Retinoblastoma

Retinoblastoma is a cancer of the retina that is the common ocular malignancy in children. Despite it being the most common ocular malignancy it is still very rare (only 50 children affected annually). It has a very good prognosis with 90% of children making it into adulthood.

🔢 Pathophysiology and classification

A retinoblastoma most commonly develops between the 3rd month of pregnancy - 5 years of age.

It occurs due to mutations in the RB1 gene - a tumour suppressor gene present on chromosome 13. There needs to be mutations present on both alleles of the RB1 gene for retinoblastoma to occur.

RB1 mutations result in a loss of function → cell proliferation and tumour development.

It may be classified by its aetiology:

1. Heritable retinoblastoma - this occurs when there is an inherited mutation of one RB1 gene from a parent and a mutation occurs on the normal copy. Approximately 90% of people who inherit an altered Rb gene will develop retinoblastoma. It is most commonly bilateral. 10% do not develop a tumour at all. Heritable retinoblastoma results in all cells in the body having an altered copy as it is a germline mutation.
2. Non-heritable retinoblastoma - this occurs when both inherited alleles are normal but there ends up being somatic mutations (non-germline mutations) in both copies of the gene. The tumour develops unilaterally in these cases.

⚠️ Risk factors

• Advanced paternal age - this increases the risk of mutations occurring in the RB1 gene during spermatogenesis.
• Viral exposure - particularly to HPV.

😷 Presentation

• Abnormal red reflex (leukocoria) - the red reflex is absent and the retina appears white as opposed to red.
• Strabismus (a misaligned or squint eye)
• Deteriorating vision
• Failure to thrive
• Proptosis - a later sign. It refers to the bulging of the from the orbit.

🔍 Investigations

Diagnosis is usually done by an ophthalmologist or an ophthalmology oncologist. Some tests done include:

• Pupillary red reflex - leukocoria
• Fundoscopy and examination under anaesthesia (indirect ophthalmoscopy) - halky, white-grey retinal mass; may show retinal detachment, vitreous seeding
• Ophthalmic A and B-scan ultrasound
• A-scan is an amplitude scan, giving details about the length of the eye.
• B-scan is a brightness scan, used to evaluate the posterior segment of the eye. This is the portion used to diagnose retinoblastoma.
• Genetic testing for the presence of RB1 mutations
• Systemic evaluation to rule out metastasis, including a lumbar puncture to check for the presence of malignant cells

💡 Biopsy of retinoblastoma is not recommended, as it can induce seeding and extraocular spread along the needle tract.

🧰 Management

The 3 goals of treatment, in order of priority, are to save the patient's:

1. Life
2. Eye
3. Vision