Retinoblastoma

Retinoblastoma represents 3% of all childhood cancers, and is the most common intraocular malignancy of childhood. It is fatal, if untreated. White eye reflex, also known as leukocoria, is the commonest sign, followed by strabismus. The pediatricians have a very important role to play in the diagnosis of this relatively rare, but easily detectable tumor. Early diagnosis yields better results. The management of retinoblastoma has gradually evolved over the past few decades, with an aim to not only preserve life and eye, but also optimize residual vision. The treatment of retinoblastoma is multimodal, with chemotherapy, focal treatment including trans-pupillary thermotherapy, cryotherapy and laser photocoagulation, radiation therapy and surgery, all playing a vital role. Intravenous chemotherapy has been the mainstay of treatment for the past two decades, and still continues to be the most extensively used eye-saving modality of treatment. Periocular and intravitreal chemotherapy have specific indications in the management of retinoblastoma. Intra-arterial chemotherapy has emerged as a promising alternative for advanced and refractory retinoblastoma, both as a primary and secondary therapy. Recent advances in genetics of retinoblastoma have also helped in improving the overall clinical management of this malignancy.     

Rétinoblastome : aspects récents

Retinoblastoma is the most frequent eye tumor in children, with an incidence of 1/15 000 births. Sixty per cent are unilateral: the median age at diagnosis is 2 years and most of these forms are not hereditary. Retinoblastoma is bilateral in 40%: the median age at diagnosis is 1 year. All bilateral and multifocal unilateral forms are hereditary. Hereditary retinoblastoma constitutes a cancer predisposition syndrome: a subject carrying a constitutional RB1 gene mutation has a greater than 90% risk of developing retinoblastoma, but is also at increased risk of developing secondary cancers. The 2 most frequent revealing symptoms are leucocoria and strabismus. Diagnosis is made by fundoscopy. US, MRI, CT scans may contribute to diagnosis. Management of patients with retinoblastoma must take into account the various aspects of the disease: the visual risk, the possibly hereditary nature of the disease and the life-threatening risk. Enucleation is still often necessary in unilateral disease; adjuvant treatment is decided according to the histological risk factors. Conservative treatment of at least 1 eye is possible in most of the bilateral cases: laser alone or combined with chemotherapy, cryotherapy and brachytherapy. The indication for external beam radiotherapy should be restricted to large ocular tumors and diffuse vitreous seeding because of the risk of late effects, including secondary sarcoma. Long-term follow-up and early information to retinoblastoma patients regarding the risk of second primary tumors and transmission is actually important.     

Conjunctival melanoma 3 years after radiation and chemotherapy for retinoblastoma

An 8-month-old infant with advanced bilateral retinoblastoma was managed with enucleation of the right eye and chemotherapy and radiotherapy of the left eye. Three years after treatment, an ill-defined, nonpigmented mass was noted in the anophthalmic right socket. Excisional biopsy revealed an amelanotic melanoma of the conjunctiva with superficial orbital invasion. There has been no tumor recurrence during 20 months of follow-up.     

A unique case of retinoblastoma masked by retinal detachment diagnosis and management.

A 4-year-old Latin American boy presented with a history of loss of vision of his left eye for 7 months. He was followed by different ophthalmologists and diagnosed with a retinal detachment. Computerized tomograms and magnetic resonance imaging demonstrated a large calcified left eye and markedly enlarged optic nerve. Based on these radiologic findings diagnosis of retinoblastoma was strongly suspected. Initially enucleation was not done because it was thought that cutting through the involved optic nerve would cause dissemination. The patient was treated with chemotherapy which resulted in marked response. Following normalization of optic nerve and after irradiation the eye was enucleated. The diagnosis of retinoblastoma was confirmed. No tumor was found in the optic nerve. The importance of imaging studies in diagnosis of retinoblastoma and the role of chemotherapy in the treatment of primary retinoblastoma are emphasized.     

A unique case of retinoblastoma masked by retinal detachment diagnosis and management

A 4-year-old Latin American boy presented with a history of loss of vision of his left eye for 7 months. He was followed by different ophthalmologists and diagnosed with a retinal detachment. Computerized tomograms and magnetic resonance imaging demonstrated a large calcified left eye and markedly enlarged optic nerve. Based on these radiologic findings diagnosis of retinoblastoma was strongly suspected. Initially enucleation was not done because it was thought that cutting through the involved optic nerve would cause dissemination. The patient was treated with chemotherapy which resulted in marked response. Following normalization of optic nerve and after irradiation the eye was enucleated. The diagnosis of retinoblastoma was confirmed. No tumor was found in the optic nerve. The importance of imaging studies in diagnosis of retinoblastoma and the role of chemotherapy in the treatment of primary retinoblastoma are emphasized. © 1992 Wiley-Liss, Inc.     

