Dysembryoplastic neuroepithelial tumor

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Dysembryoplastic neuroepithelial tumours (DNET) are benign (WHO Grade I) slow growing glioneuronal tumours arising from either cortical or deep grey matter. The vast majority are centred in cortical grey matter, arise from secondary germinal layers and are frequently associated with cortical dysplasia (up to 80% of cases). They characteristically cause intractable partial seizures (see temporal lobe epilepsy).

Epidemiology

Typically these tumours are diagnosed in children or young adults, as a result of the investigation of seizures, which have usually had childhood onset. Only a slight male predilection is present ⁸.

Clinical presentation

Patients with DNETs typically present with longstanding treatment resistant partial seizures (in 90% of cases the first seizure occurred before the age of 20 ⁸) without associated or progressive neurological deficit ⁵.

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
caudate nucleus
cerebellum: presentation is then more commonly with ataxia rather than seizures
pons

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 oriented 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
nonspecific
1. same clinical and neuroimaging features as complex DNET, but...
2. no SGNE

Focal cortical dysplasia is commonly seen in association with DNETs, and unless a component can be identified clearly separate from tumour cells, then it does not warrant a concurrent 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).

Radiographic features

DNETs are typically predominantly cortical and well-circumscribed tumours.

~~Location~~

~~The temporal lobe is the most common location, but all parts of the CNS containing grey matter are potential locations.~~

~~temporal lobe: over ~65% of cases~~ ⁸

~~frontal lobe: ~20% of cases~~

~~caudate nucleus~~

~~cerebellum: presentation is then more commonly with ataxia rather than seizures~~

~~pons~~

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.

T1
- generally hypointense c.f adjacent brain
T1 C+ (Gd)
- may show enhancement in ~20-30% of cases ⁵
- enhancement may be heterogeneous or a mural nodule
T2
- generally high signal
- high signal 'bubbly appearance'
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
T2*
- calcification relatively frequent
- haemosiderin staining uncommon as bleeding into DNETs is only occasional
DWI
- no restricted diffusion
MR spectroscopy
- non-specific although lactate may be present

Treatment and prognosis

They demonstrate essentially no growth over time, although 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 seizure medically, patients usually undergo resection and even in cases of incomplete resection, seizures frequently cease.

Differential diagnosis

Main differential diagnosis is that of other cortical tumours, with helpful distinguishing features including ^1-6:

ganglioglioma
- contrast enhancement more common
- calcification in ~50% of cases
- no 'bubbly' appearance
pleomorphic xanthoastrocytoma (PXA)
- contrast enhancement prominent
- dural tail sign often seen
diffuse low-grade astrocytoma
- IDH mutated
- lacking histological specific glioneuronal element (SGNE)
oligodendroglioma
- IDH mutated and 1p19q co-deleted
- lacking histological specific glioneuronal element (SGNE)
desmoplastic infantile 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.

If in the temporal lobe consider:

tumours (in order of decreasing frequency)
cysts
- neuroepithelial cyst
- choroid fissural cyst
other
- herpes simplex encephalitis: usually some bilateral changes, and different presentation
- limbic encephalitis: usually some bilateral changes, and different presentation
- mesial temporal sclerosis (MTS)

See also: temporal lobe tumours

If cortical elsewhere consider:

