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PubMed2006

A second leiomyosarcoma in the urinary bladder of a child with a history of retinoblastoma 12 years following partial cystectomy.

This case describes a twin with bilateral retinoblastoma who developed leiomyosarcoma of the bladder at age 17 and again at 39. At 17-years of age she was diagnosed with a leiomyosarcoma of the bladder after presenting with recurrent urinary tract infections, hematuria, and dysuria. She was treated with partial cystectomy. After a 12-year disease-free interval, she was diagnosed with a second leiomyosarcoma of the bladder. This case supports the relationship between the genetic form of retinoblastoma and leiomyosarcoma and illustrates the necessity for extensive follow-up and well-defined treatment of secondary neoplasms.

Adult↗
PubMed2003

Leiomyosarcoma of the distal femur in a patient with a history of bilateral retinoblastoma: a case report and review of the literature.

We report a case of primary leiomyosarcoma of the distal femoral shaft arising in a patient who had undergone bilateral orbital enucleation for bilateral retinoblastoma several years previously. Radiography demonstrated an osteolytic, expansive lesion with cortical destruction anteriorly in the distal femoral shaft, and these findings were confirmed on CT. MR imaging revealed an expansive intramedullary lesion with cortical breakthrough and soft tissue extension. The occurrence of a second malignancy in patients with a history of bilateral retinoblastoma is well documented. Many different histological types have been described, with osteosarcoma and leiomyosarcoma occurring with the greatest frequency.

Eye Enucleation↗
PubMed2004

Management of intraocular retinoblastoma and ocular prognosis.

Current management modalities for intraocular retinoblastoma, their indications, and ocular prognosis are reviewed. Enucleation, external beam radiotherapy, plaque radiotherapy, laser photocoagulation and hyperthermia, and cryotherapy are the modalities generally employed. Recently, neoadjuvant chemotherapy has been introduced for retinoblastoma to avoid external beam radiotherapy. New treatment modalities such as subconjunctival injection, selective ophthalmic artery injection, and vitreous injection are being investigated and have achieved favorable results. Although many modalities are employed, almost half of retinoblastoma eyes have to be enucleated. New treatment modalities are expected.

Disease Management↗
PubMed2005

Intraocular retinoblastoma: the case for a new group classification.

This article argues the case for the creation of a new group classification of intraocular retinoblastoma. The current Reese-Ellsworth group classification has not been updated since it was published 35 years ago. The proposed classification is based on the natural history of intraocular retinoblastoma and on the risk of loss of the eye following primary therapy.

Fluorescein Angiography↗
PubMed2005

Cavitary changes in retinoblastoma: relationship to chemoresistance.

OBJECTIVE: To describe the clinical features and outcome of treatment of retinoblastomas presenting with ophthalmoscopically visible cavities. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Sixteen eyes of 15 patients harboring retinoblastomas with ophthalmoscopically visible cavities treated between February 1995 and July 2003. METHODS: Patient demographics, eye and tumor characteristics, and response to treatment were recorded. MAIN OUTCOME MEASURES: Decrease in tumor size and tumor recurrence. RESULTS: The mean patient age at diagnosis was 20 months. The mean number of retinoblastomas per eye was 2 (range, 1-6). Associated subretinal fluid was graded as absent in 5 eyes, minimal in 6 eyes, mild in 4 eyes, and severe in 1 eye. None of the tumors had vitreous seeds, and 5 (31%) had subretinal seeds. Ophthalmoscopically visible calcification occupied a mean of only 3% of the tumor (median, 0%; range, 0%-30%). Intratumoral cavities were characteristically visible in the superficial portion of the tumor and had a mean diameter of 2.0 mm (median, 1.5; range, 0.5-5.0). The mean number of cavities per tumor was 2 (median, 1; range, 1-5). Three tumors were treated with enucleation, 1 with observation, and 12 with chemoreduction. Two months after chemoreduction, the mean reduction in tumor base was 19% (median, 16%; range, 0%-42%), and the mean reduction in tumor thickness was 18% (median, 12%; range, 0%-59%). During a mean follow-up of 32 months (median, 23; range, 12-58), none of the cavitary retinoblastomas recurred or gave rise to vitreous or new subretinal seeds. CONCLUSION: Retinoblastomas containing ophthalmoscopically visible cavitary spaces do not show a substantial decrease in size after chemotherapy. Cavitary changes in retinoblastoma may be a sign that the tumor is well differentiated and may impart a better prognosis.

