Retinoblastoma

Retinoblastoma

1. Retinoblastoma Rahna 66

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 u nilateral , 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. P athology Origin - Immature retinal neural cells Histopathology Tumour consist of small round basophilic cells with large hyperchromatic nuclei and scanty cytoplasm H ighly undifferentiated or well differentiated with Flexner W interseiner 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. Opthalmoscopic features Three types of growth pattern are seen Endophytic – I nto 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

8. C lassification 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

9. I nvestigation 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.

10. T reatment 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 P laque 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

11. Enucleation for G roup E and when Tumour involves more than half of retina Optic nerve is involved Glaucoma is present and anterior chamber is involved postop External B eam 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

12. 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

13. P rognosis 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

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15. Differential diagnosis • Persistent hyperplastic primary vitreous • Coats disease • Retinopathy of prematurity • Toxocara endophthalmitis • Other tumours like Retinal astrocytoma, neurofibromatosis

16. 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.