gms | German Medical Science

Questions: Human focal epilepsies present with a broad histopathological spectrum difficult to classify. This applies in particular to glio-neuronal tumors and focal cortical malformations. Most epilepsy-associated lesions occur, however, in the temporal lobe, involve cortical architecture and are non-proliferative. Here, we describe a novel diagnostic entity affecting the white matter (in the frontal lobe), and which shares features of both, malformations and tumors.

Methods: We reviewed the clinico-pathological data base of the European Epilepsy Brain Bank and identified ten patients with increased cellularity within the white matter. All patients suffered from drug-resistant focal epilepsy and underwent surgical treatment. Available clinical data, MR-imaging and post-surgical follow-ups (1–8 years) were collected and compared with histomorphological and immunohistochemical analysis. Histological parameters were quantitatively measured with particular emphasis on Olig-2 immunoreactive oligodendroglial densities in white matter and subgranular cortical layers. We also quantified cellular proliferation using Ki67-labeling indices. Double immunofluorescence experiments were applied to characterize cellular lineages of proliferating cells. The results were compared to other age-/localization matched epilepsy-associated lesions as well as autopsy controls (n=30).

Results: Preclinical monitoring suggested focal cortical dysplasia in all patients. The lesion was located in the frontal lobe in eight cases, and two specimens were obtained from the temporal lobe. Histopathological examinations did not reveal any gross architectural abnormalities of the cortical ribbon, but increased (and sometimes patchy) oligodendroglial cell numbers were visible in white matter, extending into adjacent subgranular cortical layers (prominent neuronal satellitosis). Glial cell numbers as well as proliferation was significantly increased compared to any other epilepsy-associated lesion used as control. There was no histopathological evidence for tumor infiltration (p53, IDH1) nor inflammation (CD68, CD45). In three patients, double-immunofluorescence stainings confirmed an oligodendroglial lineage of 80-100% of proliferating cells (Olig2). In seven cases, Olig-2 positive cells were proliferative in 20–46%. We were not able to identify the lineage of Olig2-negative proliferative cells in these patients (yet non-neuronal, non-astroglial, non-inflammatory).

Conclusions: Herein, we described a novel diagnostic entity and propose the term “Proliferative Oligodendroglial Hyperplasia in Epilepsy (POGHE)”. Histopathological analyses and available long-term follow-up in our patients virtually exclude a neoplastic nature. We suggest, therefore, to classify this intriguing lesion into the spectrum of Malformations of Cortical Development (MCD). Notwithstanding, the epileptogenic potential of POGHE is difficult to clarify, but may relate to the involvement of subgranular cortical areas.

The two first authors contributed equally to this work.