Immunohistochemical demonstration of neuronal and astrocytic differentiation in retinoblastoma

Sections of 51 surgically enucleated eyes from cases of retinoblastomas were examined immunohistochemically to delineate patterns of cellular differentiation. Employing the avidin-biotin immunoperoxidase technique, antibodies were used against glial fibrillary acidic protein (GFAP), S-100 protein and neuron specific enolase (NSE). Areas of uninvolved retina and/or optic nerve were used as built-in positive control. Most of the tumors showed GFAP and S-100 protein-positive perivascular glial cells that were interpreted as reactive astrocytes. In three well-differentiated retinoblastomas, glial cells were found to be interspersed randomly among tumor cells and not associated with blood vessels. These glial cells were interpreted as neoplastic based on their distribution pattern and cytologic features. In about half of the tumors, the retinoblastoma cells stained positively for NSE, indicating their neuronal tumor cells that stained positively for NSE but failed to show any evidence of photoreceptor differentiation. Based on these observations and similar differentiation patterns described in other primitive neuroectodermal tumors of the brain, it is suggested that retinoblastoma cells can differentiate not only into photoreceptor cells but also along other neuronal cell lines and rarely into glial cells.