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NCI CANCERLIT^® Search: Intraocular Melanoma - September 2002

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National Cancer Institute^®
Ultima Vez Modificado: 1 de septiembre del 2002

Cardiac metastasis from uveal melanoma.
[Management of small choroidal melanocytic tumors]
Metastatic ocular melanoma to the left ventricle inducing near-syncope attacks in an 84-year-old woman.
Melanocytoma of the choroid: angiographic and histopathologic findings.
Mutational analysis of selected genes in the TGFbeta, Wnt, pRb, and p53 pathways in primary uveal melanoma.
[Detection of tumor circulating cells in patients with ocular melanoma]
Occupation as a risk factor for uveal melanoma in Germany.
[Malignant melanoma of the uvea. Current status and prospects]
[Prognostically relevant markers of malignant melanoma of the uvea]
[Choroid melanoma. Adjuvant therapy in high risk patients and new therapy approaches in the metastatic stage]
[Endoscopic resection of malignant melanomas of the uvea after preoperative stereotactic single dose convergence irradiation with the
[Prospective nonrandomised analysis of "Sandwich Therapy" for malignant melanoma of the choroid]
[Retrospective analysis of ruthenium-106 brachytherapy for small and medium-sized malignant melanoma of the posterior choroid]
Variability of chromosomes in the VUP permanent cell line derived from uveal malignant melanoma.
[Transpupillary thermotherapy in the treatment of choroid melanoma]
Posttreatment visual acuity in patients treated with episcleral plaque therapy for choroidal melanomas: dose and dose rate effects.
Sun exposure predicts risk of ocular melanoma in Australia.

1
UI - 11742953
AU - Makitie T; Kivela T
TI - Cardiac metastasis from uveal melanoma.
SO - Chest 2001 Dec;120(6):2115

2
UI - 11753689
AU - Elizalde Montagut J
TI - [Management of small choroidal melanocytic tumors]
SO - Arch Soc Esp Oftalmol 2001 Dec;76(12):693-4

3
UI - 10936157
AU - Rosario RT; DiMaio DJ; Lapham RL; Sweeney M; Smalling R; Barasch E
TI - Metastatic ocular melanoma to the left ventricle inducing near-syncope attacks in an 84-year-old woman.
SO - Chest 2000 Aug;118(2):551-3
AD - Department of Internal Medicine, Division of Cardiology, University of Texas Medical School, Houston 77030, USA.
Cardiac tumors may represent mechanical causes for syncope by limiting left ventricular filling and/or by obstructing the left ventricular outflow tract. Malignant melanoma is known to metastasize to the myocardium or pericardium, but there are only a very limited number of reports describing endocardial involvement by the tumor. We describe herein an 84-year-old woman who presented with daily near-syncope episodes, 9 years after treatment for a choroidal melanoma. The echocardiography and the pathologic examination revealed a metastatic melanoma. This is the first reported case of an ocular melanoma metastasizing to the heart and presenting as a left ventricular intracavitary pedunculated mass.

4
UI - 11942551
AU - Lafaut BA; Mietz H; Ortmann M; Bartz-Schmidt KU
TI - Melanocytoma of the choroid: angiographic and histopathologic findings.
SO - Ophthalmic Surg Lasers 2002 Mar-Apr;33(2):158-62
AD - Department of Ophthalmology, University of Cologne, Germany.
A juxtapapillary choroidal melanocytoma that was clinically confused with a choroidal melanoma is described. The clinical examination of a 40-year-old female patient included ultrasonography, fluorescein, and indocyanine green angiography. Histopathologic and immunohistochemical study of the enucleated eye resulted in the identification of a markedly pigmented, 3.8 mm elevated choroidal melanocytic tumor observed nasally to the disk. A-scan ultrasonography showed a high initial spike with a low to medium internal reflectivity with decreasing amplitude. On fluorescein angiography, the tumor was surrounded by a rim of retinal pigment epithelium depigmentation with a well-defined comet-tail. The lesion was hypofluorescent in the early phases of the indocyanine green angiogram, but from the late venous phase appeared ill-defined hyperfluorescence. Histopathologic study revealed a juxtapapillary choroidal melanocytoma The pigmented tumor cells stained positive for HMB45 and vimentin but negative for S100, GFAP, NSE, and MNF116. No tumor cells stained positive for the proliferation marker Ki67. These findings conclude that choroidal melanocytoma may mimick choroidal melanoma. Abnormalities on fluorescein angiography may be a clinical hint to suspect a pigmented tumor different from a choroidal melanoma.

