RETINOBLASTOMA

•Retinoblastoma (Rb) is a cancer of the retina.

•most common primary ocular malignancy of childhood.

•Although this disorder can occur at any age, it usually develops in young children.

•Most cases of retinoblastoma occur in only one eye, but both eyes can be affected.

•Untreated, retinoblastoma is almost always fatal, hence the importance of early diagnosis and treatment.

INCIDENCE •11 new cases per million population-age <5yr

•90% diagnosed by 3-4yr

•98% diagnosed by 5yr

• Increased frequency of disease in developing countries

•40-70 %of children in developing countries die and in developed countries only 3-5% die

WHAT HAPPENS IN RETINOBLASTOMA • Retinoblastoma is related to chromosome 13.

•

• long arm of chromosome 13 (13q14.1-q14.2).

• Retinoblastoma occurs when a cell of the growing retina develops a mutation in the RB gene (a tumor-suppressor gene).

• This mutation causes the cell to grow out of control and become cancerous.

GENETICS

•Tumor suppressor cells

•RB gene- CHROMOSOME 13

•Dominant phenotype

RB gene +E2F protein which is a nuclear transcription factor produced during S phase

Prevents cellular replication

A mutated gene becomes phosphorylated

Phosphorylated gene cannot interact with E2F protein

Uncontrolled cell replication

INHERITANCE

•SPORADIC

•INHERITTED

SPORADIC

•Unilateral

•Unifocal

•Appear at an older age

•60% of all cases

•Children of the affected are normal

•Chromosomal anomaly is a somatic mutation.

•Relatives have a low risk of RB development.

INHERITTED •Bilateral

•Multifocal

•Occur at an early age

• 40% of all cases

•Children of the affected have 45% chance of inheritance.

•Chromosomal anomaly is a germline mutation.

•Relatives have a high risk of RB development.

•Autosomal dominant with high penetrance.

CLINICAL PRESENTATION

•Leukocoria-white pupillary reflex

• Stabismus

• Poor visual tracking

• Glaucoma

• Orbital inflammation

• Hyphema

• Irregular pupil

• Fungating ocular mass

• Pain

• Protopsis

• Rubeosis iridis

• Metastasis-bone

• Bone marrow, LN,CNS

Pseudohypopyon:

DIAGNOSIS •History and PE

•Indirect ophthalmoscopy with pupillary dilation & general anesthesia

•Number, size, location (anterior or posterior), laterality, disc diameter, subretinal fluid

OCULAR ULTRASOUND

•Accuracy:80%

•Demonstrates a mass more echogenic than the vitreous

•highly reflective intrinsic echoes of fine calcifications

CT/MRI

•90% show calcification

•Dense homogenous

•Detects intracranial disease

ROLE OF FNAC

•Overall accuracy 95%

•Indicated only in selected patients:

Genetic and/or DNA testing

St. JUDE’S STAGING

• I: Tumor unifocal/multifocal=confined to retina

• II: Tumor unifocal/multifocal=confined to globe

• III: Extraocular-extension of tumor (regional)

• IV: Distant metastasis

TREATMENT • Complex issue.

• Multidisciplinary approach: Ocular oncologist, pediatric oncologist, radiation oncologist, radiologist and child psychologist.

•Goals of treatment:

• Save life.

• Preserve vision or salvage eye

• Minimize any complications or side effects of therapy.

UNILATERAL-ENUCLEATION

• Involves removal of the eye leaving behind

lids and extraocular muscles but removing

the longest possible segment (10 to 15mm)

of optic nerve in continuity with the globe.

BILATERAL •Systemic chemotherapy

•Followed by local treatment with laser photo coagulation or cryotherapy

•Eye with no useful vision- enucleated

CRYOTHERAPY

•Under GA, pencil like probe is placed precisely on the sclera directly behind the intraocular focus of RB.

•Rapid freezing forms intracellular crystals which ruptures tumor cells and causes vascular occlusion.

PHOTOCOAGULATION

GOALS OF CHEMOTHERAPY:

•1.Reduce the use of EBRT which reduces second malignancies and orbitofacial growth anomalies in early stage.

•2.Reduce the need of enucleation in early stage.

•3.Reduce the risk of local and systemic relapse in advanced stage.

•4.Improve survival in metastatic disease.

•Vincristine, carboplatin ,etoposide

•External beam radiation- chemo and focal therapy fail

•High dose of chemo and bone marrow transplantation-better survival

•Routine eye examination

PROGNOSIS

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