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BACKGROUND: Several studies have demonstrated the effect of parent-of-origin on retinoblastoma penetrance. The purpose of the current study was to assess differences in clinical presentation of paternally versus maternally inherited retinoblastoma. METHODS: The clinical records of all children with familial retinoblastoma treated on a tertiary Ocular Oncology Service between December 1975 and May 2020 were reviewed retrospectively. RESULTS: A total of 179 patients with familial retinoblastoma were included. Paternal inheritance (PI) was identified in 109 (61%) patients and maternal inheritance (MI) in 70 patients (39%). A comparison (PI vs MI) revealed PI patients were older at presentation (57.2 vs 24.4 months [P = 0.002]) with no difference in patient sex (53% females vs 57% males [P = 0.606]) or number of family members affected (3.2 vs 3.0 family members [P = 0.255]). PI patients had more advanced classification according to the International Classification of Retinoblastoma (ICRB) (group E: 31% vs 8% [P = 0.012)] and greater largest tumor in basal diameter (9.0 vs 6.2 mm [P = 0.040]) and thickness (5.6 vs 4.0 mm [P = 0.038]); they were also less likely to be located in the macula (40% vs 60% [P = 0.004]). There was no difference in tumor laterality (69% vs 64% bilaterality [P = 0.530]). PI patients required enucleation more frequently (34% vs 14% [P = 0.007]). There was no difference in need for plaque radiotherapy (P = 0.86) or chemotherapy (P = 0.85). One PI patient developed metastatic retinoblastoma, and there were no retinoblastoma-related deaths. CONCLUSIONS: Patients with paternally inherited retinoblastoma presented at an older age, with larger, more peripheral tumors and more advanced ICRB group, and were more likely to require enucleation compared to those with maternally inherited retinoblastoma.
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Neoplasias da Retina , Retinoblastoma , Criança , Masculino , Feminino , Humanos , Lactente , Retinoblastoma/diagnóstico , Retinoblastoma/genética , Retinoblastoma/terapia , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/genética , Neoplasias da Retina/terapia , Herança Materna , Estudos Retrospectivos , Família , Enucleação OcularRESUMO
OBJECTIVE: To compare multimodal imaging findings in patients with choroidal lymphoma (CL). METHODS: Multicenter retrospective observational case series. Multimodal imaging features of patients with CL were reviewed with particular attention to the patterns of choroidal infiltration on indocyanine green angiography (ICGA) and optical coherence tomography (OCT). RESULTS: Eighteen eyes of 15 patients were included in this study. Average tumor thickness on ultrasonography was 2.6 mm (range, 1.2-5.7 mm). Choroidal infiltration on ICGA was characterized by multifocal, round areas (300-500 microns diameter) of hypocyanescence in all cases, whereas OCT at the same region disclosed diffuse choroidal infiltration. By OCT, the tumor surface contour was primarily placid (22%), dome-shaped (11%), or undulating (67%). CONCLUSIONS: In this analysis of eyes with CL, ICGA demonstrated multifocal sub-millimeter regions of choroidal hypocyanescence whereas OCT documented diffuse choroidal infiltration. This incongruence could be a distinctive diagnostic feature of choroidal lymphoma, assisting with differentiation from other pathological entities.
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Verde de Indocianina , Linfoma , Humanos , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos , Angiofluoresceinografia/métodos , Corioide/patologia , CorantesRESUMO
BACKGROUND/AIMS: To evaluate the likelihood of germline mutation in patients presenting with solitary retinoblastoma based on tumour location at first examination. METHODS: Retrospective analysis of solitary unilateral retinoblastoma for likelihood of germline mutation (family history of retinoblastoma and/or genetic testing indicating germline RB1 mutation and/or development of additional new or bilateral tumours) based on tumur location at presentation (macular vs extramacular). RESULTS: Of 480 consecutive patients with solitary retinoblastoma, 85 were in the macula (18%) and 395 were extramacular (82%). By comparison (macular vs extramacular tumours), macular tumours had smaller basal diameter (12.7 mm vs 18.9 mm, p<0.001) and smaller tumour thickness (6.1 mm vs 10.7 mm, p<0.001). Patients with macular tumours demonstrated greater likelihood for germline mutation (23% vs 12%, OR=2.18, p=0.011), specifically based on family history of retinoblastoma (13% vs 2%, OR=4.64, p=0.004), genetic testing showing germline RB1 mutation (27% vs 15%, OR=2.04 (95% CI 1.04 to 4.01), p=0.039), development of new tumours (13% vs 3%, OR=5.16 (95% CI 2.06 to 12.87), p=0.001) and/or development of bilateral disease (9% vs 2%, OR=4.98 (95% CI 1.70 to 14.65), p=0.004). CONCLUSIONS: Among patients with solitary unilateral retinoblastoma, those presenting with macular tumour (compared with extramacular tumour) show 2.18 times greater likelihood for germline mutation and an even higher likelihood of development of subsequent tumours. Solitary macular retinoblastoma should raise an index of suspicion for likely germline mutation and multifocal disease.
