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      Conjunctival melanoma: a review of conceptual and treatment advances

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          Abstract

          The aim of this study was to review the available literature and identify recent advances in the classification and management of conjunctival melanoma (CM) for clinicians working in this field. English-based articles were identified using the MEDLINE ® database, and additional cited works not detected in the initial search were also obtained. Articles were assessed according to the Australian National Health and Medical Research Council levels of evidence criteria. Review of the literature indicated that the current classification and management of CM is predominantly based upon primarily nonrandomized, single-institution, retrospective case series. While these studies provide the basis for the recent seventh edition of the tumor node metastasis staging classification, this classification more accurately reflects the current knowledge of prognostic factors for CM. Application of this revised classification system together with prospective trials will provide the opportunity for future consistent and comparable data collection across centers, and it will improve the quality of evidence upon which current classification and management of CM is based. Furthermore, the high risk of local recurrence with current standard management suggests that adjuvant therapy, particularly mitomycin C and/or brachytherapy, may improve outcomes regardless of clinical staging. Finally, the use of sentinel lymph node biopsy may have significant benefit for a select group of CM patients.

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          Most cited references63

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          KIT gene mutations and copy number in melanoma subtypes.

          We recently identified a KIT exon 11 mutation in an anorectal melanoma of a patient who had an excellent response to treatment with imatinib. To determine the frequency of KIT mutations across melanoma subtypes, we surveyed a large series of tumors. One hundred eighty-nine melanomas were screened for mutations in KIT exons 11, 13, and 17. KIT copy number was assessed by quantitative PCR. A subset of cases was evaluated for BRAF and NRAS mutations. Immunohistochemistry was done to assess KIT (CD117) expression. KIT mutations were detected in 23% (3 of 13) of acral melanomas, 15.6% (7 of 45) of mucosal melanomas, 7.7% (1 of 13) of conjunctival melanomas, 1.7% (1 of 58) of cutaneous melanomas, and 0% (0 of 60) of choroidal melanomas. Almost all the KIT mutations were of the type predicted to be imatinib sensitive. There was no overlap with NRAS mutations (11.1% of acral and 24.3% of mucosal tumors) or with BRAF mutations (absent in mucosal tumors). Increased KIT copy number was detected in 27.3% (3 of 11) of acral and 26.3% (10 of 38) of mucosal melanomas, but was less common among cutaneous (6.7%; 3 of 45), conjunctival (7.1%; 1 of 14), and choroidal melanomas (0 of 28). CD117 expression, present in 39% of 105 tumors representing all melanoma types, did not correlate with either KIT mutation status or KIT copy number. Our findings confirm that KIT mutations are most common in acral and mucosal melanomas but do not necessarily correlate with KIT copy number or CD117 expression. Screening for KIT mutations may open up new treatment options for melanoma patients.
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            Surgical management of conjunctival tumors. The 1994 Lynn B. McMahan Lecture.

            To our knowledge, there are no articles that describe the specific step-by-step details of the surgical removal of premalignant and malignant conjunctival tumors. We describe our current approach to the surgical management of squamous cell carcinoma (intraepithelial or invasive), localized melanoma, and primary acquired melanosis of the conjunctiva. The surgical method differs with limbal tumors, extralimbal tumors, and primary acquired melanosis. Limbal lesions are managed by localized alcohol corneal epitheliectomy, removal of the main mass by a partial lamellar scleroconjunctivectomy, and supplemental cryotherapy. Tumors located in the extralimbal conjunctiva are managed by alcohol application, wide circumferential surgical resection, and cryotherapy. Primary acquired melanosis is managed by alcohol epitheliectomy, removal of suspicious foci, quadrantic staging biopsies, and cryotherapy from the underside of the conjunctiva. In all cases, a "no touch" method is used and direct manipulation of the tumor is avoided to prevent tumor cell seeding into a new area. We have employed this technique on 109 patients with conjunctival squamous neoplasms and 137 patients with conjunctival melanoma, about 80 of which neoplasms were associated with primary acquired melanosis. Our observations suggest that well-planned initial surgical management using this technique decreases the chance of tumor recurrence for conjunctival melanoma and squamous cell carcinoma. We describe a detailed stepwise approach to the surgical management of conjunctival neoplasms. It requires meticulous clinical evaluation and complete removal of the tumor in one operation using a specific technique.
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              Conjunctival melanoma in the Netherlands: a nationwide study.

