Uveal Melanoma in Asians: A Review

Despite limited data, some differences in the clinical profile can be observed in Asian population when compared with presentation of uveal melanoma (UM) in white population. The incidence of UM is higher in Whites than in Asians. For the purpose of comparison with Asian population, data from North America, Europe, and Australia were considered as that of “white” population. The annual incidence of UM has been reported to be 5–6 cases/million in whites. The incidence in different parts of Asia is estimated at 0.2–0.6 per million. The age of presentation is around 40–55 years in Asians, which is younger when compared to that of whites (mean age of 58 years). At presentation, mean basal diameter of tumors in Asians is greater compared to whites but overall, medium-size tumors are most common. Clinical presentation is straightforward in majority of cases with retinal detachment, acute glaucoma, uveitis, cataract, or vitreous hemorrhage as common symptoms. Epithelioid cell-type variant carries the worst prognosis. Management options for choroidal melanoma include transpupillary thermotherapy, plaque radiotherapy, charged particle irradiation, local resection, enucleation, or orbital exenteration. Most commonly used modalities are enucleation and plaque radiotherapy.

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BAP1 Germline Mutation Associated with Bilateral Primary Uveal Melanoma

Ocular Oncology and Pathology ◽

10.1159/000499570 ◽

2019 ◽

Vol 6 (1) ◽

pp. 10-14 ◽

Cited By ~ 2

Author(s):

Michael D. Yu ◽

Babak Masoomian ◽

Jerry A. Shields ◽

Carol L. Shields

Keyword(s):

Visual Acuity ◽

Uveal Melanoma ◽

Choroidal Melanoma ◽

Pathogenic Mutation ◽

Clinical Testing ◽

Plaque Radiotherapy ◽

Systemic Metastasis ◽

History Of ◽

History Of Cancer

Purpose: To describe the occurrence of bilateral primary uveal melanoma in 2 patients with mutation on the gene encoding BRCA1-associated protein 1 (BAP1). Methods: Retrospective chart review of patients with bilateral primary uveal melanoma and subsequent positive germline BAP1 mutation. Results: There were 2 patients with bilateral uveal melanoma and BAP1 germline positivity. Neither patient demonstrated oculodermal melanocytosis. Patient 1 underwent enucleation of his right eye (OD) at the age of 44 years for a 9.6-mm-thick choroidal melanoma. He returned 4 years later with a 10.0-mm-thick choroidal melanoma in his left eye (OS) and was treated with plaque radiotherapy. He had a strong family history of cancer, and clinical testing for germline BAP1 mutation identified a pathogenic mutation in BAP1. At the 18-month follow-up, visual acuity was 20/200 OS without evidence of systemic metastasis. Patient 2 initially presented at age 54 years with extensive, diffuse iris melanoma OD, initially treated with plaque radiotherapy, but local recurrence after 3 years necessitated enucleation. Four years later, a 6.0-mm-thick ciliary body melanoma OS was found and successfully treated with plaque radiotherapy. Clinical testing for germline BAP1 mutation identified a pathogenic mutation in BAP1. At the 8-year follow-up, visual acuity was 20/40 OS without evidence of local recurrence or systemic metastasis. The patient expired secondary to an unrelated brain infarction. Conclusion: Bilateral uveal melanoma is exceedingly rare. Patients with bilateral uveal melanoma, especially when coincident with remote systemic cancers or a family history of cancer, should be evaluated for germline BAP1 mutation. Lifelong monitoring for related systemic malignancies is advised.

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VITREOUS HEMORRHAGE AFTER PLAQUE RADIOTHERAPY FOR UVEAL MELANOMA

Retina ◽

10.1097/iae.0b013e3182340cc1 ◽

2012 ◽

Vol 32 (6) ◽

pp. 1156-1164 ◽

Cited By ~ 10

Author(s):

Carlos Bianciotto ◽

Carol L. Shields ◽

Cesare Pirondini ◽

Arman Mashayekhi ◽

Minoru Furuta ◽

...

