Programmed cell death ligand-1 expression in tumor and immune cells is associated with better patient outcome and decreased tumor-infiltrating lymphocytes in uveal melanoma.

Programmed cell death-1/ligand (PD-1/PD-L1) interaction negatively regulates T cell activity. PD-L1 expression in tumor cells, antigen-presenting cells, and lymphocytes of the tumor microenvironment is associated with response to treatment with PD-1/PD-L1 inhibitors, but there is still debate on the cutoff value that correlates with responders. In uveal melanoma (UM), 40% of patients will develop liver metastases and, amongst them, 90% will succumb to their disease. The aim of this study was to analyze PD-L1 expression as a prognostic marker and as a possible therapeutic target for UM. Sixty-seven enucleated eyes from UM patients with relevant clinical information were analyzed. Univariate and multivariate analysis were used to evaluate association of PD-L1 with survival. PD-L1 expression was positive relatively to tumor cells, immune cells, and the tumor and tumor-infiltrating immune cell group scoring in 46, 34 and 55% of the cases, respectively. On univariate analysis, tumor cells and the tumor and tumor-infiltrating immune cell group PD-L1 expression was associated with a longer metastasis-free survival (P = 0.04 and P = 0.007). However, on multivariate analysis, only the tumor and tumor-infiltrating immune cell group positivity was associated with longer metastasis-free survival (P = 0.01). Furthermore, tumor cells and the tumor and tumor-infiltrating immune cell group PD-L1 expression was associated with decreased tumor-infiltrating lymphocytes (P = 0.02). PD-L1, when expressed in uveal melanoma, is associated with better patient outcome and decreased tumor-infiltrating lymphocytes. These results support the consideration of anti-PD-1/PD-L1 therapy in uveal melanoma. To determine the best cutoff value, further studies from patients enrolled in clinical trials treated with PD-1/PD-L1 inhibitors are necessary.

The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group.

PURPOSE: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. DESIGN: Retrospective, multicenter observational study. PARTICIPANTS: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. METHODS: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. RESULTS: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. CONCLUSIONS: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.

A study comparing baseline and best-corrected visual acuity after iodine-125 episcleral brachytherapy in uveal melanoma.

Purpose: The aim of this study was to analyze the course of visual acuity (VA) in visual outcomes of patients treated with iodine-125 (125I) brachytherapy in our center, based on original VA before treatment. Material and methods: Visual acuity was prospectively assessed using a case series of 305 patients treated with 125I between 1996 and 2022. To examine how VA behaves over time, we divided patient sample into 4 groups: (1) Patients with visual acuity of less than V ≤ 0.1 at baseline; (2) Patients with low to moderate VA, ranging 0.1 < V < 0.4; (3) Patients with moderate-high VA, ranging 0.4 < V < 0.8; (4) Patients with very high VA of V > 0.8. Each of the four groups was studied separately over a 60-month period to determine the percentage of patients with VA improvement, worsening, or with the same VA status. Finally, visual outcomes over time were estimated with 95% confidence interval (CI) using Kaplan-Meier analysis, and VA maintenance rates were reported at 1, 3, 5, 10, 15, and 20 years of follow-up. Results: The median follow-up time was 78.2 months (range, 6-254 months). The cumulative probabilities of survival analysis at 1, 3, 5, and 10 years were 16%, 3%, 2%, and none for the first sub-group; 46%, 20%, 17%, and 14% for the second; 65%, 53%, 29%, and 15% for the third; and 86%, 56%, 48%, and 41% for the fourth sub-group. The median survival in years was 0.30, 0.80, 3.10, and 4.40 for each sub-cohort, respectively. Conclusions: The decrease and maintenance of VA depends on the initial VA of patients. Most patients experience a marked worsening of their VA, regardless of their VA status before treatment with episcleral brachytherapy. Patients with a higher baseline VA retain VA best over time.

Long-term results of visual function in posterior uveal melanoma patients treated with I125 episcleral brachytherapy in a Spanish referral Ocular Oncology Unit.

