Quiste benigno de la glándula pineal en paciente con retinoblastoma bilateral. Reporte de caso y revisión de la literatura / Benign pineal gland cyst in a patient with bilateral retinoblastoma. Case report and literature review

Introducción: Los pacientes con Retinoblastoma (RB) hereditario se encuentran en riesgo de desarrollar otros tipos de tumores malignos primarios extraoculares durante la vida. Dentro de estos tumores se encuentra el pinealoblastoma, un tipo de neoplasia maligna que aparece en la glándula pineal y que se puede desarrollar en cualquier momento del diagnóstico del retinoblastoma bilateral. Objetivo: Presentar un caso inusual de retinoblastoma (RB) hereditario tratado y en remisión quien desarrolló un quiste pineal benigno. Diseño del estudio: Reporte de caso y revisión de literatura. Resumen del caso: Presentamos un paciente con diagnóstico de RB hereditario tratado y en remisión quien desarrolló un quiste pineal benigno durante el seguimiento clínico. Las lesiones quísticas de la glándula pineal reportadas por resonancia magnética son infrecuentes en edad pediátrica, sin embargo, su incidencia se ve aumentada en pacientes con RB, lo que genera incertidumbre sobre la posibilidad de presentar una neoplasia maligna. Aún se desconoce el mecanismo fisiopatológico de la aparición de quistes de la glándula pineal en pacientes con RB hereditario, pero podría tener relación con la alteración genética o con el tratamiento quimioterápico que reciben los pacientes para el tumor primario intraocular. Conclusión: Las características imagenológicas son fundamentales para diferenciar entre lesiones benignas y malignas de la glándula pineal en pacientes con retinoblastoma hereditario y para hacer el estrecho seguimiento junto con el examen clínico.

Background: Patients with hereditary Retinoblastoma (RB) are at risk of developing other types of extraocular primary malignancies throughout life. Among these tumors, pinealoblastoma is a type of malignancy that appears in the pineal gland and can develop at any time from the diagnosis of bilateral retinoblastoma. Objective: To present an unusual case of a patient with a diagnosis of hereditary BR who developed a pineal cyst. Study design: Case report. Case summary: We present in this article the case of a patient with a diagnosis of hereditary BR with remission who developed a pineal cyst during clinical follow-up. The cystic lesions of the pineal gland reported by magnetic resonance are infrequent in pediatric age, however its incidence is increased in patients with RB, which generates uncertainty about the possibility of the development of a primary pineal gland malignancy. The pathophysiological mechanism of pineal gland cysts in patients with hereditary RB is still unknown, but it could be related to a genetic alteration or to chemotherapy treatment that these patients receive for the primary intraocular tumor. Conclusion: The imaging characteristics are fundamental to differentiate between benign and malignant lesions of the pineal gland in patients with Hereditary Retinoblastoma and to make a close follow up.

Systematic review of the current status of programs and general knowledge of diagnosis and management of retinoblastoma / Revisión sistemática del estado actual de los programas y conocimiento general de la diagnosis y manejo de retinoblastoma

Abstract: Background: This systematic review aims to report the current knowledge of retinoblastoma (Rb) and its implications in Mexico. We analyzed clinical and demographic data of patients with Rb at select hospitals with Rb programs or that treat and refer patients with Rb, and identified the gaps in practice. We propose solutions to improve diagnosis, provide adequate treatment, and improve patient uptake. Methods: A general review was conducted on PubMed of peer-reviewed literature on Rb in Mexico. Ophthalmology Department Heads or Directors of Rb programs at seven hospitals in Mexico were contacted for data available on their patients with Rb. Results: Five hospitals provided clinical data on 777 patients with Rb in a period spanning 2000-2015. Of the 122 patients with treatment, 83.4% underwent enucleation. From 33 to 45.3% of Rb tumors in Mexico reach an advanced intraocular stage of development. Knowledge of the disease is limited, despite the fact that the Mexican Retinoblastoma Group has elaborated Rb treatment guidelines and is developing a national Rb registry. Especially in the Southern states, prevalence and outcomes are comparable to African and Asian countries, and only few patients are referred to national treatment centers. Only three institutions have comprehensive Rb programs. Conclusions: There is an immediate need in Mexico to expand primary care providers' knowledge of Rb and to expand and upgrade current Rb programs to meet the needs of the population adequately. Diagnosis and care of Rb patients in Mexico can also be improved by the establishment of a national Rb registry and a national early detection program, and by increased use of the national treatment protocol.

