National Cancer Institute®
Last Modified: November 21, 2001
UI - 20329341
AU - Singh AD; Shields CL; Shields JA; Sternberg P Jr
TI - Occurrence of retinoblastoma and uveal melanoma in the same patient.
SO - Retina 2000;20(3):305-6
AD - Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. firstname.lastname@example.org
UI - 21396163
AU - Lee HM; Kang HJ; Choi G; Chae SW; Kim CH; Hwang SJ; Lee SH
TI - Two cases of primary malignant melanoma of the lacrimal sac.
SO - Head Neck 2001 Sep;23(9):809-13
AD - Department of Otorhinolaryngology--Head and Neck Surgery, Korea University College of Medicine, Guro Hospital, 80 Guro-dong, Guro-gu, Seoul 152-703, South Korea. email@example.com
BACKGROUND: Malignancy of the lacrimal sac is rare, and primary malignant melanoma in this region is extremely rare. METHODS: We report two cases of malignant melanoma of the lacrimal sac presented with epiphora and a palpable mass in the medial canthal area. We performed radical surgery and radiation therapy. RESULTS: The light microscopic, immunohistochemical, and electron microscopic studies confirmed the diagnosis. One of the patients, a 65-year-old-woman, has no evidence of recurrence or distant metastasis 3 years after surgery and radiotherapy, whereas another patient, a 56-year-old man, died of distant metastasis 6 months after surgery and radiotherapy. CONCLUSIONS: We present two cases of malignant melanoma of the lacrimal sac that masqueraded as chronic dacryocystitis. Head and neck surgeons should be aware of this disease entity when encountered with patients with epiphora and mass in the medial canthal area. Copyright 2001 John Wiley & Sons, Inc.
UI - 21268051
AU - Sulkowski S; Sulkowska M; Famulski W; Chyczewski L; Bakunowicz-Lazarczyk
TI - A Expression of P53 protein in primary uveal melanoma.
SO - Folia Histochem Cytobiol 2001;39(2):159-60
AD - Department of Pathological Anatomy, Medical Academy, Bialystok, Poland. firstname.lastname@example.org
Malignant melanomas are the commonest intraocular tumours. The aim of the present study was the immunohistochemical analysis of P53 protein expression in 39 primary ocular melanomas treated surgically in the years 1983-1997. Expression of P53 was estimated semiquantitatively with the use of a light microscope at a magnification of x 400. At least 200 neoplastic cells per sample were analysed. The expression of P53 in 3% of melanoma cells was considered the threshold of positive reaction. The results were subjected to statistical analysis with exact Fischer's test. No statistically significant correlations were found between P53 expression and anatomoclinical properties of tumours, although increased P53 expression was observed in epithelioid-cellular melanomas and in tumours growing in women. A lack of statistically significant relationship between P53 protein level and the parameters examined, and morphological specificity of ocular melanomas hindering immunohistochemical analysis, indicate the necessity for studies on a wider group of tumours or/and use of molecular biology techniques to establish possible relations between P53 gene mutation and ocular melanoma biology.
UI - 21373757
AU - Burnier Pereira F; Burnier MN Jr; Shibata H; Wang B; Carey W
TI - Cytomorphometric parameters and the metastatic potential of cutaneous and uveal melanoma: a comparison with prognostic factors.
