Diffuse astrocytoma

Diffuse astrocytomas also referred to as low-grade infiltrative astrocytomas, are designated as WHO II tumours of the brain. The term diffuse infiltrating means there is no identifiable border between the tumour and the normal brain tissue even though the borders may appear well marginated on imaging. In the 2016 update to the WHO classification of CNS tumours, diffuse astrocytoma is synonymous with the previously described subtype of fibrillary astrocytomaGemistocytic astrocytoma remains a distinct subtype, whereas protoplasmic astrocytomas are no longer recognised as a separate entity. 

This article will focus on the general features of diffuse (fibrillary) astrocytomas (the most common type). Each subtype mentioned above is discussed in more details separately.

The term diffuse astrocytoma should not be used for a specific, non-infiltrative tumours of astrocyte-lineage such as pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma and pilocytic astrocytoma, as these have different prognoses, treatment and imaging features.

Diffuse low-grade gliomas of the cerebral hemispheres are typically diagnosed in young adults between 20-45 years old (mean 35 years of age). There is, in fact, a biphasic distribution, with one peak in childhood (6-12 years) and the other peak in early adulthood (26-46 years)1. Childhood gliomas are mostly diffuse brainstem gliomas, which are discussed separately.

There is a slight male predilection is described (M:F ~1.5) 1.

The most common presenting feature (~40% of cases) is a seizure. This is particularly the case in adults. Headaches are often also present. Depending on the size of the lesion and its location other features may be present, such as hydrocephalus and focal neurological dysfunction including personality change.

Diffuse low-grade astrocytomas are predominantly composed of a microcystic tumour matrix within which are embedded fibrillary neoplastic astrocytes with mild nuclear atypia and a low cellular density. Often microcystic spaces containing mucinous fluid are present, a typical finding in fibrillary astrocytomas, but even more characteristic and pronounced in protoplasmic astrocytomas

The occasional occurrence of gemistocytes in a diffuse astrocytoma does not justify the diagnosis of gemistocytic astrocytoma. Gemistocytic astrocytomas tend to progress more rapidly to anaplastic astrocytoma and secondary glioblastoma than fibrillary astrocytoma although they share the WHO grade II.

Mitoses, microvascular proliferation and necrosis are absent (if present they suggest a high-grade tumour). Like all tumours derived from astrocytes, fibrillary astrocytomas stain with glial fibrillary acidic protein (gFAP) 2-3.

It is well recognised that pathological classification has a high interobserver variation and thus imperfectly predicts clinical outcomes 11. Recent studies have shown that the genetic status of these tumours are more reflective of their subtypes than the histologic grading (please refer on isocitrate dehydrogenase 1 - IDH1 for a broad discussion on this topic) 11.  

MRI is the modality of choice for characterising these lesions, and in the case of smaller tumours, they may be subtle and difficult to see on CT, especially as they tend not to enhance.


Typically low grade infiltrating astrocytomas appear as isodense or hypodense regions of positive mass effect, often without any enhancement (in fact presence of enhancement would suggest high tumours), although particularly gemistocytic astrocytomas can demonstrates wispy enhancement.

Calcification is not common (10-20% of cases)1 and may be related to oligodendroglial components (i.e oligoastrocytoma).

Cystic or fluid attenuation components are also encountered, particularly in gemistocytic and protoplasmic varieties.


Reported signal characteristics include:

  • T1
    • isointense to hypointense compared to white matter
    • usually confined to the white matters and causes expansion of the adjacent cortex
  • T2/FLAIR 
    • mass-like hyperintense signals
    • 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 tumour from the start
    • the "microcystic changes" along the lines of spread of the infiltrative astrocytoma is a unique behaviour for the infiltrative astrocytoma, however, it is only appreciated in a few number of cases
    • high T2 signal is NOT related to cellularity or cellular atypia, but rather oedema, demyelination and other degenerative change 10
    • typically has facilitated diffusion, with lower ADC values suggesting higher grade
  • T1 C+ (Gd)
    • no enhancement is often the rule but 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
  • MR spectroscopy
    • typically will show elevated choline peak, low NAA peak, elevated choline:creatine ratio
    • elevated myo-inositol and mI/Cr ratio.
    • there is lack of the lactate peak seen at 1:33
    • the lactate peak represents the necrosis seen in aggressive mostly WHO grade IV tumours
  • MR perfusion: no elevation of rCBV
Nuclear medicine
  • PET
    • has FDG uptake similar to the normal white matter
    • FDG,18-F-Choline and 11C-choline PET useful for biopsy (most hypermetabolic area)

Treatment depends on clinical presentation, size of the tumour and location. In general:

  • biopsy to confirm diagnosis and observe
  • surgical resection is the rule
  • usually radiotherapy at time of recurrence or progression

Chemotherapy may have a role in recurrent and de-differentiated tumours.

Possible imaging differential considerations include:

Astrocytic tumour
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Article Information

rID: 14598
Section: Pathology
Synonyms or Alternate Spellings:
  • Diffuse astrocytoma
  • Low grade astrocytoma
  • Low grade infiltrating astrocytoma
  • Low grade diffuse astrocytoma
  • Low grade infiltrative astrocytomas
  • Diffuse low grade astrocytoma

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Cases and Figures

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    Case 1: diffuse fibrillary astrocytoma
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    Case 2: gemistocytic astrocytoma
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    MR spectroscopy
    Case 3
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    Case 4: basal ganglionic diffuse infiltration
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    Case 6: low grade glioma
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    Case 8
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