Glial clusters and perineuronal glial satellitosis in the basal ganglia of neurofibromatosis type 1.

Recent biochemical studies demonstrated that astrocytic differentiation and growth regulation are impaired in neurofibromatosis type 1 (NF1). However, non-neoplastic morphological abnormalities of glial cells in the NF1 brain have been hardly explored. We describe here characteristic glial lesions in the basal ganglia in three NF1 cases (age at death in cases 1-3: 77, 6.5, and 11 years). Clusters of 3-10 dysplastic cells similar to reactive astrocytes were observed in the amygdala, caudate nucleus, putamen, thalamus in cases 1 and 2. Gigantic astrocyte-like glial cells were noted in case 2. Perineuronal glial satellitosis was observed in the amygdala in case 1. Many glial clusters were encountered in case 3 as well, but the round nuclei of the glial cells were more hyperchromatic and showed more remarkable variation in size than those in the other cases. Glial clusters in all cases were glial fibrillary acidic protein- and/or vimentin-positive, but synaptophysin-, myelin basic protein-, and olig2-negative. The glial lesions in cases 1 and 3 were excitatory amino acid transporters 1 (EAAT1)- and EAAT2-negative, and those in case 2 EAAT1- and EAAT2-weakly positive. Proliferation markers Ki-67, proliferation cell nuclear antigen, and cyclin D1 were not expressed in any lesion. Glial clusters in case 3 showed weak to intense immunoreactivity to nestin, a stem cell marker protein. The brains of 19 cases including 14 with various degenerative diseases and five normal brains used as controls lacked the glial lesions observed in NF1 cases. Given these findings, glial clusters and perineuronal glial satellitosis may be histopathological features of the NF1 brain and are probably associated with altered regulation of astrocyte growth in NF1.