What is retinoblastoma?
What is retinoblastoma?
Retinoblastoma is a rare type of eye cancer that usually develops in early childhood, typically before the age of 5. This form of cancer develops in the retina, which is the specialized light-sensitive tissue at the back of the eye that detects light and color.
In most children with retinoblastoma, the disease affects only one eye. However, one out of three children with retinoblastoma develops cancer in both eyes. The most common first sign of retinoblastoma is a visible whiteness in the pupil called "cat's eye reflex" or leukocoria. This unusual whiteness is particularly noticeable in photographs taken with a flash. Other signs and symptoms of retinoblastoma include crossed eyes or eyes that do not point in the same direction (strabismus); persistent eye pain, redness, or irritation; and blindness or poor vision in the affected eye(s).
Retinoblastoma is often curable when it is diagnosed early. However, if it is not treated promptly, this cancer can spread beyond the eye to other parts of the body. This advanced form of retinoblastoma can be life-threatening.
When retinoblastoma is associated with a gene mutation that occurs in all of the body's cells, it is known as germinal retinoblastoma. People with this form of retinoblastoma also have an increased risk of developing several other cancers outside the eye. Specifically, they are more likely to develop a cancer of the pineal gland in the brain (pinealoma), a type of bone cancer known as osteosarcoma, cancers of soft tissues such as muscle, and an aggressive form of skin cancer called melanoma.
How common is retinoblastoma?
Retinoblastoma is diagnosed in 250 to 350 children per year in the United States. It accounts for about 4 percent of all cancers in children younger than 15 years.
What are the genetic changes related to retinoblastoma?
Mutations in the RB1 gene are responsible for most cases of retinoblastoma. RB1 is a tumor suppressor gene, which means that it normally regulates cell growth and keeps cells from dividing too rapidly or in an uncontrolled way. Most mutations in the RB1 gene prevent it from making any functional protein, so it is unable to regulate cell division effectively. As a result, certain cells in the retina can divide uncontrollably to form cancerous tumors. Some studies suggest that additional genetic changes can influence the development of retinoblastoma; these changes may help explain variations in the development and growth of tumors in different people.
A small percentage of retinoblastomas are caused by deletions in the region of chromosome 13 that contains the RB1 gene. Because these chromosomal changes involve several genes in addition to RB1, affected children usually also have intellectual disability, slow growth, and distinctive facial features (such as prominent eyebrows, a short nose with a broad nasal bridge, and ear abnormalities).
Read more about the RB1 gene and chromosome 13.
Can retinoblastoma be inherited?
Researchers’ estimate that 40 percent of all retinoblastomas are germinal, which means that RB1 mutations occur in all of the body's cells, including reproductive cells (sperm or eggs). People with germinal retinoblastoma may have a family history of the disease, and they are at risk of passing on the mutated RB1 gene to the next generation. The other 60 percent of retinoblastomas are non-germinal, which means that RB1 mutations occur only in the eye and cannot be passed to the next generation.
In germinal retinoblastoma, mutations in the RB1 gene appear to be inherited in an autosomal dominant pattern. Autosomal dominant inheritance suggests that one copy of the altered gene in each cell is sufficient to increase cancer risk. A person with germinal retinoblastoma may inherit an altered copy of the gene from one parent, or the altered gene may be the result of a new mutation that occurs in an egg or sperm cell or just after fertilization. For retinoblastoma to develop, a mutation involving the other copy of the RB1 gene must occur in retinal cells during the person's lifetime. This second mutation usually occurs in childhood, typically leading to the development of retinoblastoma in both eyes.
In the non-germinal form of retinoblastoma, typically only one eye is affected and there is no family history of the disease. Affected individuals are born with two normal copies of the RB1 gene. Then, usually in early childhood, both copies of the RB1 gene in retinal cells acquire mutations or are lost. People with non-germinal retinoblastoma are not at risk of passing these RB1 mutations to their children. However, without genetic testing it can be difficult to tell whether a person with retinoblastoma in one eye has the germinal or the non-germinal form of the disease.
Where can I find information about diagnosis, management, or treatment of retinoblastoma?
These resources address the diagnosis or management of retinoblastoma and may include treatment providers.
• DNA Test
• Gene Review
• MedlinePlus Encyclopedia: Retinoblastoma
You might also find information on the diagnosis or management of retinoblastoma in Educational resources and Patient support.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about retinoblastoma?
You may find the following resources about retinoblastoma helpful. These materials are written for the general public.
