Download - Retinoblastoma
Dr. Mahziba RahmanMCPS, FCPS
Eye Specialist & SurgeonBangladesh Eye Hospital Ltd.
• The most common primary intraocular malignancy of childhood
• 3% of all childhood cancer
• Occurs due to malignant transformation of primitive retinal cells before final differentiation
• Seldom seen after 3 yrs of age
• Incidence : 1/14000 – 1/20,000 live birth.
• 90% of case present before 3 yrs of age.
• Occurs equally in male & female.
• No racial predilection.
• 60% - 70% unilateral • 30% – 40% bilateral
• Prevents cellular replication
• Disrupton of this gene leads to growth of cancer cells
• Retinoblastoma occurs due to mutation of RB1 gene, located at 13q14
• Both alleles of RB1 must be mutated for a tumour to form.
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• Two mutations requred to produce retinoblastoma
• The‘two hit hypothesis on’ was proposed by Knudson.
Hereditary case-
• First hit –one mutated allele is inherited & present in all somatic cells.
• Second hit – Further mutagenic event effects the second allele during the person’s lifetime.
In non- hereditary cases
• Affected individuals are born with two normal alleles
• Both the mutations (hits) occur somatically with in the single retinal cell.
Heritable retinoblastoma
Non-Heritable retinoblastoma
Occurrence 40% 60%
Family History Positive Negative
Age 1 year 2 years
Predisposition to other malignancies
Present Absent
Tumour Bilateral, multifocal Unilateral
Risk to sibling 2%- healthy parents40%-affected parents
1%
• LeukocoriaLeukocoria (white pupillary reflex)- 60%• Commonest presentation• Often first noticed in family photograph
• Strabismus (20%)
• • Secondary glaucoma occasionally associated with Buphthalmos
• Red eye due to tumour induced uveitis & iris nodule , pseudohypopyon (5%)
• Orbital inflammation
mimicking orbital or preseptal cellulitis
• Orbital invasion with proptosis
• Metastatic disease involving
regional lymph node & brain.
• Raised ICP due to trilateral
retinoblastoma.
• Bilateral retinoblastoma with intracranial retinoblastoma
• Usually present in pineal gland or parasellar region
• Present in 5% of children with hereditary type
• Visual function
• Slit lamp biomicroscopy
• Indirect Ophthalmoscopy with scleral indentation
• EUA
Corneal diameters
IOP
Ophthalmoscopy
Intraretinal tumour - • Dome shaped,• Gray to white , • Fed & drained by dilated & tortuous vessels, • Developing foci of calcification - chalky white appearance.
They may grow in 3 types
Subretinal, multilobular white masses Retinal detachment may occur
Projects into vitreous as white mass May seed into vitreous
• Rare
• Unilateral
• Detected in later age ( >5 years)
• Difficult to detect
• B-scan ultrasonography To assess tumour size
• CT scan Detect calcification Not preferred as radiation can lead to second tumour
• MRI Superior for ON evaluation, extra ocular extension or to detect
pinealoblastoma Used for follow up
• Systemic investigations
• Genetic studies
• Cells have round, oval or spindle-shaped nuclei ,
twice the size of lymphocyte
• Nuclei are hyper-chromatic with scanty cytoplasm.
• High mitotic activity
• Calcification with necrosis
Many retinoblastoma are undifferentiated but varying degree of differentiation are characterized by the formation of Rosettes
1.Flexner-Wintersteiner rosettes,
2.Homer-Wright rosettes,
3.Fleurettes.
Undifferentiated tumour
Tall columnar cell surrounding a central lumen
Nuclei lie away from lumen
Cells have undergone retinal differentiation
• Less common
• The lumen of a H W rosette is filled with a tangle of eosinophilic cytoplasmic processes
• Also be found in other neuroblastic tumour
• These cells exhibit photoreceptor differentiation.• Cluster of cells with long cytoplasmic process project
through a fenestrated membrane.• Appearance resembles a bouquet of flower.
