Anterior Uveal Melanocytoma: Role of Diagnostic FNAB.

Introduction: Anterior uveal melanocytoma (AUM) pose a diagnostic challenge as they can mimic growing melanomas. Establishing a definitive diagnosis of melanocytoma necessitates cytologic or histopathologic confirmation. We describe the clinical presentation and characteristics of fifteen pathologically proven AUM cases and assess the role of fine needle aspiration biopsy (FNAB) as a safe and effective tool for diagnosis. Methods: Retrospective review of pathologically confirmed AUM cases was performed. Demographic data, presenting symptoms, clinical features, diagnostic approach, cytological and histological features, and clinical outcomes were collected. Results: Fifteen patients with pathologically confirmed AUM were identified. The mean and median age of diagnosis were 50 and 53 years, respectively (range 3-77 years). The melanocytoma was localized to the iris (5, 33%) or ciliary body (7, 47%), and 3 patients had iridociliary involvement (20%). Presentation was due to concern for growth in 4 (29%), visual symptoms in 1 (7%), and was an incidental finding in 10 (64%) patients. Pigmentation of the tumor varied with 9 (60%) appearing brown and 3 (20%) black in color. The color of 3 (20%) ciliary body tumors could not be assessed. The diagnosis was confirmed with FNAB in 6 (40%), excisional biopsy in 7 (47%), and incisional biopsy in 2 (13%). Cytologic and histologic preparations demonstrated predominance of round to polygonal cells with heavily pigmented cytoplasm and small round nuclei. One patient who underwent excisional biopsy had prior FNAB that was interpreted as suspicious for melanoma (false-positive). Instances of false-negative cytology were not observed as demonstrated by the subsequent stable clinical course during the mean follow-up of 21.2 months (range = 1.0-63.0 months). FNAB-related complications were not observed in any case. Conclusion: FNAB offers a minimally invasive and safe diagnostic approach for pathologic confirmation of AUM. However, limitations of FNAB including false-negative and false-positive biopsies must be considered when excluding underlying malignancy. Continued observation to document tumor stability should be considered.

Uveal Melanoma: Refusal of Treatment.

PURPOSE: This study aimed to explore factors for refusing treatment in patients diagnosed with uveal melanoma and their subsequent clinical course. METHODS: This study included patients with uveal melanoma who refused standard of care treatment. Patient-reported reasons and pre-existing mental health diagnoses were assessed. The sociodemographic profile was compared with the controls. Ocular survival, metastasis-free survival (MFS), and overall survival (OS) were calculated. RESULTS: Nine patients with uveal melanoma declined ocular treatment (plaque brachytherapy, n = 7 [78%]; enucleation, n = 2 [22%]). The choroidal melanomas were small (n = 1 [11%]), medium (n = 5 [56%]), and large (n = 3 [33%]) in size (COMS criteria). The sociodemographic profile of the study patients was not different from those that accepted treatment. One patient (11%) had pre-existing mental health diagnosis. Five patients (56%) eventually accepted treatment following an average delay of 19 months (range: 4-55 months) due to neovascular glaucoma or severe vision loss. MFS could not be ascertained, and OS was 67% (6/9) at 4.2 years of follow-up (mean). CONCLUSIONS: Refusal of initial recommended treatment is associated with poor ocular survival. The small sample size did not allow for an evaluation of the impact on survival.

Gene Expression Profiling Prognostication of Posterior Uveal Melanoma: Does Size Matter?

PURPOSE: Investigate the influence of tumor size by American Joint Committee on Cancer (AJCC) stage, Collaborative Ocular Melanoma Study (COMS) size, tumor largest basal diameter (LBD), and tumor thickness on prognostication by gene expression profiling (GEP) class. DESIGN: Two-center retrospective study. PARTICIPANTS: Two hundred fifteen consecutive patients diagnosed with posterior uveal melanoma over a 5-year period who were evaluated with prognostic fine-needle aspiration biopsy at the time of primary treatment. METHODS: Patient demographics, tumor clinical size, AJCC stage, COMS size, GEP class, presence of metastasis, and mortality data were collected. Metastasis-free-survival (MFS) was defined as time to metastasis or death from any cause. Comparisons were made using Pearson chi-square tests or Fisher exact tests for categorical factors, and t tests or Kruskal-Wallis tests for continuous measures. Cox proportional hazards models were fit to identify whether size measurements increased the prognostic discrimination index (C-statistic). MAIN OUTCOME MEASURES: Metastasis-free-survival. RESULTS: The average follow-up interval was 22.0 months (range, 12.0-37.0 months). Eighty-nine tumors were class 1A, 48 class 1B, and 78 class 2. Twenty-one patients developed metastatic disease detected by surveillance and confirmed by liver biopsy. Three-year MFS was 96% for class 1 and 63% for class 2. Five-year MFS was 96% for class 1 and 49% for class 2. All size measures significantly improved prognostic discrimination index by GEP class, as shown by increase in the C-statistic with addition of size variables (C-statistic 0.750 GEP alone, 0.830 GEP with AJCC [P = 0.016], 0.822 GEP with COMS [P < 0.001], 0.842 GEP with LBD [P <0.001], and 0.847 GEP with tumor thickness [P < 0.001]). Class 2 patients with metastasis had larger tumors compared with nonmetastatic class 2 tumors (AJCC class, P = 0.004; COMS class, P = 0.024; with metastasis mean thickness 6.5 mm [interquartile range (IQR), 3.8-9.5 mm]; without metastasis, 3.9 mm [SD, 3.1-6.0 mm]; P = 0.008), with metastasis mean LBD 14.9±2.8 mm, without metastasis, 12.3±2.7 mm (P < 0.001). All class 1 tumors with metastasis were large and required enucleation. CONCLUSIONS: Incorporation of tumor size enhances the prognostic discrimination index of the GEP test in patients with posterior uveal melanoma. All size tumor parameters are equivalent in their ability to enhance GEP prognostication.

Risk-stratified systemic surveillance in uveal melanoma.

BACKGROUND/AIM: Molecular prognostication provides clinically applicable prognostic information for patients with uveal melanoma. Most ocular oncologists recommend intensive metastatic surveillance for patients with high-risk tumours. However, socioeconomic variables may limit a patient's ability to adhere to recommended surveillance. We aim to analyse socioeconomic data from patients with uveal melanoma who underwent molecular prognostication to determine which variables influence adherence. METHODS: This was a retrospective review of 107 consecutive patients who were diagnosed and treated for uveal melanoma from January 2014 to June 2015. Patients were categorised into low/unknown risk and high risk for metastasis. The low-risk group was followed with hepatic ultrasonography every 6 months. The high-risk group was followed with more frequent hepatic imaging or incorporation of hepatic CT/MRI into the surveillance protocol. Adherence to surveillance recommendations was recorded for the first 2 years following primary treatment. Socioeconomic data including age at diagnosis, baseline systemic staging, gene expression profile status, marital status, insurance, distance of primary residence, median household income and Charlson Comorbidity Index score were recorded. Frequency/modality of imaging and metastatic status were also recorded. RESULTS: High-risk patients were more likely to develop metastasis than low-risk/unknown-risk patients (p<0.001). High-risk patients were more likely to have scans at baseline (p=0.008) and to have expected scans relative to low-risk/unknown-risk patients (p<0.001). There was no significant relationship between the likelihood of adhering to recommended surveillance and the other variables analysed. CONCLUSIONS: Prognostic risk level is a significant predictor of surveillance and remains significant after adjustment for socioeconomic variables. Adherence to surveillance recommendations for high-risk patients may translate into improved survival.