Estudio epidemiológico y anatomopatológico del melanoma uveal / Epidemiologic and anatomopathologic study of uveal melanoma

Objetivo: Determinar el comportamiento epidemiológico y anatomopatológico del melanoma uveal. Método: Estudio descriptivo, longitudinal y retrospectivo en pacientes enucleados por diagnóstico de melanoma uveal en el Centro Oftalmológico de Villa Clara entre enero de 2010 a mayo de 2021. Resultados: La edad media de presentación del melanoma uveal fue de 61,3 años. Las mujeres fueron ligeramente más afectadas que los hombres-56,3 por ciento. El 81,3 por ciento de los melanomas uveales se originó en la coroide. Los tumores de células epitelioides y fusiformes fueron los más representativos; ambos con un 37,5 por ciento. El grosor y diámetro basal medio en los tumores estudiados fue de 11,2 mm y 15,8 mm respectivamente; prevalecieron los tumores medianos con un 56,3 por ciento. Se encontró infiltración tumoral en 37,5 por ciento de los ojos, la infiltración escleral fue la más frecuente. Conclusiones: El melanoma uveal se presenta con mayor frecuencia en personas con edad avanzada y en la coroide. El estudio histológico confirma el diagnóstico en la totalidad de los casos. Aproximadamente 2/3 de los tumores con algún grado de infiltración son grandes y la mitad de células epitelioides(AU)

Objective: To determine the epidemiologic and anatomopathologic behavior of uveal melanoma. Methods: Descriptive, longitudinal and retrospective study in patients enucleated for diagnosis of uveal melanoma in the Ophthalmologic Center of Villa Clara from January 2010 to May 2021. Results: The average age of presentation of uveal melanoma was 61.3 years. Women were slightly more affected than men-56.3 percent. 81.3 percent of uveal melanomas originated in the choroid. Epithelioid and spindle cell tumors were the most representative; both with 37.5 percent. The average thickness and basal diameter of the tumors studied were 11.2mm and 15.8mm respectively; medium-sized tumors prevailed with 56.3 percent. Tumor infiltration was found in 37.5 percent of the eyes, scleral infiltration was the most frequent. Conclusions: Uveal melanoma occurs more frequently in people with advanced age and in the choroid. Histological study confirms the diagnosis in all cases. Approximately 2/3 of the tumors with some degree of infiltration are large and half are epithelioid cells(AU)

Scleral necrosis in patients with posterior uveal melanomas evaluated by transcleral fine needle aspiration biopsy and treated by 125I plaque / Necrose escleral em pacientes com melanoma da úvea posterior avaliados pela biópsia aspirativa com agulha fina e tratados com placa de Iodo 125

ABSTRACT Purpose: To evaluate the incidence, potential correlation with transcleral fine needle aspiration biopsy, and treatment of scleral necrosis in patients with posterior uveal melanomas treated by 125I plaque radiotherapy and assessed by transcleral fine needle aspiration biopsy. Methods: We per­formed a retrospective review of posterior uveal melanoma treated by 125I plaque radiotherapy at a single academic institution between July 2006 and July 2013. Consecutive patients diagnosed with a posterior uveal melanoma during the study period that had an anterior margin at or anterior to the equator who were evaluated by transcleral fine needle aspiration biopsy prior to 125I plaque radiotherapy were included. The main outcome measure was development of scleral necrosis, and the secondary outcome was treatment of this complication. Statistical analysis included computation of conventional descriptive statistics, cross-tabulation and chi-square tests of potential factors related to the development of scleral necrosis, and summarizing of treatment approaches and results. The incidence of treatment of scleral necrosis was calculated using the Kaplan-Meier method. Results: During the 7-year study period, 87 posterior uveal melanomas were evaluated by transcleral fine needle aspiration biopsy and treated by 125I plaque radiotherapy. The median largest basal diameter of the tumor was 13.3 mm, and the median thickness was 6.8 mm. Eight patients (9.2%) developed scleral necrosis during follow-up. Thicker tumors (> 6.5 mm) were more likely to develop scleral necrosis (n=7) than thinner tumors (p=0.05). The median interval between 125I plaque radiotherapy and detection of scleral necrosis was 19.1 months. The overall cumulative probability of scleral necrosis was 6.2% at 6 months and 14.3% at 24 months, subsequently remaining stable. For thicker tumors, the probability of scleral necrosis was 23.5% at 45.4 months. Five patients were treated by scleral patch graft (62.5%) and three by observation (37.5%). One patient underwent enucleation after two failed scleral patch attempts and recurrent scleral necrosis. The mean follow-up period for patients with scleral necrosis was 34.5 months. Conclusions: Thicker posterior uveal melanomas are more likely to develop scleral necrosis after 125I plaque radiotherapy and transcleral fine needle aspiration biopsy. While observation is sufficient for managing limited scleral necrosis, scleral patch graft is a viable alternative for eye preservation in extensive scleral necrosis.