Keyword(s):

Uveal Melanoma ◽

Vitreous Hemorrhage ◽

Plaque Radiotherapy

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Small Choroidal Melanoma: Correlation of Growth Rate with Pathology

Ocular Oncology and Pathology ◽

10.1159/000517203 ◽

2021 ◽

pp. 1-10

Author(s):

Vishal Raval ◽

Shiming Luo ◽

Emily C. Zabor ◽

Arun D. Singh

Keyword(s):

Growth Rate ◽

Retinal Pigment ◽

Choroidal Melanoma ◽

Case Series ◽

Subretinal Fluid ◽

Categorical Variables ◽

Continuous Variables ◽

Basal Diameter ◽

Orange Pigment ◽

Rpe Atrophy

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.

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Histologic Findings of Choroidal Vasculopathy in Eyes Enucleated following Radiation Therapy for Uveal Melanoma: Radiation Choroidopathy

Klinische Monatsblätter für Augenheilkunde ◽

10.1055/a-1275-0626 ◽

2021 ◽

Author(s):

Sean Platt ◽

Diva R. Salomao ◽

Jose Pulido

Keyword(s):

Radiation Therapy ◽

Uveal Melanoma ◽

Malignant Tumors ◽

Vitreous Hemorrhage ◽

Radiation Retinopathy ◽

Radiation Induced ◽

Histopathologic Analysis ◽

Choroidal Vessels ◽

Choroidal Vasculopathy

Abstract Introduction Little has been published about the choroidal vascular changes that occur years after radiation exposure. The aim of this study was to review the histological changes observed in the choroidal vasculature following radiotherapy for uveal melanoma. Methods Records from a single institution were retrospectively reviewed from June 7, 2007 to June 7, 2017; 101 patients with a diagnosis of uveal melanoma that underwent enucleation had their records reviewed. Out of these, a total of 26 eyes had undergone plaque brachytherapy prior to enucleation, which had been performed at a mean time of 7.2 years (range from 0 years to 30 years) after the initial plaque placement. A histopathologic analysis was conducted on all 26 eyes with special emphasis on the choroidal changes. Of these 26 eyes, 18 demonstrated evidence of radiation-induced vasculopathy. Results Of the 18 eyes, 10/18 (55%) had radiation retinopathy and 16/18 (89%) had radiation choroidal vasculopathy. One patient had a phthisical eye, and the choroid could not be evaluated because the characteristics of the vasculature could not be determined. Nine cases had vitreous hemorrhage (50%), all cases had radiation retinopathy, and 8/9 (89%) had radiation choroidopathy. Of the 16 cases with radiation choroidal vasculopathy, 3/16 (19%) had only intratumoral radiation choroidal vasculopathy, 3/16 (19%) had only extratumoral radiation choroidal vasculopathy, and, thus, 10/16 (32%) had both intratumoral and extratumoral radiation choroidal vasculopathy. In patients with radiation choroidal vasculopathy, 2/16 (13%) had hyalinization of the choroidal vessels. Another 3/16 (19%) cases with radiation choroidal vasculopathy had ectatic vessels. The other 11/16 (68%) had evidence of both hyalinization of the choroidal vessels as well as ectatic vessels in the choroid. Histological evidence of radiation retinopathy and choroidopathy were seen in 69% of eyes enucleated after receiving radiation therapy, which, in some cases, also had vitreous hemorrhage. Polypoidal choroidal vasculopathy, choroidal neovascularization, and retinal choroidal anastomoses (RAP-type lesions) were seen in 12 of the 16 eyes (75%). Discussion/Conclusion Irradiation of malignant tumors of the eye causes not only radiation retinopathy but also radiation choroidopathy. The role of radiation choroidopathy in the subsequent visual loss following radiotherapy and the role of anti-VEGF therapy needs to be recognized and distinguished from radiation retinopathy. Our data adds to the prior limited knowledge that radiation affects the choroid and can induce specific phenotypes similar to the clinical spectrum of CNV, PCV, and RAP.

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MR Imaging–Pathologic Correlation of Uveal Melanomas Undergoing Secondary Enucleation after Proton Beam Radiotherapy

Applied Sciences ◽

10.3390/app11094310 ◽

2021 ◽

Vol 11 (9) ◽

pp. 4310

Author(s):

Pietro Valerio Foti ◽

Corrado Inì ◽

Mario Travali ◽

Renato Farina ◽

Stefano Palmucci ◽

...