5
UI - 12202501
AU - Edmunds SC; Kelsell DP; Hungerford JL; Cree IA
TI - Mutational analysis of selected genes in the TGFbeta, Wnt, pRb, and p53 pathways in primary uveal melanoma.
SO - Invest Ophthalmol Vis Sci 2002 Sep;43(9):2845-51
AD - Centre for Cutaneous Research, St Bartholomew's and the London School of Medicine and Dentistry, Queen Mary College, University of London, London, United Kingdom.
PURPOSE: It is known that the pRb pathway cell-cycle inhibitor p16(INK4A) plays a significant role in cutaneous melanoma and that alteration of p16(INK4A), which resides within the 9p21-22 locus that also contains p15(INK4B) and p14(ARF), may occur in up to one third of uveal melanomas. The absence of TGFbeta responsiveness noted in cultured uveal melanoma cells also suggests that the TGFbeta pathway plays a role in the formation of this tumor. Therefore, mutational screening was performed in several key genes in tumor-suppressor pathways that are known to be altered in some uveal melanomas. METHODS: Using denaturing high-performance liquid chromatography (DHPLC) analysis and DNA sequencing, a series of 67 uveal melanomas were screened for inactivating mutations in the TGFbeta pathway members Smad4 and TGFbeta receptor type 2 (TGFbetaR2), the downstream cell-cycle inhibitor p15(INK4B), and the cell-cycle inhibitors p14(ARF) and p16(INK4A). p16(INK4A) was also investigated for promoter hypermethylation. Mutational analysis was also performed on the Wnt pathway gene beta-catenin, known to be mutated in approximately one quarter of cutaneous melanoma cell lines. RESULTS: Polymorphisms in p16(INK4A) were detected in 3 of 50 samples, but no inactivating mutations were detected in any of the genes screened. Promoter hypermethylation of p16(INK4A) was detected in 5 of 55 tumors, and loss of heterozygosity of the p16(INK4A) locus was detected in 5 of 16 tumors. CONCLUSIONS: Most primary uveal melanomas do not appear to contain somatic mutations in Smad4, TGFbetaR2, p14(ARF), p15(INK4B), p16(INK4A), or beta-catenin. However, methylation of the p16(INK4A) promoter and loss of heterozygosity of the p14(ARF)-p16(INK4A) locus occurs in some tumors.

6
UI - 12181879
AU - Borovanska J; Krasny J; Stribrna J; Pohlreich P; Kremen J; Sach J
TI - [Detection of tumor circulating cells in patients with ocular melanoma]
SO - Cesk Slov Oftalmol 2002 Jul;58(4):238-46
AD - Ocni klinika FN Kralovske Vinohrady a 3. LF UK, Praha.
The authors investigated a group of 51 patients (29 men and 22 women) with intraocular melanoma: 41 patients with melanoma of the chorioid, 10 patients with melanoma of the ciliary body. They evaluated the clinical and pathological finding according to the TNM classification recommended by UICC (International Union Against Cancer). In all investigated patients they assessed circulating tumour cells (melanocytes) in the peripheral blood stream based on the detection of mRNA tyrosinase and marker MART 1. When evaluating the presence of markers according to the diagnosis irrespective of time, they found in patients in the clinical stage of T2 choroidal melanoma a 19% positivity of different markers and very rare a concurrent positivity of both markers. Patients in the clinical stage T3 had a 51% positivity of one marker and 34% concurrent positivity of both markers. In melanoma of the ciliary body evidence of individual markers was positive in 17% and only in 11% both markers were positive concurrently. On comparison of therapeutic procedures from the aspect of development in time in patients treated by brachytherapy only rare positivity was found at the time of administration the radioactive plaque, following an eight-month interval after brachytherapy the positivity of markers increased to 28%. On evaluation of markers of choroidal melanoma and ciliary body melanoma resolved by enucleation had their positivity at the time of operation was 36%, and during check-ups up to one year or longer it persisted at similar levels. Concurrent presence of both markers before this operation was rare, during postoperative check-up examinations it was within a range of 23 and 33%. The presence of both markers was repeatedly proved in five patients with chooidal melanoma after enucleation of the eye, in four of them in direct correlation with a metastatic process.