RESUMO Objetivo: Avaliar incidência, possível correlação da biópsia aspirativa com agulha fina trans-escleral e manejo da necrose escleral em pacientes com melanoma da úvea posterior tratados com placa de Iodo-125 (PLACA) avaliados pela biópsia aspirativa com agulha fina trans-escleral. Métodos: Revisão retrospectiva de melanoma da úvea posterior tratados com placa de Iodo-125 entre 07/2006 e 07/2013 em uma única instituição acadêmica. Pacientes diagnosticados consecutivamente com melanoma da úvea posterior durante o intervalo desse estudo cuja margem anterior está no equador ou anterior ao mesmo e foram avaliados pela biópsia aspirativa com agulha fina trans-escleral antes do tratamento com PLACA foram incluídos. O principal desfecho avaliado foi desenvolvimento de necrose escleral e o desfecho secundário foi o manejo dessa complicação. Análise estatística incluiu computação de variáveis descritivas convencionais; tabulação e teste do Chi-quadrado de fatores potencialmente relacionados com o desenvolvimento de necrose escleral e sumarização do manejo dessa complicação. A incidência de necrose escleral foi calculada usando o método de Kaplan-Meier. Resultados: Durante o período de 7 anos desse estudo, 87 melanomas da úvea posterior foram avaliados pela biópsia aspirativa com agulha fina trans-escleral e tratados com placa. A mediana do maior diâmetro basal tumoral foi 13,3 mm e a mediana da espessura foi 6,8 mm. Oito pacientes (9,2%) desenvolveram necrose escleral durante o período de acompanhamento. Tumores mais espessos (> 6,5 mm) foram mais propensos a desenvolver necrose escleral (n=7) que tumores mais finos (p=0,05). O intervalo mediano entre PLACA e a detecção da necrose escleral foi 19,1 meses. Probabilidade cumulativa de desenvolvimento de necrose escleral foi 6,2% em 6 meses e 14,3% em 24 meses permanecendo estável subsequentemente. Em tumores espessos, a probabilidade de necrose escleral foi 23,5% em 45,4 meses. Cinco pacientes foram manejados com enxerto escleral (62,5%), 3 foram observados (37,5%). Um paciente foi enucleado após 2 enxertos esclerais com necrose escleral recidivada. Tempo de seguimento médio dos pacientes com necrose escleral foi 34,5 meses. Conclusões: Tumores espessos pareceram mais propensos a desenvolver necrose escleral após PLACA e biópsia aspirativa com agulha fina trans-escleral para melanoma da úvea posterior. Apesar de observação para necrose escleral limitada ser suficiente, enxerto de esclera é uma alternativa viável para preservação ocular em necrose escleral extensa.

Internal eye wall resection of uveal tumors: long-term evaluation / Ressecção em bloco de tumores uveais: avaliação de longo prazo

The authors report five cases of uveal tumors managed with internal eye wall resection and evaluate the long-term results. Patient age varied from 31 to 61 years. Four patients were female and one was male. Uveal tumors involved ciliary body and choroid in three patients and choroid alone in the other two. Histopathological examination demonstrated three uveal melanomas, one leiomyoma, and one meduloepithelioma. The largest tumor diameter ranged from 8 to 15 mm and tumor thickness from 5 to 11 mm. Follow-up of the patients was over a period of 6 to 23 years. Final visual acuity was 20/20 in 3 patients and 20/200 in one patient, and in the fifth patient, the affected eye was enucleated. No cases of metastatic disease or local recurrence of the tumor were observed, suggesting that internal eye wall resection is a valid alternative for the treatment of selected cases of uveal tumors.