Keyword(s):

Mr Imaging ◽

Proton Beam ◽

Uveal Melanoma ◽

Vitreous Hemorrhage ◽

Nerve Degeneration ◽

Proton Beam Radiotherapy ◽

Iris Neovascularization ◽

Weighted Sequences ◽

Histopathologic Findings ◽

Optic Nerve Degeneration

Background: Currently, radiotherapy represents the most widely employed therapeutic option in patients with uveal melanoma. Although the effects of proton beam radiotherapy on uveal melanoma end ocular tissues have been histologically documented, their appearance at MR imaging is still poorly understood. The purpose of our study was to elucidate the magnetic resonance (MR) semiotics of radiotherapy-induced changes to neoplastic tissues and ocular structures in patients with uveal melanoma undergoing secondary enucleation after proton beam radiotherapy. Methods: Nine patients with uveal melanoma who had undergone proton beam radiotherapy, MR imaging, and subsequent secondary enucleation were retrospectively selected. The histopathologic findings evaluated for irradiated tumors were necrosis, fibrosis, and viable tumor, while the histopathologic findings evaluated for extratumoral ocular/periocular tissues were radiation-related intraocular inflammation, vitreous hemorrhage, optic nerve degeneration, iris neovascularization, and periocular fibrotic adhesions. On MR images, the appearance of the abovementioned histologic features was assessed on conventional and diffusion-weighted sequences. Results: T2-weighted sequences performed better in detecting radiation-induced necrosis, fibrosis, optic nerve degeneration, and periocular fibrotic adhesions. T1-weighted sequences were preferable for identifying cataracts, vitreous hemorrhage, and inflammatory complications. Contrast-enhanced T1-weighted sequences were irreplaceable in assessing iris neovascularization, and in confirming inflammatory complications. Conclusions: In the light of their increasing role in the multidisciplinary management of patients with uveal melanoma, radiologists should be aware of the MR appearance of the effects of radiotherapy on neoplastic and ocular tissue, in order to improve the accuracy of follow-up MR examinations.

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Ischemia Is Related to Tumour Genetics in Uveal Melanoma

Cancers ◽

10.3390/cancers11071004 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1004 ◽

Cited By ~ 3

Author(s):

Niels J. Brouwer ◽

Annemijn P. A. Wierenga ◽

Gülçin Gezgin ◽

Marina Marinkovic ◽

Gregorius P. M. Luyten ◽

...

Keyword(s):

Uveal Melanoma ◽

Messenger Rna ◽

Tumour Size ◽

Hypoxia Inducible Factor ◽

The Cancer Genome Atlas ◽

Basal Diameter ◽

Von Hippel Lindau ◽

The Status ◽

Using Data ◽

Tumour Genetics

Hypoxia-inducible factor 1-alpha (HIF1a) and its regulator von Hippel–Lindau protein (VHL) play an important role in tumour ischemia. Currently, drugs that target HIF1a are being developed to treat malignancies. Although HIF1a is known to be expressed in uveal melanoma (UM), it is as yet unknown which factors, such as tumour size or genetics, determine its expression. Therefore, we aimed to determine which tumour characteristics relate to HIF1a expression in UM. Data from 64 patients who were enucleated for UM were analysed. Messenger RNA (mRNA) expression was determined with the Illumina HT-12 v4 chip. In 54 cases, the status of chromosomes 3 and 8q, and BRCA1-associated protein 1 (BAP1) protein expression (immunohistochemistry) were determined. Findings were corroborated using data of 80 patients from the Cancer Genome Atlas (TCGA) study. A significantly increased expression of HIF1a, and a decreased expression of VHL were associated with monosomy 3/loss of BAP1 expression. The relationship between BAP1 loss and HIF1a expression was independent of chromosome 3. The largest basal diameter and tumour thickness showed no relationship with HIF1a. HIF1a expression related to an increased presence of infiltrating T cells and macrophages. From this study, we conclude that HIF1a is strongly related to tumour genetics in UM, especially to loss of BAP1 expression, and less to tumour size. Tumour ischemia is furthermore related to the presence of an inflammatory phenotype.

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