Uveal malignant melanoma with extrascleral extension, treated with plaque radiotherapy.
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Aged↗
Biomedical subjects
B E Damato
Publications and source records attributed to B E Damato.
Accuracy of choroidal melanoma diagnosis by general ophthalmologists: a prospective study.
PURPOSE: To estimate the proportion of 'false positives' in patients referred with a diagnosis of suspected choroidal melanoma by general ophthalmologists to an ocular oncology centre. METHODS: A prospective study of patients referred by general ophthalmologists to an ocular oncology centre was undertaken over a 14-week period. The diagnosis was made clinically in patients receiving radiotherapy or phototherapy and was confirmed by histopathology in patients requiring fine needle aspiration biopsy (FNAB) or enucleation. RESULTS: A total of 132 new patients were seen in 10 consecutive ocular oncology clinics between 29 March 2004 and 5 July 2004. The mean age was 62 years (range 28-88 years) and 60 (55%) were female. Among the 83 suspected malignant posterior segment lesions, the suspected diagnosis included choroidal melanoma (73), choroidal metastasis (6), 'choroidal tumour' (3), and 'Solid retinal detachment' (1). Only 50 of the 73 suspected melanomas were confirmed (68.5%; 95% CI, 57-78%), the oncologist's diagnosis in the remaining 23 being choroidal naevus (10), choroidal metastasis (1), circumscribed choroidal haemangioma (2) and others (10). Only one of six patients with suspected metastases had this condition, the remainder having melanoma (1), lymphoma (1), circumscribed choroidal haemangioma (1), and others (2). The 'choroidal tumours' and 'solid detachments' were found to be chorio-retinal disciform scar (1), varix of vortex vein (1), eccentric CNV (1), and subretinal haemorrhage (1) CONCLUSION: Approximately 30% of patients referred to an ocular oncology service with the diagnosis of choroidal melanoma have an incorrect diagnosis.
Adult↗
Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3.
Defining regions of genomic imbalance can identify genes involved in tumour development. Conventional cytogenetics has identified several nonrandom copy number alterations (CNA) in uveal melanomas (UVM), which include monosomy 3, chromosome 6 abnormalities and gain of 8q. To gain further insight into the CNAs and define the regions involved more precisely we analysed 18 primary UVMs using 1 Mb BAC microarray comparative genomic hybridisation (CGH). Our analysis showed that the most common genomic imbalances were 8q gain (78%), 6p gain (67%) and monosomy 3 (56%). Two distinct CGH profiles could be delineated on the basis of the chromosome 3 status. The most common genetic changes in monosomy 3 tumours, in our study, were gain of 8q11.21-q24.3, 6p25.1-p21.2, 21q21.2-q21.3 and 21q22.13-q22.3 and loss of 1p36.33-p34.3, 1p31.1-p21.2, 6q16.2-q25.3 and 8p23.3-p11.23. In contrast, disomy 3 tumours showed recurrent gains of only 6p25.3-p22.3 and 8q23.2-q24.3. Our approach allowed definition of the smallest overlapping regions of imbalance, which may be important in the development of UVM.
Adult↗
The patient's role in the decision-making process--a perspective from the Liverpool Ocular Oncology Centre.
PURPOSE: To examine the patient's role in the decision-making process in a tertiary adult ocular oncology service. METHODS: A prospective study was carried out of patients attending for follow-up at the Liverpool ocular oncology centre (LOOC), a tertiary adult ocular oncology service. Participants were patients who attended the clinic between September and October 2003. Through supervised completion of questionnaires, the main factors observed were: patients' preferred level of participation, patients' perceived level of participation, sources of information used by patients, and which sources they found most useful. RESULTS: In all, 39 patients were included in the study. The majority of patients (69.2%) would have preferred to make a shared decision with the doctor (10.3% preferring an active role, 20.5% preferring a passive role), while 48.7% perceived having had a shared role (25.6% felt they had had an active role, 25.6% a passive one). Outside the LOOC, general ophthalmologists were the most frequently cited source of information from health professionals, and were also scored as the most useful. Family and friends were the most common source of informal information, followed by use of the Internet. Tape recordings of the consultations were reported as the most popular resource provided by the LOOC. CONCLUSIONS: Patients attending the LOOC have a strong desire for involvement in the decision-making process. Patients receive little formal or informal information outside this tertiary centre. Further work is required to assess the effectiveness of physicians' communication skills and the influence of their recommendations on patient choice.
