Conjunctival melanoma and melanocytic intra-epithelial neoplasia

Kenawy, Nihal; Lake, Sarah L.; Coupland, Sarah E.; Damato, Bertil

doi:10.1038/eye.2012.254

Cited by 67 publications

(67 citation statements)

References 52 publications

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“…Recent results showed improvement in local recurrence rates when brachytherapy alone or in combination with local chemotherapy was performed. 4,8,29 This treatment is the preferred choice at our institution.…”

Section: Discussionmentioning

confidence: 98%

A Retrospective Review of Conjunctival Melanoma Presentation, Treatment, and Outcome and an Investigation of Features Associated WithBRAFMutations

et al. 2015

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IMPORTANCE Large studies investigating clinical presentation and treatment in primary conjunctival melanoma (CM) are rare. Clinicopathological characteristics of BRAF-mutated CM have not been studied thoroughly.OBJECTIVES To determine the associations of clinicopathological tumor features and treatment with local recurrence, metastasis, and mortality and to determine the association of BRAF mutations with these features. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study at the Eye Pathology Institute, Copenhagen, Denmark. Participants included 139 patients with primary CM in Denmark from January 1, 1960, to December 31, 2012. For BRAF analysis, all patients with available formalin-fixed, paraffin-embedded tumor samples from January 1, 1994, to December 31, 2012, were included.MAIN OUTCOMES AND MEASURES BRAF mutations, local recurrence, regional and distant metastasis, melanoma-related mortality, and all-cause mortality were examined.RESULTS A poor prognosis of tumors involving the extrabulbar conjunctiva and adjacent tissue structures was confirmed in multivariable Cox proportional hazards regression models. Patients undergoing incisional biopsy more frequently developed metastasis (hazard ratio [HR], 2.46; 95% CI, 1.08-5.58; P = .03). Excision without adjuvant treatment was associated with local recurrence (HR, 1.97; 95% CI, 0.11-3.48; P = .02), metastatic disease (HR, 2.51; 95% CI, 1.07-5.91; P = .03), and all-cause mortality (HR, 1.80; 95% CI, 1.05-3.08; P = .03). BRAF mutations were identified in 19 of 47 primary CMs (40.4%) and were more frequent in younger patients (P = .005), less frequent in the extrabulbar conjunctiva (P = .05), more frequently classified as T1 tumors (P = .03), and rarely manifested with primary acquired melanosis (P = .001) or with a uniformly pigmented lesion (P = .006). Distant metastases developed in 6 of 19 BRAF-mutated CMs (31.6%) as opposed to 1 of 28 BRAF wild-type CMs (3.6%). No definitive association with distant metastasis was seen in multivariable Cox proportional hazards regression models.CONCLUSIONS AND RELEVANCE Incisional biopsy and excision without adjuvant therapy were associated with a poor outcome in patients with CM. Extrabulbar location was also associated with a poor outcome in multivariable analysis. BRAF-mutated CMs were frequent in younger patients and were rare in tumors involving the extrabulbar conjunctiva. Despite a more favorable location, BRAF-mutated tumors may be associated with more frequent distant metastasis.

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Section: Discussionmentioning

confidence: 98%

A Retrospective Review of Conjunctival Melanoma Presentation, Treatment, and Outcome and an Investigation of Features Associated WithBRAFMutations

et al. 2015

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“…1,2 The incidence is increasing and varies between 0.2-0.8% per year in the Caucasian population. It may be pigmented or non-pigmented, single or multifocal.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous Regression of a Conjunctival Malignant Melanoma

Miller

Cook

Jayaramachandran

et al. 2013

Orbit

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“…However, many in the ocular pathology and oncology fields were reluctant to classify these lesions as melanoma in situ because at least 36% of white individuals have an ocular lesion that would satisfy the clinical criteria for PAM. 4,12 Furthermore, conjunctival melanoma is a relatively rare condition, accounting for less than 3% of all ocular malignant neoplasms. 13 cluded that a broad clinical/pathologic entity such as PAM cannot convey the appropriate clinical prognosis for a given histologic finding in that it included benign lesions, such as hyperpigmentation, and also potentially malignant lesions with severe atypia.…”

Section: Panmelanocytic Markersmentioning

confidence: 99%

Usefulness of a Red Chromagen in the Diagnosis of Melanocytic Lesions of the Conjunctiva

et al. 2014

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IMPORTANCE Immunohistochemical analyses may assist in the diagnosis of precancerous and cancerous conjunctival lesions.OBJECTIVE To use Vector Red (VR) to identify an immunologic marker that is sensitive for all melanocytes and another that is sensitive and specific for activated and/or atypical conjunctival melanocytic lesions (MLs). DESIGN, SETTING, AND PARTICIPANTSEight specimens each of control lesions (normal conjunctiva and normal uvea as well as choroidal melanoma) and 8 from the diagnostic categories (conjunctival nevus, primary acquired melanosis with mild or no atypia, primary acquired melanosis with moderate to severe atypia, and conjunctival melanoma) that provided sufficient quantity and quality of tissue were available for processing. The specimens were obtained from the Ophthalmic Pathology Laboratory, The Ottawa Hospital, from 2005 to 2013. The specimens were immunolabeled with human melanoma black 45 (HMB45), melanoma antigen recognized by T cells 1 (Melan-A), S100, and Ki67 using VR and a double panmelanoma cocktail (dPANMEL) using 3,3′-diaminobenzidine (DAB) and VR. The HMB45-immunolabeled specimens were additionally developed with DAB, with and without overnight bleaching with hydrogen peroxide, 4%. Data were collected by 2 pathologists who were masked to sample grouping. MAIN OUTCOMES AND MEASURES Differentiation between benign and malignant MLs based on immunomarker profile.RESULTS Immunoreactivity was best visualized in specimens with VR. Melan-A labeled all melanocytes (100% sensitivity; panmelanocyte marker) without discriminating between benign and malignant lesions (0% specificity). Atypical melanocytes were most specifically labeled with HMB45 (96% specificity, 97% sensitivity; atypia marker). In primary acquired melanosis specimens, we found that the percentage of HMB45 (P < .001), S100 (P < .001), and Ki67 (P Յ .02) positivity increased significantly with worsening atypia. CONCLUSIONS AND RELEVANCEWe recommend VR, which rarely requires specimen bleaching, as the standard substrate for immunohistochemical analysis of conjunctival MLs. We found Melan-A and HMB45 to best characterize MLs. In conjunctival MLs, the use of VR with Melan-A and HMB45 provides substantial sensitivity for all melanocytes and for atypical melanocytes, respectively, and reduces specimen-processing time for laboratories performing immunohistochemistry on MLs.

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Conjunctival melanoma and melanocytic intra-epithelial neoplasia

Abstract: The rarity of conjunctival melanoma has impeded progress in the management of patients with this cancer; however, much progress has occurred

Cited by 67 publications

References 52 publications

A Retrospective Review of Conjunctival Melanoma Presentation, Treatment, and Outcome and an Investigation of Features Associated WithBRAFMutations

A Retrospective Review of Conjunctival Melanoma Presentation, Treatment, and Outcome and an Investigation of Features Associated WithBRAFMutations

Spontaneous Regression of a Conjunctival Malignant Melanoma

Usefulness of a Red Chromagen in the Diagnosis of Melanocytic Lesions of the Conjunctiva

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