Oncology - Retinoblastoma

Question 1

Defintion

Answer 1

Malignant tumour of the retina, and the most common malignant intraocular tumour in children

Question 2

Epidemiology

Answer 2

The average age of diagnosis is 18 months

Question 3

Aetiology

Answer 3

• Genetics- mutation in both alleles of RB1 gene (Autosomal dominant)
• Viral exposure
  Aetiology
• Advanced paternal age

Question 4

Pathophysiology

Answer 4

Retinoblastoma is primarily caused by mutations in the RB1 gene (on chromosome 13), which is responsible for regulating cell growth and division.
In individuals with hereditary retinoblastoma, one copy of the RB1 gene is inherited with a mutation from one parent. A second “hit” or mutation occurs in the other copy of the RB1 gene within the retinal cells, leading to the loss of both functional copies of the gene. This loss of function allows the uncontrolled growth of retinal cells and the formation of tumours.
The RB1 gene normally produces a protein called pRB (retinoblastoma protein), which plays a crucial role in inhibiting the cell cycle and controlling cell division. When both copies of the RB1 gene are mutated or lost, pRB cannot effectively regulate cell growth. This Pathophysiology
leads to uncontrolled cell proliferation and the formation of retinoblastoma tumours.

Prognosis is excellent with >90% surviving in adulthood

Question 5

Hereditary Retinoblastoma

Answer 5

Hereditary retinoblastoma is caused by a germline mutation in the RB1 gene that is present in all cells of the body, including the retinal cells. This form of retinoblastoma is usually bilateral (affects both eyes) and has a higher risk of recurrence.

Question 6

Sporadic Retinoblastoma

Answer 6

Sporadic retinoblastoma, on the other hand, occurs due to somatic mutations that arise in retinal cells during early development. Sporadic cases can be either unilateral (affects one eye) or bilateral.

Question 7

Symptoms

Answer 7

• Absence of red-reflex, replaced by a white pupil (leukocoria) = the most common presenting symptom
• Strabismus
• Visual problems

Question 8

Diagnosis

Answer 8

• Fundoscopy and examination under anaesthesia = chalky, white-grey retinal mass
• Ophthalmic USS

Question 9

Treatment

Answer 9

Urgent treatment is required to maximise the child’s chances of survival. Treatment may involve
● Enucleation with chemotherapy.
● External beam radiation
Management
● Photocoagulation
With treatment, 5 year survival is 90-95%

Question 10

Risk factors

Answer 10

Mutation in RB1 gene,
HPV viral exposure,
Advanced paternal age