Retinoblastoma

retinoblastomaRetinoblastoma (Rb) is a rare malignant tumor derived from the retina of the eye.


Description

Retinoblastoma is a tumor of the retina, usually seen in children, the neoplasm develops during the first two years of child’s life. It may affect one eye (unilateral retinoblastoma) or both eyes (bilateral retinoblastoma). When retinoblastoma is bilateral it is more likely to be hereditary. Sometimes it affects the pineal gland, the suprsellar or parasellar region – this condition is called trilateral retinoblastoma.

 

Incidence

Retinoblastoma comprises near 2% of all childhood cancers. This type of cancer affects 1 child in every 11,000–30,000 live births. Approximately 2/3 of all the cases are unilateral retinoblastoma and 1/3 – bilateral.

An average age when the diagnosis is made is from 1 year (in case of bilateral retinoblastoma) up to 2 years (in case of unilateral retinoblastoma).

 

Causes and risk factors

Approximately half of the cases are caused by a genetic mutation with a familial history of the disease. Retinoblastoma is inherited with the autosomal dominant inheritance pattern.   

The most common mutation seen in this type of cancer is the change in the RB1 gene – deletion on the q14 band of chromosome 13. Non-hereditary cases of retinoblastoma may be caused by the somatic mutation of the MYCN oncogene.

 

Symptoms

Symptoms of retinoblastoma include the following:

  • Leukocoria (white papillary reflex/amaurotic cat’s eye reflex) is seen in over than 50% of cases, it is characterized by an abnormal white reflection from the retina through the pupil during the eye examination;
  • Strabismus (crossed eyes) – exotropia (one or both of the eyes turn outward) or esotropia (one or both eyes turns inward), “lazy eye”;
  • Pain of the eye;
  • Eye redness;
  • Swelling or enlargement of the eye;
  • Glaucoma (increased intracranial pressure);
  • Vision deterioration/poor vision;
  • Change of the iris color;
  • Orbital, sinus and intracranial extension;
  • Hyphema (the accumulation of blood in the space between the iris and the cornea called anterior chamber);
  • Nystagmus (fast involuntary eye movements);
  • Failure to thrive/anorexia;

 

Stages

The tumor may be intraocular when only the eye is affected or extraocular when the surrounding tissues or other body parts are involved. The stages of the disease are identified according to the International (ABC) Classification System for Intraocular Staging.

 

Diagnosis

The diagnosis is made based on the next tests and examinations:

  • Slitlamp examination;
  • Examination of the retina via dilated ophthalmoscopy;
  • Digital fundus photography;
  • Ultrasound imaging of the eyeball (A and Bscan);
  • CT/MRI imaging help to detect intraocular calcification and the extension of the tumor;
  • X-ray is performed when ultrasound examination, CT and MRI are not available. Intraocular calcification may be seen;
  • Genetic analysis is performed to verify the cause of the disease and the risk for other children to develop retinoblastoma;
  • Biopsy of the tumor – microscopically deep blue cells with little cytoplasm, Flexner–Wintersteiner and Homer–Wright rosettes are detected.

See also: Retinal dysplasia

 

Treatment

Treatment of retinoblastoma includes:

  • Enucleation of the eye  is performed for patients with very large tumors that have invaded the nearby structures, this method is commonly used when all the other eye-sparing treatments failed to help;
  • External beam radiotherapy (EBR) is rarely used because of the various radiation-related complications such as secondary malignant tumor. EBR is used for treatment of intracranial, sinus retinoblastoma and retinoblastoma metastases.
  • Plaque brachytherapy is the placement of a radioactive plaque on the sclera of the affected eye. The dose of 40-45 Gy is delivered during 2-5 days. This treatment is used when the initial treatment wasn’t effective and when retinoblastoma is relatively small. Radionuclides include 125I, 103Pd, 106Ru.
  • Laser photocoagulation is performed after chemotherapyinduced tumor reduction for small posterior (≤2.5–3.0 mm) tumors. Argon lased 532 nm or infrared laser 810 nm ceases the blood supply to the tumor.
  • Cryotherapy damages the vessels by freezing them and therefore causing the necrosis of the tumor. Cryotherapy may be effective for small peripheral or anterior tumors.
  • Systemic/intravenous chemotherapy remains the main treatment method, although it may cause various side effects and istoxic in relation to the bone marrow.  It is used in the treatment of large tumors, especially bilateral ones, the tumors that have infiltrated the surrounding tissues, and when metastases are identified.
  • Intra-arterial chemotherapy is an investigational treatment when the  chemotherapeutic agents (melphalan, topotecan) are injected directly into the ophthalmic artery. It is suggested that this type of chemotherapy helps to avoid the side effects associated with systemic chemotherapy.
  • Nano-particulate chemotherapy is a subconjuctival/local injection of chemotherapeutic drugs (carboplatin).

 

Applicable medicines

Chemotherapeutical agents administered in the treatment of retinoblastoma include the following drugs:

  • Carboplatin, cisplatinum;
  • Etoposide;
  • Vincristine;
  • Doxorubicin;
  • Cyclophosphamide;

 

Prognosis
Children usually survive the tumor (the survival rate is about 70-90%, depending on the country), although they may lose their vision or have their eyes removed.