Retinoblastoma

This article is about the disease. For the protein, see Retinoblastoma protein.

Retinoblastoma
Classification and external resources
File:Rb Retina Scan.jpg Rb tumours taken with a retinoscan before and during chemotherapy
ICD-10	C69.2
ICD-9	190.5
ICD-O:	M9510/3
OMIM	180200
DiseasesDB	11434
MedlinePlus	001030
eMedicine	oph/346
MeSH	D012175

Retinoblastoma (Rb) is a rapidly developing cancer which develops in the cells of retina, the light detecting tissue of the eye. In the developed world, Rb has one of the best cure rates of all childhood cancers (95-98%), with more than nine out of every ten sufferers surviving into adulthood. Retinoblastoma is a very treatable cancer.

Classification

There are two forms of the disease; a genetic, heritable form and a non-genetic, non-heritable form. Approximately 55% of children with Rb have the non-genetic form. If there is no history of the disease within the family, the disease is labelled "sporadic", but this does not necessarily indicate that it is the non-genetic form.

In about two thirds of cases, only one eye is affected (unilateral retinoblastoma); in the other third, tumours develop in both eyes (bilateral retinoblastoma). The number and size of tumours on each eye may vary. In certain cases, the pineal gland is also affected (trilateral retinoblastoma). The position, size and quantity of tumours are considered when choosing the type of treatment for the disease.

Signs and symptoms

File:Rb whiteeye.PNG

Leukocoria in a child with retinoblastoma

File:Squint.jpg

Crossed eyes in a child with retinoblastoma

The most common and obvious sign of retinoblastoma is an abnormal appearance of the pupil, leukocoria. Other less common and less specific signs and symptoms are: deterioration of vision, a red and irritated eye, faltering growth or delayed development. Some children with retinoblastoma can develop a squint, commonly referred to as "cross-eyed" or "wall-eyed" (strabismus). However, retinoblastoma presence with advanced disease in developing countries and eye enlargement is a common finding.

Depending on the position of the tumors, they may be visible during a simple eye exam using an ophthalmoscope to look through the pupil. A positive diagnosis is usually made only with an examination under anesthetic (EUA). A white eye reflection is not always a positive indication of retinoblastoma and can be caused by light being reflected badly or by other conditions such as Coats's Disease.

In a photograph, the photographic fault red eye may be a sign of retinoblastoma, if in the photograph it is in one eye and not in the other eye.

Frequency of retinoblastoma

Retinoblastoma is rare and affects approximately 1 in 15,000 live births. In the UK, around 40 to 50 new cases are diagnosed each year.

Most children are diagnosed before the age of five years old. In the UK, bilateral cases usually present within the first year with the average age at diagnosis being 9 months. Diagnosis of unilateral cases peaks between 24 and 30 months.

Cause of retinoblastoma

In children with the heritable genetic form of retinoblastoma there is a mutation on chromosome 13, called the RB1 gene. The genetic codes found in chromosomes control the way in which cells grow and develop within the body. If a portion of the code is missing or altered (mutation) a cancer may develop.

The defective RB1 gene can be inherited from either parent; in some children, however, the mutation occurs in the early stages of fetal development. It is unknown what causes the gene abnormality; it is most likely to be a random mistake during the copy process which occurs when a cell divides.

Genetic forms of retinoblastomas are more likely to be bilateral; in addition, they may be associated with pinealoblastoma (also known as trilateral retinoblastoma) with a dismal outcome. The genetic codes found in chromosomes control the way in which cells grow and develop within the body.

Diagnosis

Screening for retinoblastoma should be part of a "well baby" screening for newborns during the first three months of life, to include:

The Red reflex: checking for a normal reddish-orange reflection from the eye's retina with an ophthalmoscope or retinoscope from approximately 30 cm / 1 foot, usually done in a dimly lit or dark room.

The Corneal light reflex: checking for symmetrical reflection of beam of light in the same spot on each eye when a light is shined into each cornea, to help determine whether the eyes are crossed.

Eye examination: checking for any structural abnormalities.

