Response Evaluation of Choroidal Melanoma After Brachytherapy Using Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI): Preliminary Findings.

Purpose: To evaluate the role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the assessment of therapeutic response in patients with choroidal melanoma treated with brachytherapy. Materials and Methods: We performed a prospective, unicentric study which included patients with choroidal melanoma and indication for brachytherapy. Three DW-MRI examinations were proposed for each patient, one before and two after treatment. The apparent diffusion coefficient (ADC) value was calculated on DW-MRI and compared with local tumor control assessed by ophthalmologic follow-up. Results: From 07/2018 to 06/2019, 19 patients were recruited, 13 of whom underwent follow-up examinations. Patients' ages ranged from 24 to 78 years and 52.9% were male. At the ocular ultrasound, the mean tumor thickness and diameter were 6.3 and 11.5 mm, respectively. Two patients (15.4%) showed signs of tumor progression during follow-up (7 and 9 months after treatment). There was no statistically significant difference in tumor size between MR before and after treatment, however, there was a significant reduction in mean ADC in patients with progression (p = 0.02). Conclusion: DW-MRI is a promising method for monitoring patients with choroidal melanoma; reduction in the mean ADC values between pre-treatment MRI and the first post-treatment MRI may be related to the lack of response to brachytherapy and increased risk of disease progression.

Trilateral retinoblastoma with unilateral eye involvement.

Retinoblastomas (RB) are the main forms of intraocular tumor in childhood, with a worldwide incidence of 1 case per 15,000 to 20,000 live births. Trilateral RB (RBT) is a rare combination of unilateral or bilateral RB with a midline intracranial neoplasm of neuroblastic origin, usually found in the pineal region or the suprasellar region, presenting variable incidence of 0.5% up to 6% among patients with RB. The article reports a case of unilateral RBT in a patient treated at Hospital A.C.Camargo.

Trilateral retinoblastoma with unilateral eye involvement / Retinoblastoma trilateral com acometimento ocular universal

SummaryRetinoblastomas (RB) are the main forms of intraocular tumor in childhood, with a worldwide incidence of 1 case per 15,000 to 20,000 live births. Trilateral RB (RBT) is a rare combination of unilateral or bilateral RB with a midline intracranial neoplasm of neuroblastic origin, usually found in the pineal region or the suprasellar region, presenting variable incidence of 0.5% up to 6% among patients with RB. The article reports a case of unilateral RBT in a patient treated at Hospital A.C.Camargo.

ResumoO retinoblastoma (RB) é a principal forma de tumor intraocular na infância, apresentando uma incidência mundial de 1 caso em cada 15 mil a 20 mil nascidos vivos. O RB trilateral (RBT) é uma rara combinação de RB unilateral ou bilateral com uma neoplasia da linha média intracraniana de origem neuroblástica, geralmente na região da glândula pineal ou na região suprasselar, apresentando incidência variável de 0,5 a 6% entre pacientes com RB. O artigo relata o caso de uma paciente com RBT com acometimento unilateral atendida no Hospital A.C.Camargo.

Amelanotic corneally displaced malignant conjunctival melanoma: a case report evaluated with impression cytology.

Here we describe the case of a 65-year-old Caucasian female who presented with an amelanotic malignant conjunctival melanoma and highlight the clinical and pathological features of this rare entity that displayed exclusive corneal invasive growth without evidence of conjunctival tumors other than primary acquired melanosis. Impression cytology aided in the initial diagnosis. The patient underwent surgical treatment. Histopathology and immunohistochemistry revealed an invasive amelanotic melanoma limited to the cornea and exhibiting S-100, Melan A, and HMB-45 positivity. The absence of pigmentation delayed early clinical detection and treatment. Awareness of this nonpigmented melanoma is important for early recognition and appropriate management.

Amelanotic corneally displaced malignant conjunctival melanoma: a case report evaluated with impression cytology / Melanoma amelanótico conjuntival maligno deslocado sobre a córnea com citologia de impressão: relato de caso

Here we describe the case of a 65-year-old Caucasian female who presented with an amelanotic malignant conjunctival melanoma and highlight the clinical and pathological features of this rare entity that displayed exclusive corneal invasive growth without evidence of conjunctival tumors other than primary acquired melanosis. Impression cytology aided in the initial diagnosis. The patient underwent surgical treatment. Histopathology and immunohistochemistry revealed an invasive amelanotic melanoma limited to the cornea and exhibiting S-100, Melan A, and HMB-45 positivity. The absence of pigmentation delayed early clinical detection and treatment. Awareness of this nonpigmented melanoma is important for early recognition and appropriate management.

