The most important congenital tumor of the NPCE is medulloepithelioma, a nonhereditary, embryonal neoplasm generally diagnosed in the first decade of life (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29). On occasion, the tumor is not recognized until adulthood (13,14,20). It arises from the medullary epithelium, or inner layer of the optic cup, prior to its differentiation into its adult derivatives. It most commonly occurs in the ciliary body, where it presumably arises from the anterior lip of the optic cup. However, medulloepithelioma has occasionally been recognized in the optic nerve (21, 22, 23, 24).

An early clinical feature is a “lens coloboma,” which is actually a notch in the lens due to congenital absence of zonule in the quadrant of the tumor. Examination of the adjacent ciliary body reveals a rather typical fleshy, pink to tan mass. Clear cysts are often present within the mass. The cysts may become a prominent part of the tumor and may even break free from the mass to float freely in the anterior chamber or vitreous cavity (3,4,27). Rarely, a medulloepithelioma may be pigmented (15,25,26).

A characteristic neoplastic cyclitic membrane can develop, sometimes suggesting the diagnosis of persistent hyperplastic primary vitreous (4,8). Secondary glaucoma occurs in 60% of cases and is most often due to iris neovascularization and secondary angle closure (4,17). Retinal detachment is a common complication. There is often a long delay in diagnosis and sometimes misdirected therapy. Patients have often undergone cataract surgery, glaucoma surgery, and vitreous surgery while the underlying tumor remained unsuspected.

Extraocular extension with orbital invasion is an uncommon complication of medulloepithelioma (3,4,10,13). Central nervous system extension has rarely been recognized. It can be fatal due to progressive intracranial growth of the neoplasm (13,27). Tumors that demonstrate extraocular extension, a very rare occurrence, can metastasize to regional lymph nodes and systemic sites.

Medulloepithelioma of the optic nerve generally presents with visual loss and an elevated amelanotic mass in the posterior pole, obscuring a view of the optic disc. In that location, the tumor can show slow growth and cause secondary exudation or retinal detachment. (21, 22, 23, 24).

Fluorescein angiography shows early hyperfluorescence and gradual late staining of the mass. Ultrasonography reveals a mass pattern with acoustic solidity and high internal reflectivity (1,6). Areas of cartilage within the mass can produce echoes very similar to those with dystrophic calcification seen with retinoblastoma (7).

Medulloepithelioma can be classified histopathologically into nonteratoid and teratoid types, and both can be cytologically benign or malignant. In our experience more than 80% of intraocular medulloepitheliomas are cytologically malignant. The nonteratoid type consists purely of cells that resemble ciliary epithelium and is sometimes called a diktyoma, derived from the Greek word meaning “fish net.” The teratoid type demonstrates heteroplastic elements such as cartilage, rhabdomyoblasts, and brain. Cysts found in both types contain a hyaluronidase-sensitive mucopolysaccharide, identical to vitreous, that is secreted by the tumor cells, forming secondary cysts (1, 2, 3, 4). Recurrent medulloepithelioma tends to have more malignant histopathologic features (10). Melanin granules are occasionally present in the cytoplasm, which explains why some tumors are clinically pigmented (15,25,26). Eyes with medulloepithelioma are often found to have degrees of persistence of the hyaloid system, another developmental abnormality (3,4).

Although most eyes with medulloepithelioma require enucleation, a small, circumscribed medulloepithelioma can be managed by iridocyclectomy. Plaque radiotherapy is an option for localized or recurrent tumor, but its role has not been clearly defined (4,14). Because deaths have occurred only in patients with advanced extrascleral extension, orbital exenteration should be considered if there is extensive orbital involvement. The role of irradiation and chemotherapy for intraocular medulloepithelioma is not established.