SO - Am J Dermatopathol 2001 Aug;23(4):304-7
AD - Henry C. Witelson Eye Pathology Laboratory, Department of Ophthalmology, The Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
The Mean of the Ten Largest Nuclei (MTLN1) is one of the most important prognostic factors in uveal malignant melanoma. This study was performed to investigate the applicability of nuclear and nucleolar measurements as a prognostic factor for cutaneous melanoma. A routine light microscope (Carl Zeiss: Axiophot EL-Einnsatz; #451888) at 640 times magnification with a Micrometer Eye Piece (Carl Zeiss: #444034) was used to evaluate the correlation of MTLN1 and Mean of Ten Largest Nuclei (MTLN) with the occurrence of metastasis in 58 primary cutaneous melanoma. For uveal melanoma, cytologic classification was used for comparison. Prognostic value was determined by univariate and multivariate linear regression analysis. MTLN1 was the only significant factor for uveal melanoma (p = 0.05). For cutaneous melanoma, all factors were significantly associated with disease progression. MTLN1 was the only one to remain significant (p + 0.027) in multivariate linear regression analysis. Nuclear and nucleolar morphometry are significant prognostic factors for uveal and cutaneous melanoma.
UI - 21411328
AU - Albert D; Syed N; Cancer Committee, College of American Pathologists
TI - Protocol for the examination of specimens from patients with uveal melanoma: a basis for checklists.
SO - Arch Pathol Lab Med 2001 Sep;125(9):1177-82
AD - Department of Ophthalmology, University of Wisconsin Hospital, Madison, USA.
UI - 21468543
AU - Brandberg Y; Kock E; Oskar K; af Trampe E; Seregard S
TI - Psychological reactions and quality of life in patients with posterior uveal melanoma treated with ruthenium plaque therapy or enucleation: a one year follow-up study.
SO - Eye 2000 Dec;14(Pt 6):839-46
AD - Department of Oncology, Karolinska Hospital, Stockholm, Sweden. email@example.com
PURPOSE: To investigate psychological reactions and quality of life among patients with posterior uveal melanoma. METHODS: Consecutive patients with uveal malignant melanoma (99/106), referred to St Erik's Eye Hospital 1995-1996, treated with rutheniuim plaque radiotherapy (n = 50) or enucleation (n = 49), were included in this non-randomised prospective comparative study. Questionnaires were completed before treatment (Hospital Anxiety and Depression Scale, HAD scale) and 2 and 12 months after diagnosis including the HAD scale, the Impact of Event Scale and the EORTC QLQ-C30. A disease-specific questionnaire was included 12 months after diagnosis. Between-group differences were analysed by chi-square, Student's t-test and ANOVA. RESULTS: A majority of the patients reported reduced 'Quality of Life' (72-85%), 'Emotional functioning' (60-74%) and 'Cognitive functioning' (51-61%). 'Fatigue' was the most frequently reported symptom (61-72%) followed by 'Insomnia' (43-58%). Anxiety and depressive symptoms were relatively frequent up to 1 year after treatment, but the levels of anxiety decreased during the first year after treatment. Disease and treatment-related problems were reported in both treatment groups 1 year after diagnosis. Enucleated patients had more problems with appearance and judging distances, whereas those treated with radiotherapy reported vision impairment to a higher extent. CONCLUSIONS: Enucleated patients reported high levels of emotional distress, problems with appearance and judging distances during the first year after treatment. Patients treated with radiotherapy reported similar levels of quality of life and emotional problems, but more problems with visual impairment. These differences in impact on disease-related functioning should be taken into account when treatment options are discussed.
UI - 21462582
AU - The Collaborative Ocular Melanoma Study Group
TI - Sociodemographic and clinical predictors of participation in two randomized trials: findings from the Collaborative Ocular Melanoma Study COMS report no. 7.