Sclerosing endophthalmitis in children: computed tomography with histopathologic correlation

Three children with histopathologically diagnosed sclerosing endophthalmitis presumably secondary to Toxocara canis were studied by orbital computed tomography. The diffuse increased intraocular density present in the CT scans was indistinguishable from that observed in Coats's disease and non-calcifying retinoblastoma. Although retinoblastoma constitutes the major life-threatening cause of leukocoria in children, a number of other simulating conditions (pseudoglioma) can cause diagnostic confusion. In some cases of leukocoria it is exceedingly difficult to exclude the possibility of retinoblastoma without having to resort to enucleation. The availability of new non-invasive tests may make the distinction between retinoblastoma and pseudogliomas more easily attainable. Computed tomography (CT) has been shown to be of particular value in this regard by demonstrating intraocular calcification within retinoblastoma and rarely in lesions that stimulate it. CT may also be used to more appropriately plan therapy for children with retinoblastoma by assessing the status of the optic nerve and orbit. The exact role of CT in the evaluation of children with leukocoria, however, has not been completely established, since the computed tomographic features of several lesions that simulate retinoblastoma have not been described. The three most common causes of pseudoglioma are persistent hyperplastic primary vitreous, Coats's disease and sclerosing endophthalmitis. The latter entity when associated with a characteristic granulomatous inflammation is considered to represent the sequela of Toxocara canis infection of the eye. This report describes the computed tomographic findings in three cases of histologically diagnosed sclerosing endophthalmitis, presumably due to Toxocara canis.     

Pearls and pitfalls of intraarterial chemotherapy for retinoblastoma

Retinoblastoma is a deadly eye cancer in children, leading to death in 50%-70% of children in undeveloped nations who are diagnosed with it. This malignancy is the most common intraocular tumor in childhood worldwide. The good prognosis in developed nations is related to early detection and advanced treatments. With the advent of intraarterial chemotherapy, neurosurgeons have taken a central role in the treatment of this pediatric condition. Intraarterial chemotherapy is a novel treatment for retinoblastoma whereby chemotherapeutic agents are precisely delivered into the ophthalmic artery, minimizing systemic toxicity. This procedure has shown impressive results and has allowed a dramatic decrease in the rate of enucleation (eye removal) in advanced and refractory retinoblastoma. Recent reports have raised some concerns about the risk of ocular vasculopathy, radiation-related toxicity, and the potential for metastatic disease after intraarterial chemotherapy. In the authors' experience of more than 3 years, tumor control is excellent with globe salvage at 67% and vascular events less than 5%, mostly related to improvement in technique. The role of this novel approach in the management of retinoblastoma has yet to be defined. As more centers are adopting the technique, the topic will decidedly become the focus of intensive future research. In this paper, the authors review and discuss current data regarding intraarterial chemotherapy for retinoblastoma.     

Secondary acute myeloid leukemia after etoposide therapy for retinoblastoma

Retinoblastoma is the most common eye tumor in children and is highly curable. Patients with hereditary retinoblastoma, have an increased risk of developing additional tumors, predominantly sarcomas. Most chemotherapy regimens used in retinoblastoma include etoposide, an epipodophyllotoxin associated with a risk of secondary myeloid leukemia. The use of etoposide in patients with a cancer predisposition syndrome such as retinoblastoma is potentially harmful, however, reports of secondary acute myeloid leukemia in patients treated with etoposide for retinoblastoma are rare. We report a case of a patient who developed secondary acute myeloid leukemia after etoposide treatment for retinoblastoma.     

Increased number of chromosome aberrations in the peripheral blood culture of a retinoblastoma patient

Chromosome studies were performed on blood lymphocytes from an eight-year-old patient whose left eye had been enucleated earlier because of retinoblastoma. GTG-banded karyotypes showed both numerical and structural chromosome aberrations, and the number of the patient's lymphocytes with chromosome aberration increased. It was concluded that retinoblastoma survivors need continuous control because of the increased risk of second primary tumors.     