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PURPOSE: Frequent activating mutations in the mitogen-activated protein kinase (MAPK) pathway genes have been identified in histiocytoses. MAPK signaling consistently upregulates cyclin D1. The goal of this study was to determine whether cyclin D1 expression by immunohistochemistry is a useful diagnostic marker for periocular histiocytoses and to further characterize their genetic basis. DESIGN: Retrospective observational case series. METHODS: Pathology records were searched for all patients with histiocytoses diagnosed between 1995 and 2020. Eleven histiocyte-rich inflammatory lesions and 10 xanthelasma served as controls. Cyclin D1 immunohistochemistry was performed on all tissues. A subset of histiocytoses was evaluated by next-generation sequencing (NGS) and droplet digital PCR (ddPCR). RESULTS: There were 36 patients, 15 males (42%) and 21 females (58%), with histiocytoses: 9 juvenile xanthogranuloma (25%), 8 adult-onset asthma and periocular xanthogranuloma (22%), 7 Langerhans cell histiocytosis (19%), 5 Rosai-Dorfman disease (14%), 5 xanthogranuloma-not otherwise specified (14%), 1 Erdheim-Chester disease (3%), and 1 histiocytic sarcoma (3%). Moderate to strong nuclear cyclin D1 expression was present in ≥50% of lesional cells in histiocytoses (23/36, 64%), significantly more when compared to histiocyte-rich inflammatory lesions (0/11, 0%, P<.001) and xanthelasma (0/10, 0%, P<.001). Cyclin D1 was expressed in <10% of lesional cells in all 11 histiocyte-rich inflammatory lesions (P<.001) and all 10 xanthelasma lesions (P<.001). MAPK pathway gene mutations were detected in 12 of 14 (86%) histiocytoses successfully assayed by NGS and/or ddPCR. CONCLUSIONS: Our study confirms that the cyclin D1 immunohistochemical stain is a useful diagnostic marker for periocular histiocytoses, correlating with underlying mutations in MAPK pathway genes.
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Histiocitose de Células de Langerhans , Neoplasias , Adulto , Ciclina D1/genética , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Feminino , Histiocitose de Células de Langerhans/genética , Histiocitose de Células de Langerhans/metabolismo , Histiocitose de Células de Langerhans/patologia , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Proteínas Quinases Ativadas por Mitógeno , Biologia Molecular , Estudos RetrospectivosRESUMO
PURPOSE: To assess the efficacy and toxicity of Iodine-125 (I-125) plaque radiotherapy for retinoblastoma following intra-arterial chemotherapy (IAC). METHODS: Clinical records of patients with retinoblastoma who received I-125 plaque radiotherapy after IAC at the Ocular Oncology Service at Wills Eye Hospital between December 1, 2009 and April 30, 2020, were retrospectively reviewed. RESULTS: Forty-one retinoblastomas in 41 eyes of 41 patients were treated with I-125 plaque radiotherapy after IAC at a median age of 32 months. The indication for plaque radiotherapy was solid tumor recurrence with or without overlying subretinal/vitreous seeds (n = 33, 80%), subretinal seeds alone (n = 6, 15%), and vitreous seeds alone (n = 2, 5%). The median irradiated basal diameter and thickness was 9 and 4 mm, respectively. Mean radiation dose to tumor apex was 3,483 centigray (cGy) delivered at mean rate of 35 cGy/hr. The irradiated site was controlled in 39 eyes (95%) at a median of 20 months after plaque radiotherapy for solid tumor (31 of 33, 94%), subretinal (6 of 6,100%), and vitreous seeds (2 of 2, 100%). A subgroup of tumors occurring within an ischemic retinal/choroidal field was identified on fluorescein angiography (n = 24) and demonstrated control in 22 of 24 (92%). Using Kaplan-Meier analysis, radiation complications at 2 years included vitreous hemorrhage (37%), retinopathy (28%), papillopathy (18%), and cataract (18%). Five eyes (12%) were enucleated for recurrence outside the irradiated area, chronic vitreous hemorrhage, and/or total retinal detachment. CONCLUSIONS: Iodine-125 plaque radiotherapy provided 95% control for retinoblastoma tumors that failed IAC, including those in ischemic fields untreatable with further chemotherapy. Radiation complications should be anticipated in eyes exposed to substantial chemotherapy. [J Pediatr Ophthalmol Strabismus. 2022;59(3):164-171.].