PURPOSES: We analyzed patient, tumor and dosimetric characteristics of subjects in a Spanish population diagnosed with uveal melanoma treated with iodine 125 (I125) episcleral brachytherapy, who presented with post-treatment loss of useful visual acuity and global evolution of visual acuity. METHODS: A single historic observational cohort study was undertaken. Patients with uveal melanoma were recruited between September 1995 and June 2015. Clinical, tumor and dosimetric data collection and visual acuity evaluations were performed under everyday practice conditions based on a useful visual acuity >0.1 on the decimal scale. The baseline analysis was performed using descriptive and survival analyses according to Kaplan-Meier curves. RESULTS: A total of 286 of the 665 patients diagnosed with uveal melanoma received episcleral brachytherapy, and 198 were included in the study. The mean follow-up time was 75.3 months (95% CI = 68.0-82.6). Patients with post-treatment useful visual acuity loss (n=94, 47%) presented the following characteristics: visual symptoms (n=80, p-value = 0.001); iris color (brown n=33, hazel green n=49, p-value = 0.047); Collaborative Ocular Melanoma Study size (medium n=80, p-value = 0.159); tumor, node, metastasis stage (T2: n=38, T3: n=38, p=0.012); shape (nodular n=67, mushroom-shaped n=26, p=0.001); posterior pole involvement (n=47, p=0.04); recurrence (n=10, p=0.001); and dose administered in the fovea, optic nerve and center of the eye (p<0.002). Using Kaplan-Meier analysis, the mean overall survival of useful visual acuity was 90.19 months, and the probability of preserving useful visual acuity was 66% for one year, 45% for five years and 33% for ten years. CONCLUSION: Patients most likely to present with visual acuity loss were those with the following profile: elderly males with dark irises who were diagnosed with visual symptoms and exhibited a medium/large melanoma with a mushroom shape in the posterior pole (near the fovea and/or optic nerve). All patients treated with episcleral brachytherapy are likely to present with visual acuity loss, which is more pronounced in the first few years following treatment.

Regression of posterior uveal melanoma following iodine-125 plaque radiotherapy based on pre-treatment tumor apical height.

PURPOSE: The aim of this study was to analyze regression rates and local control of uveal melanoma patients treated with iodine-125 ( 125I) brachytherapy based on initial tumor apical height. MATERIAL AND METHODS: Patients treated in a single institution from January 1st, 1996 to 2019 with 125I plaques (ROPES and COMS) for uveal melanoma were included in this study. Patients treated with brachytherapy for iris and those treated with transpupillary thermotherapy prior to brachytherapy were excluded. The sample was classified into 4 categories depending on initial apical tumor height (h0), i.e., h0 ≤ 2.5 (small), 2.5 < h0 ≤ 6.25 (small-medium), 6.25 < h0 ≤ 10 (medium-large), and h0 > 10 mm (large). Percentage of original tumor apical height (Δh) was collected during follow-ups. Patterns of regression were evaluated using linear least squares adjustments. Multivariable Cox regression were performed. RESULTS: In total, 305 patients met the inclusion criteria, and 27, 166, 100, and 13 were considered for small, small-medium, medium-large, and large categories, respectively. Median follow-up was 82.4, 56.8, 76.1, 89.1, and 100.1 months for the entire cohort and each sub-group, respectively. Pattern of decrease when h0 ≤ 2.5 mm was not detectable. For the rest sub-groups, changes in height could be fitted using functional form: Δh (T) = ae-bT + c, R 2 ≥ 0.97. Multivariate Cox analysis factors predictive of local control failure revealed a hazard ratio (HR) of 6.1 (95% CI: 0.7-58.2%, p = 0.05) for patients who remained similar sized after treatment for small-medium tumors. For the rest sub-groups, Cox analysis did not indicate statistical significance in any single variable. CONCLUSIONS: Height changes can be modeled by a negative exponential function for the first 7 years after treatment depending on the initial height, except for those less than 2.5 mm. Non-responding small-medium tumors multiply by 6 the probability of failure in local control.

