Trilateral retinoblastoma variant indicative of the relevance of the retinoblastoma tumor-suppressor pathway to medulloblastomas in humans - Case report

Results of recent studies have led investigators to suggest that the retino blastoma tumor-suppressor (rb) gene plays an underappreciated role in the g enesis of brain tumors. Such tumors cause significant rates of mortality in children suffering from hereditary retinoblastoma. It has been assumed tha t the pineal gland, which is ontogenetically related to the retina, account s for the intracranial origin of these trilateral neoplasms. To address thi s issue, the authors describe an unusual trilateral retinoblastoma variant. The authors provide a detailed clinicopathological correlation by describin g the case of a child with bilateral retinoblastoma who died of a medullobl astoma. The intraocular and intracranial neoplasms were characterized by pe rforming detailed imaging, histopathological, and postmortem studies. Karyo type analysis and fluorescence in situ hybridization were used to define th e chromosomal defect carried by the patient and members of her family. An insertion of the q12.3q21.3 segment of chromosome 13 into chromosome 18 at band q23 was identified in members of the patient's family. This translo cation was unbalanced in the proband. The intraocular and cerebellar neopla sms were found to be separate primary neoplasms. Furthermore, the pineal gl and was normal and the cerebellar neoplasm arose within the vermis as a med ulloblastoma. Finally, the two neoplasms had different and characteristical ly identifiable cytolological and immunohistochemical profiles. The findings of the present study, taken together with those of recent mole cular and transgenic studies, support the emerging concept that rb inactiva tion is not restricted to central nervous system regions of photoreceptor l ineage and that inactivation of this tumor suppressor pathway may be releva nt to the determination of etiological factors leading to medulloblastoma i n humans.