Os autores descrevem o caso de uma mulher branca de 65 anos que apresentava um melanoma amelanótico maligno conjuntival e destacam as características clínicas e patológicas desta entidade rara com crescimento invasivo exclusivo na córnea sem evidência de tumores na conjuntiva além de melanose adquirida primária sem pigmento. A citologia de impressão auxiliou no diagnóstico inicial. A paciente foi submetida a tratamento cirúrgico. A histopatologia e a imuno-histoquímica revelaram um melanoma amelanótico invasivo limitado sobre a córnea exibindo positividade para proteína S-100, Melan A e HMB-45. A ausência de pigmentação retardou sua identificação clínica e seu tratamento precoce. O conhecimento deste melanoma não pigmentado é importante para o reconhecimento precoce e a conduta apropriada.

Conjunctival follicular lymphoma after treatment for invasive squamous cell carcinoma.

BACKGROUNDS/AIMS: The authors describe the case of a 79-year-old Caucasian woman who presented an ocular adnexal lesion as the first clinical manifestation of a systemic follicular lymphoma, highlighting the clinicopathological features of this rare entity and its potential to be misdiagnosed as marginal zone lymphoma of the mucosa-associated lymphoid tissue. METHODS: Conjunctival impression cytology was performed for a rapid initial diagnosis of lymphoma, and subsequent histopathological and immunohistochemical studies were carried out for its confirmation and to identify the best therapeutic regimen. RESULTS: After the initial presentation and diagnosis, she was submitted to complete clinical evaluation; confluent retroperitoneal lymphadenopathy was detected through abdominal computed tomography, characterizing clinical stage III. CONCLUSION: Awareness of this lymphoma is important when making a diagnosis of ocular adnexal lymphoid neoplasms for its appropriate evaluation and management.

Phacoemulsification and foldable acrylic IOL implantation in children with treated retinoblastoma / Facoemulsificação e implante de lente intraocular acrílica dobrável em crianças com retinoblastoma

PURPOSE: To study the results of cataract surgery in children with radiation-induced cataract after treatment for retinoblastoma. METHODS: Retrospective interventional case series. Six consecutive patients diagnosed with secondary cataracts due to radiation therapy for retinoblastoma. Intervention: Phacoemulsification and foldable acrylic intraocular lens implantation. Outcomes measu- red: Visual acuity, binocular indirect ophthalmoscopy and slit-lamp biomicroscopy. Aspirated lens material and aqueous humor samples were collected during surgery. RESULTS: Six uniocular children between 3 to 5 years of age at time of surgery were studied. The mean time interval between radiotherapy and cataract diagnosis was 22.3 months. The mean follow-up after surgery was 17.2 months (range: 12 to 23 months). All eyes achieved a clear visual axis after surgery allowing monitoring of the tumor status. None developed recurrence or retinoblastoma dissemination. Histopathological analysis of the aspired material showed no tumoral cells in all samples. All patients improved vision after cataract surgery. CONCLUSIONS: Phacoemulsification with acrylic intraocular lens implantation seems to be a safe, feasible, and effective method for the removal of radiation-induced cataracts in patients with treated retinoblastoma.

