2. Retinoblastoma is a malignant tumour arising from
the neurosensory retina in one or both eyes
■ Most common intraocular malignancy in children ( 1 in 15,000- 20,000 live
births)
■ No racial or gender predisposition.
■ 90% of case present before 3 yrs of age
■ Bilaterality 23-30% cases
■ Trilateral Retinoblastoma – bilateral RB with ectopic intracranial RB (usually
pineal gland or parasellar region)
3. Genetics
• Retinoblastoma occurs due to mutation of RB1 gene, located at 13q14
• It is a tumour suppresser gene
• Both alleles of RB1 must be mutated for a tumor to form (Knudsons’s
two hit hypothesis)
4. Sporadic (Non Hereditary)
• 60% of all cases
• unilateral ,unifocal
• Affected individuals are born with two normal alleles
• Both the mutations (hits) occur somatically with in the single retinal cell.
Familial (Hereditary)
• 40% of all cases
• Bilateral, multifocal
• First hit occurs in utero in germ cells before fertilization or is inherited from a parent.
• Second hit occurs in any retinal cell during the person’s lifetime
5. Pathology
Origin - Immature retinal neural cells
Histopathology
■ Tumour consist of small round basophilic cells with
large hyperchromatic nuclei and scanty cytoplasm
■ Highly undifferentiated or well differentiated with
– Flexner Winterseiner rosettes
– Homer Wright rosettes
– Fleuretts
6. Clinical features
■ Leukocoria or yellowish white reflex or amouratic cats eye appearance - 60%
■ Strabismus ,usually convergent - 20%
■ Secondary glaucoma , buphthalmos
■ Acute uveitis with psudohypopyon (masquerade syndrome)
■ Orbital cellulitis
■ proptosis
■ Spread of tumour
■ Lymphatic spread to preauricular and neighbouring LN
■ Direct extension to optic nerve and brain
■ Distant metastasis to Lung,Bone
7.
8. Opthalmoscopic features
Three types of growth pattern are seen
■ Endophytic – Into the vitreous with seeding of tumour cells
throughout the eye
– White/pearly pink well circumscribed polypoid
mass
– Retinal vessels not seen on tumor surface
– If calcification – cottage cheese appearance
■ Exophytic – into the sub-retinal space causing retinal
detachment and Retinal vessels seen on tumor surface
■ Diffuse infiltrating tumours –flat infiltration without
discrete tumour mass
9. Classification
■ International Classification of Retinoblastoma (ICRB)
•Group A: Small intraretinal tumors (< 3mm) away from foveola and disc.
•Group B: Tumors > 3mm, located <3mm from fovea and<1.5 mm from optic disc
•Group C: Tumor with focal subretinal or vitreous seeding within 3mm of tumor.
•Group D: Tumor with diffuse subretinal or vitreous seeding > 3mm from tumor.
•Group E: Extensive retinoblastoma occupying >50% of the globe with or without
neovascular glaucoma, hemorrhage, extension of tumor to optic nerve or anterior
chamber
10. Investigation
■ Plain x-ray orbit – calcification in 75%
■ USG B-Scan - size of tumour , detects calcification
■ CT scan– demonstrate solid intraocular tumour with characteristic intratumoral
calcification
■ MRI - optic nerve invasion or intracranial extension
■ Optic nerve evaluation
■ If there is clear evidence of tumor outside the eye, metastatic evaluation
should be done:
• bone marrow examination (aspiration and biopsy).
• lumbar puncture.
• bone scan.
11. Treatment
Conservative – Tumour diagnosed at early stage – when tumour involves less than half of
retina and optic nerve is not involved
■ By systemic chemotherapy ( CVE regimen -carboplatin vincristine and etoposide)
■ Followed by focal therapy
– Cryotherapy - small tumour located anterior to equator
– Laser photocoagulation –small tumour located posterior to equator
– Thermotherapy with diode laser- small tumour located posterior to equator
away from macula
– Plaque Brachytherapy - localised vitreous disease
■ Placement of radioactive implant on sclera
corresponding to base of tumor, transsclerally irradiate
tumor.
■ Radioactive materials – Ruthenium 106 & Iodine 125
– External beam radiotherapy- diffuse disease
12.
13. Enucleation for Group E and when
– Tumour involves more than half of
retina
– Optic nerve is involved
– Glaucoma is present and anterior
chamber is involved
■ postop External Beam Radiotherapy and
chemotherapy
Palliative therapy
■ Retinoblastoma with orbital
extension/intracranial extension/distant
metastasis
■ Includes chemoradiation (CVE regimen)
■ Surgical debulking of orbit
■ And External Beam Radiotherapy
14. Follow-up
• Recurrence usually occurs with in 3 years
■ The risk period for extraocular spread after treatment is 12 to 18 months
Genetic counselling
■ Recommended for:
- Patients with family history of RB
- Parents having a child with RB
15. Prognosis
• 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
17. Differential diagnosis
•Persistent hyperplastic primary vitreous
•Coats disease
•Retinopathy of prematurity
•Toxocara endophthalmitis
•Other tumours like Retinal astrocytoma, neurofibromatosis
18. Classification
A. Primary tumours
1. Neuroblastic tumours. These arise from sensory
retina (retinoblastoma and astrocytoma) and
pigment epithelium (benign epithelioma and
melanotic malignant tumours).
2. Mesodermal angiomata e.g., cavernous
haemangioma.
3. Phakomatoses. These include: angiomatosis
retinae (von Hippel-Lindau disease), tuberous
sclerosis (Bourneville’s disease), neurofibromatosis
(von Recklinghausen’s disease and
encephalo-trigeminal angiomatosis (Sturge-Weber
syndrome).
B. Secondary tumours
1. Direct extension e.g., from malignant melanoma
of the choroid.
2. Metastatic carcinomas from the gastrointestinal
tract, genitourinary tract, lungs, and pancreas.
3. Metastatic sarcomas.
4. Metastatic malignant melanoma from the skin.
