Makindo Medical Notes

Around 4% of patients with the heritable form of retinoblastoma may also develop malignant midline neuroectodermal tumours, such as pineoblastoma. This condition is called trilateral retinoblastoma. Retinoblastoma can metastasize from the eye to the brain, central nervous system (CNS), and bones, but this is rare in developed countries.

About

• Retinoblastoma is an embryonal tumour of the retina, which develops from immature retinal cells.
• The incidence is approximately 1 in 18,000 live births.
• Retinoblastoma accounts for about 3% of all cancers diagnosed in children.
• There are two forms of the disease: heritable (genetic) and non-heritable (sporadic).

Aetiology

• Caused by mutations in the RB1 gene, a tumour suppressor gene responsible for controlling cell growth.
• Individuals inherit one defective copy of the RB1 gene in the heritable form, predisposing them to develop retinoblastoma.
• The disease affects either one or both eyes (unilateral or bilateral) and can also involve the pineal gland in cases of trilateral retinoblastoma.
• There is an increased risk of secondary cancers, particularly osteosarcoma, which is 50-500 times higher than the general population's risk.
• Most heritable cases present bilaterally, and multifocal tumours can develop.

Clinical Features

• Leukocoria: Loss of the red reflex, causing a white or yellowish reflection in one or both eyes (also known as a "cat's eye reflex").
• Strabismus: Misalignment of the eyes, often due to macular involvement.
• Advanced disease: Can present with pain, glaucoma, or buphthalmos (enlargement of the eyeball due to increased intraocular pressure).
• About 40% of cases are diagnosed in the first year of life, with around 60% of all cases being unilateral.
• Incidence of retinoblastoma drops significantly after the age of 5.

Differential Diagnosis

• Congenital cataract: A common cause of leukocoria but distinguishable from retinoblastoma.

Investigations

• Fundal eye examination: Performed under general anesthesia with a maximally dilated pupil to assess the retina and other intraocular structures.
• Ocular ultrasound (USS) and MRI: Used to visualize intraocular tumours and assess for the involvement of the optic nerve or extension into the CNS.
• Genetic testing: Blood or tumour samples can be analyzed for RB1 gene mutations to confirm the diagnosis and screen family members.

Staging of Disease

• Group A: Small tumours (3 mm or less), confined to the retina, not near important structures like the optic disc or foveola.
• Group B: Larger tumours or those close to the optic disc or foveola but still confined to the retina.
• Group C: Tumors with subretinal or vitreous seeding (spreading of tumour cells).
• Group D: Larger, poorly defined tumours with widespread seeding and possible retinal detachment.
• Group E: Large tumours extending to the front of the eye, causing complications like bleeding, glaucoma, or other features that significantly reduce the chance of saving the eye.
• Trilateral retinoblastoma: Typically develops between 20-36 months and has a poor prognosis, accounting for about half of mortality within the first ten years post-diagnosis.

Management

• In England, urgent referral is made to specialized retinoblastoma centers, such as Birmingham Children's Hospital or the Royal London Hospital, for diagnosis and treatment.
• Photocoagulation, Cryotherapy, and Transpupillary thermotherapy: Effective for small tumours.
• Systemic chemotherapy: Used for larger tumours as an adjuvant therapy, often allowing for less aggressive treatments like enucleation or external beam radiotherapy.
• Plaque radiotherapy: Effective for small, solitary tumours that are not responsive to other therapies.
• Enucleation: Removal of the affected eye, which is less common today due to advances in other treatment modalities.
• Ophthalmic artery chemotherapy: Melphalan chemotherapy administered directly to the ophthalmic artery has shown promising results.

Screening

• All children in families with a history of retinoblastoma should be screened until the age of 5.