Retinoblastoma is the most common primary ocular malignancy of childhood.

The first description of a tumor resembling retinoblastoma was by Peter Pawius of Amsterdam. He wrote of a malignancy invading the orbit, the temporal region, and the cranium, a picture now strongly suggestive of untreated retinoblastoma. The tumor was described to be filled with a “substance similar to brain tissue mixed with thick blood and like crushed stone.”

In 1805, William Hey coined the term fungus haematodes, which he used to describe a fungating mass affecting the globe of the eye and destroying its internal organization.

In 1809, the Scottish surgeon James Wardrop pieced together the random isolated facts and observations of previous authors. Despite not having a microscope at his disposal, his meticulous dissection and astute interpretations of some of these eyes led him to conclude that in most instances the tumor arose from the retina. Wardrop documented the extension of the tumor to the optic nerve and brain. Later, he described metastasis to different parts of the body.

In 1836, Langenbech, Robin, and Nystin of Paris confirmed by microscopic studies that the tumor definitely arose from the retina.

In 1864, Virchow named it a glioma of the retina, supporting glial cells as the cell of origin of the tumor.

In 1891, Flexner of Johns Hopkins was first to notice rosettes within the tumor. A few years later in 1897, Wintersteiner concurred with Flexner and proposed the name neuroepithelioma noting its resemblance to rods and cones and traced one tumor to the photoreceptor cell layer. Presently, their names are attached to these rosettes.

Most cells comprising the tumor histologically resembled the cells of an undifferentiated retina of the embryo called retinoblasts. This resemblance prompted Veorhoff to coin the term retinoblastoma, which later was adopted by the American Ophthalmological Society in 1926 as a general term for this entity.

In 1970, Tso and colleagues established that the tumor arises from photoreceptor precursors.

Pathophysiology: The most widely held concept of histogenesis of retinoblastoma holds that it generally arises from a multipotential precursor cell (mutation in the long arm of chromosome 13 band 13q14) that could develop into almost any type of inner or outer retinal cell. Intraocularly, it exhibits a variety of growth patterns, which classically have been described, as outlined below. (See Causes for more information.)

Endophytic growth

Endophytic growth occurs when the tumor breaks through the internal limiting membrane and has an ophthalmic appearance of a white-to-cream mass showing either no surface vessels or small irregular tumor vessels. This growth pattern typically is associated with vitreous seeding wherein small fragments of tissue become separated from the main tumor. In some instances, vitreous seeding may be extensive allowing tumor cells to be visible as spheroid masses floating in the vitreous and anterior chamber, simulating endophthalmitis or iridocyclitis, and obscuring the primary mass. Secondary deposits or seeding of tumor cells into other areas of the retina may be confused with multicentric tumors.

Exophytic growth

Exophytic growth occurs in the subretinal space. This growth pattern often is associated with subretinal fluid accumulation and retinal detachment. The tumor cells may infiltrate through the Bruch membrane into the choroid and then invade either blood vessels or ciliary nerves or vessels. Retinal vessels are noted to increase in caliber and tortuosity as they overlie the mass.

Diffuse infiltrating growth

This is a rare subtype comprising 1.5% of all retinoblastoma. It is characterized by a relatively flat infiltration of the retina by tumor cells but without a discrete tumor mass. The obvious white mass seen in typical retinoblastoma rarely occurs. It grows slowly compared with typical retinoblastoma.

Frequency:

—                  In the US: It is estimated that around 250-500 new cases of retinoblastoma occur in the United States yearly.

—                  Internationally: Worldwide, the incidence of retinoblastoma is recorded to be about 11 cases per million children younger than 5 years. A more commonly used estimate is 1 case of retinoblastoma per 18,000-30,000 live births, depending on the country.

In the Philippines, unpublished reports have estimated the incidence to be greater than 1 case of retinoblastoma per 18,000 live births.

Mortality/Morbidity: Survival rates for patients with retinoblastoma range from a reported 86-92%. However, this must be kept in the context of the retinoblastoma cancers. In actuality, the survival rate drops with each decade of life for patients with the genomic mutation. The genomic mutation is a gene mutation within every cell of the individual’s body. These patients typically present with either bilateral disease or unilateral-multifocal (one eye with multiple distinctly separate tumor foci) disease. These individuals have a predisposition for developing second cancers later in life.

Mortality in these individuals is consequently much higher than those with somatic mutations (ie, affecting one retinal cell only and unilateral-unifocal disease). The greatest predictor of death is extraocular extension, either directly through the sclera or via extension along the optic nerve. Several of these topics are discussed further in later sections of this article.

Race:

—                  There seems to be no racial predilection for retinoblastoma.

—                  No difference in incidence exists among blacks and whites.

Sex:

—                  Studies show that there appears to be no significant difference in the incidence of retinoblastoma by sex for children aged 0-14 years.

—                  The estimated boys-to-girls ratio is reportedly 1.12:1.

Age: Retinoblastoma is diagnosed at an average of 18 months with 90% diagnosed before patients reach age 5 years.

—                  Children who are affected bilaterally are diagnosed at an average age of 13 months, while patients with unilateral retinoblastoma are diagnosed at an average age of 24 months.

—                  When a known family history of retinoblastoma exists, patients with bilateral retinoblastoma are diagnosed at an average age of 11 months.

—                  A few cases of retinoblastoma in adults (aged 20 y and older) have been reported in the literature. Some theorize that these lesions arise from a previously existing retinocytoma that underwent malignant transformation.

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