OBJETIVOS: Estudar os resultados da cirurgia da catarata induzida pela radioterapia para o tratamento do retinoblastoma em crianças. MÉTODOS: Estudo retrospectivo intervencional em série de casos onde seis pacientes consecutivos apresentaram catarata secundária à terapia por radiação para o retinoblastoma. Intervenção: Facoemulsificação e implante de lente intraocular acrílica dobrável. Foram avaliadas: acuidade visual, oftalmoscopia binocular indireta e biomicroscopia. Material para análise histológica do cristalino e do humor aquoso foi coletado durante as cirurgias. RESULTADOS: Seis crianças, entre 3 e 5 anos de idade, com catarata secundária à radiação para tratamento de retinoblastoma foram submetidas à cirurgia de facoemulsificação com implante de lente intraocular. A média do intervalo de tempo decorrido entre a radioterapia e o diagnóstico da catarata foi 22,3 meses. O período médio de seguimento após a cirurgia foi de 17,2 meses (intervalo: 12 a 23 meses). Todos os olhos melhoraram a visão e mantiveram eixo visual livre permitindo a fundoscopia para monitorar o tumor. Nenhum paciente evoluiu com recorrência ou disseminação do retinoblastoma. A análise histopatológica do material colhido resultou em ausência de células tumorais nas amostras. CONCLUSÕES: A cirurgia de facoemulsificação com implante de lente intraocular acrílica dobrável mostrou ser um procedimento seguro e efetivo para o tratamento da catarata induzida pela radioterapia em pacientes portadores de retinoblastoma.

Abnormal orbital growth in children submitted to enucleation for retinoblastoma treatment.

Enucleation is typically performed for the treatment of advanced retinoblastoma in children. After enucleation, the orbit undergoes abnormal development. In this study, orbital asymmetry was calculated using computed tomography measurements obtained from patients who experienced enucleation for unilateral retinoblastoma. Influence factors analyzed included: type of treatment, use of orbital implants, and patient's age at diagnosis. A total of 42 children underwent enucleation with a mean follow-up period of 4.8 years. For 28 patients, treatment included enucleation alone, 14 patients received enucleation plus radiation therapy. Thirty patients kept orbital implants long term. The mean orbital volume asymmetry for treated versus contralateral orbits was 16.8%. Mean asymmetry in orbital volume was greater for patients who underwent enucleation combined to radiation therapy (23.7% vs. 13.3%, P=0.05) and for patients without long-term maintenance of the prosthetic implants (29.3% vs. 11.8%, P<0.01). In conclusion, orbital volume is abnormally affected in children after enucleation of 1 eye for the treatment of retinoblastoma, and computed tomography can precisely quantify the asymmetry that develops. Orbital implants improve volumetric growth after enucleation, with 2-fold greater orbital asymmetry achieved without an implant.

Phacoemulsification and foldable acrylic IOL implantation in children with treated retinoblastoma.

PURPOSE: To study the results of cataract surgery in children with radiation-induced cataract after treatment for retinoblastoma. METHODS: Retrospective interventional case series. Six consecutive patients diagnosed with secondary cataracts due to radiation therapy for retinoblastoma. INTERVENTION: Phacoemulsification and foldable acrylic intraocular lens implantation. OUTCOMES MEASURED: Visual acuity, binocular indirect ophthalmoscopy and slit-lamp biomicroscopy. Aspirated lens material and aqueous humor samples were collected during surgery. RESULTS: Six uniocular children between 3 to 5 years of age at time of surgery were studied. The mean time interval between radiotherapy and cataract diagnosis was 22.3 months. The mean follow-up after surgery was 17.2 months (range: 12 to 23 months). All eyes achieved a clear visual axis after surgery allowing monitoring of the tumor status. None developed recurrence or retinoblastoma dissemination. Histopathological analysis of the aspired material showed no tumoral cells in all samples. All patients improved vision after cataract surgery. CONCLUSIONS: Phacoemulsification with acrylic intraocular lens implantation seems to be a safe, feasible, and effective method for the removal of radiation-induced cataracts in patients with treated retinoblastoma.

Primary transpupillary thermotherapy for small choroidal melanoma.

