Residency · Residency · Ophthalmology
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.
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.
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.
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
- Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma. Arch Ophthalmol. 2006;124(12):1684-1693.
- 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.
- 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.
- Kaliki S, Shields CL. Uveal melanoma: relatively rare but deadly cancer. Eye (Lond). 2017;31(2):241-257.