Retinoblastoma. Fifty years of progress. The LXXI Edward Jackson Memorial Lecture.

PURPOSE: To review the progress made in understanding the genetic basis, molecular pathology, and treatment of retinoblastoma since the previous Jackson lecture on the topic was published 50 years ago. DESIGN: Perspective based on personal experience and the literature. METHODS: The literature regarding retinoblastoma was reviewed since 1963. Advances in understanding the biology and treatment of retinoblastoma provided context through the author's clinical, pathologic, and research experiences. RESULTS: Retinoblastoma was first identified in the 1500s and defined as a unique clinicopathologic entity in 1809. Until the mid-1900s, knowledge advanced sporadically, with technological developments of ophthalmoscopy and light microscopy, and with the introduction of surgical enucleation, chemotherapy, and radiation therapy. During the last 50 years, research and treatment have progressed at an unprecedented rate owing to innovations in molecular biology and the development of targeted therapies. During this time period, the retinoblastoma gene was discovered; techniques for genetic testing for retinoblastoma were developed; and plaque brachytherapy, chemoreduction, intra-arterial chemotherapy, and intraocular injections of chemotherapeutic agents were successfully introduced. CONCLUSIONS: Nearly all patients with retinoblastoma in developed countries can now be cured of their primary cancer--a remarkable achievement for a childhood cancer that once was uniformly fatal. Much of this success is owed to deciphering the role of the Rb gene, and the benefits of targeted therapies, such as chemoreduction with consolidation as well as intra-arterial and intravitreal chemotherapies. Going forward, the main challenge will be ensuring that access to care is available for all children, particularly those in developing countries.

The accidental cancer geneticist: hilário de gouvêa and hereditary retinoblastoma.

In 1872 a Brazilian ophthalmologist performed an enucleation in a young boy with retinoblastoma. This boy survived and married a woman without any family history of cancer. The couple had two daughters with bilateral retinoblastoma also seen by the same ophthalmologist, Hilário de Gouvêa. This case became the first documented report of a family with retinoblastoma in more than one generation. Here we examine the life of de Gouvêa and his contribution which raised the possibility that cancer had a genetic basis. We discuss how de Gouvêa's mind had been prepared to realize the importance of this observation. We attempt to define the conditions that allowed not only his discovery, but also the report of the findings and a dogged pursuit for credit over many years in a country which had virtually no research tradition and was still grappling with its recent colonial history.

Pieter Pauw's tumor oculorum: reappraisal of the presumed first description of retinoblastoma in 1597.

Cancer in a young child is unusual and has always aroused curiosity. Proptosis and an enormous, rapidly growing unilateral tumor in a 3-year-old boy prompted Pieter Pauw (1564-1617), a 16th-century anatomist, to perform an autopsy. His published notes from the autopsy were rediscovered in the 19th century, first by the German ophthalmologist and historian Julius Hirschberg and then by Edwin B. Dunphy, from Boston, Mass, who suggested that the child suffered from retinoblastoma, an interpretation that has held sway. Critical translation of the original Latin text suggests that an orbital tumor, such as embryonal rhabdomyosarcoma, would equally well explain Pauw's observations. His description also gives insight into the concept of a mole as a congenital as well as an intrauterine tumor in Renaissance medicine.

[History of retinoblastoma]. / Pohled do historie retinoblastomu.

The author presents a brief account on the development of knowledge regarding the clinical picture, diagnosis, dynamics of the disease, surgical and conservative therapy of the most serious intraocular malignity of child age. He emphasizes the contribution made by different authors, starting in 1597 when Pawius published the first account of an autopsy of a child affected with the tumour. He emphasizes the biological importance, the affection of the optic nerve by the tumour, the vital importance of early enucleation, the importance of distant resection of the optic nerve during removal of the eye and the importance and contribution of conservative treatment for the vital perspective of affected children.