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.