Retinoblastoma is a rare cancer that affects the retina. It is the most common eye cancer in children and its incidence ranges from 1 in 14,000 to 1 in 34,000 live births worldwide. The document discusses the epidemiology, genetics, pathology, clinical presentation, diagnostic evaluation, classification systems, management options including chemotherapy, radiation therapy, cryotherapy and enucleation, and importance of genetic counseling for families with retinoblastoma.

1. Jagdish Dukre
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2. Most common intraocular malignancy of infants
& children.
Third most common malignancy affecting
children.
In India, retinoblastoma is the leading pediatric
tumour after Wilm's tumour and lymphoma.
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3. Epidemiology
The incidence of
retinoblastoma worldwide
ranges from 1 in 14,000 live
births to 1 in 34,000 .
No predisposition
Race
Gender
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Developed
Developing
India : 1 in 15,000

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5. The Retinoblastoma Gene and Gene
Product
The first human cancer
suppressor gene to be completely
charted.
The retinoblastoma gene,
located on the long arm of
chromosome 13 (13q14).
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6. The Retinoblastoma Gene Product
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8. Knudson’s ‘two-hit’ hypothesis
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9. Pathology
1. Histology
 It is composed of small basophilic cells (retinoblasts)
with large hyperchromatic nuclei and scanty
cytoplasm.
 Many retinoblastomas are undifferentiated but
varying degree of differentiation,characterised by
formation of rosettes which are of 3 types

10. a) Flexner -Wintersteiner rosettes:
consists of central lumen
surrounded by tall columnar cells,
nuclei of which lie away from the
lumen.
b) Homer-Wright rosettes (pseudo-rosettes)
it has no lumen and cells
form around a tangled mass of
eosinophilic processes .
c) Fleurettes: cluster of cells with long
cytoplasmic processes, projecting
through a fenestrating membrane
and appearance resembles the
bouquet of flowers.

11. Pattern of tumour spread
1. Growth pattern: It may be endophytic (into the
vitreous) with seeding of tumour cells throughout
the eye or exophytic (into the sub-retinal space)
causing retinal detachment.
2. Optic nerve invasion: with spread of tumour along
the sub-arachnoid space to the brain
3. Metastatic Spread: Regional lymph nodes, lungs and
bone.

12. Growth pattern
ENDOPHYTIC
Into vitreous cavity
No overlying retinal vessels
Simulate endophthalmitis
Present as pseudohypopyon,
nodules at pupillary border.
EXOPHYTIC
Grows outwards into
subretinal space
Retinal vessels seen over it
Retinal detachment
Simulate coats disease

13. ASSOCIATED PRIMARY MALIGNANCIES
Leukemia
Neuroblastoma
Osteosarcoma
Chondrosarcoma
Rhabdomyosarcoma 13

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15. 1. Quiescent stage : Last for 6 month to 1 year.
(a) Leukocoria or Amaurotic cat’s eye appearance.
- Commonest presentation
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16. Pseudoglioma :
disease presenting as leucokoria other than retinoblastoma
- congenital cataract
- persistant hyperplastic primary vitreous
- coat’s disease
- toxocariasis
- retinopathy of prematurity
- organised vitreous haemorrhage.
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17. b. Squint :
Second most common presentation
Usually convergent
Fundus examination mandatory in childhood
stabismus
c. Nystagmus : in bilateral cases
d. Defective vision : when tumour arise late.
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18. I. Glaucomatous stage :
a. Severe pain, redness, watering, corneal clouding
Mass effect or blockage of angle of anterior
chamber
b. Tumour induced uveitis, iris nodules, pseudohypopyon
c. Orbital inflammation — resembling orbital or perseptal
cellulitis.
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19. III. Stage of extraocular extension
Globe burst at limbus followed by rapid fungation
and involvement of extraocular tissues resulting in
marked proptosis
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20. Reese-Ellsworth Classification
Group I
a. Solitary tumor, less than 4 DD in size, at or behind the equator.
b. Multiple size tumors, none over 4 DD in size, all at or behind the
equator.
Group II
a. Solitary tumor, 4 to 10 DD in size, at or behind the equator.
b. Multiple size tumors, 4 to 10 DD in size, all at or behind the equator.
Group III
a. Any lesion anterior to the equator.
b. Solitary tumors larger than 10 DD behind the equator.
Group IV
a. Multiple tumors, some larger than 10DD.
b. Any lesion extending anteriorly to the ora serrata.
Group V
a. Massive tumors involving over half the retina.
b. Vitreous seeding.
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21. The Grabowski-Abramson Classification Scheme for
Extraocular Retinoblastoma
1. Intraocular disease
a. Retinal tumours
b. Extension into choroid
c. Extension up to lamina cribrosa
2. Orbital disease
a. Orbital tumour
1. Suspicious (pathology of scattered episcleral cells)
2. Proven (biopsy proven orbital tumor)
b. Local nodal involvement
3. Optic nerve disease
a. Tumour beyond lamina but not up to cut section
b. Tumour at cut section of optic nerve
4. Intracranial metastasis
a. Positive CSF only
b. Mass CNS section
5. Hematogenous metastasis
a. Positive marrow/bone lesions
b. Other organ involvement 21