Antineoplastic Agents↗
PubMed2006

Iodine 125 plaque radiotherapy as salvage treatment for retinoblastoma recurrence after chemoreduction in 84 tumors.

PURPOSE: To assess tumor control and complications of iodine 125 (I125) plaque radiotherapy for retinoblastoma recurrence after chemoreduction (CRD). DESIGN: Interventional retrospective case series. PARTICIPANTS: Children with retinoblastoma treated on the Oncology Service, Wills Eye Hospital, initially examined from July 1994 to April 2005. METHODS: Eighty-four retinoblastomas with solid recurrence after CRD were treated with custom designed I125 plaque radiotherapy. Eyes with vitreous or subretinal seed recurrence were excluded. The CRD regimen included vincristine, etoposide, and carboplatin for 6 cycles plus local consolidation with thermotherapy or cryotherapy. The only alternatives to plaque radiotherapy in these cases would have been external beam radiotherapy (EBRT), additional chemotherapy, or enucleation. MAIN OUTCOME MEASURES: Tumor control and radiation complications. RESULTS: Tumor control was achieved in 95% of eyes by 5 years follow-up. Of the 59 recurrent tumors after CRD alone, 56 (95%) were controlled with plaque radiotherapy. Of the 25 recurrent tumors after CRD and EBRT, 100% were controlled with plaque radiotherapy. Of the 3 failures after plaque radiotherapy, the median time to failure (tumor recurrence) was 4 months and all recurrences were detected within 1 year. There were no identifiable factors predictive of plaque radiotherapy failure. Using Kaplan-Meier analysis, radiation complications at 5 years included proliferative retinopathy (19%), nonproliferative maculopathy (24%), papillopathy (16%), transient mild vitreous hemorrhage (54%), cataract (43%), iris neovascularization (NVI; 8%), and glaucoma (4%). Nonresolving vitreous hemorrhage and scleral necrosis did not occur. Radiation complications showed minimal change at 10 and 15 years of follow-up. CONCLUSIONS: Iodine 125 plaque radiotherapy offers 95% tumor control for selected retinoblastomas that fail CRD. Complications such as radiation retinopathy and mild vitreous hemorrhage should be anticipated, depending on the location, size, and extent of the tumor.

Adolescent↗
PubMed2004

Post-irradiation leiomyosarcoma of the maxilla: report of a case in a patient with prior radiation treatment for retinoblastoma.

Post-irradiation sarcoma is a well-defined complication of radiation therapy, yet few reports document such lesions in the head and neck. A 30-year-old man presented for evaluation of an expansile lesion of the left posterior maxilla. His medical history was significant for a childhood ocular malignancy - unilateral retinoblastoma - which was treated with a combination of surgical enucleation of the eye and external beam radiation therapy. Biopsy of his maxillary lesion revealed a spindle cell malignancy that was morphologically and immunohistochemically consistent with a diagnosis of leiomyosarcoma. Further investigation into the case revealed that the patient had three children, every one of whom developed unilateral retinoblastoma in infancy. Compared to the more frequent presentation of bilateral tumors in hereditary cases of retinoblastoma, such cases of heritable unilateral retinoblastoma are exceptional. Importantly, heritable forms of retinoblastoma confer a significant risk for development of second primary cancers, necessitating long-term clinical follow-up in these patients.

Adult↗
PubMed2002

Recurrence of retinoblastoma 12 years after brachytherapy.