7
UI - 12199429
AU - Monarrez-Espino J; Stang A; Bromen K; Merzenich H; Anastassiou G; Jockel
TI - KH Occupation as a risk factor for uveal melanoma in Germany.
SO - Scand J Work Environ Health 2002 Aug;28(4):270-7
AD - Institute for Medical Informatics, Biometry and Epidemiology, Medical Faculty, University of Essen, Germany.
OBJECTIVE: This study explored occupational risks linked to uveal melanoma. METHODS: The analysis pooled data from two case-referent studies (hospital- and population-based) conducted in Germany between 1995 and 1998, with incident cases matched with several referents by age, gender, and region of residence. The subjects were contacted through personal or telephone interviews. Their exposure status was based on their occupational history. Dichotomous coding for the main task and categorization into different occupational classification systems was performed. Altogether of 118 cases and 475 referents were included. Adjusted odds ratios were calculated by conditional logistic regression. RESULTS: Relevant occupations included food, beverage, and tobacco processors [odds ratio (OR) 4.7, 95% confidence interval (95% CI) 0.99-22.0] and miners (OR 2.3, 95% CI 0.92-5.99) among the men and station, engine and heavy equipment operators and freight handlers (OR 2.5, 95% CI 0.94-6.58) and medical, dental, pharmaceutical and veterinary workers (OR 2.1, 95% CI 0.71-6.02) among the women according to the International Standard Classification of Occupations, whereas, according to the European Industrial Classification, the relevant occupations were the food industry (OR 3.4, 95% CI 1.08-10.5) and the chemical and pharmaceutical industry (OR 2.8, 95% CI 1.01-7.78) among the men and machine production (OR 3.2, 95% CI 0.96-10.7) and health and veterinary sector (OR 2.4, 95% CI 0.97-5.71) among the women. CONCLUSIONS: These analyses support the potential role of occupational exposure as a risk factor for uveal melanoma. The findings must be interpreted carefully since the exposure was assessed indirectly.

8
UI - 12043284
AU - Bornfeld N
TI - [Malignant melanoma of the uvea. Current status and prospects]
SO - Ophthalmologe 2002 May;99(5):325-6

9
UI - 12043285
AU - Anastassiou G; Tschentscher F; Zeschnigk M
TI - [Prognostically relevant markers of malignant melanoma of the uvea]
SO - Ophthalmologe 2002 May;99(5):327-32
AD - Augenklinik, Universitatsklinikum Essen, Hufelandstrasse 55, 45122 Essen. gerasimos.anastassion@uni-essen.de
In addition to classic risk factors such as tumor size, tumor location, and histological cell type, a range of other potentially prognostic parameters have been discovered in the past few years. Many of these have only been described once so that they cannot be considered established markers. A few, however, such as vascular patterns or monosomy 3, were independently identified by several groups and now constitute recognized prognostic markers. The association of these factors with the disease course provides us with ever-new insights into the biology of this tumor. In particular, with the aid of new technologies such as microarray analysis, researchers around the globe hope that new and exciting discoveries will be made that can also modify therapy concepts.

