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      Ocular Metastasis as First Presentation of Large-Cell Neuroendocrine Carcinoma

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          Abstract

          Introduction

          We report a rare case of an aggressive large-cell neuroendocrine lung tumour, which presented with ocular metastasis.

          Case Presentation

          A 70-year-old lady presented with a 4-week history of left eye pain and photophobia. Ocular examination revealed left-sided episcleritis and she was treated with topical lubricants and steroids. However, she re-presented 6 months later with recurrent left eye symptoms and was found to have an iris stroma amelanotic lesion, posterior synechiae, 360-degrees rubeosis iridis, raised intraocular pressure, and trace vitreous inflammation. Ultrasound biomicroscopy revealed a left thickened iris with an associated ciliary body lesion. Sarcoid-related ocular inflammation was suspected, but a computed tomography (CT) scan of the lung revealed an incidental right upper lobe lesion. Histology from a transcorneal iris biopsy showed a high-grade neuroendocrine carcinoma, and the diagnosis of metastatic lung large-cell neuroendocrine carcinoma was confirmed via high-resolution CT scan, positron emission tomography scan, and CT-guided lung biopsy. She was given multiple courses of different chemotherapy regimens along with palliative radiotherapy. However, the tumour and its metastases continued to progress and she passed away 4 years after her initial presentation.

          Conclusion

          Ocular metastatic large-cell neuroendocrine carcinoma is rare, and the first presentation with ocular metastasis is even rarer. This case highlights the importance of early detection of ocular metastases in order to hasten oncological treatment. A low threshold for systemic investigations and ophthalmology referral in cases of unexplained, refractory ocular symptomatology is essential, given the heterogeneous presentation, rarity, and poor prognosis of these tumours, even with maximal treatment.

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          Most cited references11

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          FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3.

          Patients with neuroendocrine carcinomas (NECs) grade 3 have a poor prognosis. Etoposide-platinum combination is the standard chemotherapy but the role of a second-line therapy remains unknown. Irinotecan alone or in combination has shown some efficacy in patients treated for small cell lung cancer which had pathological similarities with neuroendocine tumors. The aim of this study is to determine safety and efficacy of the FOLFIRI regimen in patients with NECs grade 3 after failure of etoposide-platinum combination. This study was retrospective, including patients with NECs grade 3 and treated with the FOLFIRI regimen after progression or toxicity of etoposide-platinum combination in first-line. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≥3 and/or serum alkaline phosphatase ≥5×upper limit of normal value (ULN) and/or bilirubin ≥1.5×ULN were excluded. Among 39 patients who failed etoposide-platinum combination, 19 (49%; 12 women, median age 53 (29-78) years) received the FOLFIRI regimen with a median number of 6 (1-16) courses. Six patients (31%) had at least one episode of grades 3-4 toxicity (neutropenia, n=3; diarrhea, n=3) without toxic death. Six patients (31%) had objective response, 6 (31%) stable disease, and 7 (38%) tumor progression. Median progression-free survival under FOLFIRI was 4 months. Overall survival was 18 vs 6.8 months in noneligible patients. FOLFIRI regimen is a safe and potentially efficient chemotherapy given as second-line in patients with NECs grade 3 who remain in good condition and with correct liver tests after failure of etoposide-platinum combination. These results should be confirmed in a future prospective study.
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            Large cell neuroendocrine carcinoma: an aggressive form of non-small cell lung cancer.