PURPOSE: To report a case of retinoblastoma that recurred 12 years after brachytherapy. DESIGN: Interventional case report. METHODS: A 2-month-old boy presented in December 1983 with bilateral retinoblastoma and was treated with bilateral 198Au plaque radiotherapy, photocoagulation, and cryotherapy. He maintained a visual acuity of 20/200 in both eyes. In December 1995, he had a sudden decrease of vision in the right eye and vitreous hemorrhage with fluffy opacification. RESULTS: In January 1996, cytopathologic examination of large keratic precipitates in the right eye demonstrated cells consistant with retinoblastoma. The right eye was enucleated and diffuse retinoblastoma was noted histopathologically. Systemic chemotherapy was given, and there has been no local recurrence or extraocular metastasis for 5 years. CONCLUSIONS: This case emphasizes that long-term follow-up is essential for managing retinoblastoma after eye-preserving conservative therapy.

Brachytherapy↗
PubMed2000

Metastatic and nonmetastatic models of retinoblastoma.

To generate animal models of retinoblastoma that closely resemble metastatic and nonmetastatic human disease for the purposes of examining tumor biology and developing alternate treatments, human retinoblastoma cell lines were injected into the vitreal cavities of immunodeficient mice. Two reproducible animal models with contrasting biological behaviors analogous to human retinoblastoma have been developed. The Y79 retinoblastoma model demonstrated specific tumor evolution similar to that seen in human invasive and metastatic disease. Y79 retinoblastoma cells formed intraocular tumors that were initially confined to the vitreal cavity. Tumors progressively invaded the retina, subretinal space, choroid, optic nerve head, and anterior chamber of the eye. Tumors progressed into the subarachnoid space and focally invaded the brain. Metastases were detected in the contralateral optic nerve. Large tumors developed extraocular extensions. The histology of the tumors showed a poorly differentiated pattern with high mitotic rate, foci of necrosis, and calcification. The WERI-Rb model more closely resembled nonmetastatic human retinoblastoma. WERI- Rb tumors were localized in the eye with only anterior choroidal invasion at late stages. To examine potential biological differences in vitro, the retinoblastoma cell lines were cocultured with adherent choroid cells or adherent glioma cells which represent the targets of invasive retinoblastoma in vivo. Consistent with the in vivo observations, Y79 cells but not WERI-Rb cells adhere specifically to both the choroidal and the glioma cell lines.

Animals↗
PubMed2000

Vitrectomy in eyes with unsuspected retinoblastoma.

OBJECTIVE: To analyze patient management and prognosis after vitrectomy in eyes with unsuspected retinoblastoma. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Eleven consecutive patients who had undergone vitrectomy on an eye with unsuspected retinoblastoma. MAIN OUTCOME MEASURES: The two main outcome measures were ultimate patient management and the development of retinoblastoma metastasis. RESULTS: Of more than 900 consecutive patients with retinoblastoma managed on the Ocular Oncology Service at Wills Eye Hospital in Philadelphia, 11 (1%) had prior vitrectomy in an eye with viable tumor before referral to us for suspected retinoblastoma. The main preoperative diagnoses included vitreous hemorrhage in seven patients (64%), toxocariasis in two patients (18%), toxoplasmosis in one patient (9%), and endophthalmitis in one patient (9%). In no case was retinoblastoma suspected before vitrectomy. The mean patient age at vitrectomy was 6 years. Retinoblastoma was later suspected during vitrectomy in two patients (18%), on cytologic examination of the vitrectomy specimen in eight patients (73%), and after referral in one patient (9%). The mean interval between vitrectomy and referral to us was 23 days. On examination, the globe was classified as Reese-Ellsworth group Vb in all 11 patients (100%). Anterior chamber tumor cells were clinically visible in four eyes (36%), hyphema in two eyes (18%), and iris neovascularization in two eyes (18%). Retinoblastoma cells were visualized in the vitreous in seven eyes (64%) and not visualized in four eyes (36%) that had vitreous blood. Enucleation was necessary in all 11 patients (100%). Adjuvant treatment was delivered in 10 patients (91%), using orbital radiotherapy in nine patients (82%) and chemotherapy in nine patients (82%). Histopathologic evidence of retinoblastoma invasion was documented in the episclera (two eyes; 18%), anterior chamber (seven eyes; 64%), iris (five eyes; 45%), ciliary body (five eyes; 45%), choroid (three eyes; 27%), and optic nerve (four eyes; 36%; prelaminar, two eyes; postlaminar, two eyes). The vitrectomy ports, Tenon's fascia, cut end of the optic nerve, and orbit were free of tumor. Of the 10 patients who received prophylactic chemotherapy, radiotherapy, or both in addition to enucleation for prevention of retinoblastoma metastasis, none (0%) experienced metastasis or orbital recurrence during the mean follow-up of 7 years (range, 0.2-24 years) from the time of retinoblastoma diagnosis. However, one patient was referred to us after the development of metastatic retinoblastoma, and despite aggressive chemotherapy and radiotherapy after enucleation, died 24 months later. CONCLUSIONS: Retinoblastoma may present with atypical features such as vitreous hemorrhage or signs of vitreous inflammation, particularly in older children. Vitrectomy should be avoided in these cases until the possibility of underlying retinoblastoma is excluded. If vitrectomy is performed in an eye with unsuspected retinoblastoma, enucleation combined with adjuvant chemotherapy, radiotherapy, or both without delay is advised to prevent systemic tumor dissemination.

