Gemistocytic astrocytoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]Roukoz A. Karam, M.D.[3]

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 patient’s 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:

MRI component	Findings
T1	Iso-intense to hypo-intense compared to white matter Usually confined to the white matter and causes expansion of the adjacent cortex
T2	Hyper-intense compared to white matter Always follows the white matter distribution and causes expansion of the surrounding cortex Cortex may also be involved in late cases, in comparison to the oligodendroglioma, which is a cortical based tumor from the start "Microcystic changes" along the lines of spread of the infiltrative astrocytoma is a very unique behavior for the infiltrative astrocytoma, however, it is only appreciated in a few number of cases Hyper-intense T2 signal is not related to cellularity or cellular atypia, but rather edema, demyelination, and other degenerative changes
T1 with contrast	No enhancement Small ill-defined areas of enhancement are not rare; however, when enhancement is seen, it should be considered as a warning sign for progression to a higher grade
Diffusion weighted imaging (DWI)	No restricted diffusion Increased diffusibility is the key to differentiate gemistocytic astrocytoma from acute ischemia

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.