Retinoblastoma

Introduction

• It is an embryonal tumour.
• Most common primary ocular malignancy of childhood.
• It is a small round blue cell tumor arising from any of the layers of the retina.
• Usually unilateral (>75%).
• A relatively slow growing tumour.
• Late presentation is common, so blindness is a common presentation.

Epidemiology

• Condition occurs globally.
• Incidence is about one per 16,000 – 18,000 live births globally.
• Worldwide, approximately 8,000 children develop retinoblastoma each year.
• Generally is the third or fourth commonest childhood malignancy in Nigeria after Burkitt's lymphoma and leukemia (nephroblastoma more common in some studies).
• May be heritable (about 40%) or non-heritable (about 60%).
• Equal sex predilection.

Aetiology/Risk Factors

• Majority of cases are heritable.
• Mutation affecting the RB1 gene is implicated (germline or non-germline).
• Mutant allele is recessively inherited and requires a two-hit.
• Disease results from inactivation of the retinoblastoma gene (13q14).
• Encodes the retinoblastoma protein (pRb), a tumor suppressor protein that controls cell-cycle phase transition.
• Hereditary forms are usually bilateral and multifocal.

Pathology

• Originates from the precursors of rods and cone cells of the retina arising from the posterior portions of the inner and outer nuclear layers.
• It forms nodules often with satellite seedlings.
• Tumour growth may be endophytic or exophytic (subretinal fluid and retinal detachment).

Clinical Features

• 90% of cases occur before 5 years of age; most cases will occur before the 2nd year of life.
• Earlier presentation in the heritable form.
• May be detected incidentally.
• Leucokoria (white reflex or cat's eye reflex).
• Strabismus
• Pain
• Poor vision
• Orbital inflammation
• Pupillary irregularity
• Other features include nystagmus, failure to thrive, hyphema, proptosis, and fungating mass.

Leucokoria

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Leucokoria

Differential Diagnoses

• Congenital cataract
• Retinopathy of prematurity
• Xerophthalmia
• Hyperplastic primary vitreous
• Coats disease
• Rhabdomyosarcoma
• Chloroma
• Neuroblastoma
• Retroorbital capillary hemangioma

Staging

Stage	Characteristics
Stage I	Solitary or multiple tumours less than 4 disc diameter at or behind the equator of the eye
Stage II	Solitary or multiple tumours 4-10 disc diameter at or behind the equator of the eye
Stage III	Any lesion anterior to the equator, solitary tumours > 10 DD behind the equator
Stage IV	Multiple tumours greater than 10 DD, extending anterior to the ora serrata
Stage V	Massive tumours involving over half of the retina with vitreous seeding

Diagnosis/Investigations

• Careful ophthalmologic examination
• May need to be done under general anaesthesia
• Orbital ultrasound scan
• Orbital radiographs: calcification in 75% of cases
• Cranial CT scan: To determine extent of tumour
• Cranial MRI: Define extent of tumour involvement including nerve involvement

Treatment

• Treatment is determined by the size and location of the tumor.
• The primary goal is cure; the secondary goal is preserving vision.
• Unilateral: Unilateral enucleation of the eye
• Bilateral disease: Radiation to save less affected eye. Another option is chemoreduction in combination with focal therapy (laser photocoagulation or cryotherapy)
• Chemotherapy: Vincristine, etoposide, and carboplatin every 21-28 days for 6 months

• Enucleation: Removal of the entire globe and its intraocular contents, with preservation of all other periorbital and orbital structures
• Evisceration: Removal of the internal contents of the eye followed usually by placement of an orbital implant to replace the lost ocular volume
• Exenteration: Removal of the eye and its orbital contents including the extraocular muscles, orbital fat, nerves, lids, lashes, lachrymal gland, and occasionally brow

Prognosis

• Prognosis is good with early presentation.
• Most cases present late in this environment with poor prognosis for cure and preservation of vision.

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