Os autores relatam 5 casos que apresentavam tumores uveais e foram submetidos à remoção cirúrgica em bloco do tumor, avaliando resultados de acuidade visual, índice de retenção do globo ocular e de doença metastática. Quatro mulheres e um homem, com idade entre 31 e 61anos foram submetidos ao procedimento. O tumor envolvia corpo ciliar e coroide em três olhos e somente a coroide em dois. A histopatologia demonstrou que 3 tumores eram melanomas, um leiomioma e um meduloepitelioma. O maior diâmetro dos tumores foi entre 8 e 15 mm e a espessura entre 5 e 11 mm. O tempo de seguimento dos pacientes foi de 6 a 23 anos. A acuidade visual final foi de 20/20 em 3 olhos, 20/200 em outro e um olho foi enucleado. Não foram observados casos de doença metastática ou recorrência tumoral, sugerindo que a ressecção em bloco de tumores uveais é uma alternativa válida para o tratamento destes tumores em casos selecionados.

Prognostic implications of cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy / Implicação prognóstica da classificação citopatológica dos tumores melanocíticos da úvea avaliados pela biópsia aspirativa com agulha fina

PURPOSE: Determine whether cytopathologic classification of melanocytic uveal tumors evaluated by fine-needle aspiration biopsy (FNAB) is a significant prognostic factor for death from metastasis. METHODS: Retrospective analysis of cases of clinically diagnosed uveal melanoma evaluated by fine-needle aspiration biopsy from 1980 to 2006. Main outcome evaluated was death from metastasis. Associations between baseline clinical variables and cytopathologic classification were evaluated using cross-tabulation. Prognostic significance of cytopathologic classification was evaluated by Kaplan-Meier and Cox proportional hazards analysis. RESULTS: Of 302 studied biopsies, 260 (86.1%) yielded sufficient cells for cytopathologic classification. Eighty of the 260 patients who had a sufficient specimen have already died (P=0.021), 69 from metastatic uveal melanoma. Cell type assigned by cytopathology was strongly associated with metastasis/metastatic death in this series (P=0.0048). Multivariate analysis showed cytopathologic classification to be an independently significant prognostic factor for metastatic death (P=0.0006). None of the 42 patients whose tumor yielded insufficient aspirates (sampled in at least two sites) have developed metastasis or died of metastasis thus far. CONCLUSION: In this series, cytopathology of fine-needle aspiration biopsy samples obtained from uveal melanomas was strongly prognostic of death from metastasis. Insufficiently aspirates (2 or more sites sampled) proved to be prognostic of a favorable outcome (i.e., not developing metastasis).

OBJETIVO: Determinar se a classificação citopatológica de tumores melanocíticos da úvea avaliados pela biópsia aspirativa com agulha fina (BAAF) é um fator prognóstico significativo para óbito por metástases. Métodos: Análise retrospectiva de casos diagnosticados clinicamente como melanoma uveal e avaliados pela biópsia aspirativa com agulha fina entre 1980 e 2006. O evento principal analisado foi óbito por metástase. Associações entre variáveis clínicas à apresentação e classificação citopatológica foram avaliadas usando tabulação cruzada. Significância prognóstica da classificação citopatológica foi avaliada por análise de riscos proporcionais de Cox e Kaplan-Meier. RESULTADOS: Das 302 biópsias estudadas, 260 (86,1%) renderam um número suficiente de células para classificação citopatológica. Oitenta dos 260 pacientes que obtiveram um espécime suficiente (adequado) foram a óbito (P=0,021), 69 destes por melanoma uveal metastático. O tipo celular designado pela citopatologia apresentou forte associação com metástase/óbito por metástase nessa série (P=0,0048). Análise multivariada mostrou que a classificação citopatológica foi um fator prognóstico independente significativo para o óbito por metástase (P=0,0006). Nenhum dos 42 pacientes cujos tumores renderam um aspirado insuficiente (quando foram amostrados pelo menos 2 sítios) desenvolveu metástase e foi a óbito por metástase até o presente momento. CONCLUSÃO: Nessa série, a citopatologia dos espécimes obtidos pela biópsia aspirativa com agulha fina de melanomas uveais foi fortemente prognóstica para óbito por metástase. Os aspirados insuficientes (se duas ou mais áreas foram amostradas) provou ser um resultado prognóstico favorável (i.e., de não desenvolvimento de metástases).