              To evaluate risk factors for local recurrence, regional and distant metastases, and mortality associated with conjunctival melanoma. This was a retrospective study of 194 patients with histologically confirmed conjunctival melanoma diagnosed between 1950 and 2002 in the Netherlands. Data were collected from all university centers and many nontertiary hospitals, using the National Pathology and the Leiden Oncologic Registration Systems. Based on the number of incidences, this study included 70% of the conjunctival melanomas in The Netherlands. Clinical and histopathological data for conjunctival tumors were reviewed and compared with data reported in the literature. Risk factors for local, regional, and distant metastases and survival were analyzed using the Kaplan-Meier and Cox regression analyses. Of 194 patients with conjunctival melanoma, 112 had a local recurrence (median, 1; range, 1-9) during follow-up (median, 6.8 years; range, 0.1-51.5). Location was the most important risk factor for development of local recurrence, and significantly more occurred with nonepibulbar (log rank, P=0.044) tumors. Significantly fewer local recurrences occurred with tumors initially treated with excision and adjuvant brachytherapy rather than with excision only (log rank, P=0.008) or with excision and cryotherapy (log rank, P <0.038). Forty-one (21%) patients had regional lymph node metastases, mostly to the parotid or preauricular lymph nodes (n=26; 13%). Risk factors for regional metastases were tumor thickness (log rank, P <0.001) and tumor diameter (log rank, P=0.010). Forty-nine (25%) patients (mean, 4.37 years) had development of distant metastases, mainly in the lung, liver, skin, and brain. Tumor-related survival was 86.3% (95% confidence interval [CI], 81.0-91.6) at 5 years, 72% (95% CI, 79.7-64.4) at 10 years, and 67% (95% CI, 58.9-76.1) at 15 years. The main mortality risk factors were nonepibulbar location (log rank, P <0.0001) and tumor thickness (log rank, P=0.0004). Nonepibulbar tumors more often recur locally and are associated with a shorter survival independent of other risk factors. Tumor thickness is also an important predictor of regional and distant metastases, as well as survival. A prospective study is needed to compare the effect of excision with radiotherapy and excision with cryotherapy on the number of local recurrences, exenteration rate, and survival.
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                Author and article information

                Journal
                Clin Ophthalmol
                Clin Ophthalmol
                Clinical Ophthalmology
                Clinical Ophthalmology (Auckland, N.Z.)
                Dove Medical Press
                1177-5467
                1177-5483
                2013
                2013
                13 March 2013
                : 7
                : 521-531
                Affiliations
                [1 ]Save Sight Institute, Clinical Ophthalmology, The University of Sydney, Sydney, New South Wales, Australia
                [2 ]School of Optometry and Vision Science, The University of New South Wales, Sydney, New South Wales, Australia
                Author notes
                Correspondence: R Max Conway, Sydney Eye Hospital and Ocular Oncology Centre, Save Sight Institute, The University of Sydney, GPO Box 4337, Sydney, NSW 2006, Australia, Email drmaxconway@ 123456gmail.com
                Article
                opth-7-521
                10.2147/OPTH.S38415
                3601642
                23515569
                566a7cc6-2191-49d7-b815-fddba8f1363d
                © 2013 Lim et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                Categories
                Review

                Ophthalmology & Optometry
                adjuvant therapy,melanoma in situ,mitomycin c,metastases
                Ophthalmology & Optometry
                adjuvant therapy, melanoma in situ, mitomycin c, metastases

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