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Retinoblastoma
is a cancer arising from the immature retina. Symptoms and signs
commonly include leukocoria (a white reflex from the pupil) and
strabismus, and less often, inflammation and impaired vision. Diagnosis
is based on ophthalmoscopic examination and ultrasound, CT, or MRI.
Treatment of smaller 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 for cancers that have spread beyond the eye.
Retinoblastoma occurs in 1/15,000 to 1/30,000 live births and represents about 2% of childhood cancers. Most cases present in children < 2 yr, with < 5% of cases diagnosed in those > 5 yr. The disease is sometimes 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 nonheritable 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 heritable form, a germline mutation alters one allele in all cells and a later somatic mutation alters the other allele in the child's retinal cells (the 2nd hit in this “2 hit” model), resulting in the cancer. The nonheritable form likely involves somatic mutation of both alleles in a retinal cell.
Symptoms,
Signs, and Diagnosis
Diagnosis is usually made when a white reflex from the pupil (leukocoria, sometimes referred to as cat's-eye pupil) or strabismus is investigated. 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.
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 is usually confirmed by orbital ultrasound 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 should undergo molecular genetic testing, and if a germline mutation is identified, parents should undergo testing for detection of the same mutation. Subsequent offspring of parents found to have the germline mutation should undergo the same genetic testing and regular ophthalmologic examination. Recombinant DNA probes may be useful for detecting asymptomatic carriers.
Prognosis
and Treatment
If treated when the cancer is intraocular, > 90% of patients can be cured. The prognosis for metastatic disease is poor. Patients with hereditary retinoblastoma have an increased incidence of 2nd malignancies, about 50% of which arise within the irradiated area. These malignancies can include sarcomas and malignant melanoma. Within 30 yr of diagnosis, 70% have developed a 2nd malignancy.
Unilateral retinoblastoma is managed by enucleation with removal of as much of the optic nerve as possible. For those with bilateral disease, vision usually can be preserved. Options include bilateral photocoagulation or unilateral enucleation and photocoagulation, cryotherapy, or radiation therapy of the other eye. Radiation therapy is by external beam or, for very small cancers, attachment of a radioactive plaque to the eye wall in close proximity to the cancer (brachytherapy). Systemic chemotherapy, such as carboplatin and etoposide or cyclophosphamide and vincristine , may be helpful to reduce the size of large cancers or when the disease has disseminated beyond the eye. However, chemotherapy alone can seldom cure this disease. Ophthalmologic reexamination of both eyes and retreatment, if necessary, are required at 2- to 4-mo intervals.
Last full review/revision November 2005
Content last modified November 2005
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