Ocular Oncology and Pathology最新文献

Purpose: This study aimed to evaluate the outcomes of juxtapapillary choroidal melanomas treated with notched ruthenium-106 plaques.

Methods: Juxtapapillary choroidal melanomas (tumours within 2 disc diameters from the optic disc) treated with notched ruthenium-106 plaques (Eckert & Ziegler, BEBIG, Berlin, Germany) at the Scottish Ocular Oncology Service between 2009 and 2015 were retrospectively reviewed. The data were analysed with respect to various outcome measures including recurrence, complications, vision, and eye preservation.

Results: We reviewed 40 patients with a median tumour diameter of 8.4 mm (range 5-17 mm) and a median thickness of 2.5 mm (range 1.1-6 mm). AJCC tumour category distribution was 62.5% T1, 32.5% T2, and 5% T3 tumours. The mean presenting vision was 0.3 logMAR, and the mean final vision was 0.7 logMAR, with 62.5% retaining >1.0 logMAR and 50% retaining >0.3 logMAR at the final follow-up. The median follow-up was 51 months (14-100 months). Over the maximum follow-up time, 13 tumours (32.5%) recurred. Six of these were treated with salvage proton beam therapy (PBT), 2 with transpupillary thermotherapy followed by PBT, and 5 with enucleation. The final eye retention rate was 87.5%. Complications included maculopathy (10%), retinal detachment (5%), neovascular glaucoma (2.5%), and diplopia (2.5%). The observed risk of recurrence over 5 years was 31% (95% CI: 14.1%, 47.8%), and the risk of enucleation over 5 years was 11.5% (95% CI: 0.9%, 21.8%).

Conclusion: Juxtapapillary choroidal melanomas treated with notched ruthenium plaques have a high recurrence rate and frequently need salvage treatment with PBT for tumour control. This has led to a change in our practice toward offering PBT as the first-line treatment for these patients.

Background: Idiopathic systemic capillary leak syndrome (ISCLS, also known as Clarkson's disease) is a rare medical condition characterized by episodes of capillary endothelial cell dysfunction with leakage of fluid into the interstitial space resulting in severe hypotension, hemoconcentration, hypoalbuminemia, and generalized edema. Each episode can result in multiorgan failure due to systemic hypoperfusion.

Case presentation: We report a case of uveal effusion, mimicking uveal melanoma, associated with ISCLS following viral infection. A 74-year-old white male was evaluated in our ocular tumor clinic for a large intraocular mass in the right eye concerning for choroidal melanoma. We completed a review of the literature and list clinical recommendations for these cases. ISCLS, although rare, was a significant diagnostic consideration in this patient. Due to the high mortality rate of this condition, accurate diagnosis and prompt treatment was critical. We hypothesize that the mechanism of choroidal effusion development was due to reduced oncotic pressure from rapid decrease in serum albumin. Increased permeability of choroidal capillaries may be an additional mechanism leading to uveal effusion.

Conclusion: With treatment, the patient had complete resolution of his choroidal effusion with no recurrence of his ISCLS. Further research should be considered on the role of viral infections in the pathogenesis of ISCLS.

Two patients, with non-small cell lung carcinoma treated with pembrolizumab, developed bilateral diffuse uveal melanocytic proliferation (BDUMP) with interesting histopathological features. The first patient developed a right ciliary body mass concurrently with BDUMP. The globe was enucleated. The ciliary body mass was a mitotically active epithelioid uveal melanoma, invading the trabecular meshwork and peripheral corneal stroma, with over 90% of the cells expressing Cyclin D1 protein. The melanoma showed no chromosome 3 or 8 changes. The background uvea showed diffuse, bland spindle cell melanocytic proliferation with much lower Cyclin D1 expression (around 10%). In the choroid, this population was punctuated by islands of pigmented epithelioid cells, some of which were necrotic. All these islands expressed a high level of Cyclin D1, and some islands expressed nuclear preferentially expressed antigen in melanoma (PRAME). The ciliary body mass, epithelioid cell islands, and the BDUMP all expressed c-Met (the receptor for hepatocyte growth factor [HGF]). The features were those of ciliary body melanoma and choroidal melanoma "tumorlets," developing on a background of BDUMP. The second patient developed bilateral periocular skin pigmentation following a diagnosis of BDUMP, which when biopsied, showed dermal islands of paraneoplastic perivascular melanocytic cell proliferation. These cells also expressed c-Met protein. These observations implicate the HGF/c-Met axis in the pathogenesis of BDUMP, the uveal melanomas in the ciliary body and choroid in the first patient and the paraneoplastic dermal melanocytic proliferation in the second patient.

Introduction: Gene expression profiling (GEP) is widely used for prognostication in patients with uveal melanoma (UM). Because biopsy tissue is limited, it is critical to obtain as much genomic information as possible from each sample. Combined application of both GEP and next-generation sequencing (NGS) allows for analysis of RNA and DNA from a single biopsy sample, offers additional prognostic information, and can potentially inform therapy selection. This study evaluated the analytical performance of a targeted custom NGS panel for mutational profiling of 7 genes commonly mutated in UM.

Methods: One hundred five primary UM tumors were analyzed, including 37 formalin-fixed paraffin-embedded (FFPE) and 68 fine-needle aspiration biopsy specimens. Sequencing was performed on the Ion GeneStudio S5 platform to an average read depth of >500X per region of interest.

