Diagnosis, classification, and treatment of retinoblastoma.

Retinoblastoma represents approximately 4% of all pediatric malignancies and is the most common primary intraocular cancer in children. Worldwide, it is estimated that there are 5000 to 8000 newly diagnosed cases of retinoblastoma yearly. In the United States, approximately 250 to 350 cases are diagnosed each year. The first description of a child successfully treated with radiation for retinoblastoma was reported in 1903. Since that time, improvement in survival of retinoblastoma has been faster than any other cancer in children or adults. In 2003, retinoblastoma was the pediatric cancer with the highest survival. In the Western world, 99% of children will survive this cancer and over 90% will retain normal vision in at least 1 eye. Unfortunately, primarily to late detection of advanced retinoblastoma, in medically underdeveloped nations survival drops to approximately 50%. A genetic basis for the development of retinoblastoma was recognized over 70 years ago. In 1971, after noting differences in tumor development in patients with unilateral versus bilateral retinoblastoma, Knudson proposed his now famous two-hit model of tumorgenesis. The retinoblastoma gene (RB1) was the first human cancer gene cloned and was the first of a whole new class of human tumor-suppressor genes. The protein responsible for intraocular retinoblastoma is vital for terminal differentiation of many cell lineages, including differentiation of retinal progenitor cells. It is now recognized that the loss of normal functioning RB1 is an important step in the development of many adult nonocular cancers.