Retinoblastoma is the most common primary intraocular malignancy of children. The molecular genetics of retinoblastoma has been discussed previously (Chapter 6). Approximately 40% of the tumors are associated with a germline mutation in the RB gene and are therefore heritable. The remaining 60% of the tumors develop sporadically, and these have somatic RB gene mutations. Familial cases typically are associated with development of multiple tumors that are bilateral, although they may be unifocal and unilateral. All of the sporadic, nonheritable tumors are unilateral and unifocal. Patients with familial retinoblastoma also are at increased risk for the development of osteosarcoma and other soft tissue tumors.
MORPHOLOGYRetinoblastomastendtobenodularmasses,usuallyintheposteriorretina,oftenwithsatelliteseedings(
Fig.7.35A ).Onmicroscopicexamination,undifferentiatedareasofthesetumorsarefoundtobecomposedofsmall,roundcellswithlargehyper-chromaticnucleiandscantcytoplasm,resemblingundifferentiatedretinoblasts.
Differentiatedstructuresarefoundwithinmanyretinoblastomas,themostcharacteristicofthesebeingFlexner-Wintersteiner rosettes (
Fig.7.35B ).Thesestructuresconsistofclustersofcuboidalorshortcolumnarcellsarrangedaroundacentrallumen(incontrastwiththepseudorosettesofneuroblastoma,whichlackacentrallumen).Thenucleiaredisplacedawayfromthelumen,whichbylightmicroscopyappearstohavealimitingmembraneresemblingtheexternallimitingmembraneoftheretina.
Tumorcellsmaydisseminatebeyondtheeyethroughtheopticnerveorsubarachnoidspace.ThemostcommonsitesofdistantmetastasesaretheCNS,skull,distalbones,andlymphnodes.
The presenting findings include poor vision, strabismus, a whitish hue to the pupil (“cat’s eye reflex”), and pain and tenderness in the eye. The median age at presentation is 2 years, although the tumor may be present at birth. Untreated, the tumors usually are fatal, but when treated with chemotherapy, radiotherapy, and (in locally advanced tumors) enucleation, survival is the rule. As noted earlier, some tumors spontaneously regress, and patients with familial retinoblastoma are at increased risk for the development of osteosarcoma and other soft tissue tumors.
Wilms tumor, or nephroblastoma, is the most common primary tumor of the kidney in children, with most cases occurring in children between 2 and 5 years of age. This tumor illustrates several important concepts of childhood tumors: the relationship between congenital malformation and increased risk of tumors; the histologic similarity between tumor and developing organ; and finally, the remarkable success in the treatment of childhood tumors. Each of these concepts is presented in the following discussion.