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Neoplasias da Retina , Retinoblastoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Humanos , Lactente , Infusões Intra-Arteriais , Radioisótopos do Iodo/uso terapêutico , Retina/patologia , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/diagnóstico , Retinoblastoma/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Hemorragia Vítrea/tratamento farmacológicoRESUMO
PURPOSE: To evaluate the likelihood of germline retinoblastoma in patients presenting with solitary unilateral retinoblastoma, based on age at presentation. METHODS: This retrospective case series of 482 consecutive patients presenting with solitary unilateral retinoblastoma analyzed the likelihood of germline retinoblastoma, defined as family history of retinoblastoma, germline retinoblastoma mutation documented on genetic testing, and/or development of bilateral disease and/or additional new tumors. This analysis was based on age at presentation (0 to 12 months vs older than 12 to 24 months vs older than 24 to 36 months vs older than 36 months) and a sub-study was conducted on infant age at presentation (0 to 3 months vs older than 3 to 6 months vs older than 6 to 9 months vs older than 9 to 12 months). RESULTS: Of the overall group (482 consecutive patients) with solitary unilateral retinoblastoma, there were significantly different findings in the youngest age group (0 to 12 months old) with greater family history of retinoblastoma (10% vs 2% vs 1% vs 2%, P = .004), smaller median basal diameter (18.0 vs 20.0 vs 20.0 vs 20.0 mm, P = .014), smaller median tumor thickness (8.7 vs 10.0 vs 11.5 vs 10.0 mm, P = .002), greater macular tumor location (33% vs 16% vs 10% vs 8%, P < .001), and greatest likelihood of germline mutation (29% vs 17% vs 8% vs 9%, P = .001). By comparison, patients 1 year and younger (vs older than 1 year) demonstrated a 2.96 odds ratio (OR) (P = .001) for likelihood of germline retinoblastoma. For those classified as infants (1 year and younger) (n = 132 consecutive patients), the youngest patients (0 to 3 months old) demonstrated the greatest likelihood for germline mutation (61% vs 20% vs 24% vs 22%, P = .009) and greatest odds ratio (5.52, P = .002) compared to patients older than 3 to 12 months. CONCLUSIONS: The youngest patients with solitary unilateral retinoblastoma showed the greatest likelihood of germline disease when evaluating all patients (1 year and younger vs older than 1 year of age) (OR = 2.96) and the substudy of infants (3 years and younger vs older than 3 to 12 months old) (OR = 5.52). [J Pediatr Ophthalmol Strabismus. 2021;58(6):355-364.].