• MedlinePlus - Health information (3 links)
• Additional NIH Resources - National Institutes of Health (3 links)
• Educational resources - Information pages (12 links)
• Patient support - For patients and families (8 links)
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals
• ClinicalTrials.gov - Linking patients to medical research
• PubMed - Recent literature
• Online Books - Medical and science texts
Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Retinoblastoma
• OMIM - Genetic disorder catalog
White pupil "leukocoria" sign of retinoblastoma
Retinoblastoma is the most common intraocular cancer of childhood and affects approximately 300 children in the United States each year. More than 90% of children can be cured of retinoblastoma by early detection and treatment of the affected eye. Unfortunately, some children can have both eyes affected. Whenever possible, eye-cancer specialists try to save a child’s eye and preserve their vision.
Symptoms
Leukocoria (white pupil) and misaligned eyes (strabismus) are the most common signs of retinoblastoma. In other cases, the child may have developed neovascular glaucoma and may be in pain. Longstanding glaucoma can cause enlargement of the eye (buphthalmos). Children with neovascular glaucoma and enlargement of the eye are at greater risk for extraocular spread of their retinoblastoma.
An intraocular photograph of an isolated "endophytic" retinoblastoma.
A family history of retinoblastoma can be very important. Retinoblastoma was the first cancer to be directly associated with a genetic abnormality (Deletions or mutation of the q14 band of chromosome 13). Retinoblastoma can occur sporadically (without a family history) or it can be inherited (with a family history).
If a genetic mutation is found there is a 45-50% chance that the parents will have another child with retinoblastoma. If there is no family history and no mutation is found, the risk of having a second child with retinoblastoma is 2-5%. The average age of children first diagnosed with retinoblastoma is 18 months.
Diagnosis
More than 75% of children with retinoblastoma are first noted to have a “white-pupil” (which the doctors call leukocoria), or poorly aligned eyes (which the doctors call strabismus), or a red and painful eye (usually due to glaucoma). Other eye diseases which can cause these symptoms include congenital cataract, Toxocara canis, Coat’s disease, and persistent hypertrophic primary vitreous (PHPV). These diseases may look like retinoblastoma, but by performing an examination under anesthesia, specialized blood tests, digital photography, radiographic scans, and ultrasound evaluations ophthalmic oncologists can diagnose intraocular retinoblastoma in over 95% of cases. In order to be 100% correct all the time, eye-cancer specialists would have to perform a biopsy. Biopsies of intraocular retinoblastoma are avoided in order to prevent cancer cells from spreading outside of the eye.
A 3D Ultrasound Image of a large retinoblastoma with spots of calcification within the tumor.
A CT scan of a retinoblastoma demonstrates calcification within the right eye (arrow).
The presence of orbital extension, uveal involvement, and optic nerve invasion are known risk factors for the development of metastatic retinoblastoma.
Retinoblastoma extension into the optic nerve (arrow).
"Seeds" of retinoblastoma have migrated onto the iris surface.
Treatments
Retinoblastoma treatment typically requires the cooperation of an ophthalmic oncologist, pediatric oncologist, and radiation therapist. Over the last 30 years, treatment has evolved from simple enucleation (removal of the eye), to eye-sparing radiotherapy, and more recently to chemotherapy-based multi-modality therapy (for selected cases).
Though retinoblastoma has been cured by external beam irradiation, investigators have suggested that radiation may cause an increase in the risk of developing second cancers later in life.
Protocols are currently being evaluated to use chemotherapy to shrink the retinoblastoma in order to treat them with laser therapy, freezing therapy (cryotherapy), and local “plaque” radiation. Where applicable, these techniques are thought to be safer than external beam irradiation for retinoblastoma. There is little long-term data on the safety of this type of multi-modality chemotherapy.
Treatment of retinoblastoma often requires a team of doctors made up of ophthalmic, radiation and pediatric oncologists. These doctors should evaluate your child, discuss all the different forms of treatment, and make them available.
Related Links
View images of retinoblastoma
Find genetic testing services for retinoblastoma
Scientific articles written about retinoblastoma by Dr. Finger and colleagues
Other scientific articles about retinoblastoma
What is retinoblastoma?
Retinoblastoma is a cancer of the eye in children. It originates from the retina, the light sensitive layer, in eye. It is the commonest eye tumor of the eye in childhood. . This tumor may involve one (75% of cases) or both (25% of cases) eyes in a child. Untreated, retinoblastoma is almost always fatal; hence the importance of early diagnosis and treatment
Is it hereditary?
Yes in some cases it may be hereditary. Majority of cases (90%) has no family history of such disease; while a small percentage (10%) of newly diagnosed cases have other family members with retinoblastoma.