Incidence and survival characteristics of retinoblastoma in Singapore from 1968-1995

PURPOSE: To describe the incidence and survival of 69 Singapore residents with retinoblastoma in all Singapore hospitals from 1968-1995. METHODS: Data of all Singapore residents diagnosed with retinoblastoma from 1968-1995 were collected by the Singapore Cancer Registry based on notifications from physicians, pathology records, hospital discharge records, and death certificates. The medical records of 46 patients were traced, and information on laterality of tumor, spread of tumor, mode of treatment, and family history of retinoblastoma was obtained. Time trends and survival characteristics of the cohort were described. RESULTS: The incidence rate of retinoblastoma was 2.4 per 1 million for children <9 years and 11.1 per 1 million for children <5 years. The incidence of retinoblastoma has been almost uniform over time from 1968-1995, except for an apparent increase in 1988-1992. The 3-year survival rate for retinoblastoma was 83%. Survival rates were higher in children <2 years because children who present at a younger age may have tumors diagnosed at earlier stages of the disease. There was no difference in survival rates for sex, race, laterality, family history of retinoblastoma, treatment, or year of diagnosis. CONCLUSION: Retinoblastoma is the most common eye cancer in children that may cause blindness or death. The incidence rates of retinoblastoma in Singapore have remained fairly stable over 28 years, and the survival rate is higher in younger children. This study will be helpful in monitoring future disease patterns in Asian populations.     

Magnetic resonance imaging in retinoblastoma and retinocytoma: a case report

Magnetic resonance imaging (MRI) is playing a growing role in the evaluation of ocular and orbital tumors. We report the case of a 26-month-old child presenting an undifferentiated retinoblastoma with a differentiated retinocytoma component in his left eye. After the eye was enucleated, we could correlate the clinicopathologic findings with the MRI scans. Both the undifferentiated retinoblastoma and the differentiated retinocytoma components could be determined on magnetic resonance imaging. Because different levels of metabolic activity within a tumor mass may influence largely T1 and T2 parameters, accurate determination of these values may be useful in determining the differentiation of a retinoblastoma, enabling a better therapeutic approach and assessment of the response to treatment.     

Value of ophthalmoscopy and histology for the prognosis of patients with retinoblastoma

The predictive value of prognostic factors is of utmost importance for the treatment of patients with retinoblastoma. Functional results, that may be expected following sight saving therapy, can be deducted from ophthalmoscopic findings. Large tumors, tumors located centrally, the presence of extensive retinal detachment or diffuse vitreous seeding are poor prognostic signs. Histopathologic findings of the enucleated eye harbouring retinoblastoma correlate well with the incidence of metastatic disease. Patients in which the tumor has invaded the choroid, optic nerve or sclera have a high risk of developing metastases.     

Outcome of eyes with unilateral sporadic retinoblastoma based on the initial external findings by the family and the pediatrician

PURPOSE: To evaluate the enucleation rate for children with unilateral sporadic retinoblastoma based on initial external findings detected by the family and the pediatrician. PATIENTS AND METHODS: A retrospective, nonrandomized review was performed on 257 consecutive patients with unilateral sporadic retinoblastoma treated at a major ocular oncology center. Data were gathered regarding the initial external clinical finding noted by the family members, pediatrician, and ocular oncologist and then correlated with the final resulted in enucleation in 77%. Specifically, enucleation was necessary in 75% of patients with pediatrician-detected leukocoria, 46% of those with pediatrician-detected strabismus, and 86% of those with pediatrician-detected red eye, heterochromia, decreased visual acuity, or an unspecified eye problem. Enucleation was necessary in 81% of those patients in whom an ocular oncologist detected any external finding such as leukocoria, strabismus, red eye, heterochromia, or buphthalmos and in only 33% of those without external findings. CONCLUSIONS: Children with retinoblastoma who present with obvious external findings of leukocoria, strabismus, or red eye detectable by their family or pediatrician most often require enucleation. Children who manifest no obvious external findings can often avoid enucleation.     

Retinoblastoma in a child after normal autorefraction and traditional vision screening

Retinoblastoma is an ocular malignancy that can put a patient's sight and, in some instances, life at risk. Here we report the case of a 2-year-old child who presented to her pediatrician with a 2-week history of left-sided leukocoria caused by retinoblastoma. Results of traditional office-based vision screening and automated vision screening, which often identify but are not specifically designed to detect rare diseases such as retinoblastoma, had been normal in the antecedent 7 months. She underwent enucleation of the left eye and has done well postoperatively. This case highlights the importance of assessing ocular media clarity by using red-reflex testing at multiple intervals during the preschool years, particularly in light of the recently published US Preventive Services Task Force guidelines for preschool vision screening, which gave an "insufficient evidence" level for vision screening in children younger than 3 years and failed to address red-reflex examination.     