Resumen: Introducción: Esta es una revisión sistemática de los conocimientos actuales del retinoblastoma (Rb) y sus implicaciones en los centros de referencia más importantes del país. Se presenta un análisis situacional de los programas de Rb en México, se identificaron las brechas en la práctica, y se proponen soluciones para mejorar el diagnóstico, tratamiento y referencia oportuna de pacientes. Métodos: Se realizó una revisión general de la literatura publicada sobre Rb en México a través de PubMed. Los datos sociodemográficos de pacientes con Rb fueron obtenidos a través de los directores de programas de retinoblastoma en siete hospitales. Resultados: Casi una tercera parte de los casos Rb se diagnostican en estadios avanzados. A pesar de la existencia del Grupo Mexicano de Retinoblastoma, el conocimiento de esta patología entre los médicos es limitado. Las diferencias en el tratamiento son notorias en el sur del país, donde la prevalencia y los resultados son comparables con África y Asia. Solamente tres instituciones a nivel nacional tienen un programa establecido de Rb. Conclusiones: Existe la necesidad inmediata de consolidar los programas de Rb para cubrir las necesidades reales de la población. Se requiere mejorar la educación del médico de primer contacto, establecer el registro nacional de casos y el programa de detección temprana, establecer los programas de salvamento ocular nacional, y reforzar las instituciones que brindan tratamiento.

Managing the consequences of aggressive conservative treatment for refractory retinoblastoma with vitreous seeding / Lidando com as consequências do tratamento agressivo para retinoblastoma refratário com semeadura vítrea

A 4 year-old girl with bilateral, non-familial retinoblastoma (RB) was referred to our care after primary enucleation OS and active tumor OD refractory to multiple therapies (intravenous chemotherapy, laser/cryotherapy, and I-125 plaque radiotherapy). Vitreous seeding OD, initially controlled by several sessions of Ophthalmic Artery Infusion Chemotherapy (OAIC) and periocular chemotherapy, recurred shortly thereafter. The patient underwent intravitreal (IVit) Melphalan injections achieving tumor control despite the concurrent development of keratopathy, pupillary synechiae, cataract, and necrosis of the inferior fornix and the adjacent orbital fat, all secondary to the treatments administered. Repeated amniotic membrane implants and tarsorrhaphy were performed to alleviate the symptoms. Despite being tumor free for 6 months, a poor fundus view and treatment-related complications prompted us to consider enucleation, but parents declined. Following recent negative magnetic resonance imaging (MRI), her cataract was removed. She was then found to have tumor recurrence. Her eye was enucleated 12 months ago and she recovered well from the surgery. As ocular oncology embarks in eye-preserving treatments for retinoblastoma, it is important to address the cumulative effects and associated impact of such treatments and the possibility of failure.

Uma menina de 4 anos com retinoblastoma (RB) bilateral, não-familiar foi encaminhada após enucleação OE e tumor ativo OD refratário a múltiplas terapias (quimioterapia endovenosa, laser/crioterapia e braquiterapia com I-125). Semeadura vitrea OD, inicialmente controlada por inúmeras sessões de Quimioterapia Intra-Arterial Oftálmica (QIAO) e quimioterapia periocular, recorreu em seguida. Paciente recebeu injeções intravítreas de Melphalan obtendo controle tumoral apesar do desenvolvimento concomitante de ceratopatia, sinéquias pupilares, catarata, necrose do fórnice inferior e gordura periorbitária adjacente, todos secundários aos tratamentos usados. Implantes repetidos de membrana amniótica e tarsorrafias foram realizadas para melhora sintomatológica. Apesar de estar livre de tumor por 6 meses, a baixa visibilidade do fundo e complicações terapêuticas nos levaram a considerar enucleação que foi descartada pelos pais. Após recente ressonância magnética nuclear (RMN) negativa, a catarata foi removida. Foi então detectada recorrência tumoral. O olho foi enucleado há 12 meses e ela se recuperou bem da cirurgia. Enquanto a oncologia ocular embarca em tratamentos para preservar em retinoblastoma, é importante considerar os efeitos cumulativos e impacto associado desses tratamentos, e a possibilidade de fracasso.