Differential diagnosis

1. Persistent hyperplastic primary vitreous (PHPV): congenital developmental anomaly of the eye resulting from failure of the embryological, primary vitreous and hyaloid vasculature to regress, whereby the eye is shorter, develops a cataract, and may present with whitening of the pupil.

2. Coat's disease: a typically unilateral disease characterised by abnormal development of blood vessels behind the retina, leading to blood vessel abnormalities in the retina and retinal detachment to mimic retinoblastoma.

3. Toxocara canis: an infectious disease of the eye associated with exposure to infected puppies, which causes a retinal lesion leading to retinal detachment.

4. Retinopathy of prematurity (ROP): associated with low birth weight infants who receive supplemental oxygen in the period immediately after birth, it involves damage to the retinal tissue and may lead to retinal detachment.

File:MRI retinoblastoma.jpg

MRI pattern of retinoblastoma with optic nerve involvement (sagittal enhanced T1-weighted sequence)

If the eye examination is abnormal, further testing may include imaging studies, such as Computerized Tomography (CT), Magnetic Resonance Imaging (MRI), and Ultrasound. CT and MRI can help define the structure abnormalities and reveal any calcium depositions. Ultrasound can help define the height and thickness of the tumor. Bone marrow examination or lumbar puncture may also be done to determine any metastases to bones or the brain.

Morphology

Gross and microscopic appearances of retinoblastoma are identical in both hereditary and sporadic types. Macroscopically, viable tumor cells are found near blood vessels, while zones of necrosis are found in relatively avascular areas. Microscopically, both undifferentiated and differentiated elements may be present. Undifferentiated elements appear as collections of small, round cells with hyperchromatic nuclei; differentiated elements include Flexner-Wintersteiner rosettes and fluerettes from photoreceptor differentiation.

Treatment

File:External beam radiotherapy retinoblastoma nci-vol-1924-300.jpg

Historical image showing Gordon Isaacs, the first patient treated with the linear accelerator (external beam radiation therapy) for retinoblastoma in 1957. Gordon's right eye was removed January 11, 1957 because the cancer had spread. His left eye, however, had only a localized tumor that prompted Henry Kaplan (doctor) to try to treat it with the electron beam.

Treatment of retinoblastoma varies from country to country. The first priority is to preserve the life of the child, then to preserve the vision and thirdly to minimize any complications or side effects of the treatment. The exact course of treatment will depend on the individual case and will be decided by the Ophthalmologist in discussion with the Paediatric Oncologist.

Options for treatment include: chemotherapy (which can be administered locally through a thin catheter that is threaded through the groin through the aorta and the neck into the optic vessels), cryotherapy, radioactive plaques, laser therapy, external beam radiotherapy and surgery. Any combinations of these treatments may be adopted.

In recent years, there has been an effort to find alternatives to enucleation and radiation therapy.

See also

• Eye cancer
• Eye examination
• Retinoblastoma Protein

Additional images

• Wardrop retinoblastoma.jpg

  Drawing of a large retinoblastoma

• Trilateral retinoblastoma.jpg

  Aspect of trilateral retinoblastoma on MRI

• Retinoblastoma ultrasound.jpg

  An ocular ultrasound of a large retinoblastoma tumor within the eye of a three year old boy

• Retinoblastooma.jpg

  Funduscopic finding of a retinoblastoma

• Fundus retinoblastoma.jpg

  Ocular fundus aspect of retinoblastoma

• Rb.JPG

  Gross pathology of retinoblastoma tumor in enucleated eye of three year old female

• Retinoblastoma .jpg

  Large exophytic white tumor with foci of calcification producing total exudative retinal detachment

• Retinoblastoma rosette.jpg

  Flexner-Wintersteiner rosettes in Retinoblatoma

• Rtbl400.GIF

  Retinoblastoma, 400 X magnification

• RB1.JPG

  Crystal structure of the Retinoblastoma tumour suppressor protein bound to E2F peptide Polymer.

External links

• Retinoblastoma at National Cancer Institute
• Retinoblastoma International
• Retinoblastoma information from MedlinePlus
• retinoblastoma at NIH/UW GeneTests
• Retinoblastoma at the Open Directory Project

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