Retinoblastoma is a common eye cancer arising from the neurosensory retina in one or both eyes. It is the most common intraocular tumour affecting the children usually seen between 1 and 2 years of age.
Genetics
Mutations in the RB1 gene cause retinoblastoma. Mutations in both RB1 alleles within the precursor retinal cell are essential, with one mutation that may be germline or somatic and the second one that is always somatic.
Heredity
Some facts about occurence of retinoblastoma are as below:
1. Heritable retinoblastoma
Hereditary or germline retinoblastoma occurs in 40% of all cases either due to inheritance from the affected parent or sporadically in one of the gametes. In heritable retinoblastoma one of the pair of alleles of RB1 is mutated in all the cells in the body. When a further mutagenic event affects the second allele, the cell may then undergo malignant transformation. Because of the presence of mutation in all cells a large majority of these children develop bilateral or multifocal tumours. Heritable retinoblastoma patient also have a predisposition to non ocular cancers such as pinealoblastoma, osteorsarcomas, soft tissue sarcomas and melanomas.
2. Non heritable retinoblastoma
The tumour is unilateral. Not transmissible and doesn’t predispose the patients to non ocular cancers. If a patient has a solitary retinoblastoma and no positive family history, this is almost certainly non heritable so that the risk in each sibling and patient’s offspring is about 1%. Ninety percent of children with unilateral retinoblastoma will have the non hereditary form.
Symptoms
- Leucoria (white pupillary reflex) is the commonest presentation and may first be noticed in family photographs.
- Strabismus or squint, is the second commonest mode of presentation.
- Painful red eye with secondary glaucoma, which may occasionally be associated with buphthalmos.
- Poor vision
- Inflammation or pseudo inflammation
- Orbital inflammation mimicing orbital or preseptal cellulitis may occur with nectrotic tumours.
- Orbital invasion or visible extraocular growth may occur in neglected cases.
- Metastatic disease involving regional lymph nodes and brain before the detection of ocular involvement is rare.
Signs
- An intraretinal tumour is a homogeneous, dome shaped white lesion that becomes irregular often with white flecks of calcification.
- An endophytic tumour projects into the vitreous as a white mass that may ‘seed’ into the gel.
- An exophytic tumour forms multilobular subretinal white masses and causes overlying retinal detachment.
Investigation
- Red reflex test using direct ophthalmoscope is a simple screening test for leukocoria.
- Examination under anesthesia should be performed in all clinically suspected cases. It should include fundus examination of both eyes after full dilation with atropine, measurement of intraocular pressure and corneal diameter.
- Ultrasonography is used mainly to assess tumour size. It also detects calcification within the tumour and is helful in the exclusion of simulating lesions such as Coats disease.
- Wide field photography is useful for both surveying and documentation, and offers particular advantages in the management of retinoblastoma.
- CT/ MRI also demonstrate extension to optic nerve, orbit and CNS. However, CT should be used sparingly because of potential risk of radiation sarcomas.
- Plain X-rays of orbit may show calcification which occurs in 75% cases of retinoblastoma.
Complications
After the treatment for retinobastoma, there is a high risk of development of tumour again in and around the eye. Due to this reason, your child’s doctor will schedule follow-up exams to rule out recurrent retinoblastoma. Additionally, children with the inherited form of retinoblastoma have an increased risk of developing other types of cancers in any part of the body in the years after treatment, especially pineoblastoma, a type of brain tumor. For this reason, children with inherited retinoblastoma may have regular exams to screen for other cancers.
Treatment
A. Conservative tumour destructive therapy is indicated to save eyeball, when tumour is diagnosed at an early stage I, i.e., when tumour involves less than half of retina and optic nerve is not involved.
Chemotherapy: Present recommendations for the treatment are primary systemic chemotherapy (for chemoreduction) followed by focal therapy (for consolidation).
Focal therapy: Depending upon the location and size of the tumour, focal therapy can be chosen from the following modalities:
- Cryotherapy is indicated for a small tumour located anterior to equator.
- Laser photocoagulation is used for a small tumour located posterior to equator.
- Thermotherapy with diode laser is used for a small tumour located posterior to equator away from macula.
- Plaque radiotherapy is very effective against localised viterous disease and for the elevated tumours when laser is ineffective.
- External beam radiotherapy (EBR), once the mainstay of treatment, is now reserved for diffuse disease in the only remaining eye.
Note: If the above modalities are not available, the eyeball should be enucleated without hesitation.
B. Enucleation: Eyeball should be removed along with maximum length of the optic nerve taking special care not to perforate the eyeball. Enucleation is the treatment of choice for group E tumors and when:
- Tumour involves more than half of the retina.
- Involvement of Optic nerve.
- Glaucoma is present and involvement of anterior chamber.
What happens when left untreated?
If untreated the risk is almost always bad and the patient invariably dies. Rarely spontaneous regression with resultant cure and shrinkage of the eyeball may occur due to necrosis followed by calcification; suggesting role of some immunological phenomenon.
If the eyeball is removed before the occurrence of extraocular extension, prognosis is fair (survival rate 70-85%).
Poor prognostic factors are: Optic nerve involvement, undifferentiated tumour cells and massive choroidal invasion.
