Clinical Evaluation of Choroidal Melanoma
Choroidal melanoma is the second most common intraocular tumor – metastasis being the most frequent – and the most common primary intraocular malignancy in the adult population. It arises from malignant uveal melanocytes. Posterior uveal melanoma, as it is also known, has distinct clinical characteristics that facilitate its differentiation from other pigmented and non-pigmented lesions of the choroid.
Melanomas are often asymptomatic. Symptoms are not a common initial presentation of small melanomas, but can be present in larger lesions and melanomas that affect central macula. The main symptoms are decreased visual acuity, visual field defects (scotomas), metamorphopsia, photopsia and floaters. Less common symptoms are pain and red eye. The presence of symptoms is more commonly found in melanomas than in choroidal nevi.
Posterior uveal melanomas typically present as an elevated domed-shaped gray lesion of the choroid with irregular margins not sharply demarcated. When the melanoma breaks through Brüch membrane it acquires a mushroom-shaped configuration.
Several clinical characteristics should be looked for during the evaluation of a suspicious lesion:
- Color: Grayish-to-brownish neoplasm located in the choroid with overlying retinal vessels. However, there are also amelanotic tumors with a yellowish appearance.
- Thickness: choroidal melanomas tend to be lesions more than 2 mm thick. In contrast, choroidal nevi – the main disorder in the differential diagnosis – are more likely to present as flat or slightly elevated masses.
- Subretinal fluid: The presence of an exudative detachment of the neurosensory retina or the retinal pigment epithelium (RPE) is common.
- Orange pigment: Lipofuscin accumulation in the RPE overlying choroidal melanomas is a frequent finding.
- Sentinel vessel: A tortuous and dilated episcleral vessel is visible overlying a melanoma.
- Secondary glaucoma: Secondary angle-closure glaucoma can develop due to anterior displacement of the iris-lens diaphragm by the mass.
Certain features are more common in benign choroidal nevi including:
- Drusen are more commonly seen in chronic neoplasms and are more common in nevi than in melanoma.
- Halo of depigmentation around a pigmented choroidal lesion is more commonly seen in nevi and correlated with stability of the nevus. The depigmentation represents a lymphohistiocytic infiltrate.
The size of choroidal melanomas is one of the most important clinical characteristics. Size is used to classify these tumors, according to a modification of the criteria of the Collaborative Ocular Melanoma Study (COMS). This study classified melanomas using largest basal dimension and apical height in three groups: small, medium and large melanomas. Treatment strategies vary depending on this classification.
|Apical height||Largest basal diameter|
|Small||1.0 - 2.5 mm||5.0 - 16.0 mm|
|Medium||2.5 - 10 mm||less than 16 mm|
|Large||more than 10 mm||more than 16 mm|
Additional ancillary tests can aid in the clinical evaluation of a melanoma:
This is the primary diagnostic test that confirms the diagnosis of melanoma. Ultrasound also is useful in determing the size, e.g thickness (apical height) and basal dimension, extraocular extension (such as scleral nodules), and document growth during the follow up of a suspicious nevus/small melanoma.
- Standardized A-mode: Posterior uveal melanomas classically show medium to low internal reflectivity (88%), often in a decrescendo fashion, a.k.a, positive angle kappa, with regularity of structure. The internal blood flow (vascularity) of the tumor can be seen as a fast movement of the internal spikes. Uncommonly, a large melanoma may be more irregular, particularly if there is necrosis.
- B-mode: Shapes: Dome-shaped is most common, mushroom-shaped, i.e. collar button is most classic and irregular shape is uncommon. Other features: acoustically hollow zone within the tumor, choroidal excavation, and subretinal fluid.
Color Doppler ultrasound
Choroidal melanomas show pulsatile blood flow at the tumor base. This finding is not found in nevi.
Fluorescein and indocyanin green angiography (ICGA)
- Hypofluorescence: Due to blockage of the choroidal blood flow by the pigmentation inherent to the tumor.
- Hyperfluorescence: Small hyperfluorescent spots may be seen due to lipofuscin deposition at the RPE level.
- Circulation:“Double circulation” pattern consisting of an internal circulation within the lesion and the normal vascularity of the overlying retina. This characteristic is more evident in ICGA
Orange lipofuscin pigmentation possesses autofluorescent properties. Lipofuscin fluorescence is brighter than that of drusen (drusen are common in choroidal nevi).
Standard spectral domain OCT (SD-OCT)
Standard spectral domain OCT does not penetrate deeply enough for detecting the internal characteristics of choroidal neoplasms. However, it is useful in visualizing changes in the neurosensory retina and the retinal pigment epithelium (RPE). As it was mentioned earlier, posterior uveal melanomas may show serous retinal detachment in the areas adjacent to the tumor. Lipofuscin deposition is also seen at the level of the RPE.
Enhanced Depth Imaging Spectral Domain OCT (EDI-OCT)
Enhanced Depth Imaging Spectral Domain OCT is a relatively new technology that is now commercially available. It is a method that allows for the evaluation of deeper structures such as the choroid and the internal portion of the sclera. In a study of 37 eyes by Carol Shields, et al. it was found that the distinguishing characteristics of choroidal melanomas readily seen in EDI-OCT are:
- Optical shadowing (100%)
- Thinning of overlying choriocapillaris (100%)
- Subretinal fluid (92%)
- Subretinal lipofuscin deposits (95%)
- Shaggy photoreceptors (49%)
- Other retinal changes included: Loss of photoreceptors, loss of external limiting membrane, loss of inner segment-outer segment junction, irregularity of inner plexiform layer, irregularity of ganglion cell layer, intraretinal edema
Magnetic Resonance Imaging (MRI)
MRI may be used occasionally to aid in establishing a diagnosis and to look for extrascleral extension. MRI is most useful distinguishing melanoma from blood. Pigmented melanomas and subacute hemorrhage are similar in appearance on T1- and T2-weighted images, i.e. each is hyperintense on T1 and hypointense on T2. However, only melanoma demonstrates marked enhancement with administration of contrast. Of note, amelanotic choroidal melanomas will not resemble blood on exam or by MRI. An amelanotic lesion will not be hyperintense on T1-weighted images but it will still show marked enhancement with contrast.
