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Retinoblastoma is a malignant tumor of the retina arising from immature retinal neuroblasts. It is the most common intraocular cancer in children and typically presents before the age of 5 years.

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https://www.youtube.com/watch?v=SOsPWg9IQLI

https://www.youtube.com/watch?v=olNKFRAT0HQ

Epidemiology

• Incidence: ~1 in 15,000–20,000 live births
• 90% occur before age 5
• Bilateral in ~30–40% (usually hereditary)
• Unilateral in ~60–70% (usually sporadic)
• Slight male predilection in some studies

Pathogenesis

Caused by biallelic inactivation of the RB1 tumor suppressor gene (chromosome 13q14)

• Heritable form:
  • Germline RB1 mutation
  • Usually bilateral and multifocal
  • Increased risk of second malignancies (e.g., osteosarcoma)
• Sporadic form:
  • Somatic RB1 mutation
  • Usually unilateral and unifocal

![Progression of retinoblastoma: a | Anatomical features of a healthy eye. Genomic damage (indicated by a lightning bolt) leads to mutation of the retinoblastoma gene (RB1), resulting in biallelic functional loss of RB1 in a developing retinal cell (possibly a cone photoreceptor precursor cell that is dependent on retinoblastoma protein (pRB) to stop proliferation). b | Genomic instability leads to the formation of a benign retinoma; only 5% of patients have retinoma without retinoblastoma. Inset shows a small retinoma that is not visible except by optical coherence tomography. c | Intraretinal retinoblastoma arises as additional genomic changes promote uncontrolled cell proliferation; the tumour grows and seeds become independent, floating under the retina and into the vitreous. d | Retinoblastoma can invade adjacent tissues, such as the optic nerve, uvea or sclera, which constitutes a high-risk pathological feature. Eventually, retinoblastoma can extend extraocularly into the orbit and metastasize, especially to the bone marrow, or into the brain (direct or via the cerebrospinal fluid (CSF)).

Dimaras, H., Corson, T., Cobrinik, D. et al. Retinoblastoma. Nat Rev Dis Primers 1, 15021 (2015). https://doi.org/10.1038/nrdp.2015.21](attachment:a61c3f69-4e42-4d0b-8b6f-d34d0540f421:41572_2015_Article_BFnrdp201521_Fig1_HTML.webp)

Progression of retinoblastoma: a | Anatomical features of a healthy eye. Genomic damage (indicated by a lightning bolt) leads to mutation of the retinoblastoma gene (RB1), resulting in biallelic functional loss of RB1 in a developing retinal cell (possibly a cone photoreceptor precursor cell that is dependent on retinoblastoma protein (pRB) to stop proliferation). b | Genomic instability leads to the formation of a benign retinoma; only 5% of patients have retinoma without retinoblastoma. Inset shows a small retinoma that is not visible except by optical coherence tomography. c | Intraretinal retinoblastoma arises as additional genomic changes promote uncontrolled cell proliferation; the tumour grows and seeds become independent, floating under the retina and into the vitreous. d | Retinoblastoma can invade adjacent tissues, such as the optic nerve, uvea or sclera, which constitutes a high-risk pathological feature. Eventually, retinoblastoma can extend extraocularly into the orbit and metastasize, especially to the bone marrow, or into the brain (direct or via the cerebrospinal fluid (CSF)).

Dimaras, H., Corson, T., Cobrinik, D. et al. Retinoblastoma. Nat Rev Dis Primers 1, 15021 (2015). https://doi.org/10.1038/nrdp.2015.21

Clinical Features

• Leukocoria (white pupillary reflex) — most common presenting symptom
• Strabismus