Dysembryoplastic neuroepithelial tumours (DNET) are benign (WHO Grade 1) slow growing glioneuronal tumours arising from either cortical or deep grey matter. They are considered part of the heterogeneous group of tumours known as long-term epilepsy-associated tumours (LEATs).
The vast majority of DNETs are centred in cortical grey matter, arising from secondary germinal layers, and are frequently associated with cortical dysplasia (in up to 80% of cases). They characteristically cause intractable focal epilepsy (see temporal lobe epilepsy).
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Epidemiology
Typically these tumours are diagnosed in children or young adults, as a result of the investigation of seizures, which usually have childhood onset; in 90% of cases, the first seizure occurred before the age of 20 8. Only a slight male predilection is present 8.
Associations
An association with Noonan syndrome has been proposed 9,10.
Clinical presentation
The vast majority (90%) of DNETs present with longstanding treatment-resistant focal epilepsy without associated or progressive focal neurological deficits 5,13.
Pathology
Location
DNETs are most often located in the temporal lobe although all parts of the CNS containing grey matter are potential locations.
temporal lobe: over ~65% of cases 8
frontal lobe: ~20% of cases
cerebellum: present more commonly with ataxia rather than seizures
Macroscopic appearance
Macroscopically, DNETs are visible on the surface of the brain, sometimes with an exophytic component. When sectioned they demonstrate heterogeneous, often gelatinous, cut surface with nodules of firmer tissue 8.
Microscopic appearance
DNETs are a mixed glioneuronal neoplasm with a multinodular architecture and a heterogeneous cellular composition. The "specific glioneuronal element (SGNE)" is characteristic, and refers to columnar bundles of axons surrounded by oligodendrocyte-like cells which are orientated at right angles to the overlying cortical surface. Between these columns are "floating neurones" as well as stellate astrocytes 8.
Three histological forms are recognised 5:
simple: SGNE only
complex: SGNE, with glial nodules and a multinodular architecture
non-specific: no SGNE, but otherwise the same clinical and neuroimaging features as complex DNET
Focal cortical dysplasia is commonly seen in approximately half of patients who have concurrent epilepsy 13. Unless a component can be identified clearly separate from tumour cells, then it does not warrant an additional separate diagnosis. If, however, such a separate component is present, then it represents Blumcke classification IIIb focal cortical dysplasia 8.
Immunophenotype
The stellate astrocytes within the SGNE are positive for GFAP 8.
The oligodendrocyte-like cells are typically S100 and OLIG2 positive, and may also express NOGO-A and myelin-oligodendrocyte glycoprotein 8.
The floating neurones are positive for NeuN 8.
Importantly, DNETs are negative for IDH mutations, TP53 mutations, and do not demonstrate 1p19q co-deletion 8. These features are helpful in distinguishing DNETs from low-grade astrocytomas (usually IDH mutated) and oligodendrogliomas (IDH mutated and 1p19q co-deleted).
Genetics
DNETs usually harbour fibroblast growth factor receptor tyrosine kinase domain duplication (FGFR1-TKDD), shared by pilocytic astrocytomas especially when located outside of the cerebellum 11,12.
Radiographic features
DNETs are typically predominantly cortical and well-circumscribed tumours.
CT
DNETs appear as low-density masses, usually with no or minimal enhancement. When cortical, as is usually the case, they may scallop/remodel the inner table of the skull vault but without erosion. In some cases, the cranial fossa can be minimally enlarged at times.
Calcification is visible in ~30% (more common histologically) and is typically visualised in the deepest parts of the tumour, particularly adjacent to enhancing or haemorrhagic areas 8.
MRI
Typically seen as a cortical lesion with hardly any surrounding vasogenic oedema.
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T1
generally hypointense compared with adjacent brain
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T1 C+ (Gd)
may show enhancement in ~20-30% of cases 5
enhancement may be heterogeneous or a mural nodule
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T2
generally high signal
high signal "bubbly appearance"
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FLAIR
mixed-signal intensity with bright rim sign
partial suppression of some of the "bubbles"
FLAIR is helpful in identifying the small peripheral lesions with similar intensity to CSF
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T2*
calcification relatively frequent
haemosiderin staining is uncommon as bleeding into DNETs is only occasional
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DWI
no restricted diffusion
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MR spectroscopy
non-specific although lactate may be present
Treatment and prognosis
They demonstrate essentially no growth over time, although a very gradual increase in size has been described. Only one case of malignant transformation has been reported 5.
Prognosis is excellent, however, due to the difficulty in managing seizures medically, patients usually undergo resection and even in cases of incomplete resection, seizures frequently cease.
Differential diagnosis
The main differential diagnosis is that of other cortical tumours, with helpful distinguishing features including 1-6:
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contrast enhancement is more common
calcification in ~50% of cases
no "bubbly" appearance
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pleomorphic xanthoastrocytoma (PXA)
contrast enhancement prominent
dural tail sign often seen
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IDH mutated
lacking histological specific glioneuronal element (SGNE)
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IDH mutated and 1p19q codeleted
lacking histological specific glioneuronal element (SGNE)
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desmoplastic infantile astrocytomas and ganglioglioma
young children
dural involvement prominent
large often multiple lesions
Importantly the "bubbly" appearance can be seen also in multinodular and vacuolating neuronal tumours (MVNT) which are however in the juxtacortical white matter, rather than in the cortex 7.
The differential diagnosis also depends on the location of the tumour.
In the temporal lobe consider:
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tumours (in order of decreasing frequency)
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cysts
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other
herpes simplex encephalitis: usually some bilateral changes, and different presentation
limbic encephalitis: usually some bilateral changes, and different presentation
See also: temporal lobe tumours
If cortical elsewhere consider:
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