Neurosurgery notes/Tumours/Gliomas, Glioneuronal Tumors, and Neuronal Tumors/Glioneuronal and neuronal tumours/Diffuse leptomeningeal glioneuronal tumour (DLGNT)

Diffuse leptomeningeal glioneuronal tumour (DLGNT)

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Glioneuronal and neuronal tumours

General

  • Aka
    • Leptomeningeal oligodendro-gliomatosis
    • Disseminated oligodendroglial-like leptomeningeal tumour
    • Meningeal gliomatosis
    • Diffuse leptomeningeal oligodendrogliomatosis

Definition

  • Essential:
    • Oligodendroglioma-like morphology AND
    • OLIG2 and synaptophysin immunoreactivity AND
    • Chromosome arm 1p deletion AND
    • МАРК pathway alteration (mostly KIAA1549::BRAF fusion) AND (for unresolved lesions)
      • Methylation profile of diffuse leptomeningeal glioneuronal tumour
  • Desirable:
    • Childhood onset Leptomeningeal dissemination
  • Caveat:
    • This tumour type shows molecular overlap with pilocytic astrocytoma (KIAA1549::BRAF fusion) and oligodendroglioma (1 p/19q codeletion).
    • All diffuse leptomeningeal glioneuronal tumours are wildtype in IDH1 and IDH2.

Grade

  • No specific grading yet by WHO
  • Low grade mainly but have subset that have anaplastic features

Number

  • Children and teens> adults
    • Median age 5 yrs old
  • Males:females= 1.7:1

Clinical features

  • Rare seizures
  • Obstructive hydrocephalus, including headache, nausea, and vomiting. Opisthotonos and signs of meningeal or cranial nerve damage may be present.

Localisation

Intracranial leptomeninges

  • Basal cisterns
    • Posterior fossa
    • Around the brain stem
    • Along the base of the brain

Spinal leptomeninges

  • Spinal intramedullary lesions
  • Discrete intraparenchymal lesions were found in 81% of cases, most commonly in the cord

Origin

  • Unknown

Radiology

MRI

  • Nodular T2w hyperintense lesions located along the subpial surface of the brain and spinal cord may be present
  • The dominant finding is of thick nodular leptomeningeal enhancement particularly around the basal cisterns and extending over the surface of the brain and spinal cord.
  • Specific for diffuse leptomeningeal glioneuronal tumour
    • Presence of numerous small subpial cysts (high T2, low T1, FLAIR attenuating) located over the surface of the inferior parts of the cerebral hemispheres (temporal lobes, inferior frontal lobes), posterior fossa (cerebellum and brainstem) and spinal cord
      • It is thought that perhaps these represent dilatation of the perivascular spaces (Virchow-Robin spaces)
  • Importantly there is often no definitely dominant primary parenchymal mass identified. In many patients, however, discrete intraparenchymal lesions can be identified, most frequently in the spinal cord .
  • The neuroradiologist needs to be aware of this type given the similar radiological appearances to CNS infection or leptomeningeal carcinomatosis.
    • In fact, DLGNT has occasionally been misdiagnosed as tuberculosis when presenting intracranially
  • Can present as discrete parenchymal mass.
    • Therefore, diffuse or leptomeningeal growth is not necessarily present on imaging.
Image
(a) A T2-weighted axial MRI image showing marked dilation of lateral and third ventricles indicating nonobstructive hydrocephalus
(a) A T2-weighted axial MRI image showing marked dilation of lateral and third ventricles indicating nonobstructive hydrocephalus.
A close-up of a mri scan of a spine AI-generated content may be incorrect.
A 15-year-old girl presented with a 3-month history of back pain radiating to both legs.
T2w (A) shows a multi-septated cystic lesion expanding the lower thoracic cord and conus medullaris.
Small ovoid focus of less hyperintense T2w signal abnormality within the anteroinferior aspect of the lesion shows pathological enhancement on T1w-CE (B).
Intrinsic cord signal abnormality is seen extending above the level of the cystic lesion into the midthoracic cord
An x-ray of a spine AI-generated content may be incorrect.
(e) Multiple leptomeningeal enhancing nodules along the whole spinal cord in a sagittal, fat suppressed, enhanced Tl weighted image. Indentation of the spinal cord is shown in some leptomeningeal nodules
A close-up of a brain mri AI-generated content may be incorrect.
(b) A T I-weighted enhanced axial MRI image showing leptomeningeal enhancement (arrows) in the basal cisterns
 
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(d) Marked aggravation of leptomeningeal enhancement in the basal, interhemispheric, and left sylvian cisterns in an enhanced Tl -weighted axial MRI image in August 2017
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(c) Prominent leptomeningeal enhancement is noted in the basal, interhemispheric, and left sylvian cisterns in an enhanced Tl -weighted axial MRI image at the time of recurrent mental confusion (January 2017). No intra-axial enhancing lesion is observed

Histopathology

Macroscopic

  • Multifocal extension of tumour tissue along Virchow-Robin spaces and areas of limited brain invasion are common.
  • Tumour growth along peripheral nerve roots and infiltration of basal cranial nerves and ganglia may also be seen.

