- Most common primary intraocular malignancy of childhood
- Incidence: 1 in 15,000 live births in the United States
- Girls and boys are affected equally.
- Accounts for about 4% of malignant tumors in children < 15 years of age
- Approximately 95% of affected children are diagnosed before the age of 5.
- The median age of diagnosis is 18–20 months.
- Approximately 40% of cases are heritable.
- In resource-rich countries: > 95%
- In resource-limited/developing countries: < 30%
- Retinoblastoma is caused by a genetic mutation of the retinoblastoma gene (RB1 or RB) in 98% of cases.
- RB1 is a key negative regulator of the G1/S cell cycle transition and is directly or indirectly inactivated in most human malignancies.
- Nonheritable form: (60% of cases)
- Two spontaneous somatic mutations occur in the RB1 gene progenitor cells, leading to the development of retinoblastoma.
- Tends to be unilateral and unifocal
- Presents between the ages of 2 and 5
- Familial or heritable form: (40% of cases)
- The child inherits a non-functional allele of the RB1 gene, which is present in all somatic cells.
- Only 1 more (sporadic) mutation of the 2nd allele in a neuronal progenitor cell is necessary to form a retinoblastoma.
- Tends to be bilateral and/or multifocal
- Presents before the age of 1
- Cardinal signs:
- Less common signs and symptoms:
- Decreased vision
- Ocular inflammation
- Vitreous hemorrhage
- Rarely needed to confirm the diagnosis
- A biopsy is contraindicated because of the risk of tumor seeding.
- Three growth patterns are seen: exophytic (beneath the retina), endophytic (into the vitreous), and diffusely infiltrating (rare, grows within the retina).
- Urgent referral to ophthalmologist
- Ophthalmoscopic examination under anesthesia, with ultrasound imaging
- Magnetic resonance imaging (MRI) of the brain and orbits
- No need for formal staging studies (i.e., bone marrow examination, lumbar puncture, and/or radionuclide bone scan) → metastases rarely present at time of diagnosis
- Genetic testing is recommended.
Management and Prognosis
Treatment depends on the stage, with multiple “vision-sparing” therapies available:
- Small, uncomplicated extrafoveal tumors: cryotherapy or laser photocoagulation
- More advanced stages: local and systemic chemotherapy, radioactive plaques
- Anatomical or functional impairment by tumor: enucleation
- Metastatic disease:
- Rarely (2%–3%) present at time of diagnosis
- Autologous stem cell transplantation after intensive multimodal therapy
- Lifetime follow-up to detect secondary malignancies is necessary!
- Survival: > 95% in resource-rich countries; < 30% in countries with very limited resources
- Prognosis for vision depends on extent of tumor: 50% of patients reach a final visual acuity of 20/40 or better.
The differential diagnosis includes any condition that can cause leukocoria.
- Persistent fetal vasculature: failure of the embryonic primary vitreous and hyaloid vascular system to involute during gestation. Visual prognosis is poor.
- Retinopathy of prematurity (ROP): a potentially blinding eye disorder that primarily affects premature infants. The disorder is caused by neovascularization with abnormal and fragile vessels due to growth factors released by incompletely developed peripheral retinal vessels. The vessels bleed easily and cause scarring. Most cases of ROP are mild.
- Cataract: a congenital or acquired condition in which the lens of the eye becomes progressively opaque, resulting in blurred vision.
- Coats disease: an idiopathic disorder characterized by retinal telangiectasia with breakdown of the blood-retinal barrier. Most commonly affects children. Can cause retinal detachment and blindness.
- Vitreous hemorrhage (VH): the presence of blood within the vitreous cavity. Three conditions cause most VH cases: ocular trauma, posterior vitreous detachment associated with retinal detachment, and proliferative diabetic retinopathy.
- Ocular toxocariasis (ocular larva migrans): a rare infection caused by roundworms, Toxocara canis, and Toxocara cati. Presents with posterior uveitis and is associated with reduced vision, photophobia, floaters, and leukocoria.
- Familial exudative vitreoretinopathy: a group of rare inherited diseases with abnormal retinal angiogenesis causing incomplete vascularization of the peripheral retina. Can lead to secondary neovascularization with progression to blindness.
- Coloboma: a development disorder due to failure of the optic (choroid) fissure to fuse so that a defect may be present anywhere along the inferior portion of the eye, from the optic disc to the iris. A large optic disc and chorioretinal coloboma can cause leukocoria.
- Retinal astrocytic hamartoma: a usually indolent tumor that occurs in roughly half of patients with tuberous sclerosis complex. The condition is also associated with neurofibromatosis.
- Kaufman PL, Kim J, Berry JL. (2018). Retinoblastoma: Clinical presentation, evaluation, and diagnosis. UpToDate. Retrieved August 30, 2020 from: https://www.uptodate.com/contents/retinoblastoma-clinical-presentation-evaluation-and-diagnosis#H3
- Kaufman PL, Kim J, Berry JL. (2018). Retinoblastoma: Treatment and outcome. UpToDate. Retrieved August 30, 2020 from https://www.uptodate.com/contents/retinoblastoma-treatment-and-outcome?topicRef=6275&source=see_link
- Lazar, A.L. (2020). In Kumar, V., Abbas, A. K., Aster, J.C., (Eds.), Robbins & Cotran Pathologic Basis of Disease. (10 ed., pp. 1324, 290-294). Elsevier, Inc.
- Berry JL, Polski A, Cavenee WK, Dryja TP, Murphree AL, Gallie BL. The RB1 Story: Characterization and Cloning of the First Tumor Suppressor Gene. Genes (Basel). 2019 Nov 1;10(11):879. doi: 10.3390/genes10110879.
- Hurwitz RL, Hurwitz M. Retinoblastoma. National Organization for Rare Disorders (NORD). Retrieved on August 31, 2020 from: https://rarediseases.org/rare-diseases/retinoblastoma/
- Demirci H, Shields CL, Meadows AT, Shields JA. Long-term visual outcome following chemoreduction for retinoblastoma. Arch Ophthalmol. 2005;123(11):1525.
- Shields, C.L., Schoenberg, E., Kocher, K., et al. (2013), Lesions simulating retinoblastoma (pseudoretinoblastoma) in 604 cases: results based on age at presentation. Ophthalmology. 2013;120(2):311-316.