A Case of Ciliary Body Melanocytoma Presenting as a Painful Iris Mass

We report a case of ciliary body melanocytoma in a Korean patient, which presented as an intermittently painful pigmented iris mass and was successfully managed by iridocyclectomy. A 52-year-old healthy man presented with an irregularly-shaped and heavily-pigmented mass at the iris root of his right eye. Visual acuity of the right eye was 20/20 with normal intraocular pressure. Ultrasound biomicroscopy showed a 1.5x1.3-mm ciliary-body mass with extension into the iris root. Iridocyclectomy with scleral resection under a lamellar scleral flap was performed, and the histopathologic features of the resected tissue were consistent with melanocytoma of the ciliary body. The patient's visual acuity remained 20/20 with good postoperative cosmesis. During one year of follow-up, no signs of tumor recurrence were seen, and the patient reported resolution of the intermittent ocular pain in the involved eye.

Fine needle aspiration biopsy to reestablish cell culture in an animal model of uveal melanoma / Biópsia aspirativa com agulha fina para restabelecer cultura celular em modelo animal de melanoma uveal

PURPOSE: To access the reliability of fine-needle aspiration biopsy in harvesting a sufficient amount of viable melanoma cells to establish a cell culture and maintain a melanoma cell line from an animal model of uveal melanoma. METHODS: For this study, fifteen male New Zealand albino rabbits had their right eye surgically inoculated with uveal melanoma cell line 92.1. The animals were immunosupressed with cyclosporine A using a dose schedule previously published. The animals were followed for 12 weeks. Intraocular tumor growth was monitored weekly by indirect ophthalmoscopy. After the fourth week, one animal was sacrificed per week preceded by fine-needle aspiration biopsy using a sharp 25-gauge, 1-inch long needle. Two separate aspirates were made from different areas of the tumor. Each aspirate was flushed to a separate cell culture media and sent for cell culture. The cells were frozen after two weeks when there were at least 1 million cells, which is enough to maintain a cell line. Cells were defrosted for HMB-45 immuno-stains to confirm the melanoma origin. RESULTS: Cell growth was observed from the samples harvested from 11 out of the 15 animals inoculated with uveal melanoma. All cell cultures, after defrost, immunoassayed positive for HMB-45. CONCLUSION: Fine needle aspiration biopsy seems to be a reliable method to harvest cells from solid intraocular melanomas in an animal model, to establish cell culture and to maintain a melanoma cell line.

OBJETIVO: Acessar a confiança da colheita de amostra celular suficiente através da biópsia aspirativa com agulha fina para estabelescer uma cultura celular e manter uma linhagem de células de melanoma a partir de uma modelo animal de melanoma uveal. MÉTODOS: Para esse estudo, 15 coelhos albinos da Nova Zelândia foram inoculados cirurgicamente com a linhagem celular 92.1 de melanoma uveal. Os animais foram imunosuprimidos com ciclosporina A usando uma dose previamente publicada. Os animais foram acompanhados por 12 semanas. O crescimento de tumor intraocular foi monitorado semanalmente pela oftalmoscopia indireta. Após a quarta semana, um animal foi sacrificado por semana, precedido pela biópsia aspirativa com agulha fina usando uma agulha de gauge 25 e comprimento 2,5 cm. Dois aspirados separados foram realizados a partir de áreas diferentes do tumor. Cada aspirado foi descarregado em um meio de cultura individual e enviado para cultura celular. As células foram congeladas após 2 semanas de cultura ou quando haviam pelo menos 1 milhão de células, o que é suficiente para manter uma linhagem celular. As células foram descongeladas para realizar imunocitoquímica com HMB-45 e confirmar sua origem melanocítica maligna. RESULTADOS: Crescimento celular foi observado nas amostras colhidas em 11 dos 15 animais inoculados com melanoma uveal. Todas as culturas celulares, após serem descongeladas, apresentaram imunoexpressão positiva para o HMB-45. CONCLUSÃO: Biópsia aspirativa com agulha fina parece ser um método confiável para colher células de tumores oculares sólidos em um modelo animal visando estabelecer e manter essa linhagem celular de melanoma.