Supervivencia libre de enucleación de pacientes con diagnóstico de retinoblastoma tratados con quimioterapia intraarterial en el Hospital Universitario de San Vicente Fundación / Enucleation free survival of patients with retinoblastoma diagnosis treated with intraarterial chemotherapy at University-Based San Vicente Fundacion Hospital

Objetivo: describir la supervivencia libre de enucleación, respuesta al tratamiento y complicaciones de los pacientes sometidos a tratamiento con quimioterapia intraarterial (QIA) para el control del retinoblastoma en el Hospital Universitario de San Vicente Fundación (HUSVF). Tipo de estudio: estudio de cohortes. Materiales y Métodos: se incluyeron todos los pacientes con diagnóstico de retinoblastoma tratados en el husvf con qia supraselectiva de la arteria oftálmica entre agosto del 2011 y agosto de 2013. Resultados: se realizó tratamiento a 21 pacientes, 24 ojos, en un periodo de 23.5 meses. La edad media al momento de inicio de la QIA fué 19 meses (rango 5-60 meses) con un seguimiento promedio de 9.3 meses (rango 3 semanas a 23.5 meses). Se realizaron 78 cateterizaciones, siendo 9 de ellas bilaterales. El salvamento ocular se alcanzó en el 100% de los Grupo A (n1), 100% B (n=2), 100% C (n=5) y 87.5% D (n=16), según la Clasificación Internacional para Retinoblastoma (CIRB). Sólo se reportaron dos eventos adversos importantes, una hemiparesia transitoria y una reacción alérgica severa. Ninguno de los pacientes ha fallecido, ha tenido compromiso metastásico o necesidad de radioterapia externa. Sólo se realizaron dos enucleaciones. La media de supervivencia de los 24 globos oculares tratados es de 10.4 meses ± 1.6. La media de supervivencia de los 21 pacientes tratados es de 10.4 meses ±1.7. Conclusiones: los resultados muestran una respuesta satisfactoria, constituyéndose la QIA como procedimiento seguro y con baja tasa de complicaciones en el tratamiento del retinoblastoma.

Purpose: to describe globe salvage, treatment response and complications of patients following intra-arterial chemotherapy (IAC) for retinoblastoma at Hospital Universitario de San Vicente Fundacion (HUSVF). Type of study: Cohort Study. Materials and methods: We included all patients diagnosed with retinoblastoma and treated with IAC between from August 2011 to August 2013. Results: A total of 21 patients, with a total of 24 eyes, were treated with IAC over a period of 23.5 months. The mean age of patients at time of treatment was 19 months (range 5-60 months) with a mean follow-up time of 9.3 months (range 3 weeks to 23.5 months). 78 catheterizations were performed, nine of them being bilateral. Ocular salvage rate was achieved in 100% of the Group A (n1), 100% in group B (n = 2), 100% in group C (n = 5) and 87.5% in group D (n = 16), according to the International Classification for Retinoblastoma. Only two major adverse events were reported, a transient hemiparesis and a severe allergic reaction. No deaths, metastatic involvement or need for external beam radiotherapy were reported. Two eyes, from group D, required enucleation. The mean survival rate of 24 eyes treated was 10.4 months ± 1.6. The mean survival rate of the 21 patients treated was 10.4 ± 1.7 months. Conclusions: The results show a satisfactory response, becoming the IAC a safe procedure with a low complication rate in retinoblastoma treatment.

Orbital retinoblastoma: case report / Retinoblastoma orbitário: relato de caso

We describe the case of a 9-month old boy with unilateral retinoblastoma and bulftalmo. Primary enucleation was the treatment of choice due to the lack of visual prognosis. The histology of the enucleated eye showed massive choroidal invasion by the tumor and the optic nerve free of neoplastic tissue. Therefore, no adjuvant chemotherapy or radiotherapy was indicated. Three months after the enucleation, the patient returned with massive orbital retinoblastoma with exposure of the conjunctiva. Treated with chemotherapy, the patient has been in remission for 12 months. The risk factors for orbital recurrence are discussed.