SO - Control Clin Trials 2001 Oct;22(5):526-37
Collecting sociodemographic and clinical data concerning patients who choose not to enroll in a randomized clinical trial can be useful in assessing the feasibility of attaining sample size goals during the course of a trial. It can also aid in addressing the extent of generalizability of trial findings after a trial has ended. The Collaborative Ocular Melanoma Study (COMS) consists of two multicenter randomized clinical trials to evaluate the effectiveness of radiotherapy in comparison to standard enucleation (removal of the affected eye) in prolonging survival of patients with choroidal melanoma. One trial is for patients with large tumors and the other trial is for patients with medium-sized tumors. The same baseline sociodemographic and clinical data were collected for both enrolled patients and eligible patients who did not enroll in the randomized trials during the first 3 years of patient recruitment. Partial information on nonrandomized patients was collected thereafter. Recruitment ended in the large tumor and medium tumor trials on December 31, 1994, and July 31, 1998, respectively. From were evaluated for the randomized trials, of whom 4191 (61%) were eligible for enrollment. Logistic regression methods were used to identify factors predictive of trial participation. Sociodemographic factors that appeared to be associated (p < 0.15) with participation in the univariable models in the medium tumor trial were age 60 years or older, less than college education, nonmanagerial occupation, current smoking, and residing in the same state as a COMS clinical center. In the large tumor trial, males, individuals who were not college-educated, and individuals residing in the same state as a COMS clinical center were more likely to enroll. In both trials, clinical determinants of participation were larger tumor dimensions and initial visual acuity worse than 20/20 in the study eye. In multivariable regression models, the variables that were significantly predictive of enrollment (p < 0.05) in at least one of the trials were older age, residence in the same state, larger tumor basal diameter, and worse initial visual acuity in the study eye. Knowledge of possible sociodemographic and clinical predictors of differentials in patient participation for nonenrolled patients may help to refine patient education and recruitment strategies for future trials. Patient enrollment in clinical trials may be increased by heightened physician awareness of such predictors, strategies for addressing these differences, and enhanced communication between physicians and patients.
UI - 21464706
AU - Makitie T; Carpen O; Vaheri A; Kivela T
TI - Ezrin as a prognostic indicator and its relationship to tumor characteristics in uveal malignant melanoma.
SO - Invest Ophthalmol Vis Sci 2001 Oct;42(11):2442-9
AD - Ophthalmic Pathology Laboratory, Department of Ophthalmology, Helsinki University Central Hospital, Finland. firstname.lastname@example.org
PURPOSE: Immunohistochemistry was used to investigate whether uveal malignant melanoma expresses ezrin, a protein involved in cell migration and cell recognition by acting as a linker between the plasma membrane and actin cytoskeleton. Also investigated was whether ezrin immunoreactivity correlates with survival prognosis. METHODS: A monoclonal antibody, 3C12, that reacts with the carboxyl-terminal part of ezrin was used in retrospective analysis of a population-based cohort of 167 consecutive choroidal and ciliary body melanomas in eyes enucleated from 1972 through 1981, with a median follow-up of 22 years. RESULTS: Ezrin immunoreactivity in tumor cells was graded negative in 47 (36%) melanomas, positive in 74 (57%), and strongly positive in 9 (7%). The immunoreactivity tended to be homogenous throughout the tumor, with focal concentrations along the cell surface. Positive reaction was significantly associated with high microvascular density (P < 0.001) and presence of macrophages (P < 0.001), but not with tumor size, cell type, or microvascular loops and networks. The 10-year melanoma-specific survival was significantly associated with ezrin immunoreactivity (P = 0.018). After adjustment by Cox regression for tumor size, cell type, microvascular loops and networks, and microvascular density, a clinically meaningful 0.15 difference in 10-year melanoma-specific survival persisted. CONCLUSIONS: The presence of ezrin immunoreactivity in uveal malignant melanoma is associated with higher mortality and with two independent high-risk characteristics: microvascular density and number of infiltrating macrophages. Further experimental studies on the interrelationship of these three factors may shed light on the progression of uveal melanoma and perhaps that of other cancers.
UI - 21464710
AU - Scholes AG; Liloglou T; Maloney P; Hagan S; Nunn J; Hiscott P; Damato
TI - BE; Grierson I; Field JK Loss of heterozygosity on chromosomes 3, 9, 13, and 17, including the retinoblastoma locus, in uveal melanoma.
