Characterization of NCC-RbC-51, an RB cell line isolated from a metastatic site.

Retinoblastoma (RB) is a childhood eye tumor, caused by the RB1 gene mutation. Since RB is a rapidly proliferating tumor, the patient presents with a Group-D/E tumor at the time of diagnosis. Enucleation is preferred in most unilateral cases to prevent metastasis. Various cell lines have been established to study the tumor's growth pattern and target the cancer cells. The commonly used cell lines are WERI-Rb-1 and Y79, both isolated from the primary tumor of RB. Cell lines established from the metastatic site of RB have not been characterized before. In this study, we have characterized NCC-RbC-51, derived from RB tumor to cervical lymph node site and investigated its potential to represent a highly aggressive and metastatic tumor. We compared the proliferative and invasive properties of NCC-RbC-51 with a cell line isolated from the primary site, WERI-Rb-1. NCC-RbC-51 had higher rates of proliferation and apoptosis and had better invasive ability. Copy number variation analysis and the pathways predicted from these show that the pathways altered in NCC-RbC-51 could contribute to its metastatic nature. In all, the results suggest that NCC-RbC-51, a cell line isolated from metastatic site, could be a potential model to study aggressive/invasive RB.

Retinal and vitreous metastases from hepatocholangiocarcinoma.

BACKGROUND: To report a case of metastatic hepatocholangiocarcinoma to the vitreous and retina. CASE PRESENTATION: A 70-year-old male, who was recently diagnosed with hepatocholangiocarcinoma, was complaining of floaters in his right eye over the past 5 months and was referred to the Liverpool Ocular Oncology Centre. On presentation, his visual acuity in the right eye was 6/24. Fundus exam revealed a whitish, unilateral, full-thickness retinal lesion at the inferotemporal arcade of his right eye, with vitreous infiltration and subretinal fluid. The patient underwent 25G pars plana vitrectomy with biopsy, resection of the lesion and intravitreal bevacizumab injection. Histopathology testing of the surgical specimens confirmed the diagnosis of metastatic carcinoma to the eye. Two months postoperatively his visual acuity had improved to 6/7.5 and there was no sign of active disease in his right eye, while 9 months postoperatively his visual acuity decreased to 6/9.5 due to developing nuclear sclerotic cataract in his right eye. CONCLUSION: The current report presents the first case of a hepatocholangiocarcinoma metastasis to the vitreous and retina.

Retinal metastasis regression with eribulin in a heavily pretreated breast cancer patient.

The authors present the case of a heavily pretreated young woman with retinal and brain metastases from breast cancer who was successfully treated with eribulin. Eribulin was given at 1.1 mg/m(2) on day 1 and 8, every 3 weeks for a total of 12 courses. A significant reduction in the size of brain and retinal lesions was achieved after three cycles. The treatment was continued for 12 cycles, with a good profile of tolerability. In this clinical case, eribulin demonstrated to be active on brain and retinal metastases from breast cancer, although preclinical data showed limited ability to cross the blood-brain barrier.

Lesson of the month 1: Seeing snowflakes.

Melanoma-associated retinopathy is a rare paraneoplastic complication of metastatic cutaneous malignant melanoma. It may present years after the original diagnosis of melanoma. We describe a patient with this condition who presented with persistent visual symptoms.

Pathological findings in enucleated eyes after intravitreal melphalan injection.

The aim of this study is to evaluate the pathological findings of the eye after intravitreal melphalan for viable vitreous seeding from retinoblastoma. All enucleated eyes receiving an intravitreal injection of melphalan (10-50 µg in 0.05 cc) were evaluated for histological changes. Of 25 treated cases, 8 eyes needed enucleation because of phthisis, parent request, or new tumor development. One of the cases was excluded from the study because of a history of intra-arterial chemotherapy with melphalan. There was no case of needle-site scleral involvement by retinoblastoma cells. In two eyes receiving 50 µg melphalan, no viable retinoblastoma cell was detectable in the eye. Severe gliosis, vascular occlusion, retinal necrosis, hemorrhage and neovascularization were seen. Histologically, intravitreal melphalan for recalcitrant or recurrent vitreous seeds from retinoblastoma appears to provide acceptable vitreous seed control. It seems that higher doses could be destructive causing ischemic necrosis in the retina, severe gliosis and secondary neovascular changes as well as having a destructive effect on retinoblastoma cells.

Vitreoretinal lymphoma occurring after systemic chemotherapy for primary conjunctival diffuse large B cell lymphoma: A case report.