BACKGROUND: The treatment of small choroidal melanoma is controversial. Thermal laser-induced treatment is utilized by some centers but there is still sparse literature about the subject, mainly with short-term follow-up time. The efficacy of transpupillary thermotherapy (TTT) for the treatment of small choroidal melanomas was evaluated. METHODS: A prospective nonrandomized study of transpupillary thermotherapy for small (thickness ≤ 4.0 mm and basal diameter ≤ 12 mm) pigmented choroidal melanomas presenting either growth or risk factors for growth and metastasis. Ophthalmoscopic aspect, tumor control, visual acuity and complications were evaluated. RESULTS: Twenty-seven patients were treated; mean age 61 years; mean tumor thickness before treatment was 2.7 mm and base was 8.52 mm. After a mean of three treatment sessions and 45-month follow-up, mean tumor thickness decreased significantly to 1.34 mm (p < 0.001) and mean tumor base to 5.48 mm (p < 0.001). Complications were observed in 12 patients (44%) and included retinal vascular occlusion, optic disc atrophy, retinal traction, vitreous hemorrhage, rhegmatogenous retinal detachment, and maculopathy. Lesions touching the optic disc were associated with a significantly higher rate of disc atrophy after treatment (60% vs. 40%, p=0.030). Visual acuity remained the same in nine eyes (33%), improved in five (19%) and decreased during the first 6 months after treatment in 13 eyes (48%). Complete tumor control without recurrence was observed in 25 patients (93%). Recurrence at tumor margin was detected in two (7%). All eyes were preserved. One patient had tumor-related death. CONCLUSIONS: TTT is an effective treatment in the management of selected small choroidal melanoma. Decrease in visual acuity occurred early after treatment mainly associated with subfoveal and perifoveal tumors treatment and complications. Long-term randomized studies are still needed in order to better situate this treatment.

Evaluation of ototoxicity in children treated for retinoblastoma: preliminary results of a systematic audiological evaluation.

BACKGROUND: The objective of this study was to identify the ocurrence of hearing loss in children treated for retinoblastoma using a multidisciplinary approach. PATIENTS AND METHODS: Thirty-two children were evaluated pre- and post-treatment. Eleven children were treated exclusively with enucleation, fifteen with carboplatin and six with cisplatin. Otoacoustic emissions were performed with the ILO 88, before and after the treatment. RESULTS: In our study we found 5 children (24%) with hearing loss among the 21 evaluated. However in the group of children treated with carboplatin (N=15), 1 case (6.6%) presented hearing loss, while among those treated with cisplatin (N=6) we found 4 cases (66.6%) with hearing loss (p=0.0114). CONCLUSION: We concluded that patients who are treated with cisplatin are at risk for developing hearing loss.

Unusual primary ocular neoplasm in a child: leiomyosarcoma of the ciliary body.

Primary uveal-tract neoplasms are extremely rare in childhood; the most common lesions found are melanocytic. We report here the case of a 7-year-old girl who underwent enucleation of the right eye with clinical suspicion of choroid melanoma as a result of a ciliary body mass that extended to the posterior chamber. Histologically, the neoplasm featured spindle cell morphology, atypia, and mitoses. The tumor expressed smooth muscle alpha actin, pan-actin HHF-35, and desmin, whereas immunohistochemistry for melanocytic markers, such as S-100, Melan-A, and HMB-45, was negative. Based on these features, the diagnosis of leiomyosarcoma of the ciliary body was firmly established. Although several leiomyomas have been reported in the literature, there are only 2 previously reported cases of primary leiomyosarcoma of the uveal tract. Immunohistochemical expression of muscle proteins allowed distinction from the most common melanocytic tumors arising in this location.

The addition of ifosfamide/etoposide to cisplatin/teniposide improves the survival of children with retinoblastoma and orbital involvement.

This study aimed to determine the impact of the addition of ifosfamide/etoposide to a regimen containing cisplatin/teniposide on the survival of patients with retinoblastoma with orbital involvement. Thirty patients were treated at the A. C. Camargo Hospital, Brazil, from 1986 to 2002. From 1986 to April 1992 (period I, n=12), treatment consisted of 3 cycles of induction chemotherapy with cisplatin and teniposide, followed by maintenance with same drugs alternating with cyclophosphamide, vincristine, and doxorubicin every 21 days for 60 weeks. Since April 1992 (period II, n=18), the treatment consisted of 3 cycles of ifosfamide and etoposide followed by maintenance with same drugs, alternating with cisplatin and teniposide every 21 days for 36 weeks. In both periods, children were submitted to exenteration with eyelid preservation and orbital radiation therapy with 45 cGy, and also received intrathecal therapy with methotrexate plus dexamethasone and cytarabine. Kaplan-Meier method was used for survival analysis. The median age was 31 months. Most patients (86.7%) presented unilateral tumors. The 3-year overall survival was 34.4% and 72.2%, respectively, for patients treated during periods I and II (P=0.061). The addition of ifosfamide/etoposide to chemotherapy with cisplatin/teniposide improves survival in these patients, but further studies are still necessary.