SO - Invest Ophthalmol Vis Sci 2001 Oct;42(11):2472-7
AD - Unit of Ophthalmology, Department of Medicine, The University of Liverpool, United Kingdom. email@example.com
PURPOSE: To identify tumor-suppressor loci that may contribute to the pathogenesis of uveal melanoma. METHODS: Multiplex fluorescence microsatellite assays were performed on 27 uveal melanomas using markers at 3p25-p26, 3p14.2, 9p21-p23, 13q14, 13q12.3-q13, and 17p13, close to or within the von Hippel Lindau (VHL), fragile histidine triad (FHIT), p16/cyclin-dependent kinase inhibitor 2 (CDKN2A), retinoblastoma (RB1), breast cancer 2 (BRCA2), and p53 tumor suppressor loci, respectively. Further markers on chromosomes 3 and 9 were analyzed individually. RESULTS: Loss of heterozygosity (LOH) was identified in 63% of tumors, most frequently on chromosome 3 (52%), in association with epithelioid cells (P = 0.0002) and microvascular loops (P = 0.0008). In the majority of cases, LOH on chromosome 3 was detected at all informative markers. The second most common alteration was LOH at an RB1 intragenic marker (21% tumors), with retention of a more centromeric 13q marker (near BRCA2). The pattern of LOH on chromosome 9p was consistent with the involvement of a region telomeric to CDKN2A. LOH at TP53 was infrequent. CONCLUSIONS: In the majority of cases, chromosome 3 LOH involves an entire chromosome homologue, which hampers identification of the relevant suppressor loci. This LOH correlates with the presence of microvascular loops and epithelioid cells, two of the recognized histologic indicators of poor prognosis. Data for chromosomes 13 and 9 support a role for RB1 in the pathogenesis of uveal melanoma but also raise the possibility of the involvement of additional loci close to RB1 and CDKN2A.
UI - 21421664
AU - Lee H; Choi SS; Kim SS; Hong YJ
TI - A case of glaucoma associated with Sturge-Weber syndrome and Nevus of Ota.
SO - Korean J Ophthalmol 2001 Jun;15(1):48-53
AD - The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
The Sturge-Weber syndrome consists of a unilateral port-wine hemangioma of the skin along the trigeminal distribution and is accompanied by an ipsilateral leptomeningeal angioma. Glaucoma is present in approximately half of the cases. The Nevus of Ota is a melanocytic pigmentary disorder, most commonly involving the area innervated by the trigeminal nerve. Elevated intraocular pressure, with or without glaucomatous damage, is observed in 10% of the cases. We report the first case of glaucoma associated with Sturge-Weber syndrome and Nevus of Ota in Korea.
UI - 21452830
AU - Pe'er J; Stefani FH; Seregard S; Kivela T; Lommatzsch P; Prause JU;
TI - Sobottka B; Damato B; Chowers I Cell proliferation activity in posterior uveal melanoma after Ru-106 brachytherapy: an EORTC ocular oncology group study.