Relatamos paciente de 9 meses de idade com buftalmo e retinoblastoma unilateral. O paciente foi tratado com enucleação primária devido à falta de prognóstico visual. O exame do olho enucleado mostrou invasão maciça de coroide e ausência de comprometimento do nervo óptico não sendo, portanto, submetido a tratamento adjuvante de quimioterapia ou de radioterapia. Três meses após a enucleação, o paciente apresentou-se com retinoblastoma orbitário volumoso com exposição da conjuntiva. Tratado com quimioterapia permanece em remissão após 12 meses. São discutidos os fatores de risco para a ocorrência da recidiva orbitária.

Consideraciones clínicas, diagnósticas y de tratamiento en retinoblastoma / Clinical, diagnostic and therapeutic considerations in retinoblastoma

El retinoblastoma es el tumor intraocular primari o más frecuente en l a infancia. Su detección temprana y el inici o del tratamiento adecuado permi te mejorar dramáticamente l a sobrevida en estos niños. En este artícul o se hace una revisión general de l a enfermedad. Se empleó PubMed y se revisaron artículos representativos del tema, que permi tieran dar una idea general de los di ferentes avances alcanzados. Dada su cl ínica característica, el médico de atención primaria, es pieza fundamental en l a captación inicial del paciente. [Vi l lami l JF , Quintero LM, Serrano RA, Moreno IA. Consideraciones cl ínicas, diagnósticas y de tratamiento en retinoblastoma. MedUNAB 201 1; 14:180-187].

Retinoblastoma is the most common primary intraocular tumor in childhood. Its early detection and initiation of appropriate therapy , can dramatically improve the life expectancy in these children. This article is a general review of the disease. PubMed was employed and representative articles about the topic were selected in order to given us a general idea about the advances achieved. Due to clinical features, primary care physician is a fundamental part in the initial catchment of patient. [Villamil JF , Quintero LM, Serrano RA, Moreno IA. Clinical, diagnostic and therapeutic considerations in retinoblastoma. MedUNAB 2011; 14:180-187].

In vivo growth of retinoblastoma in a newborn infant.

Retinoblastoma is a rare malignancy of the retina seen exclusively in children. It is known to cause rapid growth inside the eye and hence treatment should be started as soon as it is diagnosed. We report a case in a five-day-old infant in whom treatment (chemotherapy) was delayed by a month due to high bilirubin levels secondary to physiological jaundice, which gave us the unique opportunity to measure the growth of the tumor over a month. This case emphasizes that immediate treatment is warranted once this rare disease is diagnosed.

Descripción del caso presentado en el número anterior: Retinoblastoma / Previous issue clinical case presentation: Retinoblastoma

Niña de 7 meses, previamente sana, traída a la consulta por leucocoria de 2 meses de evolución.La paciente no presenta dolor ocular ni síntomas concomitantes. Al examen oftalmológico se constata ausencia de fijación y esotropia del ojo derechocon ausencia de reflejo rojo.

Compliance in retinoblastoma.

Objective. To evaluate compliance to treatment in advanced retinoblastoma. Methods. This is a retrospective descriptive study of patients of retinoblastoma registered at our cancer center from June 2003-February 2007 to study compliance. Results. Sociodemographic data of 177 patients revealed rural:urban ratio of 2:1, median age 36 months (unilateral disease) and 24 months (bilateral disease); median symptom duration 7.2 months. Overall, 84/141 evalued cases took adequate therapy; follow-up could be achieved in 67/141 (47.5%) cases in comparison to 92.4% in Hodgkin’s lymphoma (p=0.001), 62.8% in acute myeloid leukemia (p=0.036) and 72.7% in non Hodgkin’s lymphoma (p=0.001). There was no significant impact of any sociodemographic factors on compliance. Amongst those offered enucleation upfront for intraocular disease, it was accepted in 86/93 (92.5%) eyes. Conclusions. This is one of the largest studies in relation to sociodemographic factors and clinical spectrum, and the only study from Asia evaluating compliance with recommended therapy in retinoblastoma. In order to improve ocular and patient salvage rates in Asian countries, exact causes for poor compliance in retinoblastoma need to be closely examined through a prospective study.