Retinoblastoma in children older than 5 years of age.

BACKGROUND: Retinoblastoma is a malignant tumor of the embryonic neural retina. About 80% of cases are diagnosed before age 4, with a median age at diagnosis of 2 years. OBJECTIVE: To determine characteristics and prognosis of retinoblastoma in children older than 5 years. PROCEDURES: From 1986 to 2002, medical records of 16 patients out of 453 cases referred to Hospital do Câncer AC Camargo, São Paulo, Brazil. RESULTS: Median age at diagnosis was 73.7 months (range 65-144) and there was an equal gender distribution. Fifteen patients presented with unilateral disease. The mean time between first symptoms and diagnosis was 9.6 months (range 0-48). Most cases were diagnosed in advanced stages and 15 eyes were enucleated. Eleven patients presented with intraocular tumor (1 Reese II and 10 Reese V) and five presented with extraocular disease (one CCG II and four CCG III). Twelve patients are still alive with a median follow-up of 92 months (range 65-199). CONCLUSIONS: Because of its low incidence at this age, diagnosis of retinoblastoma is usually delayed due to low level of suspicion. Therefore, it is important that physicians are aware of this disease in order to perform an earlier diagnosis, and decrease treatment-related morbidity.

Trilateral retinoblastoma.

BACKGROUND: Trilateral retinoblastoma (TRB) is a syndrome consisting of unilateral or bilateral hereditary retinoblastoma (Rb) associated with an intracranial neuroblastic tumor. Although its incidence is low, the prognosis is very poor. This article reports four cases of TRB and discusses the role of neuroimaging screening for early detection. PROCEDURE: From January 1986 to December 2003, 470 children with Rb were admitted to the Pediatrics and Ophthalmology Departments, A C Camargo Hospital, São Paulo, Brazil. RESULTS: There were four patients with pineoblastoma, two of whom had a positive familial history. The age at diagnosis of Rb was 4, 6, 10, and 24 months while the age of diagnosis of TRB was 10, 25, 57, and 72 months. One patient presented TRB at initial diagnosis of Rb. Three patients had bilateral disease and all of them had one eye enucleated, followed by chemotherapy and/or external beam radiation therapy (EBRT). One child with unilateral disease was only submitted to enucleation. In spite of intensive treatment, all patients died with progressive disease within 7, 8, 12, and 12 months after diagnosis of TRB. CONCLUSIONS: Early diagnosis as well as new therapeutic approaches are needed to achieve better results.

Risk factors for extraocular relapse following enucleation after failure of chemoreduction in retinoblastoma.

OBJECTIVE: To assess the outcome and determine risk factors for extraocular relapse in patients with retinoblastoma who had been enucleated after failure of chemoreduction. METHODS: Retrospective study (1995-2002) at three institutions. Pathological risk factors (PRF) were defined as invasion of the anterior segment, choroid, post-laminar optic nerve, subarachnoid space, or sclera according to the local pathology report. Extraocular relapse was defined as an event. RESULTS: One hundred twenty-two patients were included (17 had bilateral enucleation). Chemoreduction included vincristine, carboplatin, and etoposide (n=80, 65.6%), vincristine, and carboplatin (n=17, 13.9%), or carboplatin (n=25, 20.5%). Thirty-five also received external beam radiotherapy (28.7%). PRF included: 39 with choroidal involvement, 9 with anterior segment, 9 with scleral, and 2 with post-laminar optic nerve with subarachnoid invasion. Adjuvant chemotherapy was given to eight patients (6.5%) because of scleral invasion. Four patients had an extraocular relapse after enucleation, two of whom survive after intensive treatment including stem cell rescue. Five-year probability of event-free survival is 0.96. Only scleral invasion and bilateral enucleation were significantly associated with extraocular relapse. CONCLUSIONS: The risk of extraocular relapse is low after enucleation following failure of chemoreduction. Patients who underwent bilateral enucleation and those with scleral invasion are at higher risk of extraocular relapse.