• Congenital cataract• Retinopathy of prematurity• Persistent fetal vasculature• Coats disease• Toxocariasis• Uveitis• Retinal dysplasia• Retinoma (retinocytoma)• Retinal astrocytoma
Table: Reese-Ellsworth Classification of Retinoblastoma
Group Quick Reference Description Treatment
A Tumors≤3 mm
Small discrete tumors away from critical structures
•Confined to the retina• >3 mm from the foveola• >1.5 mm from the optic nerve
Focal therapy
B Discrete retinal tumor of any size or location
•Tumors not in group A
•No vitreous or subretinal seeding
•Subretinal fluid >3 mm from the base of the tumor
Small number of chemotherapy cycles
Focal therapy
C Minimal vitreous or subretinal seeding
•Subretinal fluid involves ¼ retina
•Subretinal & vitreous seeds ≤3 mm from the tumor
Chemotherapy
Focal therapy
Group Quick Reference Description Treatment
D Diffuse vitreous or subretinal seeding
•Massive and/or diffuse intraocular tumour
•More than one quadrant of retinal detachment
Fine greasy vitreous seeding or avascular massesSubretinal seeding include plaques
Chemotherapy
Focal therapy
E •Eyes that have been destroyed anatomically or functionally by the tumor• Eyes with one or more than the following
•Tumor touching the lens• Neovascular glaucoma•Tumor anterior to vitreous •Diffuse infiltrating retinoblastoma•Massive intraocular hemorrhage•Aseptic orbital cellulitis•Phthisis bulbi
Enucleation
• When treating retinoblastoma, it is first & foremost important to understand that it is a malignancy
• In deciding on a treatment strategy, the first goal must be -
Saving lifeSaving life,
then saving the sight
• Primary health care providers
• Pediatrician
• Ophthalmologist
• Paediatric oncologist
• Geneticist
• Important
Cause & prognosis of disease
Treatment options
Follow up
Genetic counselling
• Parents must be examined prior to treatment
• Photocoagulation
• Cryotherapy
• Plaque radiotherapy / Brachytherapy
• Transpupillary thermotheapy
• External beam radiotherapy
• Post-equatorial tumour for (IIRC group A,B,C,D)
• Tissue temperature raised > 60°c using a argon or diode laser
Encircling tumour double row of laser burns Destruction of blood supply
Regression
• Diode laser (810nm) is used over tumour surface
Temperature raised above 45°c for 1 min
Tumour cell death occurs by hyperthermia
• Pre-equatorial tumour (IIRC group A & B)
• Triple freeze thaw technique
Tumour cells killed while thawing
Full minute thaw before freezing again
• Repeated 4 weeks apart
• Solitary tumours <15mm, not near disc or macula
• Commonly used isotopes are iodine 125 & ruthenium 106
• The tumour is localized
Plaque sutured to sclera Before treatment
Before treatment
Left in situ for 3-5 days
Cottage-cheese appearance after
treatment
• Drugs used:
Carboplatin
Vincristin
Etoposide Before treatment
Cyclosporine
• Cycles: 4- 9 cycles every 3 to 4 weeks
6 months later after treatment
• Dose of 4000-4500 cGy in divided fractions over 3-4 weeks
• Indication-
Bilateral disease not responsive to laser or cryotherapy
• Should be avoided -
- Second tumour risk - Radiation retinopathy
- Cataract formation - Mid face hypoplasia
- Radiation optic neuropathy
• IIRC Group E , recurrent tumour & failure of other treatment
• Minimum manipulation of the globe
• Important to obtain a long optic nerve stump (8-12mm)
• Sent for histopathological examination & genetic studies
• Placement of orbital implant within muscle cone to allow orbital growth
• Local orbital recurrence : External beam radiation and systemic
chemotherapy
• Metastatic RB: Intensive chemotherapy with cyclosporine
• Meningeal spread of RB: Intrathecal or intra ventricular chemotherapy
• Intravitreal chemotherapy Administration of melphalan has been used for vitreous seeding High success rate Needle might create hole and allow tumour spread
• Intra-arterial chemotherapy Chemotherapy directly injected in ophthalmic artery Low dose required
Reduce systemic side-effects
• Periocular chemotherapy injection Increases intraocular level
• Complete and spontaneous necrosis
• Following treatment -Cottage-cheese calcified mass -Translucent fish-flesh mass Fig: Cottage-cheese mass
-Mixture -Flat atrophic scar
Fig: Before and after 2 cycles of chemotherapy
• Risk of secondary malignancies
• Detection of recurrence & new tumour growth
• Management of the complications of therapy
• Genetic counseling
• EUA every 2-8 wks until the age of 3 yrs
• Every 6 months until the age of 5 yrs
• Annually until the age of 10 yrs
Fig: Recurrent RB
Pictures courtesy of the department of Oculoplasty
Parent Affected child Siblings
Bilateral RB survivor
45%
Unilateral RB survivor
7%
Healthy Bilateral RB 5%
Healthy Unilateral RB 1%
• Survival rate
-95% , 5 year survival (intraocular tumour)
- 5%, 5 year survival (extraocular)
• Poor prognostic factors
-Size of timour
- Optic nerve involvement
- Extraocular spread
- Older age at presentation
• Extraocular extension
• Trilateral retinoblastoma
• Second malignancies
• Over the last decade dramatic improvement in management
• In the developed countries due to advancement in management protocol treatment now focuses on vision saving
• In developing countries much advancement still required