RETINOBLASTOMA:

• Common malignant tumour arising from the Neurosensory Retina in one or both
eyes.
Demographic Data:
• Prevalence:-most common intraocular tumour of childhood
• Age:- infancy & very young children (between 1 & 2 years age)
• No sexual predisposition
• Race: rarer in negroes than whites
• Bilaterality:- bilateral involvement in 25-30% cases. (Although one eye is affected
earlier and more extensively than the other)
Genetics & Heredity:
• Retinoblastoma Gene (RB1 gene): Tumour suppressor gene/Antioncogenic gene
o Identified as 14th band on the long arm of chromosome 13 (13q 14)
o Deletion or inactivation of both the normal alleles of this protective gene by
two mutations  leads to Retinoblastoma: KNUDSON’S HYPOTHESIS
• Some facts about occurrence of Retinoblastoma:
o Only 10% are familial – Rest 90 % are Sporadic
o Familial types Inherited by autosomal dominant mode
o Sporadic types:
 2/3rd (60% of all cases):  occur by somatic mutation
 1/3rd (30% of all cases):  occur by germline mutation
b) Thus:
 Germline/heritable cases: 30% + 10% = 40%
 Non-heritable Somatic cases: 60%
• Heritable/Germline Cases:
a) First hit mutation:
 Occurs before fertilization – in one of the two alleles of
retinoblastoma gene on the germ cells (gametes)
 40% of all cases, either due to
 Inheritance from the affected parent (autosomal dominant):
10% of all cases
 Sporadically in one of the gametes: 30% of all cases
 Mutation will occur in all somatic cells predisposes to develop
non-ocular tumours (e.g., Osteosarcoma)
b) Second hit mutation:
 Occurs late in post-zygote phase – affects the second allele of one or
more retinal cellsmultifocal & usually bilateral tumour
formation(about 15% heritable cases are unilateral)
 Some cases have trilateral retinoblastoma:- associated with
Pinealoblastoma
c) Autosomal dominant cases – transmit to 50% of offsprings. Although only 40% are affected due
to variable penetrance
• Non-Heritable/Sporadic Cases:
a) 60% of retinoblastoma cases
b) Both hit mutations occurring in the same retinal cell in the embryo after
fertilization
c) Usually unilateral & unifocal tumours
d) Cannot be passed to offsprings
e) Does not predispose to non-ocular tumours
Pathology:
• Origin: - arises as malignant proliferation of immature retinal neural cells – it is
a tumour of a group of cells called Small Round Blue Cell Tumour
• Histopathology:
a) Small round cells with large nuclei. May be highly undifferentiated or well differentiated tumour.
b) Flexner-Wintersteiner Rosettes – highly specific for retinoblastoma
c) Homer-Wright Rosettes, Pseudorosettes & Fleurettes formation
d) Other features:- areas of Necrosis & Calcification
Clinical Features:

Presenting Features Percentages

Leucocoria 60%
Strabismus 20%
Painful Red Eye 7%
Poor Vision 5%
Asymptomatic 3%
Orbital Cellulitis 3%
Unilateral Mydriasis 2%
Heterochormia Iridis 1%
Hyphema 1%

(Mne: Luke Saw Red Vision Of Mine After Holi)

• Leucocoria, Strabismus, Painful Red Eye, Poor Vision, Orbital Cellulitis, Unilateral
Mydriasis, Asymptomatic, Heterochormia iridis, Hyphema

• Staging:
a) Intra-ocular stage of Retinoblastoma
 Quiescent Presentations
 Painful Red Eye presentations
b) Stage of Extraocular Extension
c) Stage of Distant Metastasis

