Retinoblastoma


 * Epidemiology: || Most common primary ocular maIignancy of childhood. 250-500 new cases annually in the United States. Incidence worldwide is 1 case per 18,000-30,000 live births. Average age at diagnosis is 18 months with 90% of cases diagnosed before the age of 5. 1 It is bilateral in one-third of cases and unilateral in the other two-thirds. It is hereditary in about 40% of cases and most hereditary cases have bilateral disease. 2 ||
 * Etiology: || It has genetic origins and the gene is named the retinoblastoma gene. It is a mutation in the long arm of chromosome 13. The unaffected gene suppresses the disease while a mutation in the gene allows the disease to occur. 3 ||
 * Signs & Symptoms: || The most common signs & symptoms at presentation are: leukochoria, strabismus, and mass in the fundus. These all are usually apparent at 6-24 months. 4 ||
 * Diagnostic Procedures: || Have the child examined by a specialist, who will do a thorough ophthalmic examination to check the retina for a tumor. Depending on the age of the child, either a local or general anesthetic is used during the eye examination.

The specialist will make a drawing or take a photograph of the tumor in the eye to provide a record for future examinations and treatment, and may use additional tests to detect or confirm a tumor. If a newborn has a family history of retinoblastoma, the baby should be examined shortly after birth by an ophthalmologist (a medical doctor who specializes in eye care) who is experienced in treating cancers of the eye. In addition to a physical examination, the following tests may be used to diagnose retinoblastoma:
 * Ultrasound.** An ultrasound uses sound waves to create pictures of the internal organs. A transmitter that emits sound waves is moved over the child’s body. Tumors generate different echoes of the sound waves than normal tissue does, so when the waves are bounced back to a computer and changed into images, the doctor can locate masses inside the body. The procedure is painless.


 * Computed tomography (CT or CAT) scan.** A CT scan creates a three-dimensional picture of the inside of the child’s body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. Sometimes, a contrast medium (a special dye) is injected into the child’s vein to provide better detail. A CT scan helps the doctor find cancer outside of the eye.

Children who are diagnosed with retinoblastoma will be given a complete physical examination. If there are any additional symptoms or abnormal findings, children may also undergo additional tests to determine if the cancer has spread elsewhere in the body.
 * Magnetic resonance imaging (MRI).** An MRI uses magnetic fields, not x-rays, to produce detailed images of the brain and spinal column. MRIs may create more detailed pictures than CT scans and provide the specialist with a picture of the inside of the eye and the brain.
 * MRI or CT scan of the brain.** These tests may be recommended to determine if there is an abnormality of the pineal gland (a small gland in the brain). It is recommended that these scans be performed once every six months until the age of five in children with the genetic form of retinoblastoma (those with bilateral disease and those with unilateral disease with a family history of the disease). Very young children with a tumor in one eye who do not have a family history of the disease may also be at risk, and these tests may be recommended. Scans may also be recommended years after treatment for children who have received external-beam radiation therapy, either as a baseline in the event that problems arise, or to determine the cause of a symptom or sign.


 * Blood tests.** These tests evaluate the blood and check for problems with the liver and kidneys. The doctor may also look at the blood for changes in chromosome 13 . Chromosomes are the part of the cell that contains genes, and in a few cases of retinoblastoma, these genes are either missing or nonfunctional. Molecular analysis of the gene is now possible in a few medical centers to determine changes that are not visible on ordinary chromosome analysis.


 * Lumbar puncture (spinal tap).** A lumbar puncture is a procedure in which a doctor takes a sample of cerebral spinal fluid (CSF) to look for cancer cells, blood, or tumor markers (substances found in higher than normal amounts in the blood, urine, or body tissues of people with certain kinds of cancer.) CSF is the fluid that flows around the brain and the spinal cord. Doctors generally give an anesthetic to numb the lower back before the procedure.


 * Bone marrow biopsy/aspiration.** This procedure is performed to determine if any retinoblastoma cells have spread to the marrow. For this test, a small amount of bone marrow is removed from the hip with a needle and examined under a microscope. A local anesthetic will be given to numb the area before the procedure.