Treatment planning considerations for 125I eye plaque brachytherapy.

Effective cancer brachytherapy requires a treatment plan that delivers high-dose to tumor, while minimizing the dose to critical normal tissues. Therefore, an accurate knowledge of the sources and magnitude of the techniques is essential for producing robust and well optimized-plans. The purpose of this technical note is to establish general procedures and strategies for optimization and customization of the plaques loaded with radioactive seeds, particularly focusing on the definition of useful tactics to limit high doses to organs at risk and adapt the treatment time to the necessity of institution.

Uveal vs. cutaneous melanoma. Origins and causes of the differences.

Melanoma is a malignant tumour derived from melanocytes (dendritic cells originated from the neural crest and capable to produce melanin synthesis) that could be established on the skin or less frequently on the uvea. The cellular origin from both kind of melanoma seems to be the same but the melanocytes migrates to the epithelia for cutaneous melanoma, while for uveal melanoma, they migrate to mesodermic tissues. Despite the common origin, both melanomas show extreme differences in their metastatic potential, clinical response to treatments, immune response and genetic alterations. We will describe some of those differences in this review.

Radiobiological doses, tumor, and treatment features influence on local control, enucleation rates, and survival after epiescleral brachytherapy. A 20-year retrospective analysis from a single-institution: part I.

PURPOSE: To assess influence of the radiobiological doses, tumor, and treatment features on local control, enucleation rates, overall and disease-specific survival rates after brachytherapy for posterior uveal melanoma. MATERIAL AND METHODS: Local control, enucleation, overall and disease-specific survival rates were evaluated on the base of 243 patients from 1996 through 2016, using plaques loaded with iodine sources. Clinical and radiotherapy data were extracted from a dedicated prospective database. Biologically effective dose (BED) was included in survival analysis using Kaplan-Meier and Cox regressions. The 3-, 5-, 10-, and 15-year relative survival rates were estimated, and univariate/multivariate regression models were constructed for predictive factors of each item. Hazard ratio (HR) and confidence interval at 95% (CI) were determined. RESULTS: The median follow-up was 73.9 months (range, 3-202 months). Cumulative probabilities of survival by Kaplan-Meier analysis at 3, 5, 10 and 15 years were respectively: 96%, 94%, 93%, and 87%, for local control; 93%, 88%, 81%, and 73% for globe preservation; 98%, 93%, 84%, and 73% for overall survival, and 98%, 96%, 92%, and 87% for disease-specific survival. By multivariate analysis, we concluded variables as significant: for local control failure - the longest basal diameter and the juxtapapillary location; for globe preservation failure - the longest basal dimension, the mushroom shape, the location in ciliary body, and the dose to the foveola; for disease-specific survival - the longest basal dimension. Some radiobiological doses were significant in univariate models but not in multivariate ones for the items studied. CONCLUSIONS: The results show as predictive factors of local control, enucleation, and disease-specific survival rates those related with the features of the tumor, specifically the longest basal dimension. There is no clear relation between radiobiological doses or treatment parameters in patients after brachytherapy.

Radiobiological doses, tumor, and treatment features influence on outcomes after epiescleral brachytherapy. A 20-year retrospective analysis from a single-institution: part II.

