Elsevier

The Ocular Surface

Volume 10, Issue 4, October 2012, Pages 251-263
The Ocular Surface

Clinical Practice
Management of Pigmented Conjunctival Lesions

https://doi.org/10.1016/j.jtos.2012.08.002Get rights and content

Abstract

Pigmented conjunctival lesions primarily include melanoma, nevus, primary acquired melanosis (PAM), and complexion-associated melanosis. The incidence of conjunctival malignant melanoma (CMM) has significantly increased in the USA and Europe over the years, and it carries a very serious risk for metastasis and melanoma-related death. Conjunctival melanoma can arise de novo or from precursor lesions, nevus, and PAM. PAM is histologically separated into two distinct forms: PAM with atypia and without atypia. PAM with severe atypia progresses to malignant melanoma in up to 50% of cases and PAM without atypia virtually never progresses. Nevus is a benign melanocytic tumor that only rarely undergoes malignant transformation. Complexion-associated melanosis is frequently seen in more darkly pigmented individuals and does not progress to melanoma, although it can become very large. A detailed literature review on the various pigmented conjunctival lesions together with a schematic approach to diagnosis and management is presented.

Introduction

Pigmented lesions on the ocular surface mainly include conjunctival melanoma (CMM), primary acquired melanosis (PAM) with and without atypia, nevus, and complexion-associated melanosis. CMM is a malignant tumor that can destroy locally the tissues of the eye and can spread systemically and result in lymph node and distant metastasis. PAM with atypia can transform into CMM, but clinically it cannot be distinguished from PAM without atypia, which has no potential for malignant transformation. Nevus has a very small risk of developing into CMM, and complexion-associated melanosis is benign.1, 2, 3

Pigmented conjunctival lesions present a management challenge because they have overlapping clinical features, but specific risks for malignancy. In this review, we present clinically salient aspects of pigmented conjunctival lesions with the goal of enabling the ophthalmic clinician to diagnose and manage them successfully. Epidemiology, current diagnostic methods, treatment options, and possible future therapies such as targeted molecular therapy and genetic evaluation are reviewed.

Section snippets

Epidemiology of Pigmented Conjunctival Lesions

In a clinical survey of 1643 consecutive conjunctival lesions at an ocular oncology referral center (Wills Eye Institute), the tumor was classified most often as melanocytic (53%), of which nevus was most common (52%), followed by melanoma (25%), and PAM (21%).1

Clinical Examination

Clinical examination should include:

  • 1.

    History (age, history of sun exposure, previous skin cancer, other cancer, long-term presence of the lesion versus recent change, symptoms, review of old photographs).

  • 2.

    Physical examination (lymph node palpation, external skin changes, eyelid and orbital signs, location of the lesion on the conjunctiva or other tissues).

  • 3.

    Slit lamp biomicroscopy including examination of the ocular surface, fornix, tarsal conjunctiva (with eyelids everted), anterior chamber,

Conjunctival Melanoma

CMM is composed of malignant melanocytic cells, which can be demonstrated by nuclear atypia, lack of cellular organization, or prominent nucleoli. In principle, four different cell types can be observed: small polyhedral cells, large epithelioid cells, spindle cells, and balloon cells. Features suggestive of melanoma rather than nevus are: intraepithelial involvement (especially in an older individual) with pagetoid spread; an intraepithelial component that vertically extends into the

Conjunctival Melanoma

The discussion of prognosis of CMM can be divided into prognosis for local recurrence on the eye, and systemic prognosis for metastasis and death.

CMM frequently recurs locally after surgery. Recurrence or new melanoma growth at any site on the conjunctiva in the Shields series was 45% at 5 years and 59% at 10 years. The interval to first recurrence was at a median of 14 months.6

With regard to systemic involvement, CMM carries a significant risk for metastasis and melanoma-related death. In a

Management

Management should be individually tailored for specific lesions and patients. Even the most seemingly benign lesions require careful evaluation. Although complexion-associated melanosis is not reported to undergo malignant transformation, conjunctival melanoma does occur in people with dark complexions.6 Thus, every patient requires a thorough examination to identify the lesion, evaluate the risk, and plan optimal treatments, which are described below.

Management of Recurrence

It is known that both CMM and PAM have a great tendency to recur after treatment, as was described in the prognosis section. The options for treatment of recurrence are re-excision with cryotherapy and amniotic membrane placement, cryotherapy alone, topical chemotherapy with mitomycin-C or interferon-alpha-2b, radiation or, in severe cases, enucleation. The decision for treatment is made individually; however, patients with a history of melanoma and recurrent pigment should be treated

Timing of Ophthalmic Intraocular Surgery

Intraocular invasion of ocular surface malignancies after ocular surgery is a rare event, but it has been reported.59 If there is change of a pigmented lesion or if extensive PAM is present, the pigmented lesion should be dealt with prior to intraocular surgery. Preferably, a histopathologic diagnosis should be obtained either by full excision or map biopsy. The ocular surface should be free of tumor and stable prior to intraocular surgery.

Genetics of Melanoma and Potential for New Therapies

Cancer is likely a genetic disease. Cancerogenesis is driven by mutations of oncogenes, which are genes that control hallmark features of cancer, such as cell proliferation and survival. These events can be the result of abnormal activation of a pro-proliferation or deactivation of a pro-apoptotic gene. Human cancer is probably the result of a critical accumulation of such mutations.60 Knowledge about oncogenes and their mutations is pivotal for the understanding of cancer and for the

Summary and Conclusions

CMM, PAM, nevus, and complexion-associated melanosis may have overlapping clinical features, but they differ considerably in their potential for malignancy and metastasis. Thus, accurate diagnosis is essential for designing treatment. Clinical acumen, careful observation, and biopsy all play a role for these lesions to be diagnosed and managed successfully. Histological diagnosis can be made by full excision or map biopsies. CMM must be fully excised and recurrences managed aggressively. The

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    Supported in part by NIH Center Core Grant P30EY014801, Research to Prevent Blindness Unrestricted Grant, Department of Defense (DOD- Grant#W81XWH-09-1-0675), The Ronald and Alicia Lepke Grant, The Jimmy and Gay Bryan Grant, The Hager Family Grant and the Max-Kade-Foundation, NY.

    The authors have no financial interest in any concept or products described in this article.

    Single-copy reprint requests to Carol L. Karp, MD (address below).

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