10
UI - 12043286
AU - Bechrakis NE; Scheibenbogen C; Schmittel A; Servetopoulou F; Foerster
TI - MH; Keilholz U [Choroid melanoma. Adjuvant therapy in high risk patients and new therapy approaches in the metastatic stage]
SO - Ophthalmologe 2002 May;99(5):333-7
AD - Augenklinik, Universitatsklinikum Benjamin Franklin, Freie Universitat Berlin, Hindenburgdamm 30, 12200 Berlin. nikolaos.bechrakis@medizin.fuberlin.de
The treatment modality of primary uveal melanoma has up to now had no direct influence on the evolution of metastatic disease. Novel adjuvant treatment modalities are being developed on the basis of identifying significant prognostic factors for survival. The development of vaccination protocols targeting specific melanoma and/or tumor antigens has gained increasing importance and is currently being evaluated. Up to date the median survival of patients with metastases of uveal melanoma used to be approx. 5 months. In the last years median survival of selected patients with metastatic disease could be increased to 14 months by intrahepatic fotemustin influsions. Novel systemic chemotherapy protocols are currently being evaluated based on chemosensitivity studies. Furthermore, immunotherapeutical modalities are entering clinical evaluation as treatment for metastatic uveal melanoma.

11
UI - 12043287
AU - Bornfeld N; Talies S; Anastassiou G; Schilling H; Schuler A; Horstmann
TI - GA [Endoscopic resection of malignant melanomas of the uvea after preoperative stereotactic single dose convergence irradiation with the Leksell gamma knife]
SO - Ophthalmologe 2002 May;99(5):338-44
AD - Universitatsklinikum Essen, Zentrum fur Augenheilkunde, Abteilung fur Erkrankungen des hinteren Augenabschnitts, Hufelandstrasse 55, 45122 Essen. bornfeld@uni-essen.de
In cases of large volume and highly prominent melanomas of the uvea, it is rare for conventional methods of radiation therapy to enable salvage of the globe or even residual functionality of the affected eye. Complications due to the massive amount of accumulated necrotic tissue often necessitate subsequent enucleation of the blinded eye. Tumor-destroying, single-dose convergence irradiation (radiosurgery) of such tumors applied shortly before endoresection can represent a possible therapeutic alternative in these types of cases.

12
UI - 12022003
AU - Stoffelns BM; Kutzner J; Schopfer K; Frising M
TI - [Prospective nonrandomised analysis of "Sandwich Therapy" for malignant melanoma of the choroid]
SO - Klin Monatsbl Augenheilkd 2002 Apr;219(4):211-5
AD - Augenklinik des Universitatsklinikums Mainz, Germany. stoffelns@augen.klinik.uni-mainz.de
BACKGROUND: To evaluate the effectiveness of transpupillary thermotherapy (TTT) as an adjunct to ruthenium brachytherapy for treatment of choroidal melanoma with reduced radioactive dose. PATIENTS AND METHODS: In a prospective nonrandomised analysis 15 eyes with primary malignant melanoma of the choroid (posterior to the equator, thickness 13
UI - 12022004
AU - Stoffelns BM; Kutzner J; Jochem T
TI - [Retrospective analysis of ruthenium-106 brachytherapy for small and medium-sized malignant melanoma of the posterior choroid]
SO - Klin Monatsbl Augenheilkd 2002 Apr;219(4):216-20
AD - Augenklinik des Universitatsklinikums Mainz, Germany. stoffelns@augen.klinik.uni-mainz.de
BACKGROUND: Transpupillary thermotherapy is a new and most promising treatment modality for up to medium-sized choroidal melanoma at the posterior pole. We analysed the results of conventional ruthenium-106 brachytherapy in these special tumour subgroup. PATIENTS AND METHODS: Results of ruthenium-106 brachytherapy (radioactive dose to the tumour apex 150 Gy) in a series of 52 eyes with primary malignant choroidal melanoma (posterior to the equator, thickness 14
UI - 12098005
AU - Vrba M; Cihalova V; Juraskova V
TI - Variability of chromosomes in the VUP permanent cell line derived from uveal malignant melanoma.
SO - Neoplasma 2002;49(3):184-8
AD - Research Institute of Child Health, Brno, 662 62 Czech Republic.
A permanent cell line [VUP] derived 31 years ago from human malignant melanoma of the choroid has been characterized by genetically firmly anchored heteronuclearity. The most significant chromosomal changes of this cell line are: high instability of the chromosome No. 13 with the rise of new chromosomes formed by translocations, homologous stability of chromosomes 6, 15, and X. Structural changes were not revealed in chromosomes 15 and 22. The variability of chromosomes was studied both by classical conventional methods as well as with GTG banding and DNA hybridization in situ (FISH). Structural diversity was demonstrated in a number of morphologically congruent chromosomes. For example, X chromosome classified morphologically as chromosome No. 10 was determined by means of FISH technique, as a centric fragment Xq with translocated acentric fragment of other chromosomes. Furthermore, mar-t, previously considered to be q arm of chromosome No. 4, is formed by a centric fragment of chromosome No. 13 and an acentric fragment of chromosome No. 1.