PURPOSE: To assess the influence of the radiobiological doses, tumor, and treatment features on retinopathy, cataracts, retinal detachment, optic neuropathy, vitreous hemorrhage, and neovascular glaucoma at the authors' institution after brachytherapy for posterior uveal melanoma. MATERIAL AND METHODS: Medical records of 243 eyes with uveal melanoma, treated by iodine brachytherapy between 1996 and 2016 at a single center were analyzed. Clinical and radiotherapy data were extracted from a dedicated database. Biologically effective dose (BED) was included in survival analysis performed using Kaplan-Meier and Cox regressions. Relative survival rates were estimated, and univariate/multivariate regression models were constructed for predictive factors of each item. Hazard ratio and confidence interval at 95% were determined. Variables statistically significant were analyzed and compared by log-rank tests. RESULTS: The median follow-up was 73.9 months (range, 3-202 months). Cumulative probabilities of survival by Kaplan-Meier analysis at 3 and 5 years, respectively, were: 59% and 48% for retinopathy; 71% and 55% for cataracts; 63% and 57% for retinal detachment; 88% and 79% for optic neuropathy; 87% and 83% for vitreous hemorrhage; 92% and 89% for neovascular glaucoma, respectively. Using multivariate analysis, statistically significant risk factors were: age, tumor apical height, dose to foveola, and location of anterior border for retinopathy; age, dose to lens, type of plaque, and tumor shape, for cataracts; age, tumor apical height, and size of the plaque for retinal detachment; age, plaque shape, longest basal dimension, and BED to optic nerve for optic neuropathy; age, tumor apical height, and tumor shape for vitreous hemorrhage; tumor apical height and BED to foveola for neovascular glaucoma. CONCLUSIONS: Tumor factors in addition to radiation treatment may contribute to secondary effects. Enhanced clinical optimization should evaluate radiobiological doses delivered to the tumor volume and surrounding normal ocular structures.

Episcleral brachytherapy as an effective alternative in vasoproliferative tumors.

The aim of this study is to assess the results of episcleral brachytherapy as treatment of retinal vasoproliferative tumors (RVTs) in a referral Intraocular Tumors Unit (ITU). A retrospective review of all patients diagnosed with vasoproliferative tumors of the retina and treated with episcleral brachytherapy in the ITU, University Hospital of Valladolid between 2009 and 2015 was done. Five patients accomplished the inclusion criteria. All of them presented associated exudation and secondary retinal detachments (RD). Four patients had received prior treatments. Decreased tumor size and exudation regression was found in all cases after treatment. Visual acuity remained stable or increased in all patients. No recurrences have been found after twelve-months follow up. The results of the present study suggest that episcleral brachytherapy is an efficient and safe option in the management of vasoproliferative tumors, especially when large tumor or extensive subretinal fluid is present. In these cases episcleral brachytherapy could be considered as a first line treatment.

Choroidal melanoma recurrence after episcleral brachytherapy and transpupillary thermotherapy.

A 68-year-old man diagnosed with choroidal melanoma (CM) in the right eye underwent treatment with episcleral brachytherapy (I125) and transpupillary thermotherapy. Ultrasound, computed tomography, and magnetic resonance imaging were performed and revealed ocular recurrence of CM. Treatment with extended enucleation was performed. Macroscopic and microscopic examinations revealed extraocular extension and malignant cells, respectively. Immunohistochemistry demonstrated tumoral Melan-A and HMB-45 expression. No cytogenic abnormalities were detected with fluorescence in situhybridization of tumor cells using probes against chromosomes 3q27 and 8q24. The patient underwent adjuvant external beam radiotherapy for treatment of residual tumor tissue. This case represents the first reported case of recurrent CM with no cytogenetic abnormalities and the absence of metastatic disease, despite a number of the poorest prognostic factors.

Long-term results of visual function in posterior uveal melanoma patients treated with I125 episcleral brachytherapy in a Spanish referral Ocular Oncology Unit / Resultados de longo prazo da função visual em pacientes com melanoma uveal posterior tratados com braquiterapia epiescleral com I125 em uma unidade de referência em Oncologia Oftalmológica na Espanha