Treatment of retinoblastoma patients with chemoreduction plus local therapy: experience of the AC Camargo Hospital, Brazil.

To evaluate the efficacy of conservative management of intraocular retinoblastoma with chemoreduction combined with local therapy with or without plaque radiation in the preservation of the eye, and avoidance of external beam radiation therapy (EBRT) (success rate). From 1995 to 2000, 84 newly diagnosed patients with intraocular retinoblastoma were admitted to the Pediatric Department of the Hospital do Cancer A.C. Camargo, São Paulo, Brazil. All children were treated with 2 to 6 cycles of chemotherapy (carboplatin, vincristine, and etoposide) plus local therapy (cryotherapy, laser photocoagulation, and thermotherapy), or plaque radiation therapy during and/or after the chemotherapy. The Mann-Whitney test was used to compare means of quantitative variables. The chi test or the Fisher exact test were employed to verify the association between the outcome and the independent variables. For all tests alpha=5% was adopted. Success rate was higher for patients with bilateral tumors (54%) than for children with unilateral tumors (19%) (P=0.003). For patients with Reese-Ellsworth stages I, II, and III, no statistically significant differences in the success rates were noted in the group of unilateral (50%) and bilateral tumors (79.1%) (P=0.179). Among children with Reese-Ellsworth stages IV and V, the success rate was significantly higher for patients with bilateral tumors (40.7%) than for those with unilateral (0%) (P=0.012). Chemoreduction combined with local therapy, with or without plaque radiotherapy, is efficacious in avoiding enucleation and the use of external beam radiation therapy for children with intraocular retinoblastoma.

O papel do pediatra no diagnóstico precoce do retinoblastoma / The Pediatrician's ability to recognize the presenting signs and symptoms of retinoblastoma

OBJETIVO: O retinoblastoma é o tumor intra-ocular mais freqüente na infância. A forma de apresentação mais comum é leucocoria, seguida pelo estrabismo. Nos países em desenvolvimento, pela demora diagnóstica e maior tempo de encaminhamento, encontramos um grande número de pacientes portadores de tumores extra-oculares. MÉTODOS: Duzentos e trinta e nove pacientes com retinoblastoma admitidos nos departamentos de Pediatria e Oftalmologia do Hospital do Câncer AC Camargo, no período de 1986 a 1995, foram avaliados quanto ao tempo de encaminhamento e extensão do tumor. A análise estatística incluiu o cálculo de freqüências absolutas e relativas, bem como o teste exato de Fisher, para a verificação da associação entre variáveis categorias. RESULTADOS: Pacientes que foram encaminhados em um período menor que 6 meses apresentaram maior freqüência de doença intra-ocular quando comparados com pacientes com tempo de encaminhamento maior que seis meses (75 por cento vs. 25 por cento p<0,001). Não houve diferença estatisticamente significativa para tumores extra-oculares. CONCLUSÕES: O diagnóstico precoce é considerado o ponto mais importante no tratamento de pacientes com retinoblastoma. Os pediatras são capazes de detectar, em uma consulta simples de ambulatório, os sinais e sintomas desta doença e devem ter sempre em mente o diagnóstico de retinoblastoma, possibilitando o encaminhamento precoce a centros especializados.

[The Pediatrician's ability to recognize the presenting signs and symptoms of retinoblastoma]. / O papel do pediatra no diagnóstico precoce do retinoblastoma.

BACKGROUND: Retinoblastoma is the most frequent primary intraocular tumor in children. The most common presenting sign is leukocoria and the second one is strabism. In the developing countries extra ocular disease is seen more frequently because of delayed referral. METHODS: Two hundred and thirty-nine patients with retinoblastoma admitted at the Pediatrics and Ophthalmology Departments of the Hospital do Cancer AC Camargo from 1986 to 1995 were evaluated regarding lag-time and tumor extension. RESULTS: Patients referred within less than 6 months presented a higher rate of intraocular disease compared with patients having a lag-time greater than 6 months (75% vs. 25%, p<0.001). No statistically significant difference was noted for patients with extra-ocular tumors. CONCLUSION: Early diagnosis is the gold standard for patients with Retinoblastoma and the pediatrician's ability to recognize the presenting signs and symptoms can lead to early diagnosis and efficient treatment.