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    Managing conjunctival pigmented lesions

    Ability to identify nevus, primary acquired melanosis, melanoma can improve prognosis for patients



    PAM appears like a flat freckle, is usually unilateral, and starts in the basal layer of the epithelium as melanoma in situ. It can be occasionally found in non-Caucasians, also imparting a risk for melanoma in those patients.

    PAM is flat and has no cysts, but the rate of PAM transformation into melanoma at 10 years is about 12%. In one retrospective chart review of 382 consecutive patients,melanoma arose from PAM in 74% of the cases.

    “We need to beat PAM to prevent melanoma,” she said. There are clues for identifying which PAM case might turn into melanoma—the most important factor being the size of PAM.

    “Every clock hour adds a 1.7-times greater risk for transformation into melanoma,” Dr. Shields said. For example, a patient with 7 clock hours has a 12-times greater risk for transformation than the patient with only 1 clock hour.



    Conjunctival melanoma is increasing in the United States, Dr. Shields said.

    “It’s increase is mostly related to the depletion of the ozone layer and excessive sun exposure,” she said. “The rate is highest in men.”

    There are close to 200 cases in the United States per year, and the risk for metastasis is about 25% by 10 years. Melanoma generally appears pigmented, but can be nonpigmented and hide for months.

    In one study, 5 years (10 years), melanoma-related death occurred in 5% (9%) in melanoma arising from PAM, 0% (9%) in melanoma arising from nevus, and was significantly worse in those arising de novo 17% (35%), p < 0.001).2

    Melanoma management “is more than removing a lump on the surface of the eye,” she said.

    It involves precise surgical resection to achieve clean margins and avoidance of direct tumor manipulation (“no-touch” technique), cryotherapy to surrounding PAM, and reconstruction with flaps and grafts.

    The first surgery is unquestionably the most important to minimize tumor seeding. Patients with conjunctival melanoma should be managed at an experienced center to avoid tumor recurrence and metastasis, Dr. Shields suggested.

    New information on conjunctival melanoma involves such tumor biomarkers as BRAF, TERT, and PTEN. These markers could be mutated in melanoma and provide information regarding risk for metastasis. Clinicians now have targeted antibiomarker therapies that can improve prognosis.3

    “We look for molecular biomarkers in all patients to identify high-risk melanoma because we have medications for biomarkers,” she said. “It’s similar to skin melanoma management.”

    One study found 40% of patients with conjunctival melanoma have BRAF mutation, and implies a poor prognosis.4,5
    TERT is also a promoter mutation for melanoma and for melanoma survivorship, and patients with TERT mutations have poor survival rates.6

    PTEN is seen in several kinds of cancers, and can be mutated in conjunctival melanoma.

    On the upside, Dr. Shields noted that anti-BRAF medications are available, including vemurafenib and dabrafenib, that “hunt down BRAF mutations and wipe out the tumor.”


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