Retinoblastoma 👁️

Related Subjects: | Retinoblastoma | Leukocoria (White Pupillary Reflex)

👁️ Retinoblastoma is the most common intraocular malignancy of childhood. Around 4% of patients with the heritable form may also develop malignant midline neuroectodermal tumours such as pineoblastoma → this is called trilateral retinoblastoma. 📌 In high-income countries, survival rates exceed 95% with modern therapy, but in low-resource settings metastasis (to brain, CNS, bone marrow, or bone) remains a major cause of mortality.

📖 About

• Retinoblastoma = embryonal tumour of the retina arising from immature photoreceptor cells.
• Incidence ≈ 1 in 18,000 live births worldwide.
• Accounts for ~3% of all childhood cancers.
• Forms: heritable (germline RB1 mutation, often bilateral/multifocal) vs sporadic (somatic mutation, usually unilateral).

🧬 Aetiology

• Mutation of the RB1 tumour suppressor gene on chromosome 13q14.
• Two-hit hypothesis: Both alleles of RB1 must be inactivated → loss of control over G1/S checkpoint of cell cycle.
• Heritable form: Child inherits one defective allele; the “second hit” occurs somatically. → high risk of bilateral/multifocal disease.
• Trilateral retinoblastoma: Retinoblastoma + pineal/parapineal tumour (pineoblastoma).
• Secondary cancers (esp. osteosarcoma, sarcomas, melanoma) risk ↑ 50–500x in heritable form, particularly after radiotherapy.

🩺 Clinical Features

• Leukocoria: “Cat’s eye reflex” – white pupil on flash photography.
• Strabismus: Often due to macular involvement.
• Advanced disease: Pain, glaucoma, hyphema, orbital cellulitis-like picture, buphthalmos.
• 40% diagnosed <1 year of age; most unilateral. Very rare after age 5.

⚖️ Differential Diagnosis

• Congenital cataract (most common mimic of leukocoria).
• Persistent hyperplastic primary vitreous (PHPV).
• Coats’ disease (retinal telangiectasia with exudation).

🔍 Investigations

• Examination under anaesthesia with dilated fundus exam.
• Ocular ultrasound: Detects calcification (hallmark feature).
• MRI orbit/brain: Defines intraocular extent, optic nerve involvement, trilateral disease.
• Genetic testing: RB1 mutation analysis → informs prognosis & family screening.
• Bone marrow/bone scan: For suspected metastasis.

📊 Staging (International Classification of Retinoblastoma)

• Group A: ≤3 mm, confined, not near fovea/optic disc.
• Group B: Larger or close to vital structures, still confined.
• Group C: Local seeding (subretinal/vitreous).
• Group D: Diffuse seeding, retinal detachment, poor prognosis for eye salvage.
• Group E: Massive tumour, neovascular glaucoma, haemorrhage → enucleation usually required.
• Trilateral retinoblastoma: RB + pineoblastoma (very poor prognosis).

💊 Management

• Referral to UK centres: Birmingham Children’s Hospital or Royal London Hospital.
• Local therapies (for small tumours): Laser photocoagulation, cryotherapy, transpupillary thermotherapy.
• Systemic chemotherapy (“chemoreduction”): Allows focal therapies; used for bilateral/multifocal disease.
• Intra-arterial chemotherapy: Melphalan via ophthalmic artery → high efficacy, eye-salvaging.
• Intravitreal chemotherapy: For vitreous seeding (e.g. melphalan, topotecan).
• Plaque brachytherapy: Radioactive disc applied to sclera for small resistant tumours.
• Enucleation: For advanced unilateral disease (Group E).
• Avoid radiotherapy in heritable cases if possible (↑ secondary cancer risk).

🧾 Screening & Follow-up

• All children in affected families screened from birth until at least age 5 (regular EUA + imaging).
• Parents offered genetic counselling.
• Lifelong follow-up in heritable cases for secondary cancers.

🧠 Memory Aid

• “White reflex + Squint in a baby = Retinoblastoma until proven otherwise.”
• Think: R-B → Red reflex becomes White.

🧾 Clinical Case Example – Retinoblastoma

A 3-year-old boy is brought by his parents who noticed a white reflex (“leukocoria”) in photographs instead of the normal red reflex. They also report a recent inward turning of the eye (squint). Exam: absent red reflex in the right eye, mild proptosis. Family history: father lost one eye in childhood. 🧪 MRI orbit/brain: intraocular mass confined to the retina, no optic nerve invasion. Genetic testing: RB1 gene mutation. 👉 Diagnosis: Retinoblastoma (heritable form). 👉 Management: Multidisciplinary - focal therapy (laser, cryotherapy) for small tumours; chemotherapy ± enucleation if advanced; lifelong screening for second primary malignancies.