GLIONEURONAL MALFORMATIVE LESIONS AND DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMORS IN PATIENTS WITH CHRONIC PHARMACORESISTANT EPILEPSIES

Malformative glioneuronal lesions were examined in surgical specimens from 43 patients with chronic focal epilepsies in order to determine t he scope of histopathological changes and to better understand their p athogenesis. The most common lesions were hamartias composed of random ly oriented neurons and astrocytes (24 cases). Most of these lesions a lso contained clustered oligodendrocyte-like cells which were often st rongly immunoreactive for the developmentally regulated embryonal form of the neural cell adhesion molecule (E-NCAM). These hamartias were t ypically minute, multifocal, and arranged in a pattern suggestive of a migration disorder. There were eight cases with aggregates of large d isfigured neurons, oversized atypical astrocytes and ballooned multinu cleated giant cells reminiscent of tuberous sclerosis-associated chang es. Finally, there were 11 dysembryoplastic neuroepithelial tumors (DN T), an entity which has been proposed to be malformative rather than n eoplastic. The oligodendroglia-like cells in DNT were negative for E-N CAM. However, strong E-NCAM expression was present in many dysplastic neurons of tuberous sclerosis-like lesions, hamartias and DNT and in r eactive astrocytes. Significant immunoreactivity for the proliferation associated Ki-67 antigen was not observed. No similar lesions were ob served in 500 consecutive autopsies from patients without epilepsy. Ma lformative glioneuronal lesions appear to be highly epileptogenic and most likely result from a disordered cell migration and differentiatio n.