SO - Br J Ophthalmol 2001 Oct;85(10):1208-12
AD - Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel. firstname.lastname@example.org
AIM: To evaluate the cell proliferation activity in posterior uveal melanomas after Ru-106 brachytherapy. METHODS: Eyes containing choroidal or ciliary body melanoma from seven ocular oncology centres, which were enucleated after first being treated by Ru-106 brachytherapy and which had enough melanoma tissue to enable histological assessment, were included. The 57 eligible specimens were divided into a group of 44 eyes that were enucleated because of tumour regrowth, and a non-recurrent group of 13 eyes that were enucleated because of complications such as neovascular glaucoma. 46 non-irradiated eyes harbouring uveal melanoma served as a control group. All specimens underwent routine processing. They were cut into 5 microm sections, and were stained with two main cell proliferation markers: PC-10 for PCNA and MIB-1 for Ki-67. The stained sections were assessed, and the cells that were positive in the immunostaining were counted in each section. The results were evaluated by various statistical methods. RESULTS: The PC-10 score showed a statistically significant difference across the three groups (p = 0.002). The control group showed the highest PC-10 score (median 31.0 PCC/HPF) followed by the tumour regrowth group (median 4.9 PCC/HPF). The lowest PC-10 scores were found in the non-recurrent tumours (median 0.05 PCC/HPF). The MIB-1 score in the control group (median 5.77 PCC/HPF) was similar to the regrowth group (median 5.4 PCC/HPF). In contrast, the MIB-1 score in the non-recurrent tumours was statistically significantly lower (median 0.42 PCC/HPF). The PC-10 and MIB-1 scores were similar in tumours composed of either spindle cells or epithelioid cells in all groups. CONCLUSIONS: The non-recurrent melanomas demonstrate significantly lower cellular proliferation activity than melanomas that showed regrowth or that were not irradiated at all. In our hands, PCNA gave more meaningful information than Ki-67. Our findings strongly support the need for treating regrowing posterior uveal melanoma either by enucleation or re-treatment by brachytherapy. On the other hand, also in the non-recurrent uveal melanomas there are viable cells with potential for proliferation, although fewer in number, with unknown capacity for metastatic spread. Therefore, the irradiated tumours should be followed for many years, probably for life.
UI - 21452831
AU - Char DH; Miller T; Crawford JB
TI - Uveal tumour resection.
SO - Br J Ophthalmol 2001 Oct;85(10):1213-9
AD - The Tumori Eye Foundation, CPMC Davies, Stanford University, CA 94114, USA. email@example.com
AIM: To review the ocular retention rates, visual results, and metastases in uveal tumours managed with eye wall resection techniques. METHODS: This was a retrospective analysis of consecutive local uveal tumour resections performed by a single surgeon. All enucleation specimens were reviewed by one author. Both parametric and non-parametric analysis of data were performed. RESULTS: 138 eyes were scheduled for eye wall resection surgery. The mean age was 52 years (range 11-86 years). Tumours involved predominantly the iris in 14 cases, iris-ciliary body in 57, ciliary body alone in 18 patients, and in 49 cases the choroid was involved (ciliochoroidal, iris-ciliary body-choroid, or choroid). 125 eyes harboured melanomas; posterior tumours were more likely to have epithelioid cells (p<0.05). The mean follow up was 6 years. The mean clock hours in iris and iris-ciliary body tumours was 3.5. In tumours that involved the choroid the mean largest diameter was 12.9 mm and the mean thickness 8.5 mm. 105 of 138 (76%) eyes were retained. Histological assessment of surgical margins did not correlate evidence of tumour in enucleated eyes or metastatic disease. Surgical margins of more anterior tumours were more likely to be clear on histological evaluation (p<0.05). Approximately 53% of retained eyes had a final visual acuity of > or =20/40; visual results were significantly better in more anteriorly located tumours (p<0.05). All retained iris tumour cases had > or =20/40 final visual acuity. In tumours that involved the choroid nine of 31 retained eyes kept that level of visual acuity. Eight patients developed metastases; all metastatic events developed in patients with tumours that involved the choroid, and seven of eight were mixed cell melanomas. CONCLUSIONS: 76% of eyes were retained and 53% of these had a final visual acuity of > or =20/40. Only 7% of uveal melanoma patients developed metastatic disease with a mean follow up of 6 years. Survival did not appear to be compromised with eye wall resection and in very thick, more posterior melanomas it appeared that ocular retention and visual results were better than with radiation alone.
UI - 21486090
AU - Wilson MW; Schelonka LP; Siegel D; Meininger A; Ross D
TI - Immunohistochemical localization of NAD(P)H:quinone oxidoreductase in conjunctival melanomas and primary acquired melanosis.
