1/465. Sporadic bilateral retinoblastoma and 13q- chromosomal deletion. Unilateral retinoblastoma (Rb) is usually a sporadic occurrence while bilateral (multifocal) cases are often familial. Sporadic bilateral Rb associated with a long-arm deletion of a D-group chromosome has been reported in 8 children. We have studied a 6-year-old female with bilateral sporadic retinoblastoma, treated during infancy by enucleation and radiotherapy. chromosome banding studies on peripheral lymphocytes revealed an interstitial deletion from the long arm of a chromosome 13: del(13) (q12q14). Three additional patients reported in the literature had interstitial 13q- deletions, involving slightly different though overlapping regions. The only chromosomal region consistently missing in all of these 4 cases appears to be part of the lightly staining band 13q14. We, therefore, propose this site as the precise location of a gene (or genes) involved in retinal development. Our patient lacked features of the classic 13q- or 13-ring syndrome, which involves deletion of a more distal portion of the 13 long arm. When compared to reported patients with Rb and 13q-, it became apparent that there may be a separate recognizable syndrome consisting of moderate growth and developmental delay, characteristic facies and external ears, and bilateral sporadic Rb, which is associated with an interstitial 13q- deletion. ( info) |
2/465. Establishment and characterization of a second primary osteosarcoma cell line (OSrb/N-M) from a patient cured of bilateral retinoblastoma. A cell line, designated OSrb/N-M, was established from the second primary osteosarcoma that developed in a 17-year-old Japanese female patient who had suffered from bilateral retinoblastoma at infancy. The OSrb/N-M cells grew as an adherent monolayer and retained some osteogenic biochemical phenotypes. In cytogenetic analyses, this cell line revealed many structural and numerical abnormalities, however, the bands q14 of both chromosomes 13 appeared to be normal, whereas the constitutional cells displayed normal female karyotypes. Immunoblot studies using monoclonal antibodies specific to RB protein demonstrated that the tumor cells did not express RB protein, suggesting that the OSrb/N-M cells might suffer from a loss-of-function mutation at this gene locus. Thus, this cell line is useful to study the molecular mechanism for the tumorigenesis of osteosarcoma with regard to an association with retinoblastoma. ( info) |
3/465. Trilateral retinoblastoma with an RB1 deletion inherited from a carrier mother: a case report. A presentation of intracranial tumor in bilateral and unilateral retinoblastoma with or without family history is termed as trilateral retinoblastoma (TRB). It always occurs either as a pineal tumor or supra/parasellar tumor, which differ in presentation and prognosis. We report here the first case of TRB with transmission of retinoblastoma gene (RB1) deletion from an unaffected mother (a carrier), presenting as concurrent intracranial neoplasm with bilateral retinoblastoma. The presence of RB1 mutation in both child and mother could be responsible for development of intracranial neoplasm which occurred simultaneously with bilateral RB in our patient. Our patient, who had a suprasellar mass, received radiation and intrathecal chemotherapy, and died 6 months after diagnosis. The occurrence of intracranial tumor in an asymptomatic stage can be avoided by routine computed tomography (CT) and magnetic resonance imaging (MRI) scan, and improved survival can be achieved by aggressive multimodality therapy. ( info) |
4/465. Disseminated retinoblastoma successfully treated with myeloablative chemotherapy--implication for molecular detection of minimal residual disease. A useful marker for detecting minimal residual disease (MRD) has not been established yet in retinoblastoma. We assessed neuroendocrine protein gene product 9.5 (PGP9.5) expression, one of the markers for detecting MRD in neuroblastoma, in a patient with disseminated retinoblastoma. A 3-year-old boy with disseminated retinoblastoma in multiple bones and marrow was referred to our hospital. He received intensive treatment and has maintained CR for 48 months following myeloablative chemotherapy with hematopoietic stem cell transplantation (SCT). PGP9.5 expression was serially assessed by RT-PCR in peripheral blood mononuclear cells (PBMC), bone marrow cells (BMC) and mobilized peripheral blood stem cells (PBSC). Initially, his BMC consisted of 96% tumor cells which were proved to express PGP9.5 by RT-PCR. Moreover, PBMC were found to be positive for PGP9.5 indicating the presence of tumor cells in the peripheral blood. After intensive chemotherapy, PGP9.5 expression became negative in both PBMC and BMC. Prior to SCT, PBSC and BMC transplants were confirmed negative for PGP9.5 expression. It is suggested that PGP9.5 expression is a useful marker for evaluating therapeutic effects as well as detecting MRD in retinoblastoma. ( info) |
| Three survivors of retinoblastoma, one with hereditary bilateral and two with nonhereditary (spontaneous) unilateral disease, developed multifocal osteosarcoma. For one patient, unilateral retinoblastoma was followed by primitive neuroepithelioma at age 13 years. Multifocal chondroblastic osteosarcoma represented the patient's third malignant neoplasm. The course of multifocal osteosarcoma in these three patients compares to that of multifocal osteosarcoma which presents de novo in other patients without prior retinoblastoma. ( info) |