Of all the cases of retinoblastoma, in 60% of cases it does not get transmitted to the next generation, while in 40% of cases it may get transmitted in the next generation. Therefore it is important to have a genetic counseling before having a baby to determine the risk of another child getting the same disease. Also, the siblings and children of the patients with retinoblastoma should be examined periodically in their childhood to detect any possible tumor early.
What are the symptoms of retinoblastoma?
As the child does not complain of any poor vision, the tumor may remain undetected. The most common way of presentation is a white reflex (leukocoria) behind the pupil. This is sometimes called the cat's eye reflex. There may be other causes of this white reflex as well, but an evaluation by an ophthalmologist is a must in all these children to rule out the possibility of this serious and potentially life threatening disease.
It may also present as squint (crossed eye), poor vision, painful red eye, inflammation of the tissue surrounding eye, protrusion of the eye ball (proptosis) etc. Occasionally it is detected on a routine eye checkup by an ophthalmologist, especially in a child with family history of this disease.
How can it be detected early?
The most common time of detection of this tumor is around one year of age, when both eyes are involved; and around two years of age when only one eye is involved. A periodic evaluation of the child by an ophthalmologist, especially if there is a family history of this disease may help in picking up the tumor early. Whenever the child is suspected to have poor vision or if there are any of the above symptoms noted, an ophthalmologist must be consulted.
To establish the diagnosis, the doctor may need to examine the child under general anesthesia. A few special tests like ultrasonography, CT scan, X-rays, MRI, blood tests, spinal tap, bone marrow biopsy etc. may be done to establish the diagnosis and to find out the extent of the disease.
If a child has been diagnosed to have retinoblastoma in one eye, can he also develop the same disease in the other eye?
Yes. 25% of these tumors can affect both the eyes. The other eye must also be evaluated thoroughly for the presence of any tumor. Also in a few cases, the other eye may develop tumor a bit later. Therefore on the follow up visits also, the other eye should be examined.
Is the child also at a risk for other diseases or tumors?
Some of these children, especially those in which the tumor involves both the eyes, are at a risk for developing other tumors like osteogenic sarcoma (a cancerous tumor that affects the bone). The radiation therapy for the tumor (external beam radiotherapy) increases this risk of other tumors. Your ophthalmologist will discuss these issues with you.
My child has been diagnosed to have retinoblastoma. Should I get my other children examined as well?
As we know, a few of these cases may be hereditary, therefore all the siblings of the affected child must get an evaluation to rule out this disease.
What are the chances that the next child to be born would have the same disease?
These chances may range from as low as 1 in 15,000 to as high as 45%, and depend upon many factors and like whether there is a family history of such tumor, whether the tumor is involving both eyes etc. A genetic counseling should be sought when planning for another baby. Similarly, when a person with treated retinoblastoma plans to have a child, he or she must also consult the doctor for genetic counseling.
Is it curable?
Yes. If detected at an early stage, the life and many times the sight and the eye of the child may be saved. After removal of the tumor, the chances of survival are very good in these children.
What are the treatment options?
The aim of treatment in retinoblastoma, in order of priority, is to save the life, eye, sight and cosmesis of the child.
There are many treatment modalities for this tumor. These are:
• Enucleation: This means removal of the eye. The eye with the tumor is removed and is sent for a pathology report. The space is replaced by an artificial implant made of plastic, rubber or coral. The child is fitted with prosthesis or artificial eye, made to match the other eye. This artificial eye, of course, does not have any vision.
• External beam radiation: as an alternative to enucleation, this method of giving radiation treatment to the eye may treat the tumor while preserving the eye. As the tumor is very radiosensitive, this treatment method is very effective. Though the radiation may cause damage to the surrounding structures of the eye, e.g., lens (cataract), lacrimal system (dry eye), orbit (bone maldevelopment) etc. It also increases the chance of developing secondary tumor of the bone, especially in children with tumor involving both eyes.
• Localized Plaque radiation therapy: This method involves applying radioactive plaque close to the tumor on the sclera, and thus gives the radiation therapy in a localized area. It significantly decreases the local complications associated with radiation therapy.
• Photocoagulation: Laser treatment for the tumor is effective and safe for tumors that are smaller in size. In the right cases, this treatment may help in preserving eye as well as the sight of the child.
• Cryotherapy: this involves freezing of the tumor by applying a special probe on the external surface of the eye (sclera). This treatment is done under direct observation and is effective in saving the eye and sight in patients with small tumor.