Adult↗
Patient attitudes to receiving copies of outpatient clinic letters from the ocular oncologist to the referring ophthalmologist and GP.
AIM: To investigate patients' views and understanding on receiving a copy of the outpatient clinic letter from the ocular oncologist to the referring ophthalmologist and GP. METHODS: Face-to-face interviews were conducted with 52 patients attending outpatient ocular oncology follow-up clinics, in a semistructured format using a qualitative open-ended questionnaire. The clinics are held at Liverpool Ocular Oncology Centre, a tertiary specialist referral centre at St. Paul's Eye Unit in Royal Liverpool University Hospital. RESULTS: Patients' views on receiving a copy of the outpatient letter, their understanding of the letter, and improvements suggested. A total of 58% of patients had received a letter and 97% of them said they were glad they had it. Of this group 77% had shown it to family/friend. Consistent comments included: 'help with accepting the news;' 'good to be informed and to know what to expect;' 'confirmed what was said in the consultation.' Of the patients who had not received a copy of the letter, 64% replied that they would have liked a copy. A total of 80% of patients reported that they fully understood the letter. In all, 17% wanted medical terms to be explained, when asked to suggest improvements. CONCLUSIONS: Sending patients copies of the consultant outpatient letter seemed to be highly appreciated and a useful method of information giving regarding diagnosis and management.
Adult↗
Role of MC1R variants in uveal melanoma.
Variants of the melanocortin-1 receptor (MC1R) gene have been linked to sun-sensitive skin types and hair colour, and may independently play a role in susceptibility to cutaneous melanoma. To assess the role of MC1R variants in uveal melanoma, we have analysed a cohort of 350 patients for the changes within the major region of the gene displaying sequence variation. Eight variants were detected - V60L, D84E, V92M, R151C, I155T, R160W, R163Q and D294H - 63% of these patients being hetero- or homozygous for at least one variant. Standard melanoma risk factor data were available on 119 of the patients. MC1R variants were significantly associated with hair colour (P=0.03) but not skin or eye colour. The frequency of the variants detected in the 350 patients was comparable with those in the general population, and comparison of the cumulative tumour distribution by age at diagnosis in carriers and noncarriers provided no evidence that MC1R variants confer an increased risk of uveal melanoma. We interpret the data as indicating that MC1R variants do not appear to be major determinants of susceptibility to uveal melanoma.
Adult↗
Bilateral uveal melanoma: a series of four cases.
AIM: To describe the occurrence of bilateral primary choroidal melanoma in four patients. METHODS: All patients attending the Liverpool Ocular Oncology Centre with uveal melanoma between January 1993 and February 2002 were identified, and those with bilateral primary choroidal melanoma were reviewed. Their presentation and management are described. RESULTS: Four patients, all female, were identified. Patient 1 presented with a right juxtapapillary melanoma at the age of 64, which was treated with krypton laser and endoresection, and then when aged 73 required proton beam radiotherapy for a melanoma in her left eye. Patient 2 presented at the age of 82 with bilateral choroidal melanomas and underwent simultaneous bilateral plaque radiotherapy. Patient 3 presented with bilateral choroidal melanomas at the age of 75 and was treated initially with bilateral proton beam radiotherapy. Patient 4 was treated at the age of 54 with right plaque radiotherapy for a choroidal melanoma, and 3 years later needed plaque radiotherapy for a melanoma in her other eye. CONCLUSION: Bilateral choroidal melanoma is possible and should be a consideration in the continuing management of patients with choroidal melanoma.
Aged↗
Simultaneous presentation of choroidal melanoma in mother and daughter.
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Aged↗
Decreased endothelin receptor B expression in large primary uveal melanomas is associated with early clinical metastasis and short survival.