ABSTRACT Purposes: We analyzed patient, tumor and dosimetric characteristics of subjects in a Spanish population diagnosed with uveal melanoma treated with iodine 125 (I125) episcleral brachytherapy, who presented with post-treatment loss of useful visual acuity and global evolution of visual acuity. Methods: A single historic observational cohort study was undertaken. Patients with uveal melanoma were recruited between September 1995 and June 2015. Clinical, tumor and dosimetric data collection and visual acuity evaluations were performed under everyday practice conditions based on a useful visual acuity >0.1 on the decimal scale. The baseline analysis was performed using descriptive and survival analyses according to Kaplan-Meier curves. Results: A total of 286 of the 665 patients diagnosed with uveal melanoma received episcleral brachytherapy, and 198 were included in the study. The mean follow-up time was 75.3 months (95% CI = 68.0-82.6). Patients with post-treatment useful visual acuity loss (n=94, 47%) presented the following characteristics: visual symptoms (n=80, p-value = 0.001); iris color (brown n=33, hazel green n=49, p-value = 0.047); Collaborative Ocular Melanoma Study size (medium n=80, p-value = 0.159); tumor, node, metastasis stage (T2: n=38, T3: n=38, p=0.012); shape (nodular n=67, mushroom-shaped n=26, p=0.001); posterior pole involvement (n=47, p=0.04); recurrence (n=10, p=0.001); and dose administered in the fovea, optic nerve and center of the eye (p<0.002). Using Kaplan-Meier analysis, the mean overall survival of useful visual acuity was 90.19 months, and the probability of preserving useful visual acuity was 66% for one year, 45% for five years and 33% for ten years. Conclusion: Patients most likely to present with visual acuity loss were those with the following profile: elderly males with dark irises who were diagnosed with visual symptoms and exhibited a medium/large melanoma with a mushroom shape in the posterior pole (near the fovea and/or optic nerve). All patients treated with episcleral brachytherapy are likely to present with visual acuity loss, which is more pronounced in the first few years following treatment.

RESUMO Objetivo: Analisar características individuais, tu morais e dosimétricas de pacientes diagnosticados com melanoma uveal, tratados através de braquiterapia epiescleral com iodo-125 (I125), que apresentaram perda da acuidade visual útil após o tratamento e analisar a evolução global da acuidade visual em uma população da Espanha. Métodos: Este é um estudo observacional de coorte histórica considerando pacientes com melanoma uveal diagnosticados entre setembro de 1995 e junho de 2015. Foram coletados dados clínicos, tumorais e dosimétricos e medida a acuidade visual em condições de prática clínica diária, considerando uma acuidade visual útil superior a 0,1 na escala decimal. A análise de base foi efetuada por curvas Kaplan-Meier descritivas de sobrevivência Resultados: Um total de 286 dos 665 pacientes diagnosticados com melanoma uveal recebeu braquiterapia epiescleral e 198 deles foram incluídos no estudo. O tempo médio de acompanhamento foi de 75,3 meses (IC 95%: 68,0-82,6). Os pacientes com perda da acuidade visual útil após o tratamento (n=94, 47%) apresentaram as seguintes características: sintomas visuais (n=80, p=0,001), cor da íris (castanha: n=33, castanho-esverdeada: n=49; p=0,047), tamanho de acordo com o Collaborative Ocular Melanoma Study (tamanho médio: n=80, p=0,159), tumor, nódulo, estágio de metástase (T2: n=38, T3: n=38, p=0,012), forma (nodular: n=67, em forma de cogumelo: n=26, p=0,001), envolvimento do polo posterior (n=47, p=0,04), recorrência (n=10, p=0,001) e dose administrada na fóvea, no nervo óptico e no centro do olho (p<0,002). Na análise de Kaplan-Meier, o tempo médio de sobrevivência geral da acuidade visual útil foi de 90,19 meses e a probabilidade de preservação da acuidade visual útil foi de 66% por um ano, 45% por 5 anos e 33% por 10 anos. Conclusão: O perfil de paciente com maior probabilidade de perda da acuidade visual útil é o de homem idoso com íris escura, diagnosticado com sintomas visuais e melanoma de tamanho médio a grande, em forma de cogumelo no polo posterior (próximo à fóvea, ao nervo óptico ou a ambos). Todos os pacientes tratados com braquiterapia epiescleral terão perda da acuidade visual, mais pronunciada nos primeiros anos após o tratamento.

Bilateral episcleral brachytherapy in simultaneous choroidal melanoma and circumscribed hemangioma.

