One Hundred and One Dysembryoplastic Neuroepithelial Tumors: An Adult Epilepsy Series With Immunohistochemical, Molecular Genetic, and Clinical Correlations and a Review of the Literature

Abstract

Simple and complex forms of dysembryoplastic neuroepithelial tumors (DNTs) are readily recognizable but forms with diffuse growth pattern, and hybrid tumors, that is, mixed DNT and ganglioglioma (DNT/GG), are more contentious entities. Rare DNTs have shown aggressive behavior. We reviewed cortical growth patterns, immunophenotype (including CD34, nestin and calbindin), genetic profile, and outcome in 101 DNT in adults. Simple (n = 18), complex (n = 31), diffuse (n = 35) DNT, and mixed DNT/GG (n = 17) showed no difference in age of onset, associated seizure type, or outcome (67.5% free from seizure; mean follow-up, 6 years). CD34 was seen in 61%, calbindin in 57%, and nestin in 86% of all DNT types; these markers were less common in simple DNT. Peritumoral cortical changes (Layer I hypercellularity [61%], satellite nodules [51.6%]) were frequent, but dyslamination (cortical dysplasia) was not identified. Molecular genetic abnormalities identified in 17 cases were IDH1 mutation (n = 3), 1p/19q loss (n = 10), isolated loss 9q (n = 2), and PTEN loss (n = 3), which were not associated with tumor type or location, higher cell proliferation, or distinguishing clinical features (mean age of epilepsy onset, 9 years; age at surgery = 31 years; 69% free from seizure); none had progression on magnetic resonance imaging (mean follow-up, 6 years). No single feature was predictive of seizure-free outcome, but there was a trend for better outcome in CD34-positive tumors (p = 0.07). One case has shown transformation to a higher grade. This study supports the existence of a range of subtypes of DNT some with overlapping features with ganglioglioma; molecular genetic abnormalities were not predictive of atypical behavior.

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

“…They often display an intracortical, nodular growth pattern, and a specific feature of these tumors is the presence of the glioneuronal element, characterized by a typical cortical growth pattern of microcolumns of oligodendrocyte-like cells arranged along axons and vessels and separated by a myxoid matrix that contains floating neurones. Additional histopathological features, including calcifications and dysmyelination, or rarefaction of the peritumoral white matter, have been reported [14]. DNT are slowly growing WHO grade I tumors with a chance of malignant transformation of <1 % [8].…”

Dysembryoplastic neuroepithelial tumour: insight into the pathology and pathogenesis

“…Co-expression of MAP2 and CD34 was significantly more frequent in the non-specific than in complex and simple form [62]. However, the difference in MAP2 expression among different types of DNT has not been confirmed [65].…”

“…Statistically significant differences of immunohistochemical staining for CD34 among three main histological types of DNT were observed in two studies. The highest expression of CD34 was noticed for the non-specific type compared with simple and complex types [62,65]. Expression of CD34 and nestin was found to be the highest in the non-specific and diffuse form, but there was a difference in expression of these markers in the simple type [61,62].…”

“…Expression of CD34 and nestin was found to be the highest in the non-specific and diffuse form, but there was a difference in expression of these markers in the simple type [61,62]. However, Thom et al [65] observed a statistically significant correlation between CD34 and nestin staining in particular forms. Nestin is expressed during development of the central nervous system and in the majority of proliferating brain progenitor cells, thus it is considered as a neural stem cell marker [40].…”

“…It is difficult to distinguish this DNT variant from other glial tumours. The non-specific and diffuse form of DNT might be histologically similar to glioma, ganglioglioma, pilocytic astrocytoma or diffuse astrocytoma [61,65]. Nevertheless, the clinical presentation with chronic seizures, cortical localization on neuroimaging and a follow-up are similar to typical DNT.…”