Distinguishing between choroidal nevus and lesions concerning for choroidal melanoma is an important skill for all ophthalmologists, because early referral and treatment of choroidal melanoma can improve not only ocular prognosis but also life prognosis for affected patients. While choroidal nevus is a common benign intraocular tumor, such lesions have a risk for transformation to choroidal melanoma, a serious and potentially life-threatening malignancy. The overall annual risk of transformation from nevus to melanoma is estimated to be 1 out of 8,845.1,2 Discerning between choroidal nevus and choroidal melanoma is key for proper management. The following is a summary of clinical practices for the identification and management of choroidal nevus and risk factors for transformation to melanoma.
Characteristics and Differentiation of Choroidal Nevus and Melanoma
A choroidal nevus is a benign melanocytic lesion within the choroid. These nevi are analogous to moles found on the skin and are often flat or minimally elevated with well-defined margins. Choroidal nevi are often asymptomatic and typically discovered incidentally during routine ophthalmic examinations.
The defining features of a choroidal nevus are its stable size and shape over time. Unlike malignant lesions, choroidal nevi do not undergo rapid change in size. They can be pigmented, gray or brown, or nonpigmented. Additional features can include the presence of drusen, yellowish deposits that form in the subretinal pigment epithelium over time. While subretinal fluid and orange pigment can be present, these findings are more concerning for malignant transformation.
Choroidal melanoma, on the other hand, is a malignant tumor arising from the melanocytes within the choroid. It is the most common primary intraocular malignancy in adults and has the potential to metastasize, contributing to its significant morbidity and mortality risk. There is a positive correlation between thickness and likelihood to metastasize.3 The characteristics of choroidal melanoma can vary, but several key features differentiate it from a benign nevus (Figure 1).
Like nevus, choroidal melanoma can be pigmented or nonpigmented. Associated drusen may be less common in melanoma than in nevus, while subretinal fluid and orange pigment are more frequently observed. Importantly, the presence of these features, particularly in combination with growth or other changes, raises the suspicion of malignancy.
Figure 1. Color fundus photograph (A) shows a mainly amelanotic choroidal melanoma measuring 11x11x1.7 mm located temporally in the left eye with subretinal fluid and orange pigment, which appears brown in color overlying this amelanotic lesion. An acoustically hollow dome-shaped lesion with no extrascleral extension can be seen on B-scan ultrasound (B). Fundus autofluorescence imaging (C) shows hyperautofluorescent orange pigment. Optical coherence tomography (OCT) image (D) shows subretinal fluid overlying the lesion.
Risk Factors for Choroidal Melanoma
Several risk factors have been identified for the development of choroidal melanoma. One of the most significant is race, with White individuals of European descent being at a much higher risk compared to those of African or Asian descent.4,5 This increased susceptibility is believed to be linked to genetic factors that affect melanin production.
Lighter eye color, such as blue or green eyes, is another important risk factor.6 Patients with lighter eyes are known to have a higher risk of developing uveal melanoma.7
Genetic predispositions also play a role, because patients with BAP1 tumor predisposition syndrome have an increased risk of developing uveal melanoma.8 Patients with germline BAP1 mutations are more likely to have a predisposition for familial cancers like uveal melanoma, cutaneous melanoma, mesothelioma, renal cell carcinoma, and others.9 Patients who have uveal melanoma are at higher risk of metastasis if they have a loss of chromosome 3 in addition to BAP1 mutations. Additionally, some uveal melanomas are associated with many CpG>TpG mutations causing MDB4 inactivation.10 MBD4 on chromosome 3 is supposed to act as a tumor suppressor gene, so its inactivation may be implicated in predisposition to uveal melanoma.10
TFSOM-DIM and MOLES Scores
Several mnemonic devices have been developed to help with identification of high-risk choroidal nevus or early choroidal melanoma, including the TFSOM-DIM mnemonic and the MOLES acronym.
The TFSOM-DIM mnemonic (To Find Small Ocular Melanoma Doing IMaging) serves as a quick reference for identifying high-risk features on multimodal imaging that increase choroidal nevus risk for transformation into melanoma. This mnemonic is particularly useful for clinicians who need a concise and efficient method to assess the malignancy risk.11,12
TFSOM-DIM Mnemonic
T: Thickness >2 mm.
F: Subretinal fluid.
S: Symptoms (visual acuity loss to 20/50 or worse).12
O: Orange pigment.
M: Melanoma acoustic hollowness.
DIM: Diameter >5 mm.
The MOLES acronym was developed to highlight the clinical signs of choroidal melanoma. Each of 5 features (Mushroom shape, Orange pigment, Large size, Enlarging tumor, and Subretinal fluid) is scored as follows: 0 (absent), 1 (borderline), or 2 (present). The total MOLES score helps guide clinical decision-making, with higher scores indicating a greater likelihood of melanoma and warranting more aggressive monitoring and intervention.
MOLES Score
M: Mushroom shape. A mushroom or dome-shaped lesion is highly suggestive of melanoma.
O: Orange pigment. The presence of orange pigment, often visible on fundus examination, is indicative of lipofuscin accumulation, a sign of active growth.
L: Large size. Lesions larger than 5 mm in diameter are more likely to be melanoma.
E: Enlarging tumor. Any documented increase in the size of the lesion over time is a strong indicator of malignancy.
S: Subretinal fluid. The presence of subretinal fluid, detected on OCT or ultrasound, suggests that the lesion is active and possibly malignant.
Management and Follow-Up
The management of choroidal nevus and melanoma differs significantly. For choroidal nevus, regular monitoring is typically the preferred approach. This involves routine examination and imaging, which may include fundus photography, fundus autofluorescence, OCT, and ultrasound to document any changes in size or other features that might suggest malignant transformation. The frequency of monitoring is determined by the lesion’s characteristics and the patient’s overall risk profile.
Plaque radiotherapy, proton beam irradiation, and enucleation are the main treatment options for choroidal melanoma.13 The choice of treatment is guided by factors such as tumor size, location, and the patient’s visual potential. Screening for metastasis is also an important aspect of choroidal melanoma management, because up to half of patients may eventually develop metastatic disease, most frequently to the liver or lungs.5
Conclusion
Differentiating between choroidal nevus and melanoma is crucial for effective management and optimal patient outcomes. The risk factors associated with choroidal melanoma, including White/European ancestry, lighter eye color, and genetic predisposition highlight the need for a dilated eye exam in early adulthood, to allow anyone with a detected nevus to have appropriate monitoring. Regular monitoring is key to detecting choroidal nevus transformation to melanoma at the earliest possible stage, which facilitates treatment when lesions are smaller and carry lower metastatic potential. Future research should focus on improving diagnostic techniques and exploring new treatment modalities that can further enhance patient outcomes. RP
References
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