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Neoplasias da Retina , Retinoblastoma , Pré-Escolar , Mutação em Linhagem Germinativa , Humanos , Lactente , Recém-Nascido , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/genética , Retinoblastoma/diagnóstico , Retinoblastoma/genética , Estudos RetrospectivosRESUMO
PURPOSE: The objective of the study was to understand dynamic risk (conditional analysis based on patient age) for new tumor development in patients with solitary unilateral retinoblastoma. METHODS: This was a retrospective analysis. RESULTS: Of 482 patients with solitary unilateral retinoblastoma, 55 new tumors developed in 20 patients (4%). Comparison (new tumor vs. no new tumor development) revealed those with new tumor demonstrated younger mean age at presentation (10 vs. 36 months, P < 0.001), greater likelihood of family history of retinoblastoma (35% vs. 3%, P < 0.001), and greater probability of primary tumor location in the macula (50% vs. 15%, P = 0.003). Conditional risk for new tumors (at age 6, 9, 12, 18, and 24 months) declined for those who presented at 0-3 months old (25%, 15%, 15%, 8%, and 0%), >3-6 months old (17%, 14%, 6%, 6%, and 0%), >6-9 months old (not applicable [na], 6%, 6%, 0%, and 0%), and >9-12 months (na, na, 3%, 3%, and 0%). Younger patients showed greater development of bilateral tumors (P < 0.001). Of patients with new tumors, those that occurred within 1 year from presentation were located in the preequatorial region in 46%, whereas those that occurred more than 1 year from presentation were preequatorial in 78%. Patients ≤24 months at initial presentation demonstrated all new tumors by 24 months of age. Older patients (>24 months at presentation) showed new tumors up to 56 months of age. CONCLUSION: Children (≤24 months) with solitary unilateral retinoblastoma showed decreasing risk for new tumors up to 24 months of life. Later onset of new tumor was more likely located in preequatorial region.
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Coats disease is a rare, non-hereditary retinal vascular abnormality that typically presents in the first two decades of life and is characterized by idiopathic retinal telangiectasia with progressive exudation. The authors describe a patient with Coats disease in which the family neglected treatment, demonstrating the natural course of this disease. [J Pediatr Ophthalmol Strabismus. 2020;57:e82-e85.].
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Angiofluoresceinografia/métodos , Fotocoagulação a Laser/métodos , Telangiectasia Retiniana/diagnóstico , Vasos Retinianos/diagnóstico por imagem , Acuidade Visual , Feminino , Fundo de Olho , Humanos , Masculino , Telangiectasia Retiniana/cirurgiaRESUMO
BACKGROUND: Studies show that implicit bias among healthcare providers contributes to health disparities. Despite this knowledge, most medical school curricula lack formal methods for assessing and reducing implicit bias among medical students. PURPOSE: The purpose of this study was to create a longitudinal, multidisciplinary training program for first-year medical students to reduce implicit bias toward skin tone, to increase awareness of personal bias, and to measure changes in bias after a targeted intervention. METHODS: First-year medical students participated in a three-part implicit bias training program that included visits to an art museum, a lecture on medical anthropology, and an interactive sociological discussion about bias in medical research. A control group did not participate in the training. All participants took the Harvard Implicit Association Test for Skin Tone and completed a questionnaire assessing awareness of implicit bias before and after the study activities were administered. RESULTS: All participants indicated a bias toward light skin tone. In addition, a stronger bias score in the pre-test correlated with a stronger belief that the scores were inaccurate. Neither the experimental group nor the control group demonstrated a significant change in implicit bias, but the experimental group trended toward a decrease in bias. Power analysis suggested that significant results may have been obtained with a larger sample size. All participants indicated an awareness that implicit biases affect the provision of healthcare. When prompted to reflect on these biases, the experimental group provided richer, more detailed personal accounts of implicit bias in the healthcare environment after participating in the study. CONCLUSIONS: First-year medical students who participated in this study were aware that implicit bias affects the provision of healthcare and therefore plays a role in perpetuating health disparities. However, they were less able to recognize bias in themselves. Providing opportunities for medical students to recognize and confront their own implicit biases is an important goal. This study suggests that a longitudinal, multidisciplinary curricular approach to building awareness and reducing implicit bias can produce promising results in medical students. We anticipate that further development and refinement of curricular activities may lead to significant results.
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Venous thrombosis is a vascular disorder which is a consequence of Virchow's triad: hypercoagulability, venous stasis, and endothelial injury. While lower extremity deep venous thrombosis is common, upper torso thrombosis is a rare clinical condition and usually a complication of central venous catheterization or malignancy-related paraneoplastic syndromes. Herein, we present a rare case of a 64-year-old male who presented with right upper extremity and right facial swelling who was found to have a thrombus in the right internal jugular vein and right subclavian vein with no predisposing factors. He was successfully treated with anticoagulation without any complications.