Characteristic clinical findings may distinguish choroidal melanomas from regular nevi, improving detection and prognosis of early malignant tumors.
A small pigmented choroidal mass lesion is not an uncommon encounter during a routine eye examination. Choroidal nevi are common asymptomatic and relatively stationary lesions of the choroid, occurring in about 4% of Americans, and as many as 12% of Caucasians in particular.1 While intervention is not generally necessary, the clinician must investigate the possibility that the lesion actually represents a melanoma in its early form.
As the most common primary intraocular tumor, choroidal melanomas have the potential to be life-threatening. Thus, their early detection and intervention may have a critical impact on a patient’s visual and life prognosis. The diagnosis of small, early choroidal melanomas, however, can often be challenging because they share many clinical similarities with benign choroidal nevi.
Regular nevi typically have a brown or grey appearance, but not all of them are pigmented. They can be amelanotic (yellowish), or a mix on pigmented and nonpigmented cells. A specific type of nevus called a halo nevus has a pigmented center and a lighter rim.
Clinical clues that can help differentiate choroidal nevi from small melanomas include the presence of overlying drusen or fibrous metaplasia of the retinal pigment epithelium (RPE), in which the RPE thickens over the surface of the nevus (Figure 1). These features represent chronic changes of the lesion, which are indicative of its age. Small melanomas will typically lack these features because of their relatively rapid growth.
Signs of Malignancy
In contrast, certain clinical features can be suggestive of early melanoma. The use of ultrasound can aid in the diagnosis of small melanomas and typically exhibit acoustic hollowness compared to a nevus which generally shows higher reflectivity of the lesion. Another indication for malignancy is growth rate (changes in the thickness or margin of the lesion over time). Choroidal nevi typically grow very slowly—about 0.06 mm per year on average.2 More rapid growth, which can be observed with serial fundus photography or clinical exam, should tip off the clinician about a transforming nevus or early melanoma.
Certain characteristic clinical signs have been established as highly indicative of choroidal melanomas.3-6 The risk factors clinicians should look for include: orange pigment over the lesion’s surface; serous subretinal fluid; a tumor thickness of greater than 2 mm; a tumor margin within 3 mm of the optic nerve; and symptoms of decreased or distorted vision, flashes of light, and occasionally floaters (Figure 2). The more of these risk factors a lesion manifests, the more likely the lesion is to grow which is indicative of choroidal melanoma.
The overlying lipofuscin pigment deposits appear orange when overlaying a darkly pigmented lesion and brown over a lightly pigmented one. Visual symptoms tend to vary depending on the lesion’s location: those located nearer the fovea are more likely to manifest symptoms earlier, with decreased vision being the most common complaint.
On an initial evaluation of a choroidal tumor, typical examinations include indirect ophthalmoscopy, fundus photography, fluorescein angiography, and ultrasound. Autofluorescence is occasionally performed to confirm the presence of orange lipofuscin pigments, as these are easier to view with autofluorescence.
Ultrasound remains a very useful diagnostic tool for nevus and melanoma, as each presents some specific ultrasound findings. Acoustic hollowness is typical of melanomas, as well as the presence of intrinsic vascular pulsations, whereas high reflectivity is seen more commonly in nevi. Some melanomas grow outside the eye, and this can be detected with ultrasound as extraocular extensions which are not typically seen with choroidal nevi.
Compared to other methods, optical coherence tomography (OCT) is very sensitive in detecting subclinical subretinal fluid, and OCT can be helpful in the diagnosis of small, suspicious nevi. Enhanced depth OCT imaging, in particular, allows us to better view the choroid and more precisely identify the tumor margins. Fluorescein angiography, on the other hand, has limited utility in diagnosing nevus and melanoma, but is useful in certain situations. Rarely, fine needle aspiration biopsy is required for diagnostic purposes. However, this technique can be useful in obtaining genetic information of melanomas that can aid in prognostication.
Malignant transformation, although uncommon, does occur in 1 in 4,000 to 1 in 10,000 regular nevi. Usually we determine how aggressive we should be in following up based on the results of baseline examinations and the amount of clinical risk factors the patient has.
We may see the patient back in 3 months if a newly diagnosed nevus looks suspicious. But if the patient shows many chronic changes and has no risk factors, we may follow up in 6 months. Depending on the progress of the lesion at the initial follow-up visit, we may see the patient again in 6 months or a year.
Management of Choroidal Melanoma
Currently radiation therapy is the most commonly employed treatment for choroidal melanomas, primarily with plaque brachytherapy or proton beam irradiation. Since a certain dose of radiation is required to kill the tumor, these focal therapeutic methods are more effective and appropriate for small and medium-sized choroidal melanomas. For larger melanomas, which require more radiation to kill than the eye can tolerate, enucleation still remains a viable option.
Laser therapy or transpupillary thermal therapy (TTT) is another treatment option for small choroidal melanomas. The incidence of recurrence is high when TTT is used alone; when it is combined with the plaque the local tumor control rate can reach 95% to 97%.7
To date, no chemotherapy has shown lasting effectiveness in the treatment of choroidal melanomas and metastatic choroidal melanomas. My colleagues and I have been investigating targeted molecules as a potential therapeutic option for the treatment of metastatic choroidal melanomas. Work at my center has explored the use of new melanoma drugs including ipilimumab.8,9 Their effectiveness in choroidal melanoma, however, is still under investigation.
The most common metastatic site for choroidal melanomas is the liver, followed by the lungs and subcutaneous tissue. We usually monitor patients for metastasis by scanning the liver. Metastatic disease is accountable for the high mortality rate of choroidal melanoma, which varies from 17% to over 50% within 15 years. But at this point, we have no durable treatment for metastases. Medications can be delivered directly to the liver for palliative treatment, but it does not cure the disease.
THE BOTTOM LINE
Choroidal melanoma is the most important disease in the differential diagnosis of choroidal nevi. The presence of the following clinical signs indicates a greater potential of malignancy: overlying orange pigment, serous subretinal fluid, thickness > 2 mm, margin within 3 mm of the optic nerve, and the manifestation of symptoms. New choroidal nevi should be cautiously monitored and evaluated by indirect ophthalmoscopy, fundus photography, and ultrasound. Small choroidal melanomas can be effectively controlled locally by radiation and laser therapy.
Brian P. Marr, MD, is a board-certified ophthalmologist and practices at the ophthalmology department of Memorial Sloan-Kettering Cancer Center in New York, NY. He has no financial interests to disclose. Refractive Eyecare associate editor Ying Guo assisted in the preparation of this manuscript.
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