# Choroidal Melanoma: Diagnosis and Management

## Introduction

Uveal melanoma is the most common primary intraocular malignancy in adults, with an estimated incidence of 5-7 per million per year in the United States. Choroidal melanoma accounts for approximately 90% of uveal melanomas, with the remainder arising from the ciliary body or iris. Early diagnosis and appropriate management are critical, as metastatic disease carries a grave prognosis.

## Epidemiology and Risk Factors

**Peak incidence**: 6th-7th decade of life. More common in Caucasians; rare in heavily pigmented individuals. Risk factors: Light skin, light iris color (blue/grey eyes) Pre-existing choroidal nevus. **Ocular melanocytosis** (melanosis oculi) and oculodermal melanocytosis (nevus of Ota)

BAP1 tumor predisposition syndrome (familial uveal melanoma, mesothelioma, renal cell carcinoma) Dysplastic nevus syndrome. UV exposure (weak association compared to cutaneous melanoma)

## Clinical Presentation

### Symptoms

Blurred vision, visual field defect, photopsia, floaters. Up to 30% are **asymptomatic**, discovered on routine examination.

### Examination Findings

**Dome-shaped or mushroom-shaped** elevated choroidal mass. Color ranges from darkly pigmented to amelanotic (20%) **Orange pigment** (lipofuscin) overlying the tumor surface. **Subretinal fluid**: serous retinal detachment; may be extensive. Sentinel episcleral vessels in ciliary body melanoma. Rarely: vitreous hemorrhage, secondary inflammation, neovascular glaucoma.

![Fundus photograph of a pigmented dome-shaped choroidal melanoma with overlying orange pigment](images/choroidal-melanoma-fundus.jpg)

## Diagnostic Evaluation

### Ultrasonography

**B-scan**: dome or mushroom shape, **low-to-medium internal reflectivity**, acoustic hollowing, choroidal excavation, orbital shadowing. **A-scan**: low internal reflectivity with decreasing amplitude (kappa angle) Tumor thickness measured by A-scan; crucial for treatment planning. Mushroom or collar-button shape results from rupture through Bruch membrane.

### Fluorescein Angiography

Intrinsic tumor vasculature ("double circulation" pattern) Early pinpoint hyperfluorescence with late diffuse staining and leakage. Helps differentiate from choroidal hemangioma (rapid early filling) or metastasis.

### Indocyanine Green Angiography

Delineates tumor vasculature; useful for posterior tumors near the disc.

### Optical Coherence Tomography

Subretinal fluid, intraretinal edema, shaggy photoreceptor sign. Enhanced depth imaging (EDI-OCT) can visualize tumor surface characteristics.

### Systemic Staging

**Liver function tests** and liver imaging (ultrasound, CT, or MRI): the liver is the most common site of metastasis (>90%) Chest X-ray or CT chest. PET/CT in selected cases. Baseline metastatic evaluation at diagnosis.

## Differential Diagnosis

**Choroidal nevus** (most common; see TFSOM-DIM lecture) Choroidal metastasis (breast, lung; usually flat, yellow, multifocal, bilateral) Choroidal hemangioma (circumscribed: orange, dome-shaped; high internal reflectivity on A-scan) Choroidal osteoma (calcified, bone density on CT) Congenital hypertrophy of RPE (flat, well-defined, no subretinal fluid) Melanocytoma of the optic disc.

Hemorrhagic choroidal detachment or subretinal hemorrhage.

## Classification and Staging

### Size Categories (COMS Classification)

**Small**: apical height 1.0-2.5 mm, basal diameter up to 16 mm. **Medium**: apical height 2.5-10 mm, basal diameter up to 16 mm. **Large**: apical height > 10 mm or basal diameter > 16 mm.

| COMS Size | Apical Height | Basal Diameter | Primary Management |
|---|---|---|---|
| Small | 1.0-2.5 mm | <=16 mm | Observation vs. plaque brachytherapy |
| Medium | 2.5-10 mm | <=16 mm | Plaque brachytherapy (equivalent to enucleation per COMS) |
| Large | >10 mm | >16 mm | Enucleation |

### AJCC TNM Staging

Based on tumor size (largest basal dimension and thickness), ciliary body involvement, and extraocular extension. T-category correlates with metastatic risk.