            Large cell neuroendocrine carcinomas of the lung display morphologic and immunohistochemical characteristics common to neuroendocrine tumors and the morphologic features of large cell carcinomas. Surgical resection of large cell neuroendocrine carcinomas in many series has been described, with 5-year actuarial survivals ranging from 13% to 57%. Considerable debate has emerged as to whether these tumors should be classified and treated as non-small cell lung cancers or small cell lung cancers. The objective of this study was to report the outcome of surgical resection in patients with large cell neuroendocrine carcinomas. An analysis of our tumor registry was performed to identify all patients undergoing surgical resection of lung cancer between July 1, 1988, and December 31, 2002, for large cell tumors. Cases were then segregated into large cell neuroendocrine carcinomas, mixed large cell neuroendocrine carcinomas (in which at least one portion of the tumor was a large cell neuroendocrine carcinoma), or large cell carcinomas on the basis of morphology and differentiation. Follow-up was complete on all patients, with a mean follow-up of 48 months. Type of resection, mortality, and survival by stage were analyzed. Kaplan-Meier survival was determined for all patients from the date of surgical intervention. Cox proportional hazards model analysis incorporating the variables of age, sex, histology, and stage estimated the effect of large cell neuroendocrine carcinomas and mixed large cell neuroendocrine carcinomas on recurrence and death. The stage of disease in all patients was assessed according to the 1997 American Joint Committee on Cancer guidelines. Of the 2099 patients who underwent resection, 82 (3.9%) had large cell lung cancers. Perioperative mortality was 2.4%. Overall survival and freedom from recurrence at 5 years for the entire group was 47.1% and 58.4%, respectively. Overall survival by histologic subtype at 5 years was 30.2% for patients with large cell neuroendocrine carcinomas (n = 45), 30.3% for patients with mixed large cell neuroendocrine carcinomas (n = 11), and 71.3% for patients with large cell carcinomas (n = 21). Survival was significantly worse for patients with large cell neuroendocrine carcinomas than for patients with large cell carcinomas ( P = .013). The presence of large cell neuroendocrine carcinomas in the specimen (the large cell neuroendocrine carcinoma and mixed large cell neuroendocrine carcinoma groups combined) was significantly associated with decreased survival (relative risk, 2.44; 95% confidence interval 1.29-4.58; P = .003) and decreased freedom from recurrence (relative risk, 4.52; 95% confidence interval, 1.76-11.57; P < .001). Patients with large cell neuroendocrine carcinomas have a significantly worse survival after resection than patients with large cell carcinomas, even in stage I disease. Accurate differentiation of large cell neuroendocrine carcinoma from large cell carcinoma is important because it identifies those patients at highest risk for the development of recurrent lung cancer.
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              Clinicopathological characteristics, treatment and survival of pulmonary large cell neuroendocrine carcinoma: a SEER population-based study

              Background This study was designed to investigate the clinicopathological characteristics, treatment and survival of patients with pulmonary large cell neuroendocrine carcinoma (LCNEC). Methods The Surveillance, Epidemiology and End Results database was utilized to identify patients diagnosed with pulmonary LCNEC between 2004 and 2013. Kaplan–Meier analysis was conducted to determine the overall survival (OS) and cancer-specific survival (CSS) rate. Univariate survival analysis along with log-rank test, and Cox proportional hazards model were employed to detect independent prognostic factors. Results Pulmonary LCNEC accounted for 0.58% (2972/510607) of the total number of lung and bronchus carcinoma. And a total of 1,530 eligible cases were identified, with the median follow-up time of 11 months. To be specific, the 3-, 5-year OS and CSS rates were 22.8%, 16.8% and 26.5%, 20.8% respectively. Generally, pulmonary LCNEC was commonly detected in the elderly (72.2%), males (55.9%), the upper lobe (62.0%) and advanced AJCC stage (65.5%). Multivariate analysis revealed that elderly [(≥60 and <80 years) HR:1.203, 95% CI [1.053–1.375], P = 0.007; (≥80 years) HR:1.530, 95% CI [1.238–1.891], P < 0.001] and advanced AJCC stage [(stage III) HR:2.606, 95% CI [2.083–3.260], P < 0.001; (stage IV) HR:4.881, 95% CI [3.923–6.072], P < 0.001] were independent unfavorable prognostic factors, and that female (HR:0.845, 95% CI [0.754–0.947], P = 0.004)), surgery [(Segmentectomy/wedge resection) HR:0.526, 95% CI [0.413–0.669], P < 0.001; (Lobectomy/Bilobectomy) HR:0.357, 95% CI [0.290–0.440], P < 0.001;(Pneumonectomy) HR:0.491, 95% CI [0.355–0.679], P < 0.001] , chemotherapy (HR:0.442, 95% CI [0.389–0.503], P < 0.001) and radiation (HR:0.837, 95% CI [0.738–0.949], P = 0.005) were independent favorable prognostic factors. Conclusion To sum up, age at diagnosis, sex, AJCC 8th edition stage, surgery, chemotherapy and radiation were significantly associated with OS of patients with pulmonary LCNEC.
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                Author and article information

                Journal
                Case Rep Ophthalmol
                Case Rep Ophthalmol
                COP
                COP
                Case Reports in Ophthalmology
                S. Karger AG (Basel, Switzerland )
                1663-2699
                12 December 2023
                Jan-Dec 2023
                12 December 2023
                : 14
                : 1
                : 684-691
                Affiliations
                [a ]Birmingham and Midland Eye Centre, Birmingham, UK
                [b ]Sheffield Ocular Oncology Service, Royal Hallamshire Hospital, Sheffield, UK
                Author notes
                Correspondence to: Matthew Azzopardi, matthew.azzopardi.14@ 123456um.edu.mt
                Article
                535233
                10.1159/000535233
                10715755
                38090108
                5640cd74-bcbd-4a96-a990-e295836d4989
                © 2023 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 19 September 2023
                : 12 November 2023
                : 2023
                Page count
                Figures: 3, References: 11, Pages: 8
                Funding
                The authors have no additional funding resource and are self-funding this publication.
                Categories
                Case Report

                large-cell neuroendocrine tumour,ocular metastases,ocular oncology

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