creatine ratio
- Lack of the lactate peak seen at 1:33
- Lactate peak represents the necrosis seen in aggressive tumors (WHO grade IV)

### Magnetic Resonance Perfusion
- MR perfusion may be helpful in the diagnosis of gemistocytic astrocytoma, which demonstrates no elevation of relative cerebral blood volume (rCBV).

## Other Diagnostic Studies
- Biopsy of the gemistocytic astrocytoma, taken via needle during a simple surgical procedure, helps to confirm the diagnosis.

# Treatment

## Medical Therapy
Chemotherapy is recommended for patients with recurrent or de-differentiated gemistocytic astrocytomas.

## Surgery
- The predominant therapy for gemistocytic astrocytoma is surgical resection. Adjunctive radiation and nitrosourea-based chemotherapy may be required.
- Surgery: Since gemistocytic astrocytoma can behave aggressively, surgery is the mainstay of treatment.
- Radiotherapy: Radiotherapy may be used in gemistocytic astrocytoma post-operatively or at the time of recurrence or progression.
- Chemotherapy: Chemotherapy may have a role in recurrent and de-differentiated tumors.

## Primary Prevention
There are no measures for the primary prevention of gemistocytic astrocytoma.

## Secondary Prevention
There are no measures for the secondary prevention of gemiistocytic astrocytoma.