Neurosurgery notes/Tumours/Gliomas, Glioneuronal Tumors, and Neuronal Tumors/Glioneuronal and neuronal tumours/Dysembryoplastic neuroepithelial tumour (DNET)

Dysembryoplastic neuroepithelial tumour (DNET)

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Glioneuronal and neuronal tumours

Definition

  • Essential:
    • Cortical glioneuronal tumour AND
    • Presence of the specific glioneuronal element AND
    • (For unresolved lesions)
      • FGFR1 gene alteration (FGFR1 internal tandem duplication [ITD], fusion, missense mutation) OR
      • Methylation profile of dysembryoplastic neuroepithelial tumour
  • Desirable:
    • Early-onset focal epilepsy

Grading

  • WHO Grade 1

Numbers

  • 0.8-5% of all primary brain tumors.
  • Second most common glioneuronal tumour variant encountered in clinical practice
  • 17.8% of the tumours in adults and 23.4% in children
  • Occurs in children and young adults.
  • Slightly more frequent in males
  • 90% of cases, the first seizure occurs before the age of 20 years

Origin

  • Arise embryological from the secondary germinal layer
    • Subependymal layer
    • Cerebellar external granular layer
    • Hippocampal dentate fascia
    • Subpial granular layer
  • Uncertain

Localisation

  • Temporal (mesial structures): 67.3%
  • Frontal lobes: 16.3%
  • Other locations: 16.4%
    • Caudate
    • Lateral ventricles
    • Septum pellucidum
    • Trigonoseptal region
    • Midbrain and tectum
    • Cerebellum
    • Brainstem

Clinical features

  • Intractable complex partial seizures
    • Degree of control depends on completeness of removal of tumour
  • DNT growing in eloquent cortical areas may lead to substantial functional reorganization, which can render them resectable despite their location

Radiological

CT

  • DNETs appear as low-density masses, usually with no or minimal enhancement.
  • When cortical, may scallop/remodel the inner table of the skull vault but without erosion (20-70%)
  • Calcification is visible in 30%

MRI

  • T1:
    • Generally hypointense compared with adjacent brain
  • T1 C+ (Gd)
    • May show enhancement in ~20-30% of cases
    • Enhancement may be heterogeneous or a mural nodule
  • T2
    • Generally high signal
    • High signal 'bubbly appearance' = Mucinous cells with bubbly (septation) T2WI
  • 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
Images
A close-up of a brain scan AI-generated content may be incorrect.
T1
A close-up of a brain scan AI-generated content may be incorrect.
T2
A close-up of a brain scan AI-generated content may be incorrect.
Flair

PET scan

  • Hypometabolic with [18F]-fluorodeoxyglucose.
  • Negative [11C]-methionine uptake (unlike all other gliomas).

Histopathology

Microscopic

  • Mixed glioneuronal neoplasm with a multinodular architecture and a heterogeneous cellular composition.
Fig. 6.05 Dysembnjoplastic neuroepithelial tumour. A Mucin-rich cortical nodule with columnar architecture. B The so-called specific glioneuronal element is characterized by oligodendrocyte-like cells embedded in a mucoid matrix with interspersed floating neurons.
Dysembryoplastic neuroepithelial tumour. A, Mucin-rich cortical nodule with columnar architecture. B, The so-called specific glioneuronal element is characterized by oligodendrocyte-like cells embedded in a mucoid matrix with interspersed floating neurons.
  • Specific glioneuronal element (SGNE):
      • Characteristic of DNET 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
      • Three histological forms are recognised:
        • Simple: SGNE only
        • Complex: SGNE, with glial nodules and a multinodular architecture
          • Due to the presence of astrocytic or oligodendrotic differentiation
          • Have very variable appearance
        • Nonspecific: same clinical and neuroimaging features as complex DNET, but... no SGNE
      A close-up of a microscope AI-generated content may be incorrect.
  • Focal cortical dysplasia:
    • Is commonly seen in association with DNETs
    • Should be diagnosed only in areas of cortical abnormalities without tumour cell infiltration and classified as focal cortical dysplasia Type lllb (Blumcke classification of focal cortical dysplasia)
  • Ki-67 proliferation index <8%

