Retinoblastoma And Leukocoria – assessment

Description

Retinoblastoma is the most common primary malignant intraocular tumor in children. Leukocoria (a white pupillary reflex) is the presenting feature in over half of cases. The affected gene is the RPE1 gene on chromosome 13 – a tumor suppressor gene which normally restricts the growth of embryonic cells. Since these cells are present only in the first few years of life, retinoblastoma is seldom diagnosed after three years of age. The tumors are often multifocal, and usually extend initially by local invasion. Hematogenous and lymphatic dissemination can result in metastasis to regional lymph nodes, the central nervous system and distant sites.

60 percent of cases are unilateral. 85 percent of these result from somatic mutations, which are not transmissible to offspring. 15 percent contain germline mutations, which are transmitted in an autosomal dominant pattern with 80 percent penetrance. All bilateral cases contain germline mutations. Since most mutations are sporadic, there is a positive family history in less than 10 percent of patients.

Other Causes Of Leukocoria In Children

• Toxocara granuloma, a granulomatous reaction around the larva of the roundworm, Toxocara canis. Leukocoria results from the accumulation of inflammatory cells or debris in the vitreous. Usually presents at 6 to 14 years.
• Persistent hyperplastic primary vitreous, a developmental abnormality consisting of a retrolental mass suspended by elongated ciliary processes.
• Coats’ disease/retinal telangiectasis, a retinal vascular abnormality with dilated vessels that leak exudate into the subretinal space, occasionally resulting in retinal detachment and leukocoria.
• Retinopathy of prematurity may cause vitreous fibrosis, retinal detachment and leukocoria in severe cases.
• Congenital cataract is often bilateral. It may be inherited, associated with a metabolic disorder, or caused by maternal infection or birth trauma. Pediatric assessment is generally required.
• Other rare causes include vitreous hemorrhage, retinal astrocytoma or astrocytic hamartoma, retinal dysplasia, incontinentia pigmenti, viral retinitis, congenital retinal fold, retinochoroidal coloboma and familial exudative vitreoretinopathy.

Signs

Leukocoria is the most common presenting sign in young children with retinoblastoma. Strabismus is also common, and occurs when the fovea is involved or obscured. Rarer presentations include secondary glaucoma, anterior segment invasion, orbital inflammation, proptosis, failure to thrive, metastatic disease and routine examination in the context of a positive family history.

Early tumors appear as flat or round white lesions. Endophytic retinoblastomas are nodular lesions extending inward into the vitreous, often with surface vascularization. Exophytic tumors grow outward into the subretinal space; subsequent retinal detachment and hemorrhage may impair visualization of the underlying tumor. A characteristic, fluffy pattern of calcification is often seen in retinoblastoma. Tumor fragments can dislodge into the vitreous (vitreous seeding). Both retinas must be examined for multifocal or bilateral disease. Full assessment in young children requires examination under anesthesia.

Prevalence

Rare (approximately 1 in 20,000 live births), primarily affecting young children before the age of two years, although older children are occasionally affected. In a city the size of Melbourne (4 million plus), there are only around 5 cases per year and bilateral cases occur only every few years. The severity of the condition poses a diagnostic challenge for clinicians who see pediatric patients, in terms of maintaining an index of suspicion for the condition despite its rarity.

Significance

Intraocular pathology must be excluded in all children with leukocoria or strabismus. Early diagnosis and treatment of retinoblastoma optimizes survival and may salvage useful vision in one or both eyes.

Differential Diagnosis

See above – OTHER CAUSES

See Also

Toxocariasis, Coats’ disease, Persistent Hyperplastic Primary Vitreous, Cataract, Tumors of Retina – Classification, Retinopathy of Prematurity.

Management

See RETINOBLASTOMA – Management