INTRODUCTION: Ocular adnexal lymphoma and vitreoretinal lymphoma are rare forms of non-Hodgkin lymphoma. They are regarded as distinct disease entities due to the differences in molecular mechanism, management, and outcome. We present a rare case of conjunctival diffuse large B cell lymphoma (DLBCL) that developed to vitreoretinal lymphoma after systemic chemotherapy. PATIENT CONCERNS: A 60-year-old man presented with a left salmon-colored conjunctival mass. DIAGNOSIS: A biopsy was performed, and histopathologic examination showed DLBCL. Immunohistochemical staining was positive for CD20 with increased κ to λ light chain ratio. INTERVENTIONS: Bone marrow biopsy also revealed DLBCL. Gallium-67 scintigraphy showed abnormal uptake only in the left orbital lesion. Ann Arbor stage was estimated as IV. The patient underwent systemic combination chemotherapy and immunotherapy. OUTCOMES: Four months after the last course of chemotherapy, primary conjunctival DLBCL relapsed, manifesting vitreous opacity. Diagnostic vitrectomy confirmed a diagnosis of vitreoretinal lymphoma. LESSONS: Conjunctival DLBCL and vitreoretinal lymphoma are both DLBCL. After systemic chemotherapy for conjunctival DLBCL, the lymphoma may relapse in intraocular sites as secondary vitreoretinal lymphoma.

INTRAVITREAL MELPHALAN FOR TREATMENT OF VITREOUS SEEDING FROM CHOROIDAL MELANOMA.

PURPOSE: To report treatment of vitreous seeding of choroidal melanoma with monthly injections of intravitreal melphalan. METHODS: Case report. RESULTS: A 70-year-old white woman noted floaters in her left eye, and further examination revealed visual acuity of 20/30 in both eyes. Funduscopically, there was a mushroom-shaped choroidal melanoma in her left eye, measuring 9 mm in basal dimension and 4.8 mm in thickness. Notably, there was apical retinal invasion of melanoma with mild vitreous hemorrhage, without vitreous seeding. The tumor was treated with iodine-125 plaque radiotherapy using an apex dose of 70 Gy over 99 hours, designed to include the retinal invasion. The melanoma demonstrated complete regression into a nearly flat scar of 1 mm and remained stable over 4 years. Five years after radiotherapy, there were diffuse vitreous pigmented seeds of presumed melanoma origin, emanating from the site of retinal necrosis. This progressively worsened over the following 18 months, suspicious for viable melanoma cells, as visual acuity concurrently declined to 20/100. Treatment with intravitreal melphalan (10 µg/0.05 mL) was delivered on a monthly basis for 12 cycles, resulting in vitreous seeds regression, and preservation of the eye. Final visual acuity was 20/200. There were no treatment-related complications. CONCLUSION: Intravitreal melphalan can be considered in cases of vitreous seeding from uveal melanoma.

Intensive multimodality therapy for patients with stage 4a metastatic retinoblastoma.

BACKGROUND: We previously reported promising pilot results treating patients with stage 4a metastatic retinoblastoma with combined intensive conventional chemotherapy, high-dose chemotherapy with autologous hematopoietic stem cell rescue, and radiation therapy and now present an expanded and updated series. PROCEDURE: Fifteen patients with bone marrow (n = 14), bone (n = 10), orbit (n = 9), and/or liver (n = 4) disease were treated. Induction chemotherapy usually consisted of vincristine, cyclophosphamide, cisplatin, and etoposide. The high-dose chemotherapy regimen included carboplatin and thiotepa alone (n = 1) or with etoposide (n = 5) or topotecan (n = 7). RESULTS: Bone marrow cleared at first post-initiation of chemotherapy examination in all patients and stem cells were harvested after a median of 3.5 cycles of chemotherapy (range 3-6 cycles). Two patients progressed prior to high-dose chemotherapy and died. Thirteen received high-dose chemotherapy at a median of 6 months post-diagnosis of metastases (range 4-8 months). Ten are retinoblastoma-free in first remission at a median follow-up of 103 months (range 34-202 months) while three recurred (two in the CNS, one in the mandible) 14-20 months post-diagnosis of metastases. Retinoblastoma-free and event-free survival at 5 years are 67% (95% confidence interval 38-85%) and 59% (95% confidence interval 31-79%). Six of the 10 survivors received radiation therapy. Three patients developed secondary osteosarcoma 14, 4, and 9 years after diagnosis of metastatic disease. CONCLUSIONS: Intensive multimodality therapy including high-dose chemotherapy with autologous hematopoietic stem cell rescue was curative for the majority of patients with stage 4a metastatic retinoblastoma treated. The contribution of external beam radiation therapy is unclear.