SO - Curr Eye Res 2001 May;22(5):348-52
AD - Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA. firstname.lastname@example.org
PURPOSE. Mitomycin C has been used in the treatment of primary acquired melanosis and melanomas of the conjunctiva. Because there is increasing evidence that NAD(P)H:quinone oxidoreductase (EC 184.108.40.206, NQO1) or DT-diaphorase plays an important role in the bioactivation of mitomycin C, we examined pathologic specimens of these tumors for NQO1 by immunohistochemistry. METHODS. Formalin-fixed, paraffin-embedded sections with histologic diagnoses of primary acquired melanosis or conjunctival melanomas were obtained from the Eye Pathology Laboratory, University of Colorado Health Sciences Center. Detection of NQO1 in tissues was performed using standard immunohistochemical techniques with monoclonal antibodies against NQO1 and immunoperoxidase staining. Samples were examined by two independent reviewers and NQO1 staining was graded from 0 (no staining) to 3+ (intense staining). RESULTS. Eleven of 11 melanomas (95% confidence interval, 72% to 100%) and three of three lesions with primary acquired melanosis with atypia stained positively for NQO1. In the melanomas, staining was relatively uniform, while in primary acquired melanosis there was cell-to-cell variability in the staining. CONCLUSIONS. NQO1 was detected by immunohistochemistry in every examined section of primary acquired melanosis and melanoma of the conjunctiva, suggesting that NQO1 may play a role in the bioactivation of mitomycin C in these tumors.
UI - 21473785
AU - Shields CL; Shields JA; Armstrong T
TI - Management of conjunctival and corneal melanoma with surgical excision, amniotic membrane allograft, and topical chemotherapy.
SO - Am J Ophthalmol 2001 Oct;132(4):576-8
AD - Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, 900 Walnut St., Philadelphia, PA 19107, USA. email@example.com
PURPOSE: To illustrate a novel method of management for extensive conjunctival and corneal melanoma. METHODS: Interventional case report. A 40-year-old Caucasian woman presented with a large, diffuse conjunctival melanoma involving 6 clock hours of the limbus. The remaining bulbar conjunctiva and the entire corneal epithelium were affected by diffuse, flat melanosis. RESULTS: The conjunctival melanoma was completely resected microsurgically in one piece without disrupting the tumor. The conjunctival melanosis was treated with double freeze-thaw cryotherapy. The extensive conjunctival defect, involving one-half of the bulbar conjunctiva, was reconstructed with an amniotic membrane allograft. The corneal melanosis was subsequently treated with topical mitomycin C eyedrops. At 8 months follow-up, the conjunctiva and the cornea were completely healed with resolution of all pigment and 20/20 visual acuity. CONCLUSION: Preliminary evidence suggests that combined therapeutic approaches, consisting of extensive tumor removal, cryotherapy, amniotic membrane allograft, and topical mitomyin C, can be effective in the management of diffuse conjunctival and corneal melanoma arising from primary acquired melanosis.
UI - 21473786
AU - Zacks DN; Pinnolis MK; Berson EL; Gragoudas ES
TI - Melanoma-associated retinopathy and recurrent exudative retinal detachments in a patient with choroidal melanoma.
SO - Am J Ophthalmol 2001 Oct;132(4):578-81
AD - Retina Service, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA. David_Zacks@meei.harvard.edu
PURPOSE: To report a patient who presented with photopsias, night blindness, exudative retinal detachments, and melanoma-associated retinopathy in her right eye 23 years after the left eye was enucleated for a choroidal melanoma. METHODS: Assessment of fundus findings, fluorescein angiograms, and electroretinograms. RESULTS: The patient had recurrent exudative detachments of the macula in her right eye and electroretinogram responses consistent with the diagnosis of melanoma-associated retinopathy. The abdominal computed tomography (CT) scan was negative, but 13 months later, CT scanning revealed many masses in her liver. Fine-needle biopsy confirmed the diagnosis of metastatic melanoma. CONCLUSION: To our knowledge, this is the first report of melanoma-associated retinopathy in a patient with a previous choroidal melanoma.
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