Retinoblastoma is the most common intraocular malignancy of childhood, occurring in about 1 in 15,000 live births. Numerous articles have been published about this important neoplasm, only a few of which are cited here (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, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42). Unlike uveal melanoma, it has no predilection for gender or race. It can be unilateral or bilateral, with the bilateral cases invariably representing germinal mutations. The overall mean age at diagnosis is 18 months. For unilateral cases, it is 24 months, and for bilateral cases, 12 months. However, it can be present at birth or have its onset in the teenage years or adulthood (7, 8, 9).

The familial form of retinoblastoma has been associated with a deletion of the long arm of chromosome 13 (4, 5, 6). Affected patients are usually systemically normal but can sometimes have overt clinical signs of the 13q- syndrome.

Patients with the genetic mutation for retinoblastoma have a predisposition to a number of second tumors, particularly sarcomas, with osteosarcoma of long bones being the most frequent (10, 11, 12, 13, 14, 15, 16). The familial form of retinoblastoma is also associated with a higher incidence of pinealoblastoma and other parasellar tumors, neoplasms that are very similar to retinoblastoma from embryologic, anatomic, and immunologic standpoints (17, 18, 19, 20, 21, 22, 23). The association of bilateral retinoblastoma with pinealoblastoma has been termed trilateral retinoblastoma. This term can be inaccurate, in that some patients with the gene deletion and pinealoblastoma have unilateral retinoblastoma or no retinoblastoma.

Clinically, retinoblastoma begins as a small, transparent lesion in the sensory retina that may be easily overlooked with ophthalmoscopy. As the tumor enlarges, it becomes opaque white and develops a dilated retinal feeding artery and draining vein, and a secondary retinal detachment can occur. The best-known initial clinical sign is a white pupillary reflex, called leukocoria (1, 2, 3). As the tumor enlarges, it can leave its intraretinal location and assume an exophytic growth pattern, endophytic growth pattern, or a combination of the two. The exophytic pattern is characterized by growth of the tumor outward toward the subretinal space, producing an overlying retinal detachment. The endophytic pattern is characterized by seeding of tumor cells into the overlying vitreous, obscuring a clear view of the retina.

The less common diffuse growth pattern is characterized by flat growth of the tumor (24, 25, 26, 27); although diffuse retinoblastoma is usually in the posterior retina, it has rarely appeared near the ora serrata and over the ciliary body without posterior involvement (28). Retinoblastoma can produce secondary glaucoma in about 17% of cases, usually due to iris neovascularization and secondary angle closure (29). The iris neovascularization can lead to a spontaneous hyphema, a rare presenting sign (25,32). Inflammation from necrotic intraocular retinoblastoma can simulate or cause orbital cellulitis (30). Although the lens is usually clear and in the correct position, there is a rare association with cataract and subluxed lens. It can extend extrasclerally and present as an advanced fungating mass.

Retinoblastoma has a tendency to undergo spontaneous regression in about 5% of cases. Spontaneously regressed retinoblastoma was initially recognized early to have rather typical clinical features. Subsequently, a benign variant of retinoblastoma, called retinoma or retinocytoma, was described. We prefer to use the term spontaneously regressed retinoblastoma for a tumor that actually grows to a certain size and then regresses. We use the term spontaneously arrested retinoblastoma for the benign variant (retinoma; retinocytoma) that grows to a certain size and then stabilizes (1). It is most likely that some cases reported as spontaneously regressed retinoblastoma represent these spontaneously arrested tumors.

An International Classification of Retinoblastoma has recently been proposed and is expected to be used at all major centers where retinoblastoma patients are managed. The details of this classification and its implications for predicting prognosis for ocular salvage using chemoreduction and supplemental treatment have been reported (42). The classification is summarized in the following table.

The following chapters describe and illustrate clinical variations, diagnostic approaches, management, and differential diagnosis of retinoblastoma.