Staging Of Retinoblastoma:
I. Intraocular Stage Of Retinoblastoma:
a. Quiescent Presentation:
i. Leukocoria/Yellowing-White Reflex (AMAUROTIC CAT’S EYE
APPEARANCE): - commonest presenting feature
ii. Squint – second commonest presenting feature
iii. Nystagmus: - rare, noticed in bilateral cases
iv. Defective vision – very rarely
v. Opthalmic Features of retinoblastoma:
o Endophytic Retinoblastoma:
 grows inwards from Retina into the Vitreous Cavity
 Ophthalmic Examination:- tumour looks like a well-circumscribed
polypoidal mass of white or pearly pink colour
 In presence of Calcification give a typical cottage cheese
appearance
 There may be multiple growth projecting into vitreous
o Exophytic Retinoblastoma:
 Grows outwards  separated Retina from Choroid
 Fundus Examination: - appearance of exudative retinal detachment
o Diffuse Infiltrating tumours
 just a placoid thickness of retina (& not a mass)  diagnosed late
b. Painful Red Eye Presentation:
o When retinoblastoma is left untreated during quiescent stage severe pain,
redness, watering
o Symptoms occur: either due to Acute Secondary Glaucoma or
Apparent Intraocular Inflammation or Orbital Cellulitis
o Acute Secondary Glaucoma:
 Due to Tumour pushing lens-iris diaphragm forward or tumour cells clogging
the trabecular meshwork
 Eyeball is enlarged (Buphthalmous) apparent proptosis, congested
conjunctiva, hazy cornea, raised intraocular pressure
o Apparent Intraocular Inflammation:
 Picture stimulates Severe Acute Uvitis – usually associated with
psuedohypopyon/hyphaema
o Retinoblastoma masquerading as Iridocyclitis
o Orbital Cellulitis:
 Occurs with necrotic tumours
 II. Stage of Extraocular Extension:
 Progressive enlargement of tumour  globe bursts through sclera (usually near
the limbus/optic disc)
Followed by rapid fungation & involvement of extraocular tissues  marked
proptosis
II. Stage of Distant Metastasis:
 Occurs via
o Lymphatic spread:  first to Preauricular& neighbouring lymph
nodes
o Direct extension: by continuity to Optic Nerve&Brain is common
Classification Of Retinoblastoma:
• Reese-Ellsworth Classification– of prognostic value – irrelevant now.
• International Classification of Retinoblastoma: (ICRB):
a) Group A: Very Low Risk:
 Small tumours < 3 mm diameter
 Confined to retina
 Located > 3 mm from Fovea &> 1.5 mm from Optic Disc
b) Group B: Low Risk:
 Large tumours > 3 mm diameter
 Confined to retina
 Located > 3 mm from fovea &> 1.5 mm from Optic Disc
c) Group C: Moderate Risk:
 Retinoblastoma with focal seeds
 Subretinal/Vitreous seeds ≤ 3 mm from retinoblastoma
d) Group D: High Risk:
 Retinoblastoma with diffuse seeds
 Subretinal/Vitreous seeds > 3 mm from retinoblastoma
e) Group E: Very High Risk:
 Extensive retinoblastoma characterized by any one of the following:
i. Tumour touching the lens
ii. Neovascular glaucoma
iii. Tumour anterior to anterior vitreous face involving ciliary body and anterior
segment
iv. Diffuse infiltrating tumour
v. Opaque media with haemorrhage
vi. Tumour necrosis with aseptic orbital cellulitis
vii. Invasion of poslaminar optic nerve, choroid, sclera, orbit & anterior
chamber
viii. Phthisis bulbi
Differential Diagnosis:
• Differential Diagnosis of Leukocoria:
o Various conditions other than retinoblastoma, which present as leukocoria are
collectively called Pseudoglioma.
o Ex: - congenital cataract, inflammatory depostis in vitrous following a plastic cyclitis
or choroiditis, coloboma of choroid, retrolental fibroplasias (Retinopathy of
Prematurity), persistent hyperplastic primary vitreous, toxocara endophthalmitis,
exudative retinopathy of Coats.
Endophytic retinoblastoma: - should be differentiated from
•
o Retinal tumours in tuberous sclerosis and neurofibromatosis, Astrocytoma,
Patch of exudative choroiditis
• Exophytic retinoblastoma: - should be differentiated from
o Other causes of exudative retinal detachment in children (e.g., coat’s disease)
Diagnosis:
• Examination under anaesthesia:
o Fundus examination of both eyes after full mydriasis with ATROPINE 
measurement of Intraocular pressure and Corneal diameter
• Plain X-Rays of Orbit: - may show calcification – occurs in 75% cases of retinoblastoma
• Raised Lactic Dehydrogenase (LDH) level in aqueous humour.
• Ultrasonography & CT/MRI scanning: - very useful
o To demonstrate extension to optic nerve, orbit & CNS if any.
o CT scan to be avoided – due to potential risk of radiation sarcomas.
Treatment:
A. Conservative Tumour Destructive Therapy:
o To salvage the eyeball
o Indicated when tumour is diagnosed at an early stage – i.e., stage I – when
tumour involves less than half of retina & optic nerve is not involved.
o Primary systemic Chemotherapy – for chemoreduction
o Followed by Focal Therapy – for consolidation
o Chemotherapy:
 Standard dose of CVE regimen – CARBOPLATIN, VINCRISTINE,
ETOPOSIDE – For group A, B & C patients
 High dose CVE regimen – CARBOPLATIN, VINCRISTINE, ETOPOSIDE -
for group D patients
o Focal Therapy:
 Cryotherapy: - for small tumour located anterior to the equator
 Laser Photocoagulation: - for small tumour located posterior to the
equator
 Thermotherapy (with diode laser): - for small tumour located
posterior to the equator away from macula
 Plaque radiotherapy: - very effective against localised vitreous
disease adn for elevated tumours when laser is ineffective.
 External beam radiotherapy: - reserved for diffuse disease in the
only remaining eye
o If the above modalities are not available  eyeball should be Enucleated
without hesitation
B. Enucleation:
o Treatment of choice for group E tumours and when
 Tumour involves more than half of retina
 Optic nerve is involved
 Glaucoma is present and Anterior Chamber is involved
o Eyeball should be enucleated along with maximum length of Optic nerve.
o If optic nerve shows invasion – postoperative treatment:
 External beam radiotherapy
 Chemotherapy – CVE regime, may be combined with CYCLOSPORIN
C. Palliative therapy:
o In cases where prognosis for life is dismal in spite of aggressive treatment:
 Retinoblastoma with orbital extension
 Retinoblastoma with intracranial extension
 Retinoblastoma with distant metastasis
o Palliative therapy includes:
 Chemoradiation – CVE regimen
 Surgical debulking of orbit or orbital exentration
 External beam radiotherapy

Prognosis:
• If untreated  always bad – patient dies. Spontaneous regression rarely occurs
(which may be due to immunological phenomenon)
• If eyeball is enucleated before occurrence of extraocular extension  fair
prognosis
• Poor prognostic features:
o Optic nerve involvement
o Undifferentiated tumour cells
o Massive choroidal invasion