Retinocytoma associated with bilateral retinoblastoma.

A 3-year-old girl presented with left exotropia. Funduscopy demonstrated a retinocytoma associated with five discrete retinoblastomas in the left eye and three discrete retinoblastomas in her right eye. The clinical manifestations and fundus imaging findings are described.

Retinocitoma: relato de cinco casos / Retinocytoma: report of five cases

Relatamos cinco casos de retinocitoma diagnósticados em um período de 75 meses. A média de idade ao diagnóstico foi de 193,2 meses. Dois casos apresentavam tumor unilateral, um bilateral e dois exibiam retinoblastoma no olho contralateral. As características clínicas e oftalmoscópicas, as implicações genéticas e a necessidade de tratamento e acompanhamento contínuo dos pacientes com retinocitoma são discutidas.

Five retinocytoma cases diagnosed over 75 months are reported. The mean age at diagnosis was 193.2 months. Two cases were unilateral, one was bilateral and two exhibited retinoblastoma in the fellow eye. Clinical and ophthalmoscopic aspects, genetical implications and the need of treatment and continuous follow-up of retinocytoma patients are discussed.

Bases embriogênicas da persistência dos sistemas retiniano e hialoide embrionários / Embryogenic foundations of the persistence of the embryonic retinal and hyaloid systems

Os autores apresentam o relato de quatro casos de persistência completa do sistema retiniano e hialoide embrionários (PCSRHE), discutem sua patogenia baseados na embriogênese comparada procuram esclarecer os problemas que surgem no diagnóstico diferencial nos casos de leucocoria e sugerem o abandono da designação de persistência do vítreo primário (VP) hiperplásico. As razões para esta última proposta são as seguintes: 1) Não é só o VP que persiste, mas, também a retina embrionária, e a vasculatura hialoide com a haste do nervo óptico, ou restos desses elementos. 2) A palavra hiperplasia tem significado restrito em patologia, pois compreende somente os processos proliferativos não tumorais das células. Ora, tanto o vítreo primário como o secundário, definitivo do adulto, têm poucas células, as quais não aparecem como participantes da patogenia; além disso, o VP, nos casos de persistência completa, é escasso, portanto, hipoplásico, sendo um contrassenso a expressão vítreo primário hiperplásico.

The authors report 4 cases of Complete Persistence of the Embryonic Retinal and Hyaloid Systems (CPERHS), discuss their pathogeny based on compared embryogenesis, and attempt to clarify the issues that come forth in the differential diagnosis in cases of leukocoria, suggesting that the designation of Persistent Hyperplastic Primary Vitreous (PHPV) should be abandoned for the following reasons: 1) It’s not only the Primary Vitreous (PV) which persists but also the embryonic retina as well as the hyaloid vasculature with the optic nerve stalk, or the remains of these structures. 2) The term hyperplasia has a restricted meaning in Pathology as it encompasses only nontumoral processes of cell proliferation. However, both the primary and the secondary vitreous have few cells, which do not appear as participants of the pathogeny; moreover, the PV in the cases of complete persistence is scarce and therefore hypoplastic, the designation Hyperplastic Primary Vitreous being nonsensical.