• Chemotherapy: Treatment with anticancer drugs. There has been a recent preference towards treatment with systemic drugs as an additional treatment. The chemotherapy may decrease the size of the tumor and thus make it more amenable to local treatment like laser, cryotherapy and plaque radiation.
Which treatment option is the best?
The treatment of retinoblastoma is individualized for each patient. The treatment modality for a given child is decided based on many important factors. These are:
• Size of the tumor
• Location of the tumor
• Whether the tumor has spread
• Status of the other eye
• Associated complications like retinal detachment, glaucoma
• Family history
• The wishes and concerns of the parents
• Availability of the facilities
As this is a difficult decision made based on many factors, it is advised to discuss with the treating ophthalmologist about the best treatment option for the concerned child. All the advantages and disadvantages of each option must be weighed before taking a decision. It is also important to discuss the rehabilitation and the cosmetic correction after the surgery.
What is done if the child has tumor in both eyes?
In these cases, generally the worse eye is enucleated and the other eye is tried to salvage by using other methods of treatment. However, unfortunately in a few cases, both eyes may have to be removed.
Why is early detection important?
As mentioned earlier, the safer and less destructive procedures may be taken when the tumor is in its early stage. By detecting and treating the tumor early, we may save the life, sight and eye of the child.
What are the long-term consequences of retinoblastoma?
Even though retinoblastoma is a life threatening disease, it is rarely a fatal one if treated appropriately. With the correct treatment in the hands of an experienced ophthalmologist, the retinoblastoma patient has a very good chance of living a long, full, and happy life.
It is very important to have a proper follow up with the treating ophthalmologist for the eye tumor as well as for detection and treatment of possible other tumors. The frequency of follow up depends upon the type of tumor and the type of treatment given. Also in children with only one eye left, extra care must be taken to avoid injuries to the good eye.
Retinoblastoma is a rare, cancerous tumor of a part of the eye called the retina.
Causes
Retinoblastoma is caused by a mutation in a gene controlling cell division, causing cells to grow out of control and become cancerous.
In a little over half of the cases, this mutation develops in a child whose family has never had eye cancer.
Other times the mutation is present in several family members. If the mutation runs in the family, there is a 50% chance that an affected person's children will also have the mutation. They will therefore have a high risk of developing retinoblastoma themselves.
The cancer generally affects children under the age of 6. It is most commonly diagnosed in children aged 1 - 2 years.
Symptoms
One or both eyes may be affected.
They pupil may appear white or have white spots. A white glow in the eye is often seen in photographs taken with a flash. Instead of the typical "red eye" from the flash, the pupil may appear white or distorted.
Other symptoms can include:
• Crossed eyes
• Double vision
• Eyes that do not align
• Eye pain and redness
• Poor vision
• Differing iris colors in each eye
If the cancer has spread, bone pain and other symptoms may occur.
Exams and Tests
The doctor will perform a complete physical exam, including an eye exam. The following tests may be done:
• Eye exam with dilation of the pupil
• CT scan or MRI of the head
• Ultrasound of the eye (head and eye echoencephalogram)
• Bone marrow biopsy and cerebrospinal fluid examination in the case of more aggressive tumors
Treatment
Treatment options depend upon the size and location of the tumor.
• Small tumors may be treated by laser surgery or cryotherapy.
• Radiation is used for both local tumor and for larger tumors.
• Chemotherapy may be needed if the tumor has spread beyond the eye.
The eye may need to be removed (a procedure called eucleation) if the tumor does not respond to other treatments. In some cases, it may be the first treatment.
Outlook (Prognosis)
If the cancer has not spread beyond the eye, almost all patients can be cured. A cure, however, may require aggressive treatment and even removal of the eye in order to be successful.
If the cancer has spread beyond the eye, the likelihood of a cure is lower and depends on how the tumor has spread.
Possible Complications
Blindness can occur in the affected eye. The tumor can spread to the eye socket through the optic nerve. It may also spread to the brain, lungs, and bones.
When to Contact a Medical Professional
Call your health care provider if signs or symptoms of retinoblastoma are present, especially if your child's eyes look abnormal or appear abnormal in photographs.
Prevention
Genetic counseling can help families understand the risk of retinoblastoma. It is especially important when more than one family member has had the disease, or if the retinoblastoma occurs in both eyes.
Alternative Names
Tumor - retina; Cancer - retina
References
Dome JS, Rodriguez-Galindo C, Spunt SL, Santana VM. Pediatric sold tumors. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, eds. Abeloff’s Clinical Oncology. 4th ed. Philadelphia, Pa: Elsevier Churchill Livingstone; 2008:chap 99.
Update Date: 3/21/2010
Updated by: David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc., and Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital.