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RETINOBLASTOMA

Cancer in children

Introduction

Retinoblastoma is malignant endo-oculer tumor of children arising in the embryonic neural retina. Prototype model for hereditary cancer development . Frequently 1 in 15.000 18.000 live birth in developed country. No predisposition for sex and race. Average age of patients at diagnosis is 24 months in unilateral and 13 months in bilateral cases.

Genetic

Retinoblastoma can occur in a familial or sporadic form. Only 6-10% familial, classified in two group: unilateral or bilateral and heritable or non heritable. Non heritable cases are always unilateral, whereas 90% of the heritable cases are bilateral and 10% are unilateral. All bilateral cases are heritable Knudson (1971) : mathematical model to explain the hereditary of retinoblastoma is two hits must occur at a gene level for retinoblastoma. The retinoblastoma gene (RB1) was isolated at chromosome 13q 14 and cloned in 1987. Abnormality at chromosome 13q14 can be detected by conventional karyotyping studies in only 5% of the cases Molecular diagnosis of retinoblastoma plays a mayor rule in genetic counseling.

Pathology

Retinoblastoma is a tumor neuroepithelial origin which may be classified as one of the primitive neuroectodemral tumor in childhood. Classically, two types : highly undifferentiated retinoblast (most common) and differentiated photoreceptor cell with neuroepithelial rossette formation (Flexner-Wintersteiner rossette) Retinoblastoma can disseminate outside the eye, following the optic nerve and/or subarachnoid space to chiasm, the brain and the meninges. Haematogenous metastases involves CNS, facial structures, and bones of the skull. Bone and bone marrow ,liver, lung and any other organ (less)

Sign and symptoms


Sign of retinoblastoma are often first notes by parent: leukocoria ; stabismus, red, painful eye frequently accompanied by glaucoma and poor of vision. Less common sign: rubeosis iridis; orbitas cellulitis; heterochromia iridis; uni lateral mydriasis; hypemia; nystagmus and failure to thrive and abnormal facies A syndrome associated with deleetion of the long arm of chromosome 13 ( the 13q- deletion syndrome) : microcephaly;hypertelorism; microopthalmos ;epicanthal fold; micrognathia ; short neck with lateral fold, low set ears, imperforate anus, hypoplastic or absent thumbs and mental retardation.

Diagnosis

The important step in diagnosis is: under anaesthesia fully dilated pupils; with indirect opthalmoscopy and scleral depression by an opthalmologist. Diagnostic can accurately without histo patological confirmation. USG : very helpful in the differential diagnosis of children with leukocoria. CT and MRI: for evaluated the optic nerve; orbital; CNS involvement and intraocular calcification. Bone marrow aspiration and lumbar puncture for cytologic examination (LCS)

Differential diagnosis of retinoblastoma


Intraocular reetinoblastoma: Coats disease Retrolental fibroplasia Endopthalmitis Toxocara infection Meduloepitheloma Cataracts Uveitis Peersisten hiperplastic primary vitreous Astrocytic hamartomas Extraocular retinoblastoma: Orbital cellulitis Metastases neuroblastoma Orbital rhabdomyosarcoma Leukemia Lymphoma

Reese - Ellsworth Staging system for intraoculer retinoblastoma


Grroup
I
(a)

Description
Solitary tumor less than 4 dd (disc diameter) at or behind the equator Multiple tumor non large than 4 dd, all at or behind the equator Solitary tumor 4-10 dd,at or behind the equator Multiple tumor, 4-10 dd at or behind the equator Any lesion anterior to the equator Solitary tumor laarge than 10 dd behind the equator Multiple tumor, some large than 10 dd Any lesion extending anterior to the ora serrata Massive tumor involving over half the retina Vitreous seeding

(b)

II

(a) (b) (a) (b) (a) (b) (a) (b)

III

IV

Treatment
Aspect of treatment: Local therapeutic : Systemic therapy : to treat intra ocular disease for extra ocular ,regional and matastases In developed country:most present intra ocular, survival 95%. Size, number and location of tumor are taken to choose the best therapy. Bilateral retinoblastoma come with advanced intra ocular disease in one eye. In developing country retinoblastoma is diagnosis after extra ocular spread. Aim of treatment to save patients life, since death from metastatic is possible

Treatment (contd)

Surgery: Enucleation is the simplest and safest therapy * Under 2 years : facial asymmetry * Group V : require enucleation * Enucleation mandatory when present: glaucoma; anterior chamber invasion or rubeosis iridis local therapy cannot be evaluated due to a cataract or failure to follow a patient closely * Vitrectomy is contraindicated

External beam radiotherapy

Retinoblastoma is a radiosensitive and radio therapy is the elective local therapy for retinoblastoma. Long term side effect limit its use. EBRT is usually delivered using a linier accelerator to dose of 40-45 Gy involving whole retina . Most recurrences after radiotherapy can be treated with cryo or photocoagulation. Long term sequelae of radiotherapy is: growth inhibition of orbital bone; cosmetic and increase of secondary malignancy.

Plaque radiotherapy
Radioactive episcleral plaque using 60Co; 106 Ru; or 125 I. Usually for : small and medium sized single tumors not amenable to cryo or photocoagulation Recently as primary therapy after chemoreduction.

Cryo and photocoagultion


Use to treat small (usually less than 5 mm) and accessible tumors. Widely available and can be repeated several times until local control is achieved Cryotherapy : to treat anterior tumors Photocoagulation : to treat posterior tumor

Newer modality
Chemotherapy for intra ocular disease in order to decrease tumor size and make the tumors suitable for local therapy In past: chemotherapy ineffective for intraocular disease Recently : with the newer drug with greater penetration of the eye, this modality has reemerged

Chemotherapy
The agents used commonly is: Carboplatin Cisplatin Etoposide Cyclophosphamide Vincristine Adriamycine The role of intrathecal chemotherapy and cranial radiotherapy to prevent of CNS dissemination is not established.