Pigmented lesions on ocular surface require various approaches

Pigmented conjunctival lesions can be complexion-associated melanosis (CAM), racial melanosis, nevus, primary-acquired melanosis (PAM), conjunc- tival melanoma, or pigmented ocular surface squamous neoplasia. (Image courtesy of stock.adobe.com)

Reviewed by Carol L. Karp, MD

Various approaches must be taken to manage pigmented lesions that appear on the ocular surface, according to Carol L. Karp, MD, professor of ophthalmology and codirector of the Cornea Service at the Bascom Palmer Eye Institute at the University of Miami in Florida. While she spoke about the diagnosis and management of pigmented conjunctival lesions at the 61st Annual Ophthalmology Update Walter Wright Symposium in Toronto, Ontario, Canada, Karp explained that pigmented conjunctival lesions can be complexion-associated melanosis (CAM), racial melanosis, nevus, primary-acquired melanosis (PAM), conjunctival melanoma, or pigmented ocular surface squamous neoplasia.

When a patient is referred because of the presence of a pigmented lesion, clinicians should ask whether there is a history of lesions, whether the lesions were excised, and what the patient was told about that lesion (whether it was benign or not), Karp said. “For any excised lesion, I want to have the tissue re-reviewed by our ocular pathologist,” she said.

In terms of clinical examination, ophthalmologists should look everywhere on the entire bulbar surface, always everting the eyelid. Karp noted that ophthalmologists need to feel for preauricular and submandibular lymph nodes.

Technologies that can help to further characterize a lesion on the ocular surface include high-resolution optical coherence tomography (HR-OCT) and high-resolution B-scan, according to Karp. The characteristics seen on HR-OCT can help diagnose the lesion in a noninvasive fashion. “It can tell you [whether] the lesion is epithelial or subepithelial,” Karp said, adding that subepithelial lesions also have characteristics that can help with determining the diagnosis.

For 1 particular patient with a gelatinous limbal lesion that was thought to be an ocular sur- face squamous neoplasia, Karp used HR-OCT, which revealed that the lesion was not epithelial, but rather subepithelial. The patient then reported that she had a history of a pterygium removed in the past. The original tissue was obtained, Karp’s ocular pathologist reviewed the original slides, and it was determined that the original lesion was PAM with severe atypia.

“I knew this was a melanocytic tumor,” Karp said. “With the HR-OCT showing a subepithelial lesion, this was likely melanoma. In these cases, I go to a plan of excision with cryotherapy for a forniceal lesion with amniotic membrane transplant and symblepharon ring.”

CAM, conjunctival nevi, and PAM

In another case, Karp was referred a patient who had bilateral pigmented changes, especially around the limbus, which was a case of CAM, a presentation that is more common in darkly pigmented individuals. CAM has equal distribution between men and women.

“This is treated with observation,” she said. “There are no published cases of any CAM conversion to melanoma, but you have to remember that pigmented individuals can have a melanoma. Any nodularity or vascularity raises concerns about this.”

Conjunctival nevi, which also have equal distribution between women and men, are other lesions that require attention, Karp said, noting that these nevi are unilateral, well circumscribed, and long-standing. “There is a very low risk for malignant transformation of a conjunctival nevus, but it does exist,” Karp said. “The risk is less than 1%, at 0.7%, so we perform serial observation.”

Changes in conjunctival nevi that occur during puberty or pregnancy do not signal concerns, but if changes occur outside these periods, the nevi must be removed, Karp said. She described a common referral of a child with a nonpigmented lesion, where there is a “feeder vessel” and a concern for malignancy. In the case she presented, the use of HR-OCT confirmed a highly cystic subepithelial lesion. “This was a case of conjunctival nevus,” Karp said. “It was amelanotic in a young child, and the diagnosis can be challenging.”

PAM is a lesion that presents unilaterally and occurs in White patients, and more in women than men. One of the main factors to consider in management is the presence of atypia, Karp said.

“If there is severe atypia, the studies vary, but there is anywhere between [a] 32% [and] 50% chance that the lesion will transform into a conjunctival melanoma,” she said, adding that if there is an absence of atypia, there is essentially no risk for transformation.

“The amount of the ocular surface that is covered by this pigmentation is another [risk factor] for malignant transformation to melanoma,” Karp said, noting that research and guidance from Carol Shields, MD, has shown that each hour of pigmentation portends a 1.7- fold increased risk per clock hour of pigmentation on the eye surface of transformation to melanoma. “The more surface area involved, the higher the risk,” Karp said.

In terms of PAM management, Karp uses size to help guide treatment. “If it is a tiny lesion, such as less than a clock hour, I could monitor it or take it out,” Karp said. “I perform excision with adjunctive cryotherapy for medium-sized lesions located between 2 and 7 o’clock.”

For large lesions, Karp advises removal and possible combination of cryotherapy. When lesions cannot be removed because they are too extensive, topical chemotherapy in combination with cryotherapy can be administered, Karp added. Indeed, considerations in determining the risk of transformation from PAM to malignant melanoma are whether there are areas of nodularity, thickness, and increased size.

Managing focal recurrence and use of cryotherapy

Focal recurrence of any pigment on the ocular surface in a patient with a previous conjunctival melanoma requires action, Karp said, noting that action includes excision, topical mitomycin, or cryotherapy. “Cryotherapy is especially helpful for PAM [that] occurs in bad locations, such as the punctum or canalicular system,” Karp said. For cases of PAM in which Karp uses cryotherapy, she performs it at the slit lamp or minor room if it is localized, or the main operating room if it is extensive.

Conjunctival melanomas have significant risks for local destruction, metastasis, and death. “These lesions require full excision, and incision biopsies should be avoided to prevent possible seeding on malignant cells,” Karp said. When performing excision of conjunctival lesions, Karp said she performs a “no-touch” technique with 3-mm to 4-mm margins, if possible, with cryotherapy to the margins and a dry field. If the lesion is adherent to the sclera, a partial thickness sclerectomy is performed. Closure is usually with amniotic membrane. Residual postoperative conjunctival margins require topical therapy or further excision. In a case of deep margins/invasion, plaque brachytherapy will be needed, Karp explained.

There may be a role for sentinel node biopsy with conjunctival melanoma, as this can detect micrometastasis and direct therapeutic decisions, Karp said. All patients with conjunctival melanoma are comanaged by an oncologist specializing in melanoma, Karp stressed, noting that the oncologist does the systemic work-up and develops the treatment plan.

One of the biggest advances in melanoma treatment is the emergence of immune checkpoint inhibitors, Karp noted. “They have saved my patients’ lives and extended their lives,” Karp said, noting that clinicians should check melanomas for mutations to determine which immune checkpoint inhibitor is best to target the tumor.

Overall, pigmented conjunctival lesions can be challenging to manage, Karp noted. Some are low risk and can be watched, such as CAM and nevi, she said. PAM is the main risk factor for conjunctival melanoma and—unless it’s tiny—requires intervention. Conjunctival melanoma is the dreaded lesion, as it is life-threatening and requires aggressive treatment with a team approach of physicians who have expertise, Karp explained

Carol L. Karp, MD

Carol L. Karp MD
E: ckarp@miami.edu
Karp has no relevant financial disclosures.