Retinal glioneuronal hamartoma in neurofibromatosis type 1.

Abstract

Report of a Case. Our patient was born at term with buphthalmos and proptosis of her right eye, accompanied by corneal clouding and increased tearing. She was subsequently noted to have right sphenoid wing dysplasia, multiple cutaneous plexiform neuromas of the right eyelids and face (fifth nerve distribution), right hemispheric dysplastic polymicrogyria, and a seizure disorder. She was diagnosed as having NF1. The left eye was within normal limits. The patient received a Baerveldt glaucoma drainage implant at age 5.5 months. At age 8 months, a dilated fundus examination revealed temporal retinal whitening and posterior retinal hemorrhages, which were initially attributed to a retinal vein occlusion. Four months later, the patient was diagnosed clinically as having a CHRRPE (Figure 1). Enlargement of the retinal tumor was noted over the following 8 months, accompanied by the development of a vitreous hemorrhage, tractional retinal detachment, and proliferative vitreoretinopathy. At age 20 months, the right eye was enucleated owing to it being blind and painful with a fixed pupil and corneal haze. Postoperatively, she was more comfortable, no longer photophobic, and without tearing. Gross pathologic examination revealed a buphthalmic eye with a Baerveldt glaucoma drainage implant on the superonasal sclera. On oblique sectioning, the cornea was clear but thinned. The anterior chamber was filled with a tan, milky fluid. The pupil was widely dilated and the iridocorneal angle was closed by peripheral anterior synechiae. The lens and uveal tract were unremarkable. There was a funnel-shaped retinal detachment. Microscopic examination revealed an absent Bowman layer, which was replaced by an area of thin cellular fibrosis. A membrane composed of corneal endothelial cells was present over the surface of the severely contracted iris and ciliary body. The lens showed cataract formation with anterior calcific degeneration and posterior migration of the lens epithelium. The uvea was thickened by a diffuse neurofibroma typical for eyes involved with NF1. The predominant spindle cells within the neurofibroma reacted positively with S-100 protein and microtubule-associated protein 2 but were negative for glial fibrillary acidic protein, CD56 (neural cell adhesion molecule—a marker of neurons, astrocytes, and nonmyelinating Schwann cells), neurofilament, and Ki-67. Scattered clusters of larger neuronal cells with comparatively more abundant cytoplasm and large round nuclei with prominent nucleoli were also present and were positive for synaptophysin, microtubuleassociated protein 2, and neurofilament (Figure 2). The detached retina was displaced anteriorly and centrally by a fibrovascular proliferation in the vitreous. A retinal tumor replaced a broad area of the inner retina