Conjunctival Melanoma Treatment: Brown Spots on the Eye, PAM and C-MIN Explained

Noticing a brown spot on the white of your eye can be unsettling. Most pigmented spots on the conjunctiva are harmless — a nevus present since youth, or pigment that is normal in darker complexions. Conjunctival melanoma is rare but important, because the outlook is better when it is found early and when conjunctival melanoma treatment is carried out with meticulous technique.

For other surface growths, see conjunctival tumors.

What can a brown spot on the white of the eye be?

Conjunctival nevus

A nevus is a benign cluster of pigment cells, like a mole on the skin. In a Wills Eye Hospital study of 410 patients, 65% of nevi contained tiny clear cysts, a reassuring sign. Over an average of 11 years, 92% did not change in size and fewer than 1% developed melanoma.

Nevi can darken slightly during puberty or pregnancy, usually harmlessly. Removal is advised if a nevus grows, develops feeder vessels or irritates the eye, if it lies in an unusual place (the fornix, the eyelid lining or the caruncle), or if a pigmented spot first appears after about age 40.

PAM and C-MIN: when is pigment precancerous?

Primary acquired melanosis (PAM) is flat, patchy pigment that appears in one eye of a fair-skinned adult, usually in middle or later life. Under the microscope it is graded as PAM without atypia or PAM with atypia (abnormal cells) — a spectrum also called C-MIN (conjunctival melanocytic intraepithelial neoplasia) or, in the World Health Organization classification, low- or high-grade C-MIL.

The grade predicts the risk. In another study from the same center, covering 311 eyes, no PAM without atypia or with mild atypia progressed to melanoma, but 13% with severe atypia did, and more extensive pigment carried more risk. PAM is also the usual starting point of melanoma: of 382 conjunctival melanomas, 74% arose from PAM, 7% from a nevus and 19% de novo (from normal-looking conjunctiva).

Small areas (under 3 "clock hours", a quarter of the circle around the cornea) may be watched with photographs or removed. Larger, growing or thickening areas need several map biopsies, and atypical PAM is removed where accessible, with freezing treatment and, for widespread flat disease, chemotherapy drops.

What is conjunctival melanoma?

Conjunctival melanoma is a cancer of the pigment cells of the conjunctiva. It is rare — fewer than one case per million people a year — and about 91% of cases occur in fair-skinned people.

Despite the shared name, it differs from uveal melanoma inside the eye: it carries sun-related DNA damage, behaves more like skin and mucosal melanoma, and spreads first to the lymph nodes in front of the ear, under the jaw and in the neck. Testing the tumor adds useful information:

• BRAF mutations occur in roughly a third of tumors (29–46% across studies); if the disease spreads, they make targeted BRAF and MEK inhibitor tablets an option.
• NRAS (11–26%) and TERT promoter mutations (up to 54%) have been linked to a less favorable outlook.
• The PRAME stain helps the pathologist separate melanoma from a nevus.

Uveal melanoma, by contrast, is assessed with its own genetic tests.

What are the warning signs?

Conjunctival melanoma may appear as a brown-black nodule, a thickened area within flat pigment, or a pink nodule with little pigment (amelanotic melanoma), often with prominent feeder vessels. It can arise anywhere on the conjunctiva, including the fornix, the eyelid lining and the caruncle.

How is conjunctival melanoma diagnosed?

• Full surface examination at the slit lamp, with the eyelids everted, so that all pigment is mapped and photographed.
• Anterior segment OCT: nevi usually contain cysts; melanoma usually does not.
• Ultrasound biomicroscopy to measure thickness and look for invasion of the eye wall.
• Excisional biopsy: a discrete tumor is removed whole with the no-touch technique rather than cut into; surrounding pigment is sampled with map biopsies.
• Staging tests for thick, non-bulbar or recurrent tumors: lymph node ultrasound and CT, PET-CT or MRI as needed (see eye tumor diagnosis).

How is conjunctival melanoma staged?

Staging uses the 8th edition of the American Joint Committee on Cancer (AJCC) system:

After surgery, thickness is added: pT1a is a bulbar tumor 2 mm thick or less, pT1b one thicker than 2 mm. N1 means spread to regional lymph nodes and M1 distant spread (see eye cancer stages).

What does conjunctival melanoma treatment involve?

The aim is to remove every tumor cell on the surface while protecting the eye. Surgery comes first:

1. Under the operating microscope, the tumor is removed in one piece with a margin of healthy-looking conjunctiva (typically 3–5 mm), without being grasped, to avoid seeding cells.
2. Any corneal part is treated with absolute alcohol and gently removed (alcohol epitheliectomy); a tumor stuck to the white wall of the eye is removed with a thin layer of sclera.
3. The edges are frozen with a double freeze–thaw cycle (cryotherapy), and fresh instruments are used for closure.
4. The wound is closed directly or with amniotic membrane or a graft, and the specimen is laid flat and oriented for the pathologist.

Further treatment, guided by the pathology result, may include:

• Chemotherapy drops (mitomycin C 0.02–0.04% or interferon alfa-2b) for residual flat PAM/C-MIN or atypical cells at the surface margins; they do not treat a nodule.
• Radiotherapy for close or involved margins, or for multifocal or recurrent disease: a plaque on the eye surface (related to plaque brachytherapy) or proton or other external beam therapy. Evidence comes from small series.
• Sentinel lymph node biopsy checks the first draining lymph node for microscopic spread. Because nodal spread builds up over time (about 16% at 5 years and 32% at 15 years in published data), it is considered for higher-risk tumors — thicker than 2 mm, ulcerated, non-bulbar or recurrent. About 11–13% of these biopsies are positive, and temporary facial nerve weakness occurs in about 6%.

If melanoma invades the orbit extensively or keeps recurring despite eye-sparing treatment, orbital exenteration — removal of the eye and socket contents — may be needed. Spread beyond the eye is treated as for skin melanoma, with immune checkpoint inhibitors or, for BRAF V600-mutated tumors, BRAF and MEK inhibitors, although evidence in conjunctival melanoma is limited to small series. Immunotherapy before surgery to avoid exenteration remains investigational as of September 2026.

Prof. Türkoğlu plans and performs the surface surgery; radiotherapy, lymph node surgery and cancer medicines are planned and coordinated with the relevant specialist teams.

What is the outlook?

Another study from the same center followed 425 patients for an average of almost 5 years; outcomes worsened with each AJCC T category:

Across published series, local recurrence affects 33–61% of patients over time, and population data show disease-specific survival of about 83% at 5 years and 69% at 10 years. De novo melanoma carries more risk than melanoma arising from PAM or a nevus (10-year melanoma-related death 35% versus 9% in one series). In a series of 45 patients treated in Ankara, Türkiye (1998–2022), recurrence occurred in 31% and melanoma-related death in 9%.

What does follow-up involve?

Follow-up is lifelong: slit-lamp photographs, including under the eyelids, every 3–6 months at first; lymph node checks in front of the ear and in the neck, sometimes with ultrasound; and body scans for higher-risk tumors. Report new pigment or a lump near the ear or in the neck without waiting for the next visit.

Getting a specialist opinion in Antalya

Prof. Türkoğlu examines the whole ocular surface, compares the findings with earlier photographs and explains whether a pigmented lesion can be watched or should be removed. From abroad, a remote second opinion is a practical first step: send close-up photographs (with the eyelids turned out if pigment extends underneath), earlier photos, OCT scans and pathology reports, ideally with the original slides.