Cerebellar Dysplasias in Humans: Development and Possible Relationship to Glial and Primitive Neuroectodermal Tumors of the Cerebellar Vermis

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Abstract

Cerebellar dysplasias are commonly found in the white matter and nodulus of the vermis in newborns and are particularly prominent in infants with trisomy 13-15 and trisomy 18 syndromes. Little is known of the developmental biology of these structures. We have studied the development of cerebellar dysplasias in human fetuses ranging from 15 to 32 weeks gestational age and from 11 days to 15 months postnatal. The expression of developmentally regulated neuronal and glial polypeptides was investigated by immunohistochemistry using a panel of extensively characterized monoclonal antibodies. Dysplasias were first observed at 15 weeks gestation as irregularly distributed, parenchymal or perivascular clusters of primitive cells in the inferior vermis. These cell clusters resembled primitive neuroepithelial cells or cells of the cerebellar external granule cell layer and they persisted into postnatal life. They retained the capacity to undergo cell division and were weakly reactive for the low affinity nerve growth factor receptor but were negative for all other neuronal or glial proteins at all gestational ages. At about 20 weeks gestation, cerebellar dysplasias become more complex with the appearance of ganglion cells which matured histologically and phenotypically in parallel with normal dentate neurons and Purkinje cells. These dysplasias often contained a prominent glial component which was identified by immunostaining for glial fibrillary acidic protein. Our findings suggest that midline cerebellar dysplasias are normal variants of development. Whether the mitotically active cells comprising these dysplasias are targets for neoplastic transformation into cerebellar primitive neuroectodermal tumors or other types of childhood tumors such as pilocytic astrocytomas or atypical teratoid/rhabdoid tumors remains speculative.

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