Retinoblastoma

Question 1

What is an alarmsymptom?

Answer 1

White pupil

Question 2

What is the overall survival rate?

What is the ratio heriditary/ non-heriditary?

Answer 2

96%

50%/50% –> 1/1

Question 3

In heriditary RB, what is the risk of future malignancies? And for what do patients need to look out?

Answer 3

28%, for radiation

Question 4

What percentage is unilateral and what percentage is bilateral?
If you see a double sided RB, there is … chance it is heriditary
If you see a unilateral RB, there is … chance it is hereditary

Answer 4

67% is unilateral and 33% bilateral. If you see a double sided RB, there is 100% chance it is heriditary and if it is a unilateral RB there is 15% chance it is hereditary.

Question 5

What happens if you leave it untreated?

Answer 5

It metastases and can lead to death. Metastatic spread goes to bone, bone-marrow, lymphnodes and CNS.

Question 6

Screening: when to start and what is the screeningsscheme?

Answer 6

You start as soon as possible after birth with an opthalmological examination without anaestasia.
- From age 0-12 months every 2 months. From 6 months general anaesthesia is used.
- From 1 year every 3 months EUA
- From 2 years, every 4 months EUA
- From 3 years, every 6 months; without anaesthesia.
You can stop screening at age of 4.

Question 7

What are non-hereditary characteristics?

Answer 7

No germline Rb1 mutation in pheripheral blood, unilateral, unifocal RB, late onset.

Question 8

What are hereditary characteristics?

• Chromosome
• Mutation
• Sided
• Chance of future malignancies

Answer 8

Rb1 gene mutation on 13q14 chromosome. 98% autosomal dominant hereditary. 10% it is a familial inherited germline mutation. 90% it is de novo. Mostly bilateral, multifocal, early onset.
28% chance to get future malignancies; sarcoma, carcinoma, melanoma.

Question 9

What are the 5 presenting features?

Answer 9

decreased vision, swolen eyelid, orbita cellulitis, strabismus and leukocoria (cat eye, white pupil).

Question 10

What are the 4 different classes of pseudoretinoblastoma?

Answer 10

Vascular, developmental, miscelloneous, inflammatory & infectious.

Question 11

What are the 2 most frequent pseudoretinoblastoma’s?

Answer 11

Coats disease 40% (vascular) and PFV 28% (developmental)

Question 12

How can you diagnose RB?

Answer 12

Can directly be done with indirect opthalmoscopy (funduscopy) or US. MRI is planned. MRI is done also of the brain, because of trilateral retinoblastoma.

Question 13

What is trilateral RB?

Answer 13

RB in both eyes and in pineal gland or supra- or parasellar region –> 3.5% of patients with hereditary RB.

Question 14

What are the three goals in treating RB (in right order)?

Answer 14

1. Save life
2. Save sight
3. Cosmetic appearance

Question 15

What different therapies are available?

Answer 15

1. Enucleation (Removal whole eye)
2. Lasertherapy
3. Cryotherapy
4. Brachytherapy
5. Radiationtherapy
6. Systemic chemotherapy
7. Selective intra-arterial therapy
8. Intravitreal therapy

Question 16

How does enucleation work and what does the pathologist do with the eye?

Answer 16

The whole eye is removed, an internal prothesis is immediatly put in. After 4 weeks also an outside prothesis is put in. The eye is send to the pathologist, who looks at the DNA and risk factors for metastasation:
1. Massive choroidal ingrowth
2. Optic nerve ingrowth
3. Anterior chamber localisation.
If it has metastased, then 6 doses of chemotherapie (VEC).

Question 17

How does laser therapy work?

Answer 17

Laserlight heats tumor or tumor recurrence. This is for small tumors, gives small scars. You have to repeat it every 4 weeks and give 3 treatments per tumor.

Question 18

How does cryotherapy work?

Answer 18

Freezing of tumors or tumorrecurrence. For small tumors of pheripheral retina. Gives moderate large scars. Repeat cryotherapy every 4 weeks, 3 sessions per tumor.

Question 19

How does brachytherapy work?

Answer 19

For moderate large tumors or tumorrecurrence. Gives larger scars. Is done with Ruthenium 106. Leave it in for 24 hours only, hospital stay for 2-3 days.

Question 20

How does radiationtherapy work?

Answer 20

Proton beam therapy for 25 days, 25 times everyday. You only give this when it is a tumor recurrence and other treatments don’t work, or to save the last eye.

Question 21

What are short and longterm side effects and risks of radiation therapy?

Answer 21

Orbital growth deformation, radiation kerotopathy (dry eye), radiation cataract, radiation retinopathy and induced oncogenesis or sarcoma.

Question 22

When do you give systemetic chemo? and what can you give?

Answer 22

Only reduces tumor, is not curative. It works as a bridging therapy.
- Carboplatin or VEC

Question 23

What are selective intra-arterial and intravitreal treatment?

Answer 23

Intra-arterial is catheterisation for exofytic growing tumor. Child has to be >8 months or >8 kg.
Intravitreal is direct injection in the eye, helps against vitreous seedings
Both you need 2-6 treatments of malfalan, tapotecan and carboplatin.

Question 24

What is the Knudson’s two-hit hypothesis?

Answer 24

For a retinoblast it is needed that both copies are affected.
With heritable retinoblastoma: 1st hit is mutation present in germline at birth and 2nd hit is acquired mutation.
With sporadic retinoblastoma: 1st hit is acquired and 2nd hit also.

Question 25

What kind of gene is Rb1?

Answer 25

Tumor supressor gene

Question 26

In what percentage is no mutation found? How is this possible?

Answer 26

8%, this is explained by mosaicism.

Question 27

What are options for someone with RB1 mutation that wants a child?

Answer 27

• Adoption
• Testing for child rb1-mutation: during pregnancy, after birth or before pregnancy (by pre-implantation Genetic Testing PGT)m

Question 28

If a child has RB, but DNA tests show that the parents aren’t carrier. What is the chance the sibling will get RB aswell?

Answer 28

2-3% risk that sibling will get RB aswell. This is explained by mosaicism, which may be present in the parents germcells.

Question 29

How do you test if the RB is heritable?

Answer 29

By testing the eye that came out with enucleation and testing the blood. If the mutation is not found in the pheripheral blood, then it is non-heritable.

Question 30

What is “low penetrance” mutation?

Answer 30

Specific mutations (missense, exon 1, promotor, delRB1) –> gives non-penetrant carriers.

Question 31

If you have Rb1 mutation for what malignancies do you need to look out?

Answer 31

Melanoma, sarcoma (bone, muscle, connective tissue, uterus) and epithelial tumors (lung, bladder, colon, breast).

Question 32

Why imaging in oncology?

Answer 32

Screening (not in RB), staging, diagnosis, follow-up with treatment, response prediction, therapy guidance, prognosis, outcome.

Question 33

Why is CT avoided in children? (especially with Rb1 gene)

Answer 33

Because higher risk for leukemia and brain tumors.

Question 34

What does the TNM staging consist of?

Answer 34

Tumor
Node
Metasasis
(Heritable trait)

Question 35

Tumor:

• What does cT3a mean
• What does cT3b mean
• What does cT4 mean?

Answer 35

ct3a: choroidal involvement
ct3b: retrolaminar optic nerve involvement and free margins
ct4: orbital invasion

Question 36

If children are discovered with trilateral RB in asymptomatic phase, what is the survival rate?

Answer 36

50%

Question 37

What is the DD when you see a diffuse growth pattern?

Answer 37

Retinal detachment, diffuse retinal thickening

and enhancement: M.Coats, PFV, retinal dysplasia..