retinoblastoma: epidemiology, inheritance, symptoms, & treatment

Retinoblastoma is a malignant tumour that arises from the outer nuclear layer of the retina.It is the most common primary malignant intraocular tumour of childhood and second most common of all age groups.The tumour originates from the outer or inner nuclear layer of the retina and usually grows inwards into the vitreous..

Epidemiology of retinoblastoma

• Occurs in between 1 in 14,000 to 1 in 20,000 live births
• No sexual predilection
• A third of cases are bilateral
• Average age at diagnosis is 18 months to 3 years of age
• Bilateral tumours tend to present earlier than uniocular one
• There are three types of this eye cancer
• Hereditary, sporadic and chromosomal
• Chromosomal results from deletion of band 14 of the long arm of chromosome 13
• Sporadic (non-hereditary)

-May be unilateral or bilateral

-Tend to have a single focus

-All bilateral cases likely have germinal mutation

-Patients are older at the time of presentation

• Familial cases have early onset, bilateral involvement, and predisposition to development of pinealoblastoma (trilateral retinoblastoma) and osteogenic sarcoma.

Mode of inheritance of retinoblastoma

• Mode of inheritance is autosomal dominant with 90-95% penetrance
• Only 6% of patients have a positive family history
• It is inherited in 10-15% of patients. The rest are sporadic.
• Patients with familial retinoblastoma have a 50% chance of transmitting the disease
• Healthy parents with an affected child have a 5% chance of having another with the disease
• If 2 or more siblings are affected, the risk of subsequent children being affected is 50%
• A survivor of hereditary retinoblastoma has almost 50% chance that his or her children will also develop the disease

Symptoms of retinoblastoma

• Leukocoria (white pupillary reflex) most common mode of presentation, occurs in 60% of cases
• Cat eye reflex
• Strabismus this can either be esotropia or exotropia. 20% of cases present in this way.
• Secondary glaucoma may or may not be associated with buphthalmos (enlargement of the eyeball)
• Pseudo uveitis- red eye, pain, associated with hypopyon/ hyphaema (blood/pus in the eye)-this is a rare type which presents in older children with average age of 6 years
• Orbital inflammation mimicking orbital cellulitis
• Proptosis-usually a sign of orbital involvement
• Eye pain/eye discharge.
• Visual impairment
• Fungating mass of the eye
• Other malignancies that may present with protrusion of the eye in children are: Burkitt lymphoma, neuroblastoma, rhabdomyosarcoma etc.

  

Diagnosis of retinoblastoma

Diagnosis of retinoblastoma is based primarily on ophthalmoscopy.

• Indirect ophthalmoscopy after full mydriasis -Indentation is required to see tumours arising anterior to the equator
• Endophytic tumour grows from retina into the vitreous cavity
• Exophytic grows into the subretinal space leading to retinal detachment

Other examinations may be required in some cases to confirm the presence of calcium in the tumour or to exclude such conditions as toxocariasis.

Investigations of retinoblastoma

• Skull x ray
• Ultrasonography
• CT scan more sensitive than ultrasound in detecting calcification
• MRI cannot detect calcification but better than CT for detecting optic nerve involvement and detection of pinealoblastoma

Differential diagnosis of retinoblastoma

Apart from retinoblastoma, other disease condition that presents with leukoria are:

• Cataract
• Coats disease
• Retinal detachment
• Retinopathy of Prematurity
• Toxocaral granuloma (toxocariasis)
• Persistent fetal vasculature
• Retinal dysplasia
• Incontinentia pigmenti

Treatment of retinoblastoma

• Choice of treatment depends on size, location, and number of tumours present
• Surgical enucleation: Removal of the affected eye. There is special consideration if both eyes are affected
• Radiotherapy
• Photocoagulation
• Cryotherapy
• Systemic chemotherapy with Cytoxan, vincristine, doxorubicin, cyclophosphamide
• Genetic counselling

Prognosis of retinoblastoma

• Chemotherapy and focal treatment have been used to successfully cure the disease and preserve vision in 95% of US patients where extra ocular extension is rarely seen
• Metastasis is associated with poor prognosis
• Children with germ line RB1 mutation are at risk of developing secondary tumors especially osteosarcoma and malignant melanoma
• Use of radiotherapy increases risk of CA in the brain, orbit, nasal cavities
• They require useful monitoring for the rest of their lives.

Nephrotic syndrome well explained in this other page.