Results of a prospective study for the treatment of unilateral retinoblastoma.

BACKGROUND: Few prospective studies about the management of unilateral retinoblastoma with pathology risk factors (PRFs) have been published. METHODS: Patients (n = 114) were divided into four groups: Group 1 (initial chemoreduction) (n = 17). Groups 2 and 3, included patients initially enucleated with no, or lower risk PRFs: (n = 65) and with higher risk PRFs (n = 30), respectively. The later included postlaminar optic nerve involvement (PLONI) (n = 23), tumor at resection margin of optic nerve (n = 5) or isolated scleral invasion (n = 2). Group 3 received adjuvant chemotherapy including a total eight cycles of carboplatin and etoposide, alternating with cyclophosphamide, idarubicin, and vincristine. Orbital radiotherapy (45 Gy) was given to patients with invasion to the resection margin. Group 4 included patients with metastatic disease (n = 2). They were given neoadjuvant therapy followed by surgery and high-dose chemotherapy and autologous stem cell rescue. RESULTS: Five-year event-free survival is 0.94 (1 for Group 1, 0.94 for Group 2, 0.96 for Group 3, and 0 for Group 4). Events included. Group 2: Systemic relapse (n = 2) and combined orbital and CNS relapse (n = 1). Relapsing patients had PLONI (n = 2) and isolated focal choroidal invasion (n = 1). Group 3: CNS relapse (n = 1) in a patient with tumor at the resection margin of optic nerve. Group 4: CNS relapse (n = 2). Only one relapsed patient survived. Eight of 17 eyes treated conservatively were preserved. CONCLUSIONS: The survival of patients with unilateral retinoblastoma was excellent and 60% were spared from adjuvant treatment. Our intensive regimen was likely to be effective for prevention of metastasis in patients with higher risk PRFs.

Vitreous and retinal metastasis from gastric cancer.

PURPOSE: Intraocular metastasis from gastric cancer is not common and metastatic carcinoma to the vitreous or retina is exceedingly rare. We describe a case of gastric cancer metastatic to the vitreous and retina. METHODS: Retrospective, single-center case report. RESULTS: A 64-year-old woman with advanced gastric cancer with multiorgan metastatic disease presented with decreased visual acuity. Ophthalmoscopy revealed extensive overlying vitreous seeds and macular infiltrations in both eyes. Fine-needle aspiration cytology from the vitreous confirmed the diagnosis of metastatic carcinoma. CONCLUSIONS: We report an extremely rare case of vitreous and retinal metastasis from gastric cancer. Ophthalmologists and oncologists should be aware that gastrointestinal cancer can cause intraocular metastasis in the form of vitreous seeds and retinal infiltration.

A CASE OF RETINAL METASTASIS OF LARYNGEAL SQUAMOUS CELL CARCINOMA WITH HISTOPATHOLOGIC CONFIRMATION BY VITRECTOMY-ASSISTED EN BLOCK EXTRACTION.

BACKGROUND/PURPOSE: To present a case report of retinal metastasis of laryngeal squamous cell carcinoma that was diagnosed by a histopathologic finding from the surgically extracted tumor tissue. METHODS: A 66-year-old man, who was suffered from the treatment-resistant laryngeal carcinoma, was referred to our department because of visual field defect in his right eye. A fundus examination revealed a parafoveal white retinal lesion, which rapidly expanded to the central fovea and decreased the visual acuity. A tissue extraction by 27G pars plana vitrectomy was performed to confirm the diagnosis. RESULTS: The abnormal retinal tissue was extracted en block through 10-mm sclerocorneal tunnel during pars plana vitrectomy. The histopathologic findings revealed that the retinal lesion was retinal metastasis of laryngeal carcinoma. CONCLUSION: We must keep in mind that retinal metastasis can be one of the differential diagnoses for white retinal lesions of unknown cause.

SIMULTANEOUS CHOROIDAL AND RETINAL METASTASES FROM LUNG CARCINOMA.

