Figure 11-42 Retinoblastoma. A, Massive invasion of the globe posteriorly by retinoblastoma with bulbous enlargement of the optic nerve (arrow) caused by direct extension. B, A cross section of the optic nerve taken at the surgical margin of transection. Tumor (arrows) is present in the nerve at this point, and the prognosis is poor.

Figure 11-43 Retinoblastoma has invaded the optic nerve and extended to the margin of resection posterior to the lamina cribrosa (asterisk). This is an extremely poor prognostic sign.

Massive uveal invasion, in contrast, theoretically increases the risk of hematogenous dissemination. Spread to regional lymph nodes may be seen when a tumor involving the anterior segment grows into the conjunctival substantia propria, especially when the trabecular meshwork is involved.

Retinocytoma

Retinocytoma is characterized histologically by numerous fleurettes admixed with individual cells that demonstrate varying degrees of photoreceptor differentiation (Fig 11-44). Retinocytoma should be distinguished from the spontaneous regression of retinoblastoma that is the end result of coagulative necrosis. See the discussion in Chapter 19.

Figure 11-44 Retinocytoma. Note the exquisite degree of photoreceptor differentiation with apparent stubby inner segments

(arrow).

Also referred to as retinoma, retinocytoma differs from retinoblastoma in the following ways:

Retinocytoma cells have more cytoplasm and more evenly dispersed nuclear chromatin than do retinoblastoma cells. Mitoses are not observed in retinocytoma.

Although calcification may be identified in retinocytoma, necrosis is usually absent.

Medulloepithelioma

Also known as diktyoma, medulloepithelioma is a congenital neuroepithelial tumor arising from primitive medullary epithelium. This tumor usually occurs in the ciliary body but has also been documented in the retina and optic nerve. Clinically, medulloepithelioma may appear as a lightly pigmented or amelanotic, cystic mass in the ciliary body, with erosion into the anterior chamber and iris root (see Part II, Intraocular Tumors, Chapter 19, Fig 19-12). Although the tumor develops before the medullary epithelium shows substantial signs of differentiation, cells are organized into ribbonlike structures that have a distinct cellular polarity (Fig 11-45). These ribbonlike structures are composed of undifferentiated round to oval cells possessing little cytoplasm. Cell nuclei are stratified in 3 to 5 layers, and the entire structure is lined on one side by a thin basement membrane. One surface secretes a mucinous substance, rich in hyaluronic acid, that resembles primitive vitreous. Stratified sheets of cells are capable of forming mucinous cysts that are clinically characteristic. Homer Wright and Flexner-Wintersteiner rosettes can also be seen.

Figure 11-45 Medulloepithelioma. Histology shows a ciliary process (between arrows) surrounded by ribbons, cords, and small sheets of blue tumor cells with pockets of vitreous (asterisks) and occasional Flexner-Wintersteiner rosettes

(arrowhead). (Courtesy of George J. Harocopos, MD.)

Medulloepitheliomas that contain solid masses of neuroblastic cells indistinguishable from retinoblastoma are more difficult to classify. Medulloepitheliomas that have substantial numbers of undifferentiated cells with high mitotic rates and that demonstrate tissue invasion are considered malignant, although patients treated with enucleation have high survival rates, and “malignant” medulloepithelioma typically follows a relatively benign course if the tumor remains confined to the eye.

Heteroplastic tissue, such as cartilage or smooth muscle, may be found in medulloepitheliomas. Tumors composed of cells from 2 different embryonic germ layers are referred to as teratoid medulloepitheliomas. Malignant teratoid medulloepitheliomas demonstrate either solid areas of undifferentiated neuroblastic cells or sarcomatous transformation of heteroplastic elements.

Fuchs Adenoma

Fuchs adenoma, an acquired tumor of the nonpigmented epithelium of the ciliary body, may be

associated with sectoral cataract and may simulate other iris or ciliary body neoplasms. Fuchs adenomas consist of hyperplastic, nonpigmented ciliary epithelium arranged in sheets and tubules with alternating areas of PAS-positive basement membrane material.

Combined Hamartoma of the Retina and RPE

A combined hamartoma of the retina and RPE is characterized clinically by the presence of a slightly elevated, variably pigmented mass involving the RPE, peripapillary retina, optic nerve, and overlying vitreous (see Chapter 17, Fig 17-15). Frequently, a preretinal membrane is present that distorts the tumor’s inner retinal surface. The lesion is often diagnosed in childhood, supporting a probable hamartomatous origin, but it is possible that the vascular changes are primary, with secondary changes in the adjacent RPE.

The tumor is characterized by thickening of the optic nerve head and peripapillary retina, with an increased number of vessels. The RPE is hyperplastic and frequently migrates into a perivascular location. Vitreous condensation and fibroglial proliferation may be present on the surface of the tumor.

Adenomas and Adenocarcinomas of the RPE

Neoplasia of the RPE is uncommon and is distinguished from hyperplasia of the RPE principally by the absence of a history of, or pathologic features suggesting, prior trauma or eye disease. Adenomas of the RPE typically retain characteristics of RPE cells, including basement membranes, cell junctions, and microvilli. Adenocarcinomas are distinguished from adenomas by greater anaplasia, mitotic activity, and invasion of the choroid or retina. No metastases have ever been documented to occur in patients with RPE adenocarcinomas.

Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook. 4th ed. Philadelphia: Saunders; 1997:1291–1313.