Retinoblastoma: History of His Identification, Characterization and Treatment

Abstract

The first description of a tumor resembling retinoblastoma (RB) was provided on 1597 by Pieter Pauw, who described a malignancy invading the orbit, the temporal region, and the cranium, filled with a "substance similar to brain tissue mixed with thick blood and like crushed stone". Since then, a number of retinal tumors were described and named until the 1922 when Verhoeff called these tumors RB, a term that the American Ophthalmological Society adopted in 1926. In 1971 Knudson focused on RB, and proposed his ‘two-hit’ theory of the molecular etiology of RB. In 1986, the RB1 gene was identified and the ‘two-hit’ theory of Knudson was validated. Successively, new studies in developing retinal cells suggested that two mutational events are not enough for malignant transformation and that other hits are associated with RB development. Since RB was discovered it has gone from a state in which near all children inevitably die, to the current condition in which, in developed world, more than 99% of children survive. Overall, RB can be defined as a curable cancer, provided it does not happen events which make the therapy a palliative, as metastasis, trilateral RB or secondary tumors. To establish plan treatments it is required to stage RB. This is possible by the “International Classification for Intraocular Retinoblastoma” which has divided intraocular retinoblastomas into 5 groups (A-E) based on the chances to save the eye using current treatment options. This staging system can provide information about the most effective current treatments. The current available therapeutic options for RB are numerous, with the indications to use specific modality or a combination of modalities varying according to the extent of the disease.