Retinoblastoma

computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the head Eye exam with dilation of the pupil Ultrasound of the eye (head and eye echoencephalogram) 2 || Reprinted from Pathpedia, 2013. 3
 * **Epidemiolgy:** || Retinoblastoma is the most common intraocular malignancy in children. 1 Most children are diagnosed before the age of 4. About 250 new cases are diagnosed in the United States each year. ||
 * **Etiology:** || Since this disease is commonly diagnosed before the age of 4, there are not many risk factors associated with the malignancy. However, retinoblastoma is hereditary in 40% of cases and is transmitted by an autosomal-recessive trait. 1 When a deletion or mutation of chromosome 13 occurs, it could cause this genetic abnormality. Also, the hereditary form many times comes with bilateral disease. ||
 * **Signs & Symptoms:** || The pupil may appear white or have white spots. A white glow in the eye is often seen in photographs taken with a flash. Instead of the typical "red eye" from the flash, the pupil may appear white or distorted. Other symptoms can include 2 :
 * Crossed eyes
 * Double vision
 * Eyes that do not align
 * Eye pain and redness
 * Poor vision
 * Differing iris colors in each eye ||
 * **Diagnostic Procedures:** || Bone marrow biopsy and cerebrospinal fluid examination in the case of more aggressive tumors
 * **Histology:** || The tumor arises from undifferentiated neuroectodermal cells that are the precursors of retinal neuroepithelium. 3

The above image is a large tumor (arrow on the right) that detaches the retinal epithelium (thin long arrow facing down). Note the proximity of the tumor origin with the retinal epithelium. The optic nerve is shown on the left (arrowhead). || Reprinted from International Journal Radiation Oncology Biology Physics, 2013. 6
 * **Lymph node drainage:** || The affected regional lymph nodes include perauricular, submandibular and cervical lymph nodes. 1 ||
 * **Metastatic spread:** || Metastatic spread of retinoblastoma is typically through hematogenous routes since there are no intraocular lymphatics. The most common sites of spread are to bone marrow, skull, long bones, and brain. 1 ||
 * **Grading:** || A two-grade, three-grade, or four-grade system may be used. If a grading system is not specified, then the following is used 1 :
 * GX - Grade cannot be assessed
 * G1 - Well differentiated
 * G2 - Moderately differentiated
 * G3 - Poorly differentiated
 * G4 - Undifferentiated ||
 * **Staging:** || Condensed American Joint Committee on Cancer (AJCC) TNM Definitions for Retinoblastoma 4 :
 * T1: No more than 2/3 eye volume and no subretinal or vitreous seeding.
 * T1a,b,c: Classified by retinal tumor size (more or less than 3 mm) and/or distance from optic nerve and fovea, and/or distance of tumor base from subretinal fluid.
 * T2: No more than 2/3 eye volume; some vitreous or subretinal seeding; some retinal detachment.
 * T2a,b: Classified by presence or absence of large, diffuse clumps of tumor cells (“snowballs”).
 * T3: Severe intraocular disease.
 * T3a,b: Classified by presence or absence of complications, for example tumor-associated neovascular or angle closure glaucoma, tumor extension into the anterior segment, hyphema, vitreous hemorrhage, or orbital cellulitis.
 * T4: Extraocular disease.
 * T4a,b,c,d: Classified by invasion to optic nerve, to or beyond optic chiasm, or orbit.
 * N1,2: Involvement of regional or distant lymph nodes.
 * M1: Systemic metastasis. Subdivided in to M1a,b,c,d depending on what part of CNS is involved. ||
 * **Radiation side effects:** || Short-term effects may include skin reactions. Radiotherapy can damage surrounding normal body tissues. This may eventually lead to cataracts and damage to the retina or optic nerve, which could reduce vision. 5 Radiation can also interfere with the growth of bone and other tissues near the eye, which can affect the way the area around the eye looks over time. ||
 * **Prognosis:** || The prognosis of a retinoblastoma patient is dependent on a variety of factors, most importantly its spread. If there is invasion of the orbits or optic nerves, central nervous system (CNS) dissemination, or heritable bilateral tumors, the prognosis is poor. Unlike many cancers, the size, growth pattern, and differentiation of the tumor does not play a large part. 1 ||
 * **Treatments:** || For tumors that are less advanced, the primary treatment is radiation therapy. 1 By using a technique to spare the lens, the radiation treatments are often able to spare the vision of the patient. However, in order to decrease the possibility of recurrence, the entire retina must be treated. Typically a lateral field and an anterior field are used together, or one or the other. When radiation therapy is used alone, the treatment dose is taken to 40-45 Gray (Gy) in 20-30 fractions at 1.5-2.0 Gy per fraction. If chemotherapy is used to try and reduce the tumor size, the radiation doses are only taken to 35-40 Gy. If the patient is blind at the time of diagnosis, a unilateral tumor would result in enucleation. ||
 * **TD 5/5:** || Tolerance doses that will cause a minimum 5% complication rate within 5 years 5 :
 * Retina 5500 cGy
 * Lens 1000 Gy
 * Optic chiasm 4500 cGy
 * Optic nerve 5000 cGy
 * Growing cartilage and bone (child) 1000 cGy ||
 * **Additional images:** || [[image:Retinoblastoma.gif width="570" height="361"]]

The above image shows an intensity-modulated radiation therapy (IMRT) technique with four noncoplanar fields.

Reprinted from International Journal Radiation Oncology Biology Physics, 2013. 6

The image above shows the isodose curves of the IMRT technique. ||
 * **References:** || # Chao KS, Perez CA, Brady LW. // Radiation Oncology Management Decisions // . 3rd ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2011.
 * 1) Retinoblastoma. Health Guide. New York Times Web site. http://health.nytimes.com/health/guides/disease/retinoblastoma. Accessed July 1, 2013.
 * 2) Retinoblastoma. Pathpedia Web site. http:www.pathpedia.com/education/eatlas/histopathology/eye_and_ocular_adnexa/retinoblastoma.aspx. Accessed July 1, 2013.
 * 3) Retinoblastoma. American Cancer Society Web site. http://www.cancer.org/cancer/retinoblastoma/detailedguide/index. Accessed June 27, 2013.
 * 4) Washington CM, Leaver D. //Principles and Practice of Radiation Therapy//. 3rd ed. St. Louis, MO: Mosby Elsevier; 2010.
 * 5) Reisner ML, Viegas CMP, Grazziotin RZ, et al. Retinoblastoma: Comparative analysis of external radiotherapy techniques, including an IMRT technique. //Int J Radiat Oncol Biol Phys//. 2007;67(3):933-941. doi:10.1016/j.ijrobp.2006.09.057. ||

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