![B-scan ultrasonography showing a mushroom-shaped choroidal melanoma with acoustic hollowing](images/choroidal-melanoma-bscan.jpg)

## Management

### Observation

Appropriate for **small indeterminate melanocytic lesions** lacking high-risk features. Serial photography, ultrasonography, and OCT every 3-6 months. Treat if documented growth or development of risk factors.

### Radiation Therapy

**Plaque brachytherapy** (iodine-125, ruthenium-106): standard of care for small and medium melanomas. Radioactive plaque sutured to sclera overlying the tumor base. Delivers 85 Gy to tumor apex over 3-7 days. COMS trial: equivalent survival to enucleation for medium tumors. Complications: radiation retinopathy, radiation optic neuropathy, cataract, neovascular glaucoma. **Proton beam radiation**: alternative for posterior or peripapillary tumors.

**Stereotactic radiosurgery** (Gamma Knife, CyberKnife): selected cases.

### Enucleation

Indicated for large tumors, tumors with extensive extraocular extension, blind painful eye. COMS demonstrated no survival benefit of pre-enucleation radiation. Orbital implant placement at time of enucleation; prosthesis fitted 6-8 weeks later.

### Other Modalities

**Transpupillary thermotherapy (TTT)**: adjunct to plaque brachytherapy for small tumors. **Photodynamic therapy**: limited role; occasionally for small tumors. **Local resection**: transscleral or endoresection in specialized centers. **Exenteration**: rarely indicated; reserved for extensive orbital invasion.

![Iodine-125 plaque brachytherapy device for treatment of choroidal melanoma](images/plaque-brachytherapy-melanoma.jpg)

## Prognostic Factors and Genetic Testing

### Clinical and Histologic Prognostic Factors

Tumor size (strongest clinical predictor), ciliary body involvement, extraocular extension. Cell type: epithelioid cell predominance carries worse prognosis than spindle cell. Mitotic rate, microvascular loops, lymphocytic infiltration.

### Genetic and Molecular Prognostic Testing

**Chromosome 3 monosomy**: strongest genetic predictor of metastasis (50% metastatic rate at 5 years) Chromosome 8q gain: associated with metastasis, especially with monosomy 3. **Gene expression profile (GEP)**: Castle Biosciences DecisionDx-UM. Class 1A: very low metastatic risk. Class 1B: intermediate risk. Class 2: high metastatic risk (analogous to monosomy 3)

**BAP1 mutation**: loss of BAP1 protein correlates with metastatic disease. PRAME expression: additional prognostic biomarker.

### Metastatic Surveillance

Liver imaging and LFTs every 6 months for at least 10 years. More frequent surveillance for high-risk (Class 2 / monosomy 3) patients. Currently no proven adjuvant therapy to prevent metastasis (clinical trials ongoing) **Tebentafusp** (bispecific T-cell engager): FDA-approved for metastatic uveal melanoma (HLA-A*02:01 positive); first agent to improve overall survival.

## Key Clinical Pearls

Choroidal melanoma typically shows low internal reflectivity with acoustic hollowing on B-scan ultrasound, distinguishing it from most simulating lesions. The COMS trial established plaque brachytherapy as equivalent to enucleation for medium-sized melanomas in terms of survival. Chromosome 3 monosomy and Gene Expression Profile Class 2 identify patients at highest risk for metastatic disease. The liver is the site of metastasis in over 90% of cases; lifelong hepatic surveillance is essential.

## References

1. Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma. *Arch Ophthalmol*. 2006;124(12):1684-1693.
2. Shields CL, Furuta M, Thangappan A, et al. Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. *Arch Ophthalmol*. 2009;127(8):989-998.
3. Nathan P, Hassel JC, Rutkowski P, et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. *N Engl J Med*. 2021;385(13):1196-1206.
4. Kaliki S, Shields CL. Uveal melanoma: relatively rare but deadly cancer. *Eye (Lond)*. 2017;31(2):241-257.