Retinoblastoma is a rare cancer, occurring in about one in 20,000 children.  The disease occurs most often in children under the age of 4, and makes up 2.8% of all cancers in children less than 14 years of age.  Retinoblastoma originates in a part of the eye called the retina.  The retina is a thin layer of nerve tissue that coats the back of the eye and allows a person to see.  Retinoblasts (immature cells of the retina) multiply during gestation and early life to make enough cells to create the retina.  As children age, the cells mature and are no longer able to divide and multiply, a process called differentiation.  Retinoblastoma can occur in one eye (unilateral retinoblastoma) or both eyes (bilateral retinoblastoma).

There are two types of retinoblastoma:

Genetic Retinoblastoma
The genetic form occurs in 25% of children.  These children are born with a change in one copy of the RB1 gene in every cell in the body.  If the second copy of the gene undergoes a change, a retinoblastoma tumor can develop.  Since every cell has the first copy of RB1 mutated, it is relatively easy for more than one cell to undergo a change in the second copy.  Most children with the genetic form develop retinoblastoma in both eyes (bilateral retinoblastoma).

Most children (80%) with the genetic form do not have a parent with retinoblastoma; however, the change in the gene occurred in either the egg or the sperm of one parent prior to conception.  If a child has the genetic form of retinoblastoma and neither parent has the tumor, the chance that retinoblastoma will occur in another child in the family is less than 5%.  However, the risk of tumor in the offspring of a child with the genetic form of retinoblastoma is about 50%.  Having the genetic form of the disease also increases a child’s risk of developing other cancers later in life.

Characteristics of the genetic form of retinoblastoma:

• Presence of more than one tumor is common
• Tumors often affect both eyes
• Tumors may be present in other parts of the body
• There is an increased risk for other cancers later in life

Non-hereditary Retinoblastoma

Most children with retinoblastoma (75%) do not have the genetic form.  Instead, both RB1 genes in a single retinoblast (immature cell) undergo the mutation sometime after conception or birth.  Researchers do not know how or why this occurs.  Non-hereditary retinoblastoma tumors develop in only one eye (unilateral).  These children do not have an increased risk of developing other cancers, and their offspring have the same risk of developing retinoblastoma as other children in the population.

Abnormalities of chromosome 13

Some children are born with 13q deletion syndrome or other abnormalities of chromosome 13 (the chromosome on which the RB1 gene is located) and are at high risk of developing retinoblastoma.  Children with these conditions are more at risk for retinoblastoma, but they account for only a small fraction of cases.  These syndromes usually require medical care, so you would know if your child had one of them.

Symptoms of Retinoblastoma

Doctors usually identify retinoblastoma on a routine well-baby exam.  Parents also notice symptoms such as:

• A pupil that looks white or red instead of black
• A crossed eye (looking either toward the nose or toward the ear)
• Poor vision
• A red, painful eye
• An enlarged pupil
• Differently colored irises

Diagnosing Retinoblastoma

A diagnosis of retinoblastoma is made by examining the eyes.  A white pupil or strabismus (crossed eyes) will usually be noticed by a parent or pediatrician.  Because this disease is relatively rare, children are typically referred to a special ophthalmologist who is familiar with the treatment of retinoblastoma.  The child may need to be examined under general anesthesia to define the extent of the tumor in the eye(s) and to record the information in photographs or diagrams.  The specialist may also use additional tests to detect tumors.  The following tests are commonly used to provide the specialist with a picture of the inside of the eye and the brain.

• Ultrasound
• CT (CAT) scan
• MRI

Children diagnosed with retinoblastoma will require a complete physical examination.  If there are any symptoms or abnormal findings, the child may also need additional tests to see if the cancer has spread to other parts of the body.  Tests that may be performed include:

• Blood tests
• Lumbar puncture
• Bone marrow aspirate

Other tests frequently performed after the diagnosis of retinoblastoma include:

• Audiogram
• Genetic testing and/or screening

Staging

After retinoblastoma has been detected, the doctor will determine the extent of disease in the eye and the presence of disease outside of the eye.  This is called staging, and it helps the doctors plan the appropriate treatment.  Two staging systems are used for retinoblastoma, one for assessing the amount of disease inside of the eye which correlates with the probability of saving the eye and vision, and another system that evaluates the presence of disease outside of the eye.  For staging the eye, the International Classification for Intraocular Retinoblastoma is used.  This classification system uses a letter (A-E) to signify the extent of the disease; the more extensive the child's disease, the higher the class.  This designation will determine the treatment that will most effectively cure the cancer and preserve the child’s sight.
Group A
Small intraretinal tumors away from foveola and disc

• All tumors are 3 mm or smaller in greatest dimension, confined to the retina and
• All tumors are located further than 3 mm from the foveola and 1.5 mm from the optic disc

Group B
All remaining discrete tumors confined to the retina

• All other tumors confined to the retina not in Group A
• Tumor-associated subretinal fluid less than 3 mm from the tumor with no subretinal seeding

Group C
Discrete Local disease with minimal subretinal or vitreous seeding

• Tumor(s) are discrete
• Subretinal fluid, present or past, without seeding involving up to 1/4 retina
• Local fine vitreous seeding may be present close to discrete tumor
• Local subretinal seeding less than 3 mm (2 DD) from the tumor

Group D
Diffuse disease with significant vitreous or subretinal seeding

• Tumor(s) may be massive or diffuse
• Subretinal fluid present or past without seeding, involving up to total retinal detachment
• Diffuse or massive vitreous disease may include “greasy” seeds or avascular tumor masses
• Diffuse subretinal seeding may include subretinal plaques or tumor nodules

Group E
Presence of any one or more of these poor prognosis features

• Tumor touching the lens
• Tumor anterior to anterior vitreous face involving ciliary body or anterior segment
• Diffuse infiltrating retinoblastoma
• Neovascular glaucoma
• Opaque media from hemorrhage
• Tumor necrosis with aseptic orbital cellulites
• Phthisis bulbi

For evaluating the amount of disease outside the eye, several systems are used.  However, the most important points are to see if the retinoblastoma has spread outside of the eye into the orbit or the optic nerve, and if it has spread into the brain or elsewhere in the body (bones, bone marrow or liver).

Last updated September, 2011

About Retinoblastoma
In Treatment for Retinoblastoma
After Treatment for Retinoblastoma