MD2B - Pediatric Oncology: Retinoblastoma

Amy Feldman, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: July 23, 2006

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Overview

Retinoblastoma is the most common primary intraocular (meaning within the eye) tumor to occur in children. It is a relatively uncommon type of pediatric cancer, accounting for only 3% of all malignancies in children younger than 15 years. In the United States, approximately 200 new cases of retinoblastoma are diagnosed each year. The majority of cases are diagnosed in children under the age of 2, and 95% occur before the age of 5. Males and females are affected equally, as are Caucasians and African- Americans. Retinoblastoma can be inherited or it can occur sporadically. In 5-10% of cases, there is a positive family history for the disease. The tumor occurs unilaterally in 75% of cases, and bilaterally in 25% of cases. The prognosis for retinoblastoma is good, with 90% of children achieving long-term survival.

Cause

Retinoblastoma is one of the few types of cancer where the cause is well understood. Retinoblastoma occurs when there is a mutation to both alleles (copies) of the retinoblastoma gene on chromosome 13. Normally this gene suppresses tumor activity. When both alleles are mutated, tumors are no longer suppressed and uncontrolled cell growth occurs.

Retinoblastoma is a tumor that occurs in "germline" (40%) and sporadic (60%) forms. "Germline" disease includes those patients with a positive family history of retinoblastoma, and those patients who have sustained a new germline mutation at the time of conception. A positive family history is present in only 5-10% of children who develop this disease. A "two-hit" model has been used to explain the difference in clinical features between the germline and sporadic forms of the disease. In the germline form, one allele is already mutated at birth in every cell of the body. When a second mutation occurs, a tumor forms. Therefore, in this form of the disease there is a risk for bilateral tumor formation. In addition, the same genetic abnormality that leads to retinoblastoma also can lead to osteogenic sarcoma (bone tumor), soft tissue sarcoma, and malignant melanoma (skin cancer). Patients with heritable retinoblastoma must be carefully monitored and screened for other malignancies throughout their lives.

In the sporadic form, no mutations are present at birth and both alleles must mutate for cancer to develop. Therefore, children with the non-inherited form of retinoblastoma most frequently (though not always) have unilateral, not bilateral disease.

Symptoms

Retinoblastoma can present with various abnormalities in function or appearance of the eye. The most common symptom is leukocoria (the pupil appears to have a white reflex rather than the normal red reflex). The second most common symptom of retinoblastoma is strabismus (the eyes appear crossed or misaligned). Other presenting symptoms include decreased vision, glaucoma, retinal detachment, vitreous hemorrhage, proptosis (bulging of the eye), orbital cellulitis (infection), and heterochromia (two different colored eyes). Eye pain can occur secondary to glaucoma and fever can occur secondary to infection and necrosis (tissue breakdown).

Diagnosis

Any child with an eye abnormality or positive family history for retinoblastoma should be evaluated by a physician. Under anesthesia, an ophthalmologist can perform a dilated examination so that the retina (portion of the eye where retinoblastoma arises) can be directly observed. Ultrasounds, CT scans, and MRI scans of the head, eye, and the surrounding structures can aid in diagnosis and prognosis. Many benign conditions can mimic retinoblastoma.

Treatment

There are many treatment options available for children with retinoblastoma. The choice of treatment depends upon patient age and tumor size, location, and spread. The primary goal of treatment is to eradicate the cancer, but important secondary goals include preserving vision when possible and minimizing treatment side effects.

Surgery

  • Globe sparing: only a portion of the eye is removed
  • Enucleation: a surgical procedure during which the eye is removed. This surgery is performed on patients who have large tumors that extend into surrounding structures or those patients with loss of vision or eye pain. Enucleation is also used in children who have tumor recurrence after globe sparing surgery

Radiation therapy

Retinoblastoma is generally responsive to radiation. Radiation can be delivered in the form of external beam radiotherapy or plaque radiotherapy. The major drawback to external beam radiotherapy is that it can induce secondary cancers.

Cryotherapy

Use of a freezing process to destroy small tumors.

Laser Therapy

Use of an argon laser beam to treat small tumors.

Phototherapy

Use of a light beam to destroy the blood vessels supplying a tumor.

Chemotherapy

Chemotherapy now plays an important role in the treatment of retinoblastoma. Chemotherapy may prevent the need for external beam radiotherapy sparing the patient risk of secondary malignancies.

Prognosis

The overall five-year survival rate for children with retinoblastoma in the United States is around ninety percent. If undiagnosed and untreated, retinoblastoma destroys the eye and then begins to extend beyond the orbit. Metastatic spread usually begins after six months, and death occurs within a matter of years.

References

Abramson, DH, Beaverson, K, Sangani, P, et al. "Screening for retinoblastoma: presenting signs as prognosticators of patient and ocular survival." Pediatrics 2003; 112:1248.

Gallie BL, Dunn JM, Chan HS, et al. "The genetics of retinoblastoma. Relevance to the patient." Pediatr Clin North Am 38 (2): 299-315, 1991.

Herzog C. "Retinoblastoma." In: Behrman ed: Nelson Textbook of Pediatrics 17th Edition. Saunders, 2004, pp.1720-1723.

Hurwitz RL, Shields CL, Shields JA. "Retinoblastoma." In: Pizzo PA, Poplack DG, eds.: Principles and Practice of Pediatric Oncology. 5th ed. Philadelphia, PA : Lippincott, Williams and Wilkins, 2006, pp.865-886.

L Aventura, M. "Retinoblastoma." Emedicine online.

"Retinoblastoma." National Cancer Institute Web Site.

Shields, JA. "Misconceptions and techniques in the management of retinoblastoma." The 1992 Paul Henkind Memorial Lecture. Retina 1992; 12:32.

Wong FL, Boice JD, Abramson DH, et al. "Cancer incidence after retinoblastoma." JAMA 1997; 278:1262-1267.

Young, JL, Smith, MA, Roffers, SD, et al. "Retinoblastoma." In: Cancer Incidence and Survival among Children and Adolescents: United States SEER Program, 1975-1995, Ries, LA, Smith, MA, Gurney, JG, et al (Eds), National Cancer Institute, Bethesda, MD, 1999. p.73.