Immuno-phenotype

  • +
    • GFAP (present in scatter stellate astrocyte but absent in oligodendrocyte-like cells)
    • S100
    • OLIG2
    • NOGO-A
  • -
    • IDH mutations
    • TP53 mutations
Fig. 6.07 Dysembryoplastic neuroepithelial tumour. Floating neurons show immunoreactivity for synapto- physin, whereas small oligodendrocyte-like cells are immunonegative.
Dysembryoplastic neuroepithelial tumour. Floating neurons show immunoreactivity for synaptophysin, whereas small oligodendrocyte-like cells are immunonegative.

Genetic

  • Gains of whole chromosomes 5 and 7 were found in approximately 20% and 30% respectively
  • FGFR1 alterations 40-80%
    • Upregulate the МАРК and PI3K pathways
  • BRAF V600E mutation 50%
  • Not TP53 mutations, Co-deletion of whole chromosome arms 1p/19q, H3F3A K27M mutations
  • Can occur in NF1 or XYY syndrome

Management

  • Surgery
    • Complication rates low
  • There is no evidence to support radio- or chemotherapy for DNTs.
    • Adjuvant therapy has been associated with malignant transformation.

Prognosis

  • Epileptological results (Luyken et al., 2003)
    • Engel class I outcomes of approximately 80% even in cases with refractory epilepsy which remain stable over many years .
  • Risk factors for the development of recurrent seizures during long-term follow-up after operation
    • A longer preoperative history of seizures
    • Presence of residual tumour
      • Residue tumour can have malignant transformation (Thom et al., 2011).
        • It therefore seems wise to recommend serial imaging follow- up to DNT patients in particular in cases with residual tumour
    • Presence of cortical dysplasia adjacent to DNT
  • Malignant transformation is a rare event

Differential diagnosis

  • Vs low grade glioma
    • Glioma are deeper and has more significant mass and oedema
    • DNTs lack mutations in IDH1 or IDH2, GFAP (absent in oligodendrocyte-like cells of diffuse astrocytoma), MAP2
  • Vs gangliomas
    • Similar because
      • The dysplastic ganglion cells of gangliogliomas may not be present in small or non-representative samples,
      • These tumours may show a multinodular architecture,
      • Small gangliogliomas may show predominant cortical topography,
      • The clinical presentation of gangliogliomas is often similar to that of DNTs.
    • Differentiating factors
      • Ganglioglioma should be suspected when the tumour shows perivascular lymphocytic infiltration, a network of reticulin fibres, and/or a large cystic component, or when the tumour has prominent immunoreactivity for the class II epitope of CD34.
      • DNETs do not contain dysplastic ganglion cells such as those described in gangliogliomas (i.e. binucleated neurons, large neurons that are either pyramidal or similar to resident cortical neurons, and unequivocal clustering not otherwise explicable by anatomical region
  • Vs Pleiomorphic xanthoastrocytoma PXA
      • DNET
      PXA
      Arise embryological from the secondary germinal layer
      • Subependymal layer
      • Cerebellar external granular layer
      • Hippocampal dentate fascia
      • Subpial granular layer
      From subpial astrocyte → superficial with leptomeningeal involvement (67%)
      Frontal and temporal
      Temporal (50%)
      Bubbly (septations) on T2WI
      Mural nodule with cystic component (multiloculated or single cystic)
      67% have dural tail (leptomeningeal involvement)
      Isointense nodule and hyperintense cystic on T2WI
      Grade 1
      Mucinous cells
      Grade 2
      <20 yrs
      <20 yrs
      3% of all primary brain Ca
      1% of all astrocytomas