The most devastating aspect of cancer is the metastasis of tumour cells to organs distant from the original tumour site. The major problem facing oncologists treating uveal melanoma, the most common cancer of the eye, is metastatic disease. To lower mortality, it is necessary to increase our understanding of the molecular genetic alterations involved in this process. Using suppression subtractive hybridisation, we have analysed differential gene expression between four primary tumours from patients who have developed clinical metastasis and four primary tumours from patients with no evidence of metastasis to date. We have identified endothelin receptor type B as differentially expressed between these tumours and confirmed this observation using comparative multiplex RT-PCR. In a further 33 tumours, reduced endothelin receptor type B expression correlated with death from metastatic disease. Reduced expression also correlated with other known prognostic indicators, including the presence of epithelioid cells, chromosome 3 allelic imbalance and chromosome 8q allelic imbalance. Endothelin receptor type B expression was also reduced in four out of four primary small cell lung carcinomas compared to normal bronchial epithelium. We also show that the observed down-regulation of endothelin receptor type B in uveal melanoma was not due to gene deletion. Our findings suggest a role for endothelin receptor type B in the metastasis of uveal melanoma and, potentially, in the metastasis of other neural crest tumours.
Adult↗
Palliative vitrectomy for intraocular metastasis from cutaneous melanoma.
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Aged↗
Malignant melanoma and massive retinal gliosis in phthisis bulbi.
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Eye Enucleation↗
Overexpression of epidermal growth factor receptor restricted to macrophages in uveal melanoma.
OBJECTIVE: To determine whether expression of the epidermal growth factor receptor (EGFR) is of prognostic value in uveal melanoma. METHODS: Thirty consecutive patients treated for primary posterior uveal melanoma by enucleation or local resection were studied. Tumors were examined for EGFR and CD68 expression by immunohistochemistry on formalin-fixed, paraffin-embedded sections. Extracted DNA from paired frozen tumor and blood samples was examined for loss of heterozygosity on chromosome 3 using polymerase chain reaction-based microsatellite analysis. Immunoreactivity for EGFR was correlated with clinicopathological, chromosome 3, and follow-up data. RESULTS: Immunoreactivity for EGFR was observed in 7 (23%) of 30 uveal melanomas, but was restricted to solitary or small groups of cells with macrophage-like morphology. Immunoreactive cells were confirmed as macrophages using an antibody to the macrophage marker CD68. Chromosome 3 loss, epithelioid cells, and microvascular loops were detected in 17 (57%), 22 (73%) and 19 (63%) of the 30 tumors, respectively. Metastatic disease was detected in 5 patients (17%). No correlation was found between any of these variables and EGFR positivity. CONCLUSIONS: The absence of EGFR immunoreactivity in tumor cells does not support the use of EGFR expression as a prognostic indicator in patients with uveal melanoma. Future EGFR studies in uveal melanoma should be interpreted with caution in view of our findings that tumor-associated macrophages can express this receptor.
Antigens, CD↗
Loss of heterozygosity on chromosomes 3, 9, 13, and 17, including the retinoblastoma locus, in uveal melanoma.
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.
Acid Anhydride Hydrolases↗
Transformation of cell type in uveal melanomas: a quantitative histologic analysis.
OBJECTIVE: To describe the cytologic transformation and tumor progression in a series of uveal melanomas. METHODS: Fifteen cases of uveal melanoma, treated by primary transscleral local resection without primary adjuvant treatment, needed enucleation because of local tumor recurrence. Cytologic and cell morphometric features of the primary tumor and the intraocular recurrence were compared, with evaluation of the amounts of intermediate cells, epithelioid cells, mitotic figures, and nucleolar area. RESULTS: The cases were categorized into 2 groups, according to their cytologic characteristics. In the first group (5 cases), there was no cytopathological transformation in the recurrent tumor. The nucleolar area was increased in only 1 case. In the second group (10 cases), the recurrent tumors showed transformation into a more epithelioid cell type. In all but 1 case there was an increase in epithelioid cells in the tumor recurrence. The nucleolar area was increased significantly in all cases. The mean local recurrence interval in all cases was 15.3 months, with no difference between the groups. Death from metastases occurred in 7 cases in which the nucleolar area was 4.2 microm(2) in the primary tumor. CONCLUSIONS: These findings demonstrate that, in an individual tumor, the cytologic phenotype can change considerably even after a relatively short time, resulting in an increase in tumor-related mortality. CLINICAL RELEVANCE: Studies on the natural course of uveal melanoma have been very limited and based purely on observations on the progression of melanomas in terms of size and alteration of various clinical characteristics.
Adult↗
Genetic predisposition to ocular melanoma.