Posterior uveal melanomas spread via vortex veins to the vascular system. Most metastasis are to the liver (92%), but the tumor can also spread to the lungs and the skin. Uncommonly, melanoma can demonstrate extension into optic nerve and brain. There is a lack of consensus on the optimum screening methodology for uveal melanoma. Among the tests that may be ordered during the metastatic workup for a patient with choroidal melanoma are:
- CT Chest/Abdomen/Pelvis with contrast
- Laboratory: Liver function tests with liver ultrasound
- PET CT
Most uveal melanomas have no genetic predisposition. Only about 1% are thought to be inherited. An alteration in tumor suppressor genes found on chromosome 3 is associated with some hereditary melanomas. There are two germline mutations responsible for hereditable melanoma: loss of BAP 1 expression as in BRAC1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) and more recently, inactivation of Methyl-CpG Binding Domain 4 (MBD4).
There is evidence that choroidal melanomas may arise from choroidal nevi, since nevi cells have been found in histopathological samples of melanomas. Thus, Shields and colleagues analyzed 2,514 cases of choroidal nevi to determine predictive features of growth into melanoma. Using the data obtained in this study, they developed a mnemonic for these predictive features: “To Find Small Ocular Melanoma Using Helpful Hints Daily”.
- T: Thickness > 2 mm
- F: Fluid (subretinal)
- S: Symptoms (decreased vision, flashes or floaters)
- O: Orange pigment (presence of)
- M: Margin within 3 mm of the optic disc
- UH: Ultrasonographic hollowness
- H: Absence of surrounding halo. Nevi usually show a surrounding clear halo consisting of atrophied retina.
- D: Absence of drusen. Drusen are chronic changes seen more commonly in slow growing lesions such as choroidal nevi than in melanomas.
The above are listed in the order in which they impact growth. If three or more of this factors are present, the risk of growth is 50%.
- Carol L Shields MD. Choroidal Nevus: When to Suspect Melanoma. 1-minute videos. American Academy of Ophthalmology. https://www.aao.org/1-minute-video/choroidal-nevus-when-to-suspect-melanoma Accessed June 28, 2019.
- American Academy of Ophthalmology. Choroidal melanoma. https://www.aao.org/image/choroidal-melanoma-4 Accessed June 28, 2019.
- Walpole S, Pritchard AL, Cebulla CM et al. Comprehensive study of the clincial phenotype of germline BAP1 variant-carrying families worldwide. J Natl Cancer Inst 2018;110:1328-41
- Derrien A, Rodrigues M, Eeckhoutte A, et al. Germline MBD4 mutations and predisposition to uveal melanoma. J Natl Cancer Inst 2021;113:80-7.
- Lewis DA, Albert DM. Chapter 138: Choroidal Nevi. In: Ryan SJ, et. al. Retina. 5th ed. Elsevier, 2013.</li
- Chapter 12: Uveal Tract. In: AAO Basic Clinical and Science Course Section 4: Ophthalmic Pathology and Intraocular Tumors. American Academy of Ophthalmology, San Francisco, 2011-2012.
- Cheung A, Scott IU, Murray TG, Shields CL. Distinguishing a Choroidal Nevus from a Choroidal Melanoma. Ophthalmic Pearls, EyeNet Magazine. Feb, 2012.
- Chapter 8: Oncology. In: Yannuzzi LA. The Retinal Atlas. Elsevier, 2010.
- Chapter 11: Posterior Segment. In: Trattler W, Kaiser PK, Friedman NJ. Review of Ophthalmology. 2nd. Ed. Elsevier. 2012.
- Collaborative Ocular Melanoma Study Group. Baseline echographic characteristics of tumors in eyes of patients enrolled in the Collaborative Ocular MelanomaStudy: COMS report no. 29.
- Singh P, Sinhg A. Choroidal melanoma. Oman J Ophthalmol. 2012 Jan-Apr; 5(1): 3–9.
- Wolff-Korman P, Korman B, Hazeneratz G. Duplex and color Doppler ultrasound in the differential diagnosis of choroidal tumors. Acta Ophthalmol 1992;204:66–70. Ophthalmology. 2008 Aug;115(8):1390-7, 1397.
- Gunduz K, Pulido JS, Bakri SJ, et al. Fundus autofluorescence in choroidal melanocytic lesions. Retina 2007;27:681–7.
- Shields CL, Furuta M, Berman EL, et al. Choroidal nevus transformation into melanoma: analysis of 2514 consecutive cases. Arch Ophthalmol 2009;127:981–7.
- Shields CL, Kaliki S, Rojanaporn D, Ferenczy SR, Shields JA. Enhanced Depth Imaging Optical Coherence Tomography of Small Choroidal Melanoma. Arch Ophthalmol. 2012 Jul;130(7):850-6.
- Torres VL, Brugnoni N, Kaiser PK, et al. Optical coherence tomography enhanced depth imaging of choroidal tumors. Am J Ophthalmol 2011;151:586–93.
- Collaborative Ocular Melanoma Study Group. Design and methods of a clinical trial for a rare condition: the Collaborative Ocular Melanoma Study. COMS Report No. 3. Control Clin Trials. 1993 Oct;14(5):362-91.