Dysembryoplastic Neuroepithelial Tumor

Definition

Clinical Features

• Unusual
• Pharmacoresistant partial seizures
• Young:
  • exceptionally >20 years of age1–4

Pathogenesis

• Evidence for origin from secondary germinal layer during embryogenesis is:
  • superficial localization
  • often cortical dysplasia
  • young age at presentation1

Gross Pathology

• Most supratentorial and cerebral, particularly temporal lobes:
  • similar lesions recorded in:
    • septum pellucidum5
    • caudate nucleus6
    • brainstem and cerebellum7
• May be multifocal8

Histopathology

• ‘Specific glioneuronal element’:
  • common to both ‘simple’ and ‘complex’ histologic variants1–4
  • required for morphologic diagnosis
  • characteristically multinodular proliferation of oligodendrocyte-like cells (OLCs) that:
    • appear to be arranged along bundled axons and ramifying capillaries (often perpendicular to cortical surface)
    • are separated by a myxoid matrix in which well-differentiated neurons seem to float (Fig. 1
      

      Fig. 1: Dysembryoplastic neuroepithelial tumor. Extensive myxoid change and disposition of small, oligodendrocyte-like cells along axonal fiber bundles and capillaries lend an alveolar or ‘patterned’ appearance to the specific glioneuronal element of this distinctive lesion. Not shown here, mature neurons often appear to float in the mucoid matrix.

      )
  • mitoses absent or exceedingly rare
  • MIB-1 labeling indices usually <1–2%
  • readily seen on low power examination
  • frequently background architectural disorganization (dysplasia) of cortex
  • OLCs can also be disposed about:
    • myxoid microcysts in alveolar fashion or
    • a fine fibrillar meshwork in cribriform rosetted array
  • simple variants:
    • may contain stellate GFAP-immunoreactive astrocytes
  • complex variants:
    • harbor additional glial components that may be indistinguishable from conventional oligodendroglioma, pilocytic or fibrillary astrocytoma:
      • micronodular or more diffuse arrangement
      • can show considerable cytologic atypism
      • sometimes:
        • low level mitotic activity
        • microvascular proliferation
      • rarely necrosis1
• May be anomalous hamartomatous vasculature
• Curiosities include examples:
  • admixed with ganglioglioma9
  • a lesion interpreted as melanotic DNT variant10
• Ultrastructurally OLCs show:
  • dense core granules
  • axo-somatic synapses11

Special Stains and Immunohistochemistry

• OLCs:
  • usually S-100 protein positive
  • GFAP negative
  • may be immunoreactive for myelin oligodendrocyte glycoprotein12
  • subsets label for neuron-associated antigens such as:
    • NeuN
    • N-methyl-d-aspartate receptor subunit NR113

Diagnosis

• Controversial ‘nonspecific’ DNTs:
  • clinically benign and nonrecurring after simple removal
  • may assume guises of oligodendroglioma, oligoastrocytoma, pilocytic or fibrillary (including high-grade) astrocytoma in unalloyed form14 and do not show:
    • specific glioneuronal element
    • multinodular growth pattern
  • criteria for identification are:
    • association with partial seizures (with or without secondary generalization) beginning <20 years of age
    • absence of associated neurologic deficits or presence of a nonprogressive congenital deficit only
    • supratentorial localization and cortical topography on CT/MRI
    • absence of associated edema or mass effect other than that related to cystic components

Other Investigations

• Neuroradiology:
  • tend to lie largely if not entirely within expanded cortical ribbon (Fig. 2
    

    Fig. 2: Dysembryoplastic neuroepithelial tumor. A gyriform focus of increased signal attests to the largely cortical localization of this superficial lesion, seen in a FLAIR MR sequence. Also characteristic is the absence of mass effect or white matter changes indicative of edema.

    )
  • multinodular bright signal qualities in T2-weighted MRIs
  • remodeling of adjacent calvarium:
    • attests to indolent expansion
  • typically:
    • T1 hypointense
    • devoid of mass effect or associated edema
  • minority show discrete foci of nodular or ring enhancement

Differential Diagnosis

• Conventional glial neoplasms (particularly oligodendrogliomas):
  • differentiated by neuroradiology
  • oligodendrogliomas :
    • typically do not label for NeuN13
    • may contain trapped NeuN-positive neurons of small size that complicate segregation by immunohistochemical means alone
    • commonly chromosome 1p deletion15

Management

• Simple excision:
  • usually curative
• Subtotal resection:
  • examples usually stable on neuroradiologic surveillance1–4

Prognosis

• Comparably favorable outcome following complete surgical extirpation of complex variants showing mitotic activity, microvascular proliferation or necrosis:1
  • few lesions recorded so judgment must be reserved
• Rarely act as substrate for aggressive bona fide glioma16