Retinoblastoma: a three-year-study at a Brazilian medical school hospital

OBJECTIVE: To present the characteristics and treatment outcomes of patients with retinoblastoma. METHODS: A retrospective case series was conducted to review the records of all new patients diagnosed with retinoblastoma between 2003 and 2005. Eyes with early disease, or advanced disease with potential vision were treated with chemotherapy (carboplatin and etoposide) in conjunction with early local therapy (laser or cryo). Radiotherapy was used in cases where the disease did not respond to the above protocols or in recurrent cases. Eyes in the late stage of disease with no potential vision in the initial examination or eyes and where conservative treatment had failed were enucleated. RESULTS: In total, we reviewed 28 new cases of retinoblastoma, 15 of which were unilateral and 13 of which were bilateral (46 percent). These data correspond to a mean of 9.3 new cases per year (0.77 case/ month). The mean age at diagnosis was 33.8 months for unilateral cases, and 19.15 months for bilateral cases (p=0.015). Leucocoria was the major presenting symptom (75 percent). All but one patient with unilateral disease had the affected eye enucleated due to advanced disease (mean follow-up: 39.91 months). Among the 13 bilateral cases, 13 eyes (50 percent) were enucleated, 11 eyes (42.4 percent) were saved with chemotherapy in conjunction with local therapy and 2 eyes (7.6 percent) were saved using external beam radiotherapy (mean follow-up: 41.91 months). In unilateral and bilateral disease, pathology data revealed choroid involvement in 50 percent and 30 percent, respectively, and optic nerve invasion in 92 percent and 50 percent, respectively. CONCLUSION: In this population, retinoblastoma was diagnosed too late and most eyes were consequently enucleated. In cases with bilateral disease, half of the eyes were preserved.

Actualización en retinoblastoma / Updates in retinoblastoma

El retinoblastoma es un tumor de baja frecuencia, que se manifiesta por leucocoria o estrabismo. El pronóstico de la enfermedad es dramáticamente distinto si el diagnóstico es hecho tempranamente, por lo que nuevas estrategias por promover su diagnóstico precoz y tratamiento multidisciplinario están cobrando especial importancia en países en vías de desarrollo, que aún presentan elevadas tasas de mortalidad de la enfermedad.

Retinoblastoma en pediatría, experiencia en un hospital pediátrico / Retinoblastoma in children, experience at a pediatric hospital

Methods: Retrospective analysis of clinical charts of 41 children (59 eyes) diagnosed with retinoblastoma and treated by a multidisciplinary team at Hospital Luis Calvo Mackenna in Santiago-Chile, between 1999 and 2007. The information included gender, laterality, diagnosis age, presenting signs, tumor spread, treatment modality and survival rate. Results: A total of 23 cases (56 percent) were unilateral and 18 cases (44 percent) were bilateral. The mean age at diagnosis was 21.6 months (range 2 - 84) and 27 children (65.9 percent) were male. The most common presenting signs were leucokoria (51.2 percent), strabismus (24.4 percent) and proptosis (4.9 percent). Enucleation was performed in 48 eyes (81.3 percent), being the only required treatment in 17 children (41.5 percent). The remaining 24 patients received systemic and/or local therapy with chemotherapy, focal therapy and external beam radiation. 5 children died during the follow - up study period, due to extraocular extension to the orbit, central nervous system and bone marrow. Conclusion: In spite of high enucleation rate as initial therapy for retinoblastoma, the survival rate with this current treatment protocol is similar to those from developed countries.

Se presenta un estudio retrospectivo de las fichas clínicas de 41 niños (59 ojos) con diagnóstico de retinoblastoma tratados por un equipo multidisciplinario en el Hospital Luis Calvo Mackenna, Santiago, Chile, entre los a±os 1999-2007. Se recolectó información respecto al género, edad al diagnóstico, signos de presentación, lateralidad, diseminación del tumor, tipos de tratamiento y sobrevida. Veintitrés casos (56 por ciento) fueron unilaterales y 18 (44 por ciento) bilaterales. La edad promedio al momento del diagnóstico fue de 21,6 meses (rango 2-84) y 27 niños (65,9 por ciento) fueron hombres. Los signos de presentación más frecuentes fueron leucocoria (51,2 por ciento), estrabismo (24,4 por ciento) y proptosis (4,9 por ciento). Se realizó enucleación en 48 ojos afectados (81,3 por ciento), siendo el único tratamiento necesario en 17 niños (41,5 por ciento). Los 24 pacientes restantes recibieron tratamientos complementarios locales y/o sistémicos en la modalidad de quimioterapia, terapia focal y radioterapia externa. Durante el período de seguimiento del estudio fallecieron 5 niños, todos ellos con extensión extraocular de la enfermedad hacia la órbita, sistema nervioso central o médula ósea. Conclusiones: No obstante el alto porcentaje de pacientes con retinoblastoma que requieren enucleación como terapia inicial, la tasa de sobrevida con el protocolo actual de tratamiento es comparable a la de países desarrollados.