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

Abstract

Results of recent studies have led investigators to suggest that the retinoblastoma tumor-suppressor (rb) gene plays an underappreciated role in the genesis of brain tumors. Such tumors cause significant rates of mortality in children suffering from hereditary retinoblastoma. It has been assumed that the pineal gland, which is ontogenetically related to the retina, accounts for the intracranial origin of these trilateral neoplasms. To address this issue, the authors describe an unusual trilateral retinoblastoma variant. The authors provide a detailed clinicopathological correlation by describing the case of a child with bilateral retinoblastoma who died of a medulloblastoma. The intraocular and intracranial neoplasms were characterized by performing detailed imaging, histopathological, and postmortem studies. Karyotype analysis and fluorescence in situ hybridization were used to define the 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 translocation was unbalanced in the proband. The intraocular and cerebellar neoplasms were found to be separate primary neoplasms. Furthermore, the pineal gland was normal and the cerebellar neoplasm arose within the vermis as a medulloblastoma. Finally, the two neoplasms had different and characteristically identifiable cytolological and immunohistochemical profiles. The findings of the present study, taken together with those of recent molecular and transgenic studies, support the emerging concept that rb inactivation is not restricted to central nervous system regions of photoreceptor lineage and that inactivation of this tumor suppressor pathway may be relevant to the determination of etiological factors leading to medulloblastoma in humans.

Integrated Genomics Identifies Five Medulloblastoma Subtypes with Distinct Genetic Profiles, Pathway Signatures and Clinicopathological Features

“…This might suggest a common origin of these tumors and medulloblastomas with retinal antigens. Patients with hereditary retinoblastoma harboring a mutation in RB1 are at increased risk of developing pineoblastoma, supratentorial PNET and there is one case report of a medulloblastoma in such a patient [62], [63]. Although RB1 mutations have never been detected in other medulloblastomas [64], some experimental tumor models suggest a role for the RB pathway in this tumor.…”

Molecular genetics of supratentorial primitive neuroectodermal tumors and pineoblastoma

“…Rare cases of this disease with cerebellar/fourth ventricular PNET/medulloblastoma have been reported. 53,57 Nevertheless, we are aware of only one case of cerebral PNET reported in association with retinoblastoma. Dorfmuller, et al, 50 described a child in whom a temporal-parietal supratentorial PNET developed 5 years after radiation therapy for a unilateral retinoblastoma.…”

Retinoblastoma in the eye of a llama (Llama glama)

“…The hereditary form of retinoblastoma in humans has been associated with a mutation in the tumor suppressor gene ( rb ) located on human chromosome 13q14 1–4 . Mutation of this gene predisposes affected children to intraocular retinoblastomas as well as intracranial neoplasia 5–7 . There remains considerable debate regarding whether retinoblastomas should be diagnosed in animals without confirmation of the rb mutation 1,2,8 …”

“…[1][2][3][4] Mutation of this gene predisposes affected children to intraocular retinoblastomas as well as intracranial neoplasia. [5][6][7] There remains considerable debate regarding whether retinoblastomas should be diagnosed in animals without confirmation of the rb mutation. 1,2,8 Ocular neoplasms morphologically resembling retinoblastomas have been diagnosed as medulloepitheliomas and reported in two llamas, and several other animal species including dogs, cats, horses, chickens and cockatiels.…”