Uveal melanoma is the most common primary intraocular malignancy, with an annual incidence of 6 per million. The environmental factors known to increase the risk of cutaneous melanoma appear to be less important in ocular melanoma and it is conceivable that host factors have a greater impact. The coexistence of ocular and cutaneous melanoma in some patients suggests a predisposition to both types and implicates mutations in the CDKN2A gene in a proportion of these cases. An association between ocular melanoma and breast and/or ovarian cancer has also been reported and recent studies of breast cancer families strongly implicate BRCA2 as a predisposition gene. Other more common genes predisposing to ocular melanoma may be of low penetrance. An example of a gene in this class is MC1R, which affects host response to ultraviolet radiation. Identification of genes conferring an increased risk of ocular melanoma should provide insights into the pathogenesis of this tumour. Furthermore, it offers an opportunity to identify individuals at a high risk who may benefit from targeted surveillance. At present the identification of such individuals is restricted to the small number belonging to BRCA2 families and those with the atypical mole syndrome.
Genes, BRCA1↗
Auditing outcomes after treatment of Scottish patients with uveal melanoma in Liverpool.
Uveal melanoma is the most common primary intraocular malignant tumour, although it is a rare condition. Between January 1993 and December 1997 a total of 120 patients were referred from Scotland to the Ocular Oncology Service at St. Paul's Eye Unit in Liverpool. Of these, 98 had uveal melanoma, which was treated with primary enucleation (24), or by conservative methods, consisting of plaque radiotherapy (30), proton beam radiotherapy (19), trans-scleral local resection (19), or endoresection (6). After conservative treatment, 92% of eyes were retained, with 65% of eyes maintaining the same level of vision as at presentation or better. The main complications were retinal detachment (8), death from metastatic disease (7) and local tumour recurrence (4). This study gives an overview of the treatment of uveal melanoma and demonstrates that most patients with uveal melanoma can be treated conservatively, with the large majority retaining the eye and good vision.
Adult↗
Management of Irish patients with intraocular melanoma referred to Liverpool, England.
PURPOSE: This study reviews the results of patients referred from Ireland for treatment of an intraocular melanoma at the Ocular Oncology Service at St Paul's Eye Unit, Liverpool. PATIENTS AND METHODS: There were 57 patients with a median age of 55 years. Management included plaque radiotherapy (14), proton beam radiotherapy (17), local resection (10), endoresection (6), and enucleation (10). Fifty-two tumours involved the choroid. The tumours had a mean diameter of 11.4 mm and a mean thickness of 5.2 mm. RESULTS: The follow-up period had a median of 267 days. Retention of the eye was achieved in all 47 cases who underwent conservative management. Ninety percent of patients retained a vision of counting fingers, with an acuity of 6/12 or better in 50%. CONCLUSION: This group of patients gives an indication of the results that can be expected when uveal melanoma is managed by a variety of conservative techniques in a specialised ocular oncology service.
Brachytherapy↗
Delays in the diagnosis of uveal melanoma and effect on treatment.
PURPOSE: To investigate the mode of presentation of uveal melanomas, delays in their diagnosis and the effect of delayed diagnosis on treatment outcome. METHODS: An analysis was carried out of 50 consecutive patients undergoing treatment for uveal melanoma at the Ocular Oncology Service in Liverpool. The mode of presentation of the tumour, onset of symptoms and subsequent management were determined by interview at the time of treatment. RESULTS: Seventy-two per cent of patients had one or more symptoms directly attributable to the tumour. These included blurred vision (36%), photopsia (22%), visual field loss (16%), floaters (4%) and metamorphopsia (4%). Forty-two per cent of patients experienced delays in the diagnosis and treatment due to misdiagnoses such as macular degeneration and naevus or due to the lesion being missed at the initial visit. Patients who had experienced delays in diagnosis received treatment after a mean of 6.6 months compared with 4.2 weeks for those who did not experience any delay (p = 0.003). Such patients were more likely to be treated by enucleation (52% vs 17%, p = 0.008) than by an eye-conserving method such as radiotherapy or trans-scleral local resection. CONCLUSIONS: The primary aim of treatment of uveal melanoma is to reduce the risk of death from metastases and a secondary aim is to conserve the eye with as much vision as possible. This study identifies common reasons for delays in the diagnosis of uveal melanoma. While the effect of early treatment on survival remains controversial, this study shows that patients who have their tumours diagnosed promptly are more likely to be treated by an eye-conserving method than by enucleation.
Adult↗