TUBER AND SUBEPENDYMAL GIANT-CELL ASTROCYTOMA ASSOCIATED WITH TUBEROUS SCLEROSIS - AN IMMUNOHISTOCHEMICAL, ULTRASTRUCTURAL, AND IMMUNOELECTRON MICROSCOPIC STUDY

The cellular nature of the giant eosinophilic cells of tuber and of th e cells comprising subependymal giant cell astrocytoma (SEGA) in tuber ous sclerosis (TS) remains unclear. To assess the characteristics of t hese lesions, 13 tubers and 6 SEGA were immunohistochemically studied with glial and neuron-associated antigens. In addition to conventional ultrastructure, 6 tubers and 8 SEGA were subjected to immunoelectron microscopic study for glial fibrillary acidic protein (GFAP) and somat ostatin. Eosinophilic giant cells of tubers were positive for vimentin (100%), GFAP (77%) and S-100 protein (92%); such cells were also foun d to a various extent to be reactive for neuron-associated antigens, i ncluding neurofilament (NF) proteins (38%) or class III beta-tubulin ( 77%). SEGA also showed variable immunoreactivity for GFAP (50%) or for S-100 protein (100%); NF epitopes, class III beta-tubulin, and calbin din 28-kD were expressed in 2 (33%), 5 (83%) and 4 (67%) cases, respec tively. Cytoplasmic staining for somatostatin (50%), met-enkephalin (5 0%), 5-hydroxytryptamine (33%), beta-endorphin (33%) and neuropeptide Y (17%) was noted in SEGA, but not in tubers. Ultrastructurally, the g iant cells of tubers and the cells of SEGA contained numerous intermed iate filaments, frequent lysosomes and occasional rectangular or rhomb oid membrane-bound crystalloids exhibiting lamellar periodicity and st ructural transition to lysosomes. Some SEGA cells showed features sugg estive of neuronal differentiation, including stacks of rough endoplas mic reticulum, occasional microtubules and a few dense-core granules. Furthermore, in one case of tuber, a process of a single large cell wa s seen to be engaged in synapse formation. Intermediate filaments with in a few cells of both lesions were decorated by gold particle-labeled GFAP antiserum. Within the tumor cells of SEGA, irregular, non-membra ne-bound, electron-lucent areas often contained somatostatin-immuno re active particles, whereas the latter could not be detected in tuber. T he present study provides further evidence of divergent glioneuronal d ifferentiation, both in the giant cells of tubers and the cells of SEG A. The findings of similar cells at different sites, including the sub ependymal zone, white matter (''heterotopias''), and cortex indirectly supports the idea that these lesions of TS result from a migration ab normality.