6/465. Advanced bilateral retinoblastoma treated conservatively with lens sparing external beam radiation therapy: report of three cases. From 1995 through 1998, 3 children with bilateral advanced retinoblastoma were treated primarily with external beam radiation therapy; 6 eyes were irradiated with a lens sparing technique, doses varied from 5500 to 5700 cGy, and follow-up period ranged from 14 to 36 months. Recurrent tumors were found in 3 eyes, and a new growing tumor in one eye. Three eyes underwent enucleation eventually; one eye refused enucleation and finally developed optic nerve extension. The overall ocular cure rate was 2/6 (33.3%). One eye sustained visual acuity of 20/30, the other eye retained some peripheral vision; both eyes were blind in one patient. There were no deaths, metastasis, or secondary malignant tumors in our study. Advanced bilateral retinoblastoma with simultaneous radiation therapy instead of bilateral enucleation does not increase the risk of death, and more children will enjoy the benefits of retaining some vision in the affected eye through the use of this conservative therapeutic regimen. ( info) |
7/465. retinoblastoma as a congenital primary intracranial tumor. This report describes a rare case of retinoblastoma presenting as a congenital primary intracranial tumor. A 7-day-old infant presented with generalized seizures. He had a family history of retinoblastoma. Computed tomography of the brain revealed a midline suprasellar tumor without evidence of retinal tumors. Subtotal resection of the tumor was performed. Histopathologic findings were diagnostic of retinoblastoma. The patient sustained profound ischemic brain damage and was not given definitive further therapy. He died days after the diagnosis was made. retinoblastoma can present as an isolated ectopic intracranial tumor without associated retinal tumors. ( info) |
| BACKGROUND/PURPOSE: retinoblastoma results from mutations or loss of both alleles of the retinoblastoma gene. Although retinoblastoma is usually recognized clinically, some forms of the disease can elude diagnosis. The purpose of this study was to determine whether the use of molecular genetics to detect a loss of heterozygosity (LOH) in the retinoblastoma gene could assist the ocular pathologist in the diagnosis of this malignancy. methods: Deoxyribonucleic acid (dna) was obtained from tumor cells microdissected from three ocular specimens from two patients with diffuse retinoblastoma. polymerase chain reaction was used to detect two microsatellite markers (D13S153 and D13S118) of the retinoblastoma gene. loss of heterozygosity was identified when one of the two polymorphic alleles was present in the dna from normal tissue but absent or reduced in the dna obtained from tumor cells. RESULTS: loss of heterozygosity was identified in all three specimens from the two patients with diffuse retinoblastoma. In one patient, the diagnosis of retinoblastoma was based on identification of LOH from tumor cells obtained from vitrectomy. CONCLUSIONS: This study demonstrates that identification of LOH in retinoblastoma cells not only can contribute to our understanding of the molecular genetics of this tumor, but also can help the ocular pathologist in the diagnosis of atypical forms of the disease. ( info) |
| We present a case of multifocal osteosarcoma (MFOS) arising 11.5 years after successful treatment of bilateral retinoblastoma. The clinical, imaging and pathological findings at onset, after therapy, and during follow-up are described. Fluorescent in situ hybridization did not reveal a deletion of the RB-1 retinoblastoma gene, although the presence of an inactivating mutation invisible to this method cannot be ruled out. The MFOS may have been a second multifocal tumor associated with the original retinoblastoma or a post-irradiation sarcoma with extensive metastases. ( info) |
| PURPOSE: To determine the rate of retinal detachment after treatment of retinoblastoma, to describe the clinical features and management, and to discuss possible pathogenic mechanisms. methods: We retrospectively analyzed the charts of 80 patients (83 eyes) with retinoblastoma treated conservatively between 1963 and 1994, looking specifically for cases that developed a retinal detachment after treatment. RESULTS: Five patients (5 eyes, stages IVa to Vb) developed a retinal detachment after treatment. Of these, four had undergone external radiotherapy and one had an episcleral cobalt plaque. retinal detachment developed within three months after radiotherapy and relentlessly progressed in all four eyes over a period of five months to four years. In the eye that received the episcleral cobalt plaque, the detachment remained localized inferiorly. Even though no retinal break could be detected in four eyes, the clinical features were suggestive of a rhegmatogenous detachment: there was retinal thinning adjacent to the regressed tumors, and the evolution was much longer than that of an exudative retinal detachment. A scleral buckling procedure was performed in two eyes and the retina was successfully reattached. The retinal detachment was not operated on in the three other eyes: the hole was too posterior in one eye; retinal surgery was refused in the second eye; and the retinal detachment remained localized inferiorly in the third eye. CONCLUSION: A retinal detachment developed in 6% of eyes after conservative treatment of retinoblastoma. The possibility of a rhegmatogenous origin should be considered even if no retinal break is detected. In the absence of tumor activity, a scleral buckling repair could be carefully considered if the retinal detachment threatens the macula, and if its evolution is not indicative of an exudative detachment. ( info) |