Neuronal and mixed glioneuronal
tumors traditionally have comprised a very small percentage of intrinsic
central nervous system neoplasms, although they are somewhat more common among juvenile
brain tumors and in the temporal lobe. Neuronal differentiation increasingly is recognized in
pleomorphic xanthoastrocytoma, intraventricular
neurocytoma, and
subependymal giant cell astrocytoma. However, the diagnostic distinctions between subtle
ganglioglioma (with rare neurons) and infiltrating
glioma with entrapped neurons and between infiltrating
oligodendroglioma and parenchymal
neurocytoma are problematic but may be clinically important. Recently, it was proposed that perisomatic
synaptophysin immunostaining in the human central nervous system reliably and selectively discriminates neoplastic from nonneoplastic neurons. Using this criterion, the number of brain stem and spinal cord
gangliogliomas could be increased substantially. We canvassed
synaptophysin immunostaining patterns in the normal brain stem, cerebellum, and forebrain, and found that
synaptophysin-positive neurons are distributed broadly in the normal human brain. In disturbed neocortical tissue, such as near
vascular malformations,
synaptophysin-positive neurons and irregular white-matter
synaptophysin immunostaining are visualized. Although
synaptophysin-positive neurons are found in
gangliogliomas and archipelagos of
synaptophysin reactivity are found in
neurocytomas, these patterns clearly are not pathognomonic for glioneuronal
tumors and must be interpreted with caution whenever other histologic or ultrastructural evidence of neuronal differentiation is lacking.