-<p><strong>Dysembryoplastic neuroepithelial tumours</strong> <strong>(DNET)</strong> are benign (WHO Grade I) slow growing glioneuronal tumours arising from either cortical or deep grey matter. The vast majority are centred in cortical grey matter, arise from <a href="/articles/secondary-germinal-layers">secondary germinal layers</a> and are frequently associated with <a href="/articles/focal-cortical-dysplasia">cortical dysplasia</a> (up to 80% of cases). They characteristically cause intractable partial seizures (see <a href="/articles/temporal-lobe-epilepsy">temporal lobe epilepsy</a>). </p><h4>Epidemiology </h4><p>Typically these tumours are diagnosed in children or young adults, as a result of the investigation of seizures, which have usually had childhood onset. Only a slight male predilection is present <sup>8</sup>. </p><h4>Clinical presentation</h4><p>Patients with DNETs typically present with longstanding treatment resistant partial seizures (in 90% of cases the first seizure occurred before the age of 20 <sup>8</sup>) without associated or progressive neurological deficit <sup>5</sup>. </p><h4>Pathology</h4><h5>Macroscopic appearance</h5><p>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 <sup>8</sup>. </p><h5>Microscopic appearance</h5><p>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 oriented at right angles to the overlying cortical surface. Between these columns are "floating neurones" as well as stellate astrocytes <sup>8</sup>.</p><p>Three histological forms are recognised <sup>5</sup>: </p><ol>
+<p><strong>Dysembryoplastic neuroepithelial tumours</strong> <strong>(DNET)</strong> are benign (WHO Grade I) slow growing glioneuronal tumours arising from either cortical or deep grey matter. The vast majority are centred in cortical grey matter, arise from <a href="/articles/secondary-germinal-layers">secondary germinal layers</a> and are frequently associated with <a href="/articles/focal-cortical-dysplasia">cortical dysplasia</a> (up to 80% of cases). They characteristically cause intractable partial seizures (see <a href="/articles/temporal-lobe-epilepsy">temporal lobe epilepsy</a>). </p><h4>Epidemiology </h4><p>Typically these tumours are diagnosed in children or young adults, as a result of the investigation of seizures, which have usually had childhood onset. Only a slight male predilection is present <sup>8</sup>. </p><h4>Clinical presentation</h4><p>Patients with DNETs typically present with longstanding treatment resistant partial seizures (in 90% of cases the first seizure occurred before the age of 20 <sup>8</sup>) without associated or progressive neurological deficit <sup>5</sup>. </p><h4>Pathology</h4><h5>Location</h5><p>DNETs are most often located in the temporal lobe although all parts of the CNS containing grey matter are potential locations. </p><ul>
+<li>
+<a href="/articles/temporal-lobe">temporal lobe</a>: over ~65% of cases <sup>8</sup>
+</li>
+<li>
+<a href="/articles/frontal-lobe">frontal lobe</a>: ~20% of cases</li>
+<li><a href="/articles/caudate-nucleus">caudate nucleus</a></li>
+<li>
+<a href="/articles/cerebellum">cerebellum</a>: presentation is then more commonly with ataxia rather than seizures</li>
+<li><a href="/articles/pons">pons</a></li>
+</ul><h5>Macroscopic appearance</h5><p>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 <sup>8</sup>. </p><h5>Microscopic appearance</h5><p>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 oriented at right angles to the overlying cortical surface. Between these columns are "floating neurones" as well as stellate astrocytes <sup>8</sup>.</p><p>Three histological forms are recognised <sup>5</sup>: </p><ol>
