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Retinoblastoma

by David N. Korones, MD

Retinoblastoma is a cancer arising from the immature retina. Symptoms and signs commonly include leukocoria (a white reflex in the pupil), strabismus, and, less often, inflammation and impaired vision. Diagnosis is based on ophthalmoscopic examination and ultrasonography, CT, or MRI. Treatment of small cancers and bilateral disease may include photocoagulation, cryotherapy, and radiation therapy. Treatment of larger cancers is enucleation. Chemotherapy is sometimes used to reduce cancer volume and to treat cancers that have spread beyond the eye.

Retinoblastoma occurs in 1/15,000 to 1/30,000 live births and represents about 3% of childhood cancers. It is usually diagnosed in children < 2 yr; < 5% of cases are diagnosed in those > 5 yr. The cancer may be hereditary. About 25% of patients have bilateral disease, which is always heritable. Another 15% of patients have heritable unilateral disease, and the remaining 60% have nonhereditary unilateral disease.

The pathogenesis of inheritance appears to involve mutational deactivation of both alleles of a retinoblastoma suppressor gene located on chromosome 13q14. In the hereditary form, a germline mutation alters one allele in all cells, and a later somatic mutation alters the other allele in the retinal cells (the 2nd hit in this 2-hit model), resulting in the cancer. The nonhereditary form probably involves somatic mutation of both alleles in a retinal cell.

Symptoms and Signs

Patients typically present with leukocoria (a white reflex in the pupil, sometimes referred to as cat’s-eye pupil) or strabismus. Much less often, patients present with inflammation of the eye or impaired vision. Rarely, the cancer has already spread, via the optic nerve or the choroid or hematogenously, resulting in an orbital or soft-tissue mass, headache, anorexia, or vomiting.

When the diagnosis is suspected, both fundi must be closely examined by indirect ophthalmoscopy with the pupils widely dilated and the child under general anesthesia. The cancers appear as single or multiple gray-white elevations in the retina; cancer seeds may be visible in the vitreous.

Diagnosis

  • Orbital ultrasonography, CT, or MRI

  • Sometimes bone scan, bone marrow aspirate and biopsy, and lumbar puncture

Diagnosis is usually confirmed by orbital ultrasonography or CT. In almost all cancers, calcification can be detected by CT. However, if the optic nerve appears abnormal during ophthalmoscopy, MRI is better for finding cancer extension into the optic nerve or choroid. Whenever extraocular spread is suspected, testing should include a bone scan, a bone marrow aspirate and biopsy, and lumbar puncture.

Children who have a parent or sibling with a history of retinoblastoma should be evaluated by an ophthalmologist shortly after birth and then every 4 mo until age 4 yr. Patients with retinoblastoma require molecular genetic testing, and if a germline mutation is identified, parents should also be tested for the same mutation. If subsequent offspring of parents have the germline mutation, the same genetic testing and regular ophthalmologic examination are required. Recombinant DNA probes may be useful for detecting asymptomatic carriers.

Prognosis

If the cancer is treated when it is intraocular, > 90% of patients can be cured. Prognosis for patients with metastatic disease is poor.

In patients with hereditary retinoblastoma, incidence of 2nd cancers is increased; about 50% arise within the irradiated area. These cancers can include sarcomas and malignant melanoma. Within 30 yr of diagnosis, 70% develop a 2nd cancer.

Treatment

Unilateral retinoblastoma is managed by enucleation with removal of as much of the optic nerve as possible.

For patients with bilateral cancer, vision can usually be preserved. Options include bilateral photocoagulation or unilateral enucleation and photocoagulation, cryotherapy, and irradiation of the other eye. Radiation therapy is by external beam or, for very small cancers, brachytherapy (attachment of a radioactive plaque to the eye wall near the cancer).

Systemic chemotherapy, such as carboplatin plus etoposide, or cyclophosphamide plus vincristine, may be helpful to reduce the size of large cancers or to treat cancer that has disseminated beyond the eye. However, chemotherapy alone can seldom cure this cancer.

Ophthalmologic reexamination of both eyes and retreatment, if necessary, are required at 2-mo to 4-mo intervals.

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Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • CYTOXAN (LYOPHILIZED)
  • No US brand name
  • MARQIBO KIT
  • ETOPOPHOS

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