Microscopic

  • CSF
    • Elevated protein
    • Negative cytology
  • Intense desmoplastic fibrous response admixed with cells with perinuclear haloes and cytoplasmic swelling similar to oligodendroglial cells.
  • Ki-67:1.5%
    • If > 4% poor prognosis
      • Fig. 6.35 Diffuse leptomeningeal glioneuronal tumour. A Marked expansion and hypercellularity of the leptomeninges. B A small intraparenchymal component may be present, usually in the spinal cord. Infiltration of overlying leptomeninges by neoplastic cells (arrows) is typical. C Extensive leptomeningeal dissemination in spinal cord may result in intimate coating of nerve roots. D Cerebellar leptomeninges. Infiltration by bland oligodendroglial-like cells throughout the CNS is a key histological feature.
      Diffuse leptomeningeal glioneuronal tumour. A, Marked expansion and hypercellularity of the leptomeninges. B, A small intraparenchymal component may be present, usually in the spinal cord. Infiltration of overlying leptomeninges by neoplastic cells (arrows) is typical. C, Extensive leptomeningeal dissemination in spinal cord may result in intimate coating of nerve roots. D, Cerebellar leptomeninges. Infiltration by bland oligodendroglial-like cells throughout the CNS is a key histological feature.
      Fig. 6.36 Diffuse leptomeningeal glioneuronal tumour. A The tumour cells are GFAP-negative. B Tumour cells show extensive nuclear immunoreactivity for OLIG2. C Diffuse leptomeningeal glioneuronal tumourwith anaplastic features. The Ki-67 proliferation index is elevated, suggestive of a more aggressive clinical behaviour.
      Diffuse leptomeningeal glioneuronal tumour. A, The tumour cells are GFAP-negative. B, Tumour cells show extensive nuclear immunoreactivity for OLIG2. C, Diffuse leptomeningeal glioneuronal tumour with anaplastic features. The Ki-67 proliferation index is elevated, suggestive of a more aggressive clinical behaviour.
      Fig. 6.37 Diffuse leptomeningeal glioneuronal tumour. A Extension along the perivascular Virchow-Robin space is evident within the adjacent brain parenchyma of this tumour. B Synaptophysin positivity is seen in this tumour. C FISH studies using BRAF (red) and KIAA 1549 (green) probes show increased copy numbers and yellow fusion signals.
      Diffuse leptomeningeal glioneuronal tumour. A, Extension along the perivascular Virchow-Robin space is evident within the adjacent brain parenchyma of this tumour. B, Synaptophysin positivity is seen in this tumour. C, FISH studies using BRAF (red) and KIAA1549 (green) probes show increased copy numbers and yellow fusion signals.

Immunophenotype

  • Oligodendroglia-like tumour cells
    • +: KIAA1549-BRAF fusion, OLIG2, S100, MAP2,
    • Variable: GFAP and synaptophysin
    • -: IDH mutation

Genetic profile

  • KIAA1549- BRAF gene fusions
    • 75% of cases
  • Solitary 1p deletion
    • 59%
  • 1p/19q codeletion
    • 18%
  • No BRAF V600E mutation or IDH mutations

Prognosis

  • Poor prognosis
    • High Ki67 Index >4%,
    • Glomeruloid microvascular proliferation
  • Slow progression
    • 33% live for more than 10 yrs

Differential diagnosis

  • Intraparenchymal diffuse astrocytic or Oligodendroglioma
    • Similarities
      • Positive for 1p/19q co-deletion for oligodendroglioma
    • Differentiating factor
      • Diffuse leptomeningeal glioneuronal tumour has no IDH mutations
      • Presence of KIAA1549-BRAFfusion
  • Leptomeningeal carcinomatosis
  • Leptomeningeal seeding from another primary CNS tumour
  • Tuberculous leptomeningitis
  • Pleomorphic xanthoastrocytomas
    • PXA: pleomorphic histology and presence of BRAF V600E mutation