Retinoblastoma : Current Concepts in Diagnosis and Management
Retinoblastoma is the most common intraocular malignancy of childhood. It is responsible for 1% of all deaths from cancer in age group under 15 years. Retinoblastoma was described as early as 1597 by Petrus Pawius in Amsterdam but the exact nature of tumor was poorly understood during the next two hundred years. Retinoblastoma is derived from retinal cells of the immature neural epithelium. Reported incidence of retinoblastima is 11 cases per million children under 5 years or 1/18000 live births. In 90% of cases, the tumor arises before two years of age and is diagnosed before 4 years. Retinoblastoma can be inherited as familial in 8% or sporadic in 94%. In 1962, Stellard proposed that there is deletion of a portion of long arm of chromosome 13 which is termed as 13q 14 locus in retinoblastoma. Usually there is a mutation or deletion of RBI gene. Retinoblastoma can be of endophytic type which grows towards vitreous cavity and usually there is positive family history. Exophytic retinoblastoma grows towards choroid. Usually there is associated retinal detachment and glaucoma. Diffuse infilterative type usually occurs in older children associated with relatively flat infilteration of retina by tumor cells and hence diagnosis is usually delayed.
Leukocoria is the commonest presentation occurring in 50% children followed by strabismus (20%), exotropia (11%), esotropia (9%), red, painful eye with glaucoma (7%), poor vision (5%) and orbital cellulitis like condition (3%). Atypical presentation of RB can have hyphema (1%), not eating, failure to thrive (0.5%), white spots on iris (0.5%), strange expressions (0.5%), heterochromia iridis (1%), unilateral mydriasis (2%), pseudo-hypopyon, vitreous haemorrhage, uveitis, indolent endophthalmitis, calcified intraocular abscess, prolonged fever, proptosis, nystagmus, serous RD and corneal involvement as keratitis or ulcer.
Diagnostic work-up should include clinical examination comprising of external ocular examination, Slit lamp biomicroscopy, Indirect Ophthalmoscopy of both eyes. Fundus fluorescein angiography usually shows dilated feeding vessels in the arterial phase, hyper vascularity in the venous phase and late staining of mass. Ultrasonography is very useful in telling whether tumour is solid or cystic. It detects tumour as small as 2mm. It is the best modality to detect calcification and helps in following changes in tumour size. CT Scan helps in following changes in tumour size, defining extent of RB and in detecting tumour calcification. RB appears as hypointense in T2 weighted MRI and hyperintense on T1 and proton weighted MRI. It demonstrates spread along optic nerve, sub-arachnoid seedling and involvement of brain. For fine needle biopsy, limbal transiris approach is used in cases with metastasis to uvea with no evidence of primary non-ocular tumour. Immuno-histochemical studies like Aqueous Neuron Specific Enloase (NSE), both alpha and gamma show increased levels. Aqueous LDH leves are increased and show elevated ratio of serum LDH5 to LDH1 levels. Aqueous Cytology shows a positive angiogenesis assay. CEA, Alpha feto protein, Lymphocyte toxicity testing,32 P uptake also help in diagnosis but have become obsolete now. Bone marrow aspiration and biopsy, examination of CSF, bone films, bone scan, whole body CT, MRI, should be done to rule out metastasis. COX-2, a prostaglandin synthase (causes angiogenesis and tumorogenesis) is overexpressed (96%) in retinoblastoma specimens examined by labelled-streptavidinbiotin method (Karim MM et al, AJO, 2000) as observed in colorectal cancers. Some well differentiated retinoblastoma express rhodopsin and S-antigen, proteins that participate in phototransduction of vision.
Management of retinoblastoma has gradually changed over the past few decades. There is a trend away from enucleation and external beam radiotherapy towards focal conservative treatments. This is primarily because of earlier detection of the disease and more focused treatment modalities. The goals of treatment are, most importantly, to save the child’s life and, secondly, to salvage the eye or vision if possible.