PURPOSE: To describe the efficacy of episcleral brachytherapy in a choroidal melanoma and circumscribed hemangioma arising in both eyes of the same patient. CASE REPORT: We present the case of a 47 year old man who presented decreased visual acuity a few months preceding initial consult. On fundoscopy, he presented a melanotic lesion in the right eye, and a red-orange choroidal mass in the macular area of the left eye. MATERIAL AND METHODS: B scan-ultrasound, fluorescein, and indocyanine green angiography, confirmed the diagnosis of choroidal melanoma in the right eye, and circumscribed choroidal hemangioma in the left eye. Episcleral brachytherapy with (125)I was performed in both eyes consecutively. RESULTS AND CONCLUSIONS: Bilateral episcleral brachytherapy successfully treated both tumors, preserving the eyes and useful visual function.

Embryonal rhabdomyosarcoma of the caruncle in a 4 year-old boy: case report.

Rhabdomyosarcoma is a rare tumor, with an annual incidence of 4.3 cases per million children. Even thought, it is the most common soft tissue sarcoma in childhood, with a mean age of 6 to 8 years at diagnosis. A 4 year-old boy presented with a history of a fast growing (1-month) nodular lesion in the caruncle of his left eye. Slit lamp examination showed a vascularized solid nodular lesion in the semilunar fold. The lesion was surgically removed obtaining infiltrated edges with tumoral cells. A second surgery was performed with free tumour edges. The diagnosis of embryonal rhabdomyosarcoma, botryoid type, of intermediate differentiation was made. The treatment for botryoid rhabdomyosarcoma is basically surgical with the combined use of adjuvant polychemotherapy. In adolescent or adult patients (not in infants where growth bone disturbances can occur) external beam radiotherapy can be combined with chemotherapy. Rhabdomyosarcomas of the conjunctiva without orbital extension are rarely reported. We presented a case of a child with a rare tumor which we had a high suspicion of malignancy and early diagnosis and treatment and child is free of systemic disease 6 and half years later. Our research group believes that the key in these tumors is the high index of suspicion and early treatment.

Episcleral brachytherapy for uveal melanoma: analysis of 136 cases.

PURPOSE: To assess the results of I-125 episcleral brachytherapy (EB) in uveal melanoma: tumour control, visual acuity (VA), eye preservation and survival. PATIENTS: Prospective and consecutive study of patients with a diagnosis of uveal melanoma at the Ocular Oncology Unit in the Valladolid University Teaching Hospital treated with EB between September 1997 and June 2008. Ocular examination and extraocular and systemic extension data were registered in a database at the time of the diagnosis and during the follow-up. RESULTS: Among a total of 310 patients diagnosed between September 1997 and June 2008, 136 were treated with EB (mean age, 58.3). Mean follow-up was 55.3 months. As for tumour type, 66.9% were nodular and 39% mushroom shaped. With respect to size, 80.9% were medium, 7.4% small and 11.8% large. After 4.6 years of follow-up, tumours were controlled in 97.1%, with a 55.1% reduction in mean height; only 2.9% of patients showed recurrence. VA was maintained in 16.2% of patients and 17.6% showed an increase; 33% had retinopathy and 14.6% optic neuropathy. Only 5.1% of patients underwent enucleation due to complications and there has been 1 melanoma-related death to date. CONCLUSIONS: I-125 EB is effective in tumour control, allowing preservation of the eye and useful visual function for the majority of patients.

Choroidal melanoma recurrence after episcleral brachytherapy and transpupillary thermotherapy / Recorrência melanoma de coroide após a braquiterapia episcleral e termoterapia transpupilar

ABSTRACT A 68-year-old man diagnosed with choroidal melanoma (CM) in the right eye underwent treatment with episcleral brachytherapy (I125) and transpupillary thermotherapy. Ultrasound, computed tomography, and magnetic resonance imaging were performed and revealed ocular recurrence of CM. Treatment with extended enucleation was performed. Macroscopic and microscopic examinations revealed extraocular extension and malignant cells, respectively. Immunohistochemistry demonstrated tumoral Melan-A and HMB-45 expression. No cytogenic abnormalities were detected with fluorescence in situhybridization of tumor cells using probes against chromosomes 3q27 and 8q24. The patient underwent adjuvant external beam radiotherapy for treatment of residual tumor tissue. This case represents the first reported case of recurrent CM with no cytogenetic abnormalities and the absence of metastatic disease, despite a number of the poorest prognostic factors.

