Description

Retinoblastoma is a malignant tumor of the retina. Due to current treatment options, survival rates are high in developed countries. Primary management focuses on the best treatment approach to spare the child’s life, while secondary goals focus on sparing vision and reducing risk of secondary malignancies.

Epidemiology

• Retinoblastoma is the most common intraocular malignancy in children.
• Hereditary retinoblastoma commonly presents with bilateral disease or multiple tumors in unilateral disease
• Median age at diagnosis for unilateral disease is 24 months and less than 12 months for bilateral disease.
• 25% of patients will present with bilateral disease.
• No association with race, gender, or laterality of eye involvement
• The greatest disease burden is found in countries with the largest populations and high birth rates such as Asia and Africa.

Risk Factors

• Hereditary retinoblastoma, in which patients have a germline Rb gene mutation
  • 25–45% of all retinoblastoma cases are hereditary.
• Family history of retinoblastoma in parents or siblings warrants early screening and continued follow-up to monitor for development of disease.

Pathophysiology

• Tumor development requires loss of function of the RB1 gene, which resides on chromosome 13.
• Constitutional loss of one RB1 allele predisposes a patient to cancer. Loss of the second allele or other mutations of retinal cells will initiate formation of retinoblastoma.
• Sporadic or nonhereditary retinoblastoma has no germline RB1 mutation but instead requires biallelic inactivation of the RB1 gene in a single retinal cell.
• There are 3 common growth patterns:
  • Intraretinal (growth only in the retina)
  • Endophytic (inner surface of retina to vitreous)
  • Exophytic (outer surface of retina to subretinal space)
  • Tumor cells that break off from the primary mass will invade the vitreous and grow independently in the vitreous.
• Children with loss of RB1 with large chromosomal deletions of surrounding genes are at risk for developmental anomalies such as facial dysmorphism and mental and/or motor impairment.
• Initial classification of tumor extent is imperative for assessment of prognosis and outcomes.
• International Classification of Retinoblastoma (ICRB), also known as the ABC classification system, is predictive of treatment success following systemic chemotherapy and focal laser treatment. However, the older Reese-Ellsworth classification system is still commonly used.
  • ICRB groups eyes from less advanced disease, group A, to most advanced disease, group E.
  • ICRB predicts high-risk retinoblastoma seen in group D or E eyes.
• High-risk features on histology include tumor invasion of the optic nerve and massive choroidal invasion. High-risk features will lead to metastases in about 24% of patients if not treated with systemic chemotherapy as compared to 4% of those treated with systemic chemotherapy.
• Patients with bilateral retinoblastoma are at risk for involvement of the pineal gland, termed trilateral retinoblastoma.

Etiology

Mutations in the RB1 gene lead to predisposition of retinal tumors.