-</ol><p><a href="/articles/focal-cortical-dysplasia">Focal cortical dysplasia</a> is commonly seen in association with DNETs, and unless a component can be identified clearly separate from tumour cells, then it does not warrant a concurrent separate diagnosis. If, however, such a separate component is present, then it represents <a href="/articles/blumcke-classification-of-focal-cortical-dysplasia">Blumcke classification IIIb</a> focal cortical dysplasia) <sup>8</sup>. </p><h5>Immunophenotype</h5><p>The stellate <a href="/articles/astrocytes">astrocytes</a> within the SGNE are positive for <a href="/articles/glial-fibrillary-acid-protein-gfap">GFAP</a> <sup>8</sup>. </p><p>The oligodendrocyte-like cells are typically <a href="/articles/s100">S100</a> and <a href="/articles/olig2">OLIG2</a> positive, and may also express <a href="/articles/nogo-a">NOGO-A</a> and myelin-oligodendrocyte glycoprotein <sup>8</sup>. </p><p>The floating neurones are positive for <a href="/articles/neun">NeuN</a> <sup>8</sup>. </p><p>Importantly, DNETs are negative for <a href="/articles/isocitrate-dehydrogenase-idh">IDH</a> mutations, <a href="/articles/tp53">TP53</a> mutations, and do not demonstrate <a href="/articles/1p19q-codeletion">1p19q co-deletion</a> <sup>8</sup>. These features are helpful in distinguishing DNETs from <a href="/articles/low-grade-infiltrative-astrocytoma">low-grade</a><a href="/articles/low-grade-infiltrative-astrocytoma"> astrocytomas</a> (usually IDH mutated) and <a href="/articles/oligodendroglioma">oligodendrogliomas</a> (IDH mutated and 1p19q co-deleted). </p><h4>Radiographic features</h4><p>DNETs are typically predominantly cortical and well-circumscribed tumours.</p><h5>Location</h5><p>The temporal lobe is the most common location, but all parts of the CNS containing grey matter are potential locations. </p><ul>
~~-<li>~~
~~-<a href="/articles/temporal-lobe">temporal lobe</a>: over ~65% of cases <sup>8</sup>~~
~~-</li>~~
~~-<li>~~
~~-<a href="/articles/frontal-lobe">frontal lobe</a>: ~20% of cases</li>~~
~~-<li><a href="/articles/caudate-nucleus">caudate nucleus</a></li>~~
~~-<li>~~
~~-<a href="/articles/cerebellum">cerebellum</a>: presentation is then more commonly with ataxia rather than seizures</li>~~
~~-<li><a href="/articles/pons">pons</a></li>~~
-</ul><h5>CT</h5><p>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. </p><p>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 <sup>8</sup>. </p><h5>MRI</h5><p>Typically seen as a cortical lesion with hardly any surrounding vasogenic oedema. </p><ul>
+</ol><p><a href="/articles/focal-cortical-dysplasia">Focal cortical dysplasia</a> is commonly seen in association with DNETs, and unless a component can be identified clearly separate from tumour cells, then it does not warrant a concurrent separate diagnosis. If, however, such a separate component is present, then it represents <a href="/articles/blumcke-classification-of-focal-cortical-dysplasia">Blumcke classification IIIb</a> focal cortical dysplasia) <sup>8</sup>. </p><h5>Immunophenotype</h5><p>The stellate <a href="/articles/astrocytes">astrocytes</a> within the SGNE are positive for <a href="/articles/glial-fibrillary-acid-protein-gfap">GFAP</a> <sup>8</sup>. </p><p>The oligodendrocyte-like cells are typically <a href="/articles/s100">S100</a> and <a href="/articles/olig2">OLIG2</a> positive, and may also express <a href="/articles/nogo-a">NOGO-A</a> and myelin-oligodendrocyte glycoprotein <sup>8</sup>. </p><p>The floating neurones are positive for <a href="/articles/neun">NeuN</a> <sup>8</sup>. </p><p>Importantly, DNETs are negative for <a href="/articles/isocitrate-dehydrogenase-idh">IDH</a> mutations, <a href="/articles/tp53">TP53</a> mutations, and do not demonstrate <a href="/articles/1p19q-codeletion">1p19q co-deletion</a> <sup>8</sup>. These features are helpful in distinguishing DNETs from <a href="/articles/low-grade-infiltrative-astrocytoma">low-grade</a><a href="/articles/low-grade-infiltrative-astrocytoma"> astrocytomas</a> (usually IDH mutated) and <a href="/articles/oligodendroglioma">oligodendrogliomas</a> (IDH mutated and 1p19q co-deleted). </p><h4>Radiographic features</h4><p>DNETs are typically predominantly cortical and well-circumscribed tumours.</p><p> </p><h5>CT</h5><p>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. </p><p>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 <sup>8</sup>. </p><h5>MRI</h5><p>Typically seen as a cortical lesion with hardly any surrounding vasogenic oedema. </p><ul>

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