Approximately 3% of cancer in children less than 15 years of age is retinoblastoma. Retinoblastoma affects the retina (layers of nerves near the back of the eye that include the light-detecting rods and cones).
It can develop in immature cells of the retina as well as mature nerves in the eye. The tumor grows to replace normal retina cells and other parts in the eye. It may eventually spread to the optic nerve where it can proceed to infiltrate the brain and spread to other parts of the body, primarily the bone marrow and lymph nodes but also the liver, kidney, lung, and bone.
Retinoblastoma that affects only one eye is called unilateral retinoblastoma. Bilateral retinoblastoma affects both eyes. Unilateral or bilateral retinoblastoma in conjunction with another tumor within the skull is a syndrome called trilateral retinoblastoma.
Retinoblastoma is caused by mutations in the RB gene on chromosome 13. The gene encodes a protein called retinoblastoma protein that suppresses tumor formation when the RB gene is not mutated. Despite the genetic basis, more than half of retinoblastomas are sporadic (non-inherited) and result from spontaneous mutations.
Signs and Symptoms
The most common symptom of retinoblastoma is a white or yellow appearance of the eye (leukocoria) in photographs taken with a flash. A yellow-colored eye may also be apparent in low artificial light. The second most common symptom is a crossed eye. The eye can either turn outwards toward the ear or inwards toward the nose. Children with this condition may seem to be squinting.
Less common eye-related symptoms include redness and irritation, enlarged or dilated pupil, differently colored pupils, and reduced vision. Some children with retinoblastoma have symptoms that do not involve the eye, such as delayed development and trouble eating or drinking.
Diagnosis
Tumors are often visible during a standard eye exam; they appear as whitish lumps on the retina. However, a positive diagnosis is made by examining the eyes through dilated pupils while the child is under general anesthesia.
Imaging techniques are often used to confirm a diagnosis and assess the extent of the malignancy. Computerized tomography (CT) is used to assess tumor volume. Magnetic resonance imaging (MRI) can detect cancer that has spread to the optic nerve and to other tissues outside the eye.
Staging
The International Classification System for Intraocular Retinoblastoma is commonly used in retinoblastoma treatment protocols:
- Group A: Small tumors in the retina but which have not affected the foveola (a small area of the retina containing specialized cones) and the optic disc
- Group B: All tumors not in Group A but confined to the retina; Some fluid accumulation beneath the retina
- Group C: Discrete tumors with few cancerous cells located beneath the retina or the vitreous (the gel-like substance of the eye)
- Group D: Tumor has penetrated deep below the retina and into the vitreous
- Group E: One or more of the following: galucoma, diffuse infiltrating retinoblastoma, tumor touching the lens, tumor extending to the front one-third of the eye, hemorrhage, tumor necrosis, or a shrunken, non-functioning eye
Treatment
Anucleation (removal of the eye) is often performed in advanced, unilateral disease or when useful sight cannot be preserved. Anucleation in children with bilateral disease is often only used if the cancer has returned and when useful vision is absent.
Three frequently used treatments include thermotherapy, cryotherapy, and photocoagulation (light coagulation, laser photocoagulation). In the first, heat is used to destroy small tumors. In cryotherapy, tumors are rapidly frozen, which cuts off the blood supply. Photocoagulation uses a photocoagulator to coagulate the blood supplying the tumor.
Brachytherapy is used to target one large tumor or several moderately-sized tumors. It involves the placement of radioactive plaques at the base of the tumor. These are allowed to sit in place for a period of two to four days.
Chemotherapy and external beam radiation are used to treat bilateral tumors. Chemotherapy reduces tumor size (chemoreduction) and prepares the tumor for treatment with cryotherapy, thermotherapy, or photocoagulation. It is also used for cancer that is resistant to other treatments. External beam radiation is used sparingly and involves directing radiation toward the whole tumor area and part of the optic nerve. Radiation is used in younger children for whom the cancer has returned following other treatments.
Typical approaches to retinoblastoma that has spread outside the eyes include high-dose chemotherapy, external beam radiation, and bone marrow transplantation.
Prognosis
In developed countries, 95% of retinoblastomas are cured. However, many children have long-term vision problems, the severity of which depends on the location and size of the tumor as well as treatment. Retinoblastoma causes 5% of childhood blindness and 1% of deaths related to a cancer.
Retinoblastoma that has returned after treatment usually occurs within six months of therapy. The likelihood of a recurrent tumor is dependent on a family history of the disease, the size or thickness of the tumor, and age at diagnosis. The outcome of recurrent cancer is very good for small tumors confined to the eye.