Unilateral solitary choroid metastasis from breast cancer: rewarding results of external radiotherapy.

Intraocular metastatic tumor is the commonest intraocular malignancy in adults, with uveal tract the commonest site. In nearly 85% of cases the choroid is the afflicted site due to its vascularity. Breast and lung are the common primaries. In breast primaries, this could be the first metastatic disease. This condition should always be kept in mind in patients with visual symptoms. Fundus examination, ultrasonography and CT/MRI of the orbit help in diagnosis. Early recognition and timely treatment can save the visual function thus imparting good quality of life to the patient. External beam radiotherapy is a good local form of treatment. Hormone therapy in hormone receptor positive tumors can have additional benefits. Here we report a case of unilateral solitary choroid metastasis in a case of breast cancer treated with external beam radiotherapy.

Clinicopathologic correlations in eyes enucleated after uveal melanoma resection with positive surgical margins.

We identified three eyes that had undergone enucleation after transscleral resection of uveal melanoma. Two enucleated eyes with microscopically positive margins of resection exhibited no evidence of residual melanoma and these patients were alive without metastasis with at least four years' follow-up. One eye with a transected melanoma contained residual melanoma and that patient died with metastatic melanoma to the liver three years after enucleation. There appear to be at least two general types of positive surgical margins of resection of uveal melanoma: microscopically positive margins and macroscopically positive (transected) margins of resection.

Pesquisa de células malignas circulantes em pacientes com melanoma maligno de coróide / Detection of circulating malignant cells in patients with uveal melanoma

OBJETIVO: Avaliar a possibilidade de identificação de células malignas circulantes nas amostras de sangue periférico de pacientes brasileiros com melanoma maligno de coróide enviadas para análise no exterior. MÉTODOS: Os marcadores melan-A e tirosinase foram usados para detectar a presença de células malignas circulantes, pela transcrição reversa seguida de reação em cadeia da polimerase e análise seqüencial de DNA (RT-nested-PCR), em seis pacientes com melanoma maligno de coróide, diagnosticados no Brasil. RESULTADOS: Cinco pacientes deste grupo (83,33 por cento) foram considerados positivos. A reação de RT-nested-PCR foi positiva para melan-A em quatro (66,7 por cento) e positiva para tirosinase em quatro (66,7 por cento) dos seis pacientes testados. Três (50 por cento) pacientes foram positivos para os dois marcadores. Um (16,7 por cento) paciente foi negativo para ambos marcadores. CONCLUSÃO: A pesquisa de células malignas circulantes usando RT-nested-PCR, foi positiva na maioria dos pacientes estudados. A qualidade das amostras de sangue periférico dos pacientes brasileiros foi mantida no material preservado mesmo após ter sido enviado ao exterior.

PURPOSE: The purpose of our study was to detect circulating malignant cells (CMCs) in oversea-shipped blood samples of patients with uveal melanoma diagnosed in Brazil. METHODOS: Melan-A and tyrosinase were the two markers used for the detection of CMCs, using reverse transcriptase nested polymerase chain reaction (RT-nested-PCR) in 6 patients with uveal melanoma. The expression of beta-actin and GAPDH were used to assess the quality of the material. RESULTS: Five patients (83.33 percent) tested positive for the presence of CMCs. The RT-nested-PCR was positive for melan-A in 4 patients (66.7 percent) and positive for tyrosinase in 4 (66.7 percent) of the 6 patients. Three (50 percent) patients were positive for both markers. One (16.7 percent) patient was negative for both markers. All negative controls were negative. CONCLUSION: The quality of the blood samples shipped overseas, from patients with uveal melanoma, was preserved. The detection of CMCs using RT-nested-PCR was positive in the majority of the patients.