A retinoblastoma is composed of small round cells with scant cytoplasm and a deeply staining nucleus, resembling embryonal retinal cells. It appears grossly as a white, friable tumor with dense calcifications. Tumors that arise from the internal nuclear layer, the nerve fiber layer, the ganglion cell layer, or the external nuclear layer grow toward the subretinal space, pushing the retina inward and leading to retinal detachment [48]. This type of retinoblastoma is known as the //exophytic// type. Tumors that arise from the inner layers of the retina and grow toward the vitreous are known as the //endophytic// type.6 || dd= (Disk diameter which is 1.6 mm) Group I (quite favorable) a. Solitary tumor (less than 4 dd at or behind the equator) b. Multiple tumors (none over 4 dd at or behind the equator) Group II (favorable) a. Solitary tumor (4-10 dd. at or behind the equator) b. Multiple tumors (4-10 dd. behind the equator) Group III (doubtful) a. Any lesion anterior to the equator b. Solitary lesions (larger than 10 dd. behind the equator) Group IV (unfavorable) a. Multiple tumors (some larger than 10 dd) b. Any lesion extending anteriorly to the ora serrata Group V (quite unfavorable) a. Massive tumors involving over half the retina b. Vitreous seeding. 8 || 12 || __**References**__ 1. Aventura Isidro M. //Retinoblastoma.// Available at: [|//http://emedicine.medscape.com/article/1222849-overview//]//.// Accessed February 12, 2010. 2. Chao KS, Perez CA., Brady LW. //Radiation Oncology - Management Decisions//. 2nd ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2002:177. 3. Aventura Isidro M. //Retinoblastoma.// Available at: [|//http://emedicine.medscape.com/article/1222849-overview//]//.// Accessed February 12, 2010. 4. Chao KS, Perez CA., Brady LW. //Radiation Oncology - Management Decisions//. 2nd ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2002:177. 5. [|www.cancer.net/Cancer+Types/Retinoblastoma.com] Accessed Febuary 12, 2010. 6. Lenhard,E. Raymond. Jr.,MD., Osteen, T. Robert, Gansler,Ted,.MD. The American Cancer Society's Clinical Oncology. 1st edition. Atlanta,GA. 2001. Pictures pg 586 7. Chao KS, Perez CA., Brady LW. Radiation Oncology- Management Decisions. 2nd edition. Philadelphia, PA: Lippincott, Williams & Wilkins; 2002 pg 177-178 8. Chao KS, Perez CA, Brady LW. //Radiation Oncology-Management Decisions//. 2nd ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2002 9. Chao KS, Perez CA, Brady LW. Radiation Oncology-Management Decisions. 2nd ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2002 10. Hand CM, Kim SJW, Waldow SM. Overview of radiobiology. In: Washington CM, Leaver D, eds. //Principles and Practice of Radiation Therapy//. 2nd ed. St. Louis, MO: Mosby; 2004:80-81. 11. Kehwar TS, Sharma SC. Use of normal tissue tolerance doses into linear quadratic equation to estimate normal tissue complication probability. Available at: http;//www.rooj.com/Normal%20Tissue%20/Comp.htm. Accessed February 12, 2010. 12. www2.massgeneral.org accessed 2/13/2010 Fig. 1,2 & 3 .
 * Hearing test.** Children with retinoblastoma taking certain chemotherapy may have their hearing tested (called an audiology test) to make sure the drugs are not causing hearing loss. 5 ||
 * Histology: || 
 * Lymph Node Drainage: || No lymph node drainage or spread found . 7 ||
 * Metastatic Spread: || Local spread described by Reese-Ellsworth staging but distant metastases are not documented ||
 * Grading: || No separate grading system specified ||
 * Staging: || Reese-Ellsworth System
 * Radiation Side Effects: || The potential problem of secondary neoplasms (i.e., osteosarcoma) after chemoirradiation remains open. As the risks of second malignancy is increased, new primary cancer rates after 50 years for patients receiving radiation therapy are 5% for nonhereditary retimoblastoma and 51% for hereditary retinoblastoma. The rate drops to 27% for patients not receiving radiation therapy. ||
 * Prognosis: || Factors that carry a poor prognosis include orbital invasion, involvement of the optic nerve, central nervous system dissemination, and heritable bilateral tumors, tumor parometers such as size, growth pattern (endophytio or exophytic), and differentiation do not significantly influence the systemic prognosis. ||
 * Treatments: || Enucleation is indicated in unilateral tumor in which the eye is blind, or when the retinoblastoma fills most of the eye, especially when there is concern for tumor invasion into the optic nerve or choroid. External-beam radiation continues to be an important methos of treating less advanced retinoblastoma. Systemic chemotherapy in patients with Reese-Ellsworth eye groups I, II, or III in conjunction with local opthalmic therapies (cryotherapy, laser photocoagulation, thermotherapy, or plaque radiation therapy) can eleminate the need for enucleation or external beam radiation therapy without significant systemic toxicity. Chemoreduction with vitreous seeds and subretinal seeds showed initial regression and often complete dissappearance of the retinoblastoma. Radiation Techniques-The Willis Eye Tumor Group recommends doses of 45-50 Gy to the tumor apex; dose should be 35-40 Gy if irradiation is combined with chemotherapy. It is necessary to treat the entire retina to avoid tumor recurrence in the anterior part of the eye. Single lateral field, a single anterior field, or a combination of both anterior and lateral fields are options for irradition fields. Most techniques using a lateral field involve blocking of the anterior half of the field producing a D-shaped field. It is important to encompass the entire retinal anlage when designing the anterior half-beam block of the lateral field. 9 ||
 * TD5/5: || Major organs at risk and their TD5/5: the major organ would be the eye and the usual result would be blindness. Retina - 55 Gy, Cornea - 50 Gy, Lens - 500 cGy. 10 Optic nerve - average of 50 Gy and the optic chiasm - average of 50 Gy. 11 ||
 * Treatment plan || Proton isodose distribution of a retinoblastoma treatment plan.