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

• Protoplasmic astrocytoma appear to have a predilection for the frontal and temporal lobes.

Microscopic Pathology

• On microscopic histopathological analysis, gemistocytic astrocytoma is characterized by:

• Neoplastic protoplasmic astrocytes

• Scant cytoplasm
• Rounded prominent nuclear contour
• Flaccid processes

• Low cellular density
• Mild nuclear atypia (enlarged, irregular contour, hyperchromasia, and coarsened nuclear chromatin pattern)
• Mucinous fluid containing microcystic spaces (prominent feature)
• 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
• Herpes simplex encephalitis
• Anaplastic astrocytoma
• Oligodendroglioma
• Angiocentric glioma

Epidemiology and Demographics

Age

• Protoplasmic 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 protoplasmic 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 protoplasmic astrocytoma. On CT scan, protoplasmic astrocytoma is characterized by:

• Hypodense mass
• Positive mass effect
• No enhancement
• Cystic or fluid attenuation, due to the aforementioned prominent mucinous microcystic component

MRI

• Brain MRI is helpful in the diagnosis of protoplasmic astrocytoma. On MRI, protoplasmic astrocytoma is characterized by:

MRI component	Findings
T1	Hypointense compared to white matter
T2	Hyperintense compared to white matter
Fluid-attenuated inversion recovery (FLAIR)	Large areas of T2 hyperintensity suppress on FLAIR These are not macrocystic, but rather represent the areas with abundant microcystic change)
T1 with contrast	Little or no enhancement
Diffusion weighted imaging (DWI)	No restricted diffusion

Other Imaging Findings

Magnetic Resonance Spectroscopy

• MR spectroscopy may be helpful in the diagnosis of protoplasmic astrocytoma, which demonstrates elevated choline:creatine ratio

Magnetic Resonance Perfusion

• MR perfusion may be helpful in the diagnosis of protoplasmic astrocytoma, which demonstrates no elevation of relative cerebral blood volume (rCBV).

Electroencephalogram

• Electroencephalogram (EEG) is performed in cases of protoplasmic astrocytoma to record the continuous electrical activity of the brain and locate the seizure activity.

Biopsy

• Biopsy of the protoplasmic 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 protoplasmic astrocytoma

Surgery

Radiotherapy

Chemotherapy