RESUMO Um homem de 68 anos de idade com diagnóstico de melanoma de coroide no olho direito foi submetido a tratamento com braquiterapia episcleral (I125) e termoterapia transpupilar. Ultrassonografia, tomografia computadorizada e ressonância magnética foram realizadas para avaliar a presença de recorrência ocular ou doença sistêmica. Enucleação ampliada foi realizada para tratar a recorrência ocular. O exame macroscópico e microscópico revelou o tipo de célula tumoral e a extensão extraocular. Colorações por Melan-A e HMB-45 foram realizadas. A fluorescência por hibridização in situ com sondas para os cromossomos 3q27 e 8q24 não mostraram anormalidades citogenéticas. O paciente foi submetido a radioterapia externa adjuvante para o tratamento de tumor residual orbitário. Este caso representa a o primeiro relato de paciente sem anomalias citogenéticas e sem doença metastática, apesar de demonstrar alguns dos mais pobres fatores prognósticos.

Embryonal rhabdomyosarcoma of the caruncle in a 4 year-old boy: case report / Rabdomiossarcoma embrionário da carúncula em um menino de 4 anos: relato de caso

Rhabdomyosarcoma is a rare tumor, with an annual incidence of 4.3 cases per million children. Even thought, it is the most common soft tissue sarcoma in childhood, with a mean age of 6 to 8 years at diagnosis. A 4 year-old boy presented with a history of a fast growing (1-month) nodular lesion in the caruncle of his left eye. Slit lamp examination showed a vascularized solid nodular lesion in the semilunar fold. The lesion was surgically removed obtaining infiltrated edges with tumoral cells. A second surgery was performed with free tumour edges. The diagnosis of embryonal rhabdomyosarcoma, botryoid type, of intermediate differentiation was made. The treatment for botryoid rhabdomyosarcoma is basically surgical with the combined use of adjuvant polychemotherapy. In adolescent or adult patients (not in infants where growth bone disturbances can occur) external beam radiotherapy can be combined with chemotherapy. Rhabdomyosarcomas of the conjunctiva without orbital extension are rarely reported. We presented a case of a child with a rare tumor which we had a high suspicion of malignancy and early diagnosis and treatment and child is free of systemic disease 6 and half years later. Our research group believes that the key in these tumors is the high index of suspicion and early treatment.

Rabdomiossarcoma é um tumor raro, com uma incidência anual de 4,3 casos por milhão de crianças. É o sarcoma de partes moles mais comum na infância, com uma idade média de 6 a 8 anos no momento do diagnóstico. Um menino de 4 anos apresentou-se com uma história de um crescimento rápido (1 mês) lesão nodular em carúncula de seu olho esquerdo. O exame biomicroscópico mostrou uma lesão vascularizada sólida nodular na prega semilunar. A lesão foi removida cirurgicamente com obtenção de bordas infiltradas com células tumorais, segunda cirurgia foi feita com bordas tumorais livres. O diagnóstico de rabdomiossarcoma embrionário, tipo botrióide, de diferenciação intermediária foi feita. O tratamento para a rabdomiossarcoma botrióide é basicamente cirúrgico com o uso combinado de poliquimioterapia adjuvante. Em pacientes adolescentes e adultos (e não em lactentes onde os distúrbios do crescimento ósseo pode ocorrer) radioterapia externa pode ser combinada com a quimioterapia. Rabdomiossarcomas da conjuntiva sem extensão orbital são raramente relatadas. Apresentamos um caso de uma criança com um tumor raro que tivemos uma alta suspeita de malignidade e diagnóstico precoce e tratamento e criança é livre de doença sistêmica 6 anos e meio depois. Nosso grupo de pesquisa acredita que a chave para esses tumores é o alto índice de suspeita e tratamento precoce.