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26. USG
 objective assessment of
tumor dimension
presence of calcium, a high
reflective echoes are seen.
but if the tumor has
extended in to the optic
nerve, then the presence of
calcium blocks the
ultrasound penetration
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27. CT scan
MRI
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28. Metastatic work up
Cases with
Suspected extrascleral spread.
Optic nerve invasion on imaging studies.
Presentation with glaucoma/ orbital cellulitis.
Anterior chamber seeding.
Gross choroidal invasion.
Suspected metastasis.
Blood investigation (count,LFT, RFT) .
Lumber puncture.
Bone marrow biopsy.
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30. Objective in order of priority
 Survival of the patient.
 Preservation of the globe.
 Focus on visual acuity.
 Therapy is tailored to each individual case:
 based on the overall situation.
 including threat of metastatic disease.
 risks for second cancers.
 systemic status.
 laterality of the disease.
 size and location of the tumour(s).
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33. Modalities
Cryotherapy.
Laser photocoagulation.
Thermotherapy.
Plaque therapy.
Chemotherapy.
Enucleation.
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34. Cryotherapy
Indication
primary treatment of small tumours (4 mm in
diameter & 3 mm in height).
located anterior to the equator near the ora
serrata.
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35. Triple-freeze-thaw
technique.
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36. Laser photocoagulation
Indication
Tumors smaller than 4.5 mm in diameter that are
confined to the retina with no evidence of
seeding.
Not involving OD or macula.
Photocoagulation using low energy 532nm argon
or 810 nm diode laser achieve focal consolidation
after chemotherapy.
At least 3 sessions are required
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37. Usually performed using an indirect
ophthalmoscope delivery system and
relatively long exposure durations (1
second or more up to a continuous
exposure).
First an intense confluent white
chorioretinal coagulation
approximately 1–2 mm wide entirely
around the retinal tumor is created.
Any feeding retinal blood vessels are
treated until they appear to be
occluded.
Finally, the tumor is treated directly
until it also appears homogeneously
and intensely white.
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38. Transpupillary thermotherapy
Indication
Tumours 2 mm thick & 3 mm diameter &
confined to retina.
For tumours adjacent to fovea or optic nerve
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39. Tumour heating using a
diode infrared laser(810 nm)
Thermochemotherapy.
Temp – 42 – 60 °C
(below coagulative
threshold)
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40. External beam radiotherapy
Method of delivering whole eye irradiation to treat
advanced retinoblastoma, particularly when there is diffuse
vitreous seeding
total dose of 35–40 Gy is given in fractionated doses over a
period of 4–5 weeks.
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41. Complications
Temporal bone suppression.
Cataract.
Radiation retinopathy.
Optic neuropathy.
Keratopathy.
Secondary cancers in the field of irradiation
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42. Plaque therapy
Indication
Tumour <15 mm in base & 6 – 8 mm in thickness
At least 2 mm from OD or fovea.
Failed with chemoreduction, laser photocoagulation or
cryotherapy.
principal isotopes used in radioactive eye plaques are iodine-
125 and ruthenium-106.
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43. Schipper Technique
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44. Complications
Maculopathy.
Papillopathy.
Transient mild vitreous haemorrhage.
Cataract.
Iris neovascularisation.
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45. Chemotherapy
- Vincristine : also known as Oncovin or VCR.
blocks mitosis in metaphase
- Carboplatin : also known as Paraplatin.
inhibits both DNA & RNA synthesis
- Etoposide : also known as VP-16 or VePesid.
blocks cell cycle in late S-G2 phase
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46. Primary chemotherapy with i.v. carboplatin, etoposide &
vincristine given in 3 - 6 cycles
Single agent chemoreduction with carboplatin
Subtenon carboplatin injection
Objective – reduce tumour size so that focal treatment can
be applied to a smaller tumour volume in order to
preserve more vision
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Chemoreduction

48. Enucleation
Indication
advanced disease with no
hope of useful vision
Concern of invasion of
tumour into optic nerve,
choroid or orbit
Secondary glaucoma, pars
plana seeding or anterior
chamber invasion
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49. Technique
Long section of optic nerve
should be removed
Gentle removal without seeding
into orbit
Fresh tissue is harvested for DNA
analysis
Surgeon must change the sterile
gloves after this step to avoid the
risk of tumour contamination
into the child’s orbit
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50. Genetic counseling
To identify individuals with heritable mutation in
RB1 gene and to inform families of the implication
of this finding.
The test results allow us to focus on high risk
screening on those who carry a heritable mutation
and provide reassurance to individuals with
sporadic, non heritable retinoblastoma.
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