Conjunctival Melanoma

Conjunctival melanoma is a rare malignancy (about 0.2 to 0.8 per million per year) arising from melanocytes of the conjunctiva.

• Origins: primary acquired melanosis with atypia (about 75 percent), pre-existing nevus (about 20 percent), or de novo (about 5 percent).
• Mean age about 60 years. More common in fair skinned individuals.
• Mutations: BRAF V600E (about 30 percent), NRAS, NF1, and TERT promoter mutations; different from uveal melanoma.
• Prognosis: local recurrence in about 50 percent, nodal metastasis in 20 to 25 percent, distant metastasis in about 25 percent; overall 10-year mortality about 25 to 30 percent. Poorer with thickness over 2 mm, non-limbal location (fornix, caruncle, palpebral conjunctiva), multifocal disease, and nodular type.

• Pigmented (or amelanotic, pink) nodule or flat lesion on the bulbar conjunctiva, limbus, caruncle or fornix, often with prominent feeder vessels.
• Diffuse acquired pigmentation of the surrounding conjunctiva, extension onto the cornea (pigmented corneal extension), bleeding or ulceration.
• Irritation, a visible lump or a change of existing pigmented lesion.
• Advanced disease: orbital extension with proptosis, preauricular, submandibular or cervical lymphadenopathy.
• Possible spread to lungs, liver, brain, and bone.

• Slit lamp examination with full lid eversion (to assess all conjunctival surfaces), photography, and anterior segment OCT (thickness).
• Excisional biopsy using no touch technique for small lesions; incisional biopsy only for large, diffuse lesions. Histology: tumour thickness (millimetres), margins, pagetoid spread, lymphovascular invasion, mitotic count. Molecular testing (BRAF, NRAS, KIT).
• Staging: palpation of regional nodes, ultrasound of preauricular and cervical nodes; sentinel node biopsy for tumours over 2 mm thick; MRI orbits and head for orbital extension; CT chest and abdomen or PET-CT in higher stage disease.
• Dilated fundus examination to exclude ciliary body or uveal involvement.

• Wide local excision (no touch technique) with 4 mm margins, with alcohol (absolute alcohol) epitheliectomy of adjacent cornea, and double freeze thaw cryotherapy to the conjunctival margins and base. Reconstruct with amniotic membrane, mucous membrane graft, or primary closure.
• Adjuvant therapy to reduce recurrence: topical mitomycin C 0.04 percent four times daily for 1 week on and 1 week off for 2 to 3 cycles for residual or diffuse pigmented disease, or topical interferon alpha-2b 1 million IU/mL four times daily; brachytherapy (strontium-90 or ruthenium-106, up to 60 to 100 Gy to the surface) or external beam radiotherapy for high risk disease or positive margins.
• Orbital exenteration for orbital extension not controlled by other methods or for extensive multifocal disease.
• Nodal disease: sentinel node biopsy, regional lymphadenectomy, parotidectomy where indicated.
• Metastatic or unresectable disease: immune checkpoint inhibitors (nivolumab 480 mg every 4 weeks, pembrolizumab 200 mg every 3 weeks, or ipilimumab 3 mg/kg with nivolumab 1 mg/kg every 3 weeks for 4 doses then nivolumab maintenance), BRAF V600-targeted therapy (dabrafenib 150 mg twice daily plus trametinib 2 mg daily).
• Follow up every 3 months for 2 years, every 6 months to 5 years, then annually, with nodal examination and imaging.