Results: The 7-gene panel achieved a positive percent agreement of 100% for detection of both single-nucleotide variants and insertions/deletions, with a technical positive predictive value of 98.8% and 100%, respectively. Intra-assay and inter-assay concordance studies confirmed the assay's reproducibility and repeatability.

Discussion/conclusion: The 7-gene panel is a robust, highly accurate NGS test that can be successfully performed, along with GEP, from a single small-gauge needle biopsy sample or FFPE specimen.

Purpose: The aim of the study was to evaluate equivalence of growth rate and pathologic confirmation in small choroidal melanoma (SCM).

Design: This study is a case series.

Subjects participants and controls: A total of 61 patients with a choroidal melanocytic tumor of size 5.0-16.0 mm in the largest basal diameter and 1.0-2.5 mm in thickness were classified into the pathology-confirmed group (n = 19), growth-confirmed group (n = 30), and with combined observations (n = 12).

Methods: Distribution of clinical variables (age, gender, laterality, tumor dimensions, tumor location, and presence of orange pigment, subretinal fluid, drusen, and retinal pigment epithelial [RPE] atrophy) between the groups was analyzed. Patient and disease characteristics were summarized as the median and interquartile range for continuous variables and the frequency and percentage for categorical variables. Comparisons were made using the Wilcoxon rank sum test for continuous variables and either Fisher's exact test or the χ² test for categorical variables with a p value threshold of 0.05 for statistical significance. Growth rate (change in basal dimension/12 months) diagnostic of SCM was quantified.

Main outcome measures: The primary aim of this study was to test the hypothesis that "growth" was diagnostic of SCM with the secondary aim of quantifying the malignant "growth rate" (growth rate of SCM).

Results: The clinical characteristics among all 3 groups were similar except more patients with symptoms (68 vs. 20 vs. 42%, p = 0.004) and juxtapapillary location (p = 0.03) were in the pathology group than in the growth-confirmed group. Those in the combined and growth-confirmed groups had more patients with drusen (11 vs. 60 vs. 50%, p = 0.003) and RPE atrophy (11 vs. 23 vs. 67%, p = 0.003), respectively, than in the pathology group. The median time to detect growth was 9 months (range 3-26 months). The mean growth rate in basal dimension was 1.8 mm/12 months (range, 0.0-7.4 mm; [95% CI: 1.32-2.28]).

Conclusions and relevance: Choroidal melanocytic lesions exhibiting a defined growth rate can be clinically diagnosed as SCM without a need for biopsy.

Importance: Diagnosis of small choroidal melanoma is based upon clinical features and presence of factors predictive of local malignant growth. Prognostic biopsy quantifies risk of metastasis.

Objective: The aim of this study is to explore relationship between clinical characteristics and metastatic potential of a small choroidal melanoma.

Design: Retrospective review of 53 patients with small choroidal melanoma treated in a tertiary oncology clinic. Patients were derived from 3 cohorts, with pathologic confirmation, with growth confirmation, and those treated only on clinical basis. Based upon prognostic biopsy outcomes, each case was classified into low or high metastatic potential groups. Distribution of clinical characteristics such as age, laterality, symptoms, tumor dimensions, tumor distance from optic nerve and fovea, presence of surface orange pigment, drusen, retinal pigment epithelial atrophy, and subretinal fluid was analyzed between metastatic groups.

Main outcome measures: Distribution of clinical characteristics between low or high metastatic potential groups was analyzed.

Results: A total of 53 patients [mean age, 61 years (range, 27-81 years); 32 (60%) men and 21 (40%) women] were classified into pathology confirmed group (n = 13), growth confirmed group (n = 26), and with clinical group (n = 14). Prognostic biopsy in the growth, pathology, and clinical groups revealed low metastatic potential in 23, 10, and 11 patients, respectively, and high metastatic potential in 3 patients in each group. Distribution of clinical characteristics between low or high metastatic potential groups was not statistically significantly different.

Conclusion: Clinical characteristics do not identify metastatic potential of a small choroidal melanoma.

Purpose: The aim of this study was to demonstrate the role of carbon fiducial markers (fiducials) for guiding radiotherapy in the management of uveal melanoma (UM).

Methods: This is a retrospective interventional case series at a single-center ocular oncology practice. The medical records were reviewed retrospectively for all patients with UM treated with stereotactic radiosurgery using episcleral fiducials. We report our short-term experience with surgical placement of fiducials, UM localization, treatment outcomes, and optimization approaches.

Results: We evaluated 11 cases of UM (mean age: 65 years; 64% female). The placed fiducials were numbered from 2 to 4, each secured to the sclera with a surgical microscope or surgical loupes and either 5-0 or 8-0 nylon sutures at 50% scleral depth and 3 mm beyond the tumor margin. Over a median follow-up of 11 months (range: 4.2-43.2 months), no recurrences of intraocular UM were observed. One case of enucleation after stereotactic radiosurgery developed because of radiation-related surface irritation, ocular dryness, and secondary keratopathy. Two patients (18%) with 5-0 nylon sutures required fiducial removal because of suture exposure, successfully accomplished in an outpatient setting.

Conclusions: Fiducials represent a viable alternative to tantalum rings for guiding stereotactic radiotherapy to manage UM and provide additional definition of the tumor border with linear orientation that helps optimize targeted radiation delivery. Fiducial placement with a 3-mm margin from the visible tumor border should not result in clinically important radiation dose attenuation at the tumor margins. Anteriorly placed fiducials may cause discomfort, yet they are easily removed in the outpatient setting.