BACKGROUND: Intraocular metastasis is most commonly found within the choroid because of its luxurious blood supply, whereas metastasis to the retina, from a separate blood supply, is very rare. We report a rare case of synchronous metastases from lung carcinoma to the choroid of the right eye and the retina of the left eye and a complaint of low vision in the right eye. METHODS: We report a 63-year-old woman with progressive reduction of vision in her right eye for 1 year without previous history of cancer. The patient underwent comprehensive ophthalmic examination that included a multimodal evaluation: near-infrared reflectance scanning laser ophthalmoscopy, blue autofluorescence, and enhanced-depth imaging spectral domain optical coherence tomography (EDI SD-OCT; Heidelberg Engineering, Heidelberg, Germany). RESULTS: Ophthalmoscopic examination revealed a yellow choroidal mass measuring 6 × 6 mm with overlying subretinal fluid and involving the macular area in the right eye. In the left eye, there was a superior juxtapapillary yellow-colored mass involving the retina and measuring 1 × 1 mm. Optical coherence tomography revealed the subretinal fluid contouring a dome-shaped choroidal mass in the right eye and intraretinal nodular tumor superior to the optic disk of the left eye. Chest computed tomography revealed a pulmonary nodule measuring 2.5 mm × 1.4 mm, and biopsy of the liver metastasis confirmed the diagnosis of mucinous lung carcinoma. CONCLUSION: The final diagnosis was presumed choroidal metastasis in the right eye and retinal metastasis in the left eye from underlying mucinous carcinoma of the lung.

[Pseudotumoral ARMD (Age Related Macular Degeneration)--case report]. / DMLV forma pseudotumorala.

The authors present the case of a 76-year-old man with excised colon carcinoma, who has remained with zones of high grade metaplasia even after the surgery and who came in our Clinic for declined vision in both eyes, progressive and more obvious in the left eye and the presence of an absolute scotoma in the upper hemi-field of the left eye. On fundoscopic exam, one can see a zone with pseudotumoral aspect and the diagnostic problem the team was confronted with was to choose between a choroidal metastasis and a pseudotumoral ARMD. After multiple investigations the patient is diagnosed with pseudotumoral ARMD.

RETINAL METASTASIS FROM SQUAMOUS CELL CARCINOMA OF THE LUNG: A CASE PRESENTATION.

BACKGROUND/PURPOSE: To present a case with retinal metastasis from squamous cell carcinoma of the lung. METHODS: Case report. RESULTS: A 54-year-old man presented with blurry vision in his left eye. His medical history was significant for Stage IV squamous lung carcinoma. He was undergoing chemotherapy and had a known metastasis. He had a slightly elevated whitish lesion associated with retinal hemorrhages in the left posterior pole. Optical coherence tomography showed a full-thickness retinal mass. No involvement of the choroid could be detected. Further investigation demonstrated a de novo metastasis in the right frontal lobe of the brain. CONCLUSION: The lesion showed remarkable regression with subsequent systemic chemotherapy.

Retinochoroidal findings and lung cancer: first report in mexican population. / Alteraciones retinocoroideas y cáncer pulmonar: primer reporte en población mexicana.

INTRODUCTION: Lung cancer (LC) is the most common tumour, and the leading cause of cancer-related death worldwide. Although cases of choroidal metastasis and cancer-associated retinopathy have been reported in LC, no studies have been conducted on the Mexican population to describe retinochoroidal findings during the course of LC, and the relationship with its stage. OBJECTIVE: To evaluate patients with a diagnosis of LC, and to describe the posterior segment findings in relationship to the stage of LC. MATERIALS AND METHODS: A cross-sectional and descriptive study was conducted on 50 patients with LC (100 eyes). The demographic data included age, gender, histological type, evolution time, stage, treatment, and comorbidities. The measurement variables included visual acuity (LogMAR), anterior segment biomicroscopy, retinal photography, fluorescein retinal angiography, optical coherence tomography, and electroretinogram. All patients were evaluated by two ophthalmologists. RESULTS: The study included a total of 26 men and 24 women, with a mean age of 65 years, and a mean time from LC diagnosis of 6 months. The principal histological type was adenocarcinoma (70%), and most (50%) were in stage II at the time of evaluation, with 15 (30%) patients having a metastasis (stage IV). The changes in the posterior segment included choroidal metastasis (16%), retinal metastasis (10%), cancer-associated retinopathy (6%), and vascular occlusions (4%). The majority of patients who presented with posterior segment alterations were in stage IV. CONCLUSIONS: Vascular occlusions, cancer-associated retinopathy, choroidal and retinal metastases may be found in LC, with an incidence higher than that reported in the literature, especially in advanced stages of LC, although they can be found from stage II in asymptomatic patients.