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