Retinoblastoma

Question 1

Retinoblastoma is more likely to be bilateral when age <____.

Answer 1

<1 year

Question 2

What are the two clinical forms of retinoblastoma? What percentage of patients have each? Median time to diagnosis?

Answer 2

1. Non-heritable, unilateral or unifocal - 75% of patients; median time to diagnosis 29-30 months
2. Heritable, bilateral, multifocal - 25% of patients; median time to diagnosis 14-16 months

Question 3

What is the germline mutation in heritable retinoblastoma? What percentage are inherited from carrier parent vs. de novo?

Answer 3

• RB1
• Carrier parent: 25%
• De novo: 75%

Question 4

What is the syndrome associated with germline RB1 deletions? What percentage of patients?

Answer 4

• 13q- syndrome; intellectual disability and dysmorphic features
• 3-5%

Question 5

Additional “second hit” events in retinoblastoma after biallelic RB1 inactivation?

Answer 5

• MDM2 and MDM4 amplification (p53 pathway)

- Epigenetic: BCOR mutations; SYK upregulation

Question 6

What percentage of patients with retinoblastoma have wild type RB1? What do they have instead? What is the prognosis?

Answer 6

• 1.5%
• MYCN amplification
• Associated with wore outcome

Question 7

RB1 germline mutation is associated with ____% penetrance to develop retinoblastoma.

Answer 7

> 90%

Question 8

What percentage of patients with bilateral retinoblastoma have an RB1 germline mutation?

Answer 8

100%

-Can be mosaic - 10% of patients with “de novo” bilateral

Question 9

What percentage of patients with unilateral retinoblastoma have an RB1 mutation?

Answer 9

15%

Question 10

What percentage of patients with a germline RB1 mutation develop unilateral retinoblastoma?

Answer 10

15%

Question 11

When is genetic counselling /offer of genetic testing indicated for retinoblastoma?

Answer 11

Indicated in ALL patients with retinoblastoma and their families, regardless of laterality

Question 12

What is needed to screen relatives?

Answer 12

Specific mutation of the proband

Question 13

All offspring and newborn siblings must be screened ____ and every ____weeks until genetic testing is complete.

Answer 13

At birth and every 4 weeks

Question 14

Babies with positive testing (RB1 mutation) require ____ for screening every ____ weeks due to penetrance of the mutation.

Answer 14

• Dilated eye exams

- Every 4 weeks

Question 15

Clinical presentation of intraocular retinoblastoma

? Advanced intraocular? Extraocular?

Answer 15

• Intraocular: Leukocoria (65-75%), Strabismus (10-15%), Nystagmus (5-10%)
• Advanced Intraocular: Buphthalmos, Glaucoma, Periorbital cellulitis
• Extraocular: Proptosis + LN, Metastases

Question 16

Evaluation for retinoblastoma?

Answer 16

• Examination under anesthesia (both eyes)
• -Direct visualization of tumour(s)
• -Evaluation of corneal diameters and intraocular pressure
• Imaging
• -Ocular US
• -MRI orbits and brain
• –Evaluation of optic nerve prior to enucleation
• –Evaluation of CNS (trilateral retinoblastoma)
• Bone scan, bone marrow aspirate/biopsy and CSF cytology ONLY if advanced disease: high-risk histology after enucleation, or extraocular retinoblastoma
• Genetic counselling