Protoplasmic 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: Protoplasmic astrocytomas; Diffuse astrocytoma; Low grade astrocytoma

Overview

Protoplasmic astrocytoma is a rare variant of diffuse low grade astrocytoma with histological and imaging features which are fairly characteristic. It has been suggested that protoplasmic astrocytoma represents a variant of dysembryoplastic neuroepithelial tumors (DNET), as they share histological as well as imaging features. Currently, they are classified as a subtype of diffuse low-grade astrocytoma.

Pathophysiology

Gross Pathology

• 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.

Microscopic Pathology

• 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
• No mitoses, microvascular proliferation, and necrosis

Immunohistochemistry

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

Differentiating Protoplasmic Astrocytoma from other Diseases

• Protoplasmic astrocytoma must be differentiated from:

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

Epidemiology and Demographics

Age

• Gemistocytic astrocytoma is a rare disease that tends to affect young adults.
• The mean age at diagnosis is 32 years.

Gender

• Males are more commonly affected with gemistocytic astrocytoma than females. The male to female ratio is approximately 1.67 to 1.

Natural History, Complications and Prognosis

Natural History

• 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.

Complications

• Common complications of gemistocytic astrocytoma include:

• Hydrocephalus
• Malignant transformation to anaplastic astrocytoma or glioblastoma multiforme.

Prognosis

• Gemistocytic astrocytoma has a poorer prognosis than the other matched WHO grade II (low-grade) astrocytic tumors (fibrillary astrocytoma, protoplasmic astrocytoma, and oligoastrocytoma).
• The 5-year survival rate of patients with gemistocytic astrocytoma is approximately 30%.
• The median survival time with treatment is only 2.5 years.
• 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

History and Symptoms

History

• When evaluating a patient for protoplasmic astrocytoma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review.

Symptoms

• Symptoms of protoplasmic astrocytoma include:

• Headaches
• Seizures
• Changes in mood
• Hemiparesis
• Changes in personality
• Changes in vision
• Speech difficulties

CT

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

• Isodense or hypodense 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	Isointense to hypointense compared to white matter Usually confined to the white matter and causes expansion of the adjacent cortex
T2	Hyperintense compared to white matter Always follow the white matter distribution and cause expansion of the surrounding cortex Cortex can 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 Hyperintense 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 the gemistocytic astrocytoma from the 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).

Biopsy

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

Treatment

• 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.

Treatment of gemistocytic astrocytoma

Surgery

Radiotherapy

Chemotherapy