Adolescent↗
PubMed2001

Third (fourth and fifth) nonocular tumors in survivors of retinoblastoma.

OBJECTIVE: This study aimed to investigate the incidence, timing, pattern, and distribution of, as well as survival as a result of, third, fourth, and fifth primary tumors in survivors of retinoblastoma. DESIGN: This study was a retrospective case series of patients diagnosed with retinoblastoma and a second malignant neoplasm. Records were examined for demographic, prior treatment, and second tumor information, as well as any evidence of the development of a third, fourth, or fifth nonocular tumor. When possible, telephone inquiries were conducted for follow-up. PARTICIPANTS: The study included 1506 patients followed in the Ophthalmic Oncology Center at New York-Presbyterian Hospital, New York Weill Cornell Medical Center, 211 of whom developed a second tumor and had sufficient treatment data to be useful for analysis. MAIN OUTCOME MEASURES: The development of third and additional nonocular tumors and survival from these tumors were the primary outcome measures. RESULTS: Of 211 second-tumor patients, 142 died before an additional malignancy developed (median survival time, 1.8 +/- 0.3 years) and in 28, third tumors developed (5-year incidence rate, 11%; 10-year incidence rate, 22%; median time to third tumor development, 5.8 +/- 8.3 years). The 5- and 10-year survival rates for this group were 41% and 30%, respectively (median survival time, 4.1 +/- 1.0 years). Of 28 patients in whom third tumors developed, 27 (96%) had received radiation therapy for their retinoblastoma. The most common sites for third tumors were soft tissues of the head (36% of all third tumors) and skin (36% of all third tumors). In six patients, a fourth tumor developed, and in two patients a fifth tumor developed. All fourth and fifth tumors were found in the soft tissues of the head, the skin, or the bones. CONCLUSIONS: Survivors of retinoblastoma in whom second malignant neoplasms develop are at a higher risk for the development of additional tumors than they were for the development of a second tumor. The locations and expected ages at which additional tumors develop are consistent with the patterns we have seen in second tumors.

Adolescent↗
PubMed2003

New retinoblastoma tumor formation in children initially treated with systemic carboplatin.

PURPOSE: To determine the frequency and timing of new intraocular tumor formation in children with hereditary retinoblastoma initially treated with systemic carboplatin. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: This study included 34 children (57 eyes) with hereditary bilateral retinoblastoma initially treated with systemic carboplatin at the Robert M. Ellsworth Ophthalmic Oncology Center at NewYork-Presbyterian Hospital from 1994 through 2000. MAIN OUTCOME MEASURES: New tumor formation after initial treatment with systemic carboplatin. RESULTS: There were a total of 165 tumors in 57 eyes. There were 63 new tumors in 27 eyes (47%) after administration of systemic carboplatin, for a mean of 1.1 new tumors per eye. The mean patient age at time of new tumor presentation was 9 months, with 57% of new tumors developing within 4 months of carboplatin treatment. Kaplan-Meier analysis showed that children who were treated when younger than 6 months of age were more likely to have new tumors (60%) compared with those treated after 6 months of age (31%; P = 0.0182). CONCLUSIONS: New intraocular tumors continue to develop after systemic carboplatin; most new tumors appeared within 4 months of treatment.

Antineoplastic Agents↗