Pathology of Supratentorial Dysembryoplastic Neuroepithelial Tumors in Children

Pathophysiology

  • Intracortical tumors: DNETs are intracortically localized tumors, with a relatively sharp margin between tumor and adjacent brain.  Most authors consider DNETs as neoplastic tumors, since recurrences and malignant transformation are possible.
  • Epileptogenesis: The epileptogenesis in DNET is complex. Several authors have demonstrated that there may be epileptic foci inside the tumor itself, in the adjacent region of cortical dysplasia, and also in the surrounding normal brain tissue (2, 10). Using (11C)flumazenil PET scan, Richardson et al. (33) demonstrated low levels of benzodiazepine-GABA receptor binding within DNETs, probably contributing to epileptogenesis.
  • Nonspecific form?: In 1999, Daumas-Duport et al. (12) described a nonspecific form of DNET in patients with long-standing epilepsy. These nonspecific DNETs do not contain glioneuronal elements but are cortical and subcortical. The distinction between these tumors and low-grade gliomas is controversial.

Molecular/Genetic Pathology

  • IDH1 negative:  Capper et al. (7) reported that all cases of DNET were negative for the isocitrate dehydrogenase 1 (IDH1) mutations frequently found in astrocytomas, oligoastrocytomas, and oligodendrogliomas. This finding may allow a better differential diagnosis, especially with regard to oligodendrogliomas. Similarly, Kuhlmann et al. (42) found no expression of the oligodendroglial marker Nogo-a in two cases of DNET, while this marker is positive in 71% of oligodendrogliomas.
  • Apoptotic proteins and dysplasia: Chamberlain and Prayson examined apoptotic proteins (bcl-XL, bax, bcl-2, and p53) in a number of brain disorders. In focal cortical dysplasia, as in gangliogliomas and DNETs (both dysplasia-associated neoplasms), they demonstrated aberrant expression of these markers, suggesting a possible common mechanism of development for these two coexistent diseases (8, 26).

Histopathology

  • Grade I histologically: The W.H.O. classification puts DNETs in the category of glioneuronal tumors, grade I. ‘Simple’ DNETs are composed of exclusively these glioneuronal elements, while the ‘complex’ DNETs also contain additional glial nodules and foci of cortical dysplasia (6, 11, 13, 16).
  • Histology: The glioneuronal elements consist of floating neurons and oligodendrocyte-like cells attached to the axons of neurons, in a myxoid interstitial fluid. The myxoid matrix in most cases forms multiple pseudocysts (without epithelial lining) of different dimensions, from microcysts to large peripheral cysts. A columnar organization may be apparent. Contrary to gangliogliomas, there are no abnormal dysplastic neurons. Histologically, mitotic activity can be demonstrated with Ki67 labeling.

H&E stain of a DNET: This low-power view demonstrates the intracortical location of the tumor

H&E stain of a DNET: At higher power, the myxoid clear areas can be seen, as well as some floating neurons (e.g. central in the image). Courtesy of R. Sciot, MD, PhD, Department of Neuropathology, K.U.Leuven, Belgium