15
UI - 11912837
AU - De Potter P; Levecq L
TI - [Transpupillary thermotherapy in the treatment of choroid melanoma]
SO - J Fr Ophtalmol 2001 Nov;24(9):937-43
AD - Unite d'Oncologie Oculaire, Service d'Ophtalmologie, Cliniques Universitaires St-Luc Avenue Hippocrate, 10, 1200 Bruxelles. depotter@ofta.ucl.ac.be
PURPOSE: To report the results of primary transpupillary thermotherapy (TTT) for selected posterior pole choroidal melanomas. MATERIAL AND METHODS: Prospective non randomized study including 34 patients with choroidal melanoma treated with TTT using near-infrared radiation (810 nm) delivered from the diode laser. All treated tumors had either documented growth or clinical risk factors for future growth and/or metastasis. The treatment was delivered using a specially modified infrared diode laser through a slit lamp adaptor. A contact lens was placed on the cornea to view the fundus and focus the laser beam. Treatment was initiated using a 60-second exposure and a low energy level at 300 mW with a 3.0 mm beam width. The energy was raised stepwise by 50 to 100 mW until the surface of the tumor develop a light grayish discoloration. The TTT sessions were delivered at 3-month intervals. RESULTS: Among these 34 patients with choroidal melanoma, 29 patients presented with primary choroidal melanoma. Five tumors (15%) were late recurrences after conservative treatment. The mean initial tumor basal diameter was 7.2 mm and tumor thickness was 2.9 mm. Seventeen tumors (50%) touched the optic disc and 10 (29%) were under the fovea. After a mean of three treatment sessions and 20 months of follow-up, the mean tumor thickness gradually decreased to 2.3 mm at month 3 and 2.0 mm at month 6 after the initial TTT. The percent reduction of tumor thickness was 20% at month 3 and 29% at month 6. The mean final thickness was 1.7 mm. Treatment was successful in 33 patients (97%). Tumor regrowth was documented in one patient (3%) and required plaque radiotherapy. After treatment, visual acuity was the same or better than the pretreatment visual acuity in 21 eyes (62%) and worse in 13 eyes (38%). Intraocular complications included retinal traction in 12 eyes (34%) and vascular occlusion in 3 eyes (9%). CONCLUSION: This series confirms the efficacy of transpupillary thermotherapy in the management of selected posterior pole choroidal melanomas. Longer follow-up is still required to assess late local recurrence and the impact on metastatic disease.

