Low grade infiltrative astrocytomas, also often referred to as diffuse 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. They include a number of subtypes:
- fibrillary astrocytoma
- protoplasmic astrocytoma
- gemistocytic astrocytoma
- and mixed tumours (e.g. oligoastrocytoma)
This article will focus on the general features of fibrillary astrocytomas (the most common type). Each subtype mentioned above is discussed in more details separately.
The term should not be used for a specific, non-infiltrative WHO grade I tumours of astrocyte-lineage such as pleomorphic xanthoastrocytoma (PXA), subependymal giant cell astrocytoma (SGCA) and pilocytic astrocytoma, as these have different prognosis, 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 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:
- isointense to hypointense compared to white matter
- usually confined to the white matters and causes expansion of the adjacent cortex
- 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 very unique behavior 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
- no restricted diffusion
- increased diffusibility is the key to differentiate the diffuse astrocytoma from the acute ischemia
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
- MR perfusion: no elevation of rCBV
- has FDG uptake similar to the normal white matter
- FDG,18-F-Choline and 11C-choline PET useful for biopsy (most hypermetabolic area)
Treatment and prognosis
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:
- infarction: major vascular territory
- cerebritis, encephalitis: herpes simplex encephalitis, ADEM
- anaplastic astrocytoma
- cortical based tumours: oligodendroglioma, angiocentric glioma
- WHO classification of CNS tumours
- WHO grading of CNS tumours
- VASARI MRI feature set
- diffuse astrocytic tumours
- prognostic markers
- diffuse astrocytoma grading
- low grade astrocytoma
- anaplastic astrocytoma
- glioblastoma variant
- glioblastoma vs cerebral metastasis
- treatment response
- Stupp protocol
- glioma treatment response assessment in clinical trials
- multicentric glioblastoma
- multifocal glioblastoma
- radiation-induced gliomas
- gliomatosis cerebri (growth pattern)
- localised astrocytic tumours
- specific locations
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