Retinoblastoma Flashcards
What is an alarmsymptom?
White pupil
What is the overall survival rate?
What is the ratio heriditary/ non-heriditary?
96%
50%/50% –> 1/1
In heriditary RB, what is the risk of future malignancies? And for what do patients need to look out?
28%, for radiation
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
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.
What happens if you leave it untreated?
It metastases and can lead to death. Metastatic spread goes to bone, bone-marrow, lymphnodes and CNS.
Screening: when to start and what is the screeningsscheme?
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.
What are non-hereditary characteristics?
No germline Rb1 mutation in pheripheral blood, unilateral, unifocal RB, late onset.
What are hereditary characteristics?
- Chromosome
- Mutation
- Sided
- Chance of future malignancies
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.
What are the 5 presenting features?
decreased vision, swolen eyelid, orbita cellulitis, strabismus and leukocoria (cat eye, white pupil).
What are the 4 different classes of pseudoretinoblastoma?
Vascular, developmental, miscelloneous, inflammatory & infectious.
What are the 2 most frequent pseudoretinoblastoma’s?
Coats disease 40% (vascular) and PFV 28% (developmental)
How can you diagnose RB?
Can directly be done with indirect opthalmoscopy (funduscopy) or US. MRI is planned. MRI is done also of the brain, because of trilateral retinoblastoma.
What is trilateral RB?
RB in both eyes and in pineal gland or supra- or parasellar region –> 3.5% of patients with hereditary RB.
What are the three goals in treating RB (in right order)?
- Save life
- Save sight
- Cosmetic appearance
What different therapies are available?
- Enucleation (Removal whole eye)
- Lasertherapy
- Cryotherapy
- Brachytherapy
- Radiationtherapy
- Systemic chemotherapy
- Selective intra-arterial therapy
- Intravitreal therapy
How does enucleation work and what does the pathologist do with the eye?
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).
How does laser therapy work?
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.
How does cryotherapy work?
Freezing of tumors or tumorrecurrence. For small tumors of pheripheral retina. Gives moderate large scars. Repeat cryotherapy every 4 weeks, 3 sessions per tumor.
How does brachytherapy work?
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.
How does radiationtherapy work?
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.
What are short and longterm side effects and risks of radiation therapy?
Orbital growth deformation, radiation kerotopathy (dry eye), radiation cataract, radiation retinopathy and induced oncogenesis or sarcoma.
When do you give systemetic chemo? and what can you give?
Only reduces tumor, is not curative. It works as a bridging therapy.
- Carboplatin or VEC
What are selective intra-arterial and intravitreal treatment?
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.
What is the Knudson’s two-hit hypothesis?
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.
What kind of gene is Rb1?
Tumor supressor gene
In what percentage is no mutation found? How is this possible?
8%, this is explained by mosaicism.
What are options for someone with RB1 mutation that wants a child?
- Adoption
- Testing for child rb1-mutation: during pregnancy, after birth or before pregnancy (by pre-implantation Genetic Testing PGT)m
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?
2-3% risk that sibling will get RB aswell. This is explained by mosaicism, which may be present in the parents germcells.
How do you test if the RB is heritable?
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.
What is “low penetrance” mutation?
Specific mutations (missense, exon 1, promotor, delRB1) –> gives non-penetrant carriers.
If you have Rb1 mutation for what malignancies do you need to look out?
Melanoma, sarcoma (bone, muscle, connective tissue, uterus) and epithelial tumors (lung, bladder, colon, breast).
Why imaging in oncology?
Screening (not in RB), staging, diagnosis, follow-up with treatment, response prediction, therapy guidance, prognosis, outcome.
Why is CT avoided in children? (especially with Rb1 gene)
Because higher risk for leukemia and brain tumors.
What does the TNM staging consist of?
Tumor
Node
Metasasis
(Heritable trait)
Tumor:
- What does cT3a mean
- What does cT3b mean
- What does cT4 mean?
ct3a: choroidal involvement
ct3b: retrolaminar optic nerve involvement and free margins
ct4: orbital invasion
If children are discovered with trilateral RB in asymptomatic phase, what is the survival rate?
50%
What is the DD when you see a diffuse growth pattern?
Retinal detachment, diffuse retinal thickening
and enhancement: M.Coats, PFV, retinal dysplasia..