Braquiterapia com rutênio-106 em melanomas uveais - resultados preliminares: experiência uni-institucional / Ruthenium-106 brachytherapy for uveal melanomas - preliminary results: a single institutional experience

OBJETIVO: Analisar os resultados preliminares da braquiterapia com rutênio-106 em pacientes portadores de melanomas uveais. MATERIAIS E MÉTODOS: No período de abril de 2002 a julho de 2003, 20 pacientes com diagnóstico de melanoma uveal foram tratados com braquiterapia com rutênio-106. A dose calculada no ápice tumoral variou de 55 Gy a 100 Gy. Pacientes com lesões com altura maior que 5 mm foram submetidos a termoterapia transpupilar concomitante à colocação da placa oftálmica. RESULTADOS: Quanto à localização da lesão, esta se encontrava na coróide em 75 por cento dos casos, na íris em 15 por cento e no corpo ciliar em 10 por cento dos pacientes. Com seguimento mediano de 19 meses, a sobrevida livre de progressão para a braquiterapia e para a associação com a termoterapia transpupilar foi de 69 por cento e 87 por cento, respectivamente. Observou-se redução significante da altura tumoral após o tratamento. Nenhum dos pacientes foi submetido a enucleação. CONCLUSÃO: Nossos resultados preliminares mostram que a braquiterapia com rutênio-106 é uma opção adequada para o tratamento conservador de melanomas uveais em termos de controle local, manutenção do globo ocular e visão útil, com índice aceitável de complicações.

OBJECTIVE: To analyze the early response of uveal melanomas in patients treated with ruthenium-106 brachytherapy. MATERIALS AND METHODS: In the period between April 2002 and July 2003, 20 patients diagnosed with uveal melanoma were submitted to ruthenium-106 brachytherapy. The calculated dose delivered at the apex of the tumor ranged between 55 Gy and 100 Gy. Patients with lesions greater than 5 mm were submitted to transpupillary thermotherapy concomitantly with ophthalmic plaque insertion. RESULTS: As regards the lesions site, 75 percent of the lesions were located in the choroid, 15 percent in the iris, and the remainder 10 percent in the ciliary body. In a median 19-month-follow-up, the progression-free survival for brachytherapy was 69 percent, and 87 percent for associated brachytherapy and transpupillary thermotherapy. A significant tumor height reduction was observed after treatment. No patient was submitted to enucleation. CONCLUSION: Our preliminary results show that ruthenium-106 brachytherapy is an appropriate method for conservative treatment of patients with uveal melanomas in terms of local management, ocular and visual acuity preservation with an acceptable complications incidence rate.

Malignant ocular melanoma in a dog

A mongrel male dog of three years old was referred to the Seoul National University Veterinary Teaching Hospital following a one month history of glaucoma. On ophthalmic examination, hyphema, glaucoma, uveitis, iridal mass, and loss of vision were noted in the right eye. Ultrasonography and computed tomography revealed a mass with involvement of the entire uvea. Radiographic evaluation did not reveal any evidence of distant metastasis. The right eye was surgically removed because of the high likelihood of neoplasia. A histologic diagnosis of malignant uveal melanoma was made.

Medulloepithelioma of the ciliary body.

A rare case of medulloepithelioma of the ciliary body is described. The tumour necessitated enucleation of the eye; histopathological diagnosis was benign nonteratoid medulloepithelioma of the ciliary body.

Uveal melanoma; diagnosis and differentiation by magnetic resonance imaging

In this study, 26 patients with intraocular diseases were evaluated by magnetic resonance imaging. Malignant uveal melanoma was diagnosed in 16 patients underwent surgery with a histopathological confirmation of melanoma. MRI allowed the detection of uveal melanoma with their characteristic signal intensity secondary to the paramagnetic properties of the melanin. In addition, tumor characterization improved the detection of tumor margins and extraocular extension. MRI also proved to be valuable for differentiating uveal melanoma from associated subretinal effusion, choroidal detachment and other tumors [choroidal hemangioma, metastases and retinoblastoma]

Meduloepitelioma justa-papilar: apresentaçäo de um caso / Medulloepithelioma: report of a case

Os autores apresentam um caso de meduloepitelioma justa-papilar, forma muito rara de tumor intra-ocular. Apresentam ainda, suas principais características clínicas, ecográficas e anatomopatológicas