16
UI - 11958893
AU - Jones R; Gore E; Mieler W; Murray K; Gillin M; Albano K; Erickson B
TI - Posttreatment visual acuity in patients treated with episcleral plaque therapy for choroidal melanomas: dose and dose rate effects.
SO - Int J Radiat Oncol Biol Phys 2002 Mar 15;52(4):989-95
AD - Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. drrjones@hotmail.com
PURPOSE: To determine the relationship between the long-term visual function and the dose and dose rates delivered to critical ocular structures in patients with choroidal melanoma treated with 125I episcleral plaque radiotherapy. MATERIALS AND METHODS: From 1987 to 1994, 63 patients underwent 125I episcleral plaque (Collaborative Ocular Melanoma Study [COMS] design) application for the treatment of choroidal melanoma. The mean tumor height was 4.5 mm (range 1.7-8.3). Doses and dose rates at the tumor apex, macula, and optic disc were calculated. Forty-three records were scored to assess whether a decrease in visual acuity of >2 lines on a standard Snellen eye chart had occurred. Patient age and the presence of hypertension or diabetes were noted. Statistical analysis was performed to assess both the rate at which visual decline had occurred and the presence of significant factors that had contributed to this decline. RESULTS: With a median follow-up of 36 months, the 3-year actuarial survival rate was 93.6%. The 3-year actuarial local control rate was 86.9%. The median time to visual loss after therapy was 18.7 months. The 3-year actuarial rate of visual preservation was 40.5%. Multivariate analysis demonstrated higher macula dose rates (p = 0.003) to forecast visual decline. Macula dose rates of 111 +/- 11.1 cGy/h were associated with a 50% risk of significant visual loss. CONCLUSION: Patients in our series treated with 125I plaque brachytherapy for choroidal melanoma experienced favorable tumor control, but with a measurable incidence of visual decline. Higher dose rates to the macula correlated strongly with poorer posttreatment visual outcome. This information may be valuable in selecting the optimal dose rates to treat choroidal melanomas and to predict the risk of visual decline.

17
UI - 12209995
AU - Vajdic CM; Kricker A; Giblin M; McKenzie J; Aitken J; Giles GG;
TI - Armstrong BK Sun exposure predicts risk of ocular melanoma in Australia.
SO - Int J Cancer 2002 Sep 10;101(2):175-82
AD - Cancer Research and Registers Division, New South Wales Cancer Council, Sydney, Australia.
Previous studies examining sun exposure and ocular melanoma have produced inconsistent results. We investigated this association in a population-based case-control study in Australia. Cases (n = 290) aged (n = 893) were randomly selected from the electoral rolls and frequency-matched to cases by age, sex and state. A self-administered questionnaire and a telephone interview measured sun exposure on weekdays and weekends at 10, 20, 30 and 40 years of age and over the whole of life for specific jobs and recreations. Multivariate logistic regression models of ocular melanoma and sun exposure contained age, sex, region of birth, eye color and measures of ocular and cutaneous sun sensitivity as covariates. Choroid and ciliary body melanoma (n = 246) was positively associated with time outdoors on weekdays and, less persuasively, total time outdoors but not ambient solar irradiance. Odds ratios increased with increasing exposure to OR 1.8 (95% confidence interval 1.1-2.8) for the highest quarter of sun exposure on weekdays up to 40 years of age for men and women together. The strongest positive associations were for total exposure up to 40 years of age, lifetime occupational exposure and total exposure at about 20 years of age in men; all had odds ratios between 2 and 3 in the highest exposure categories. There was inconclusive evidence for an association between sun exposure and iris (n = 25) or conjunctival (n = 19) melanomas. Sun exposure is an independent risk factor for choroidal and ciliary body melanoma in Australia. Copyright 2002 Wiley-Liss, Inc.

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NCI CANCERLIT^® Search: Intraocular Melanoma - September 2002

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NCI CANCERLIT® Search: Intraocular Melanoma - September 2002

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NCI CANCERLIT^® Search: Intraocular Melanoma - September 2002