Prolonged survival of a child with metastatic retinoblastoma

A boy was discovered to have retinoblastoma in his right eye at age 29 months. The eye was enucleated and showed invasion of the choroid and optic nerve on examination. Bone marrow aspiration was negative in January 1981. Orbital recurrence was noted 1 month later and bone marrow aspiration was positive 2 months later. MAD-DOC chemotherapy and radiation therapy to the right orbit and brain were initiated immediately. The tumor has remained in remission since completion of the chemotherapy 18 months later. A preleukemic syndrome occurred in July 1984, and a successful bone marrow transplantation was performed in November 1984. He resumed normal growth and has remained well. Metastatic retinoblastoma should no longer be thought of as invariably fatal.     

SIOP‐PODC recommendations for graduated‐intensity treatment of retinoblastoma in developing countries

Retinoblastoma remains incurable in many regions of the world. The major obstacles to cure are delayed diagnosis, poor treatment compliance, and lack of evidence‐based recommendations for clinical management. Although enucleation is curative for intraocular disease, in developing countries retinoblastoma is often diagnosed after the disease has disseminated beyond the eye. A SIOP‐PODC committee generated guidelines for the clinical management of retinoblastoma in developing countries and developed a classification system based on the resources available in those settings. Recommendations are provided for staging and treatment of unilateral and bilateral retinoblastoma and counseling of families for whom compliance is an issue. Pediatr Blood Cancer 2013; 60: 719–727. © 2013 Wiley Periodicals, Inc.     

Sinonasal adenocarcinoma: a rare second malignancy in long term retinoblastoma survivors

Retinoblastoma is the most common primary cancer of the eye in children. The incidence of second tumors in survivors of bilateral retinoblastoma and in survivors of unilateral retinoblastoma who presumably carry a germline RB1 mutation is documented. This article describes the previously unrecognized association of sinonasal adenocarcinoma as a second malignancy in retinoblastoma survivors. We present three cases who received radiation therapy as a part of their treatment and developed sinonasal adenocarcinoma as a second malignancy. Sinonasal adenocarcinoma should be considered as a second malignancy in retinoblastoma survivors who present with vague sinus symptoms.     

Retinoblastoma

Retinoblastoma was diagnosed in 74 patients between July 1967 and February 1987. Thirty cases (40%) were bilateral; 39 were female and 35 were male. Treatment in bilateral cases consisted of enucleation of the more involved eye and a combined approach of supervoltage irradiation, cryocoagulation, and photocoagulation to the remaining eye. In unilateral cases the involved eye was enucleated and the uninvolved eye observed. Four patients had bilateral enucleation at their initial presentation and four others had the second eye enucleated after unsuccessful tumor treatment. One patient died from metastatic retinoblastoma, one patient died after intrathecal chemotherapy without the evidence of tumor, and one patient died with trilateral retinoblastoma. Seventy-one of 74 patients (96%) currently survive with a follow-up of 1 month to 19 years. Two-year survival is 65 of 68 (95.5%).     

Diffuse infiltrating retinoblastoma associated with persistent primary vitreous

A two-and-a-half-year-old male child presented with unilateral leukocoria. Clinical examination disclosed what was believed to be a mild form of persistent hyperplastic vitreous associated with total retinal detachment and exophytic retinoblastoma. The enulceated eye contained diffuse infiltrating retinoblastoma with tumor cells involving a stalk of persistent primary vitreous without hyperplasia.     

Combined local treatment and chemotherapy in the management of bilateral retinoblastomas in Hungary

This retrospective study supports that brachytherapy combined with cytostatic therapy may effectively contribute to tumor control. The second eye of 13 patients with bilateral retinoblastoma was treated with plaque brachytherapy after the enucleation of the first eye. Eleven patients received systemic cytostatic therapy. The mean follow up was 60 (+/-42 SD) months. Twelve patients are alive and free of tumor, 8 of them with acceptable visual acuity. After cytostatic therapy, late nephropathy was observed in 2 patients. In conclusion, brachytherapy combined with cytostatic therapy will be an option in the management of bilateral retinoblastoma after the enucleation of the first eye.