Differential Diagnosis

This section describes the most common lesions considered in the differential diagnosis of posterior uveal melanoma.

Accurate diagnosis of a choroidal nevus, discussed earlier in this chapter, is associated with clinical experience and availability of ancillary testing modalities. For the evaluation and management of posterior pigmented lesions with characteristics predictive of growth, patients may be referred to ocular oncology centers. No single clinical factor is pathognomonic for benign versus malignant choroidal melanocytic lesions. Less than 10% of benign choroidal nevi have surface lipofuscin, and 15% or less are associated with subretinal fluid (see Fig 17-8B, D, F). In addition, 11%–58% of choroidal nevi have overlying drusen, a frequency that increases with the age of the patient. The presence of surface drusen reflects chronicity of a melanocytic choroidal tumor but can also be seen in melanomas that have transformed from a formerly quiescent nevus. More than 20% of choroidal melanocytic tumors thicker than 3 mm are melanomas, and far fewer than 1% of those thinner than 1 mm are melanomas. Tumors that are 1–3 mm in thickness are more difficult to classify with certainty on the basis of clinical evaluation alone; therefore, often close surveillance for growth is warranted. The risk of malignancy increases substantially for lesions with a basal diameter larger than 6 mm.

Risk factors for the growth of small choroidal melanocytic lesions have been well characterized; they include 5 clinical features that have given rise to the mnemonic “to find small ocular melanomas” (see Clinical Pearl).

The following factors are also concerning for melanoma:

• larger size at presentation

• absence of drusen or degenerative RPE changes

• homogeneous low internal reflectivity on ultrasonography

• hot spots on fluorescein angiography

To document growth of the tumor, the clinician may periodically photograph it and perform OCT and/or B-scan ultrasonography. Slow growth does not necessarily suggest or confirm malignancy. In a study of 284 benign choroidal nevi, 31% showed slow, progressive enlargement (median increase in diameter = 1 mm) over a long observation period (7 years or more). The frequency of enlargement may be higher in patients younger than 40 years (54%) than in those older than 60 years (19%). Enlarging nevi may not develop any new lipofuscin or subretinal fluid suggestive of malignant change. Thus, when rapid or progressive growth occurs or new risk factors appear, definitive treatment should be considered.

When risk factors for growth are identified, transscleral or transvitreal fine-needle aspiration biopsy (FNAB) for cytology and molecular testing is an alternative to observation. Cytologic evaluation of cells obtained by FNAB of a small melanocytic tumor requires an experienced cytopathologist, because cellularity of the FNAB specimen may be low and diagnosis based on samples that typically have limited cellularity is challenging. The role of prognostic molecular testing in this setting remains an area of debate.

Melanocytoma (magnocellular nevus) of the choroid or optic nerve head typically appears as a dark brown to black elevated lesion. Optic nerve melanocytoma is usually located eccentrically over the optic nerve head and may be elevated. It often has fibrillary or feathery margins as a result of extension into the nerve fiber layer (see Chapter 15, Fig 15-12). Because a melanocytoma rarely transforms into melanoma, it is important to differentiate the two. However, choroidal melanocytomas, particularly large ones, can be challenging to differentiate from choroidal melanomas without biopsy. As mentioned previously, for large or growing lesions, biopsy should be considered.

Congenital hypertrophy of the RPE (CHRPE) refers to sharply defined, flat, very darkly pigmented lesions that range from 1 mm to more than 10 mm in diameter. Patients are asymptomatic, and the lesion can be noted at any age. In younger patients, CHRPE often appears homogeneously black (Fig 17-11A); in older individuals, foci of depigmentation (lacunae) often develop (Fig 17-11B), and the lesion may slowly enlarge. The histologic findings are identical to those of grouped pigmentation of the retina, also known as bear tracks or grouped CHRPE (Fig 17-11C). In patients with Gardner syndrome, a subtype of familial adenomatous polyposis, the presence of multiple atypical CHRPE-like patches appears to be a marker for the development of colon carcinoma. These lesions are distinct from multifocal CHRPE in that they do not have sectoral distribution and have irregular depigmented margins (Fig 17-11D).

Patients with age-related macular degeneration (AMD) may present with macular or extramacular subretinal neovascularization, hemorrhage, and fibrosis, accompanied by varying degrees and patterns of pigmentation (Fig 17-12A). Hemorrhage, a finding commonly associated with neovascular (exudative) AMD, usually does not occur with melanomas unless the tumor has broken through Bruch membrane. Clinical evaluation of the fellow eye is helpful in documenting AMD. OCT shows predominantly subretinal and intraretinal abnormalities. Ultrasonography reveals high or heterogeneous reflectivity rather than low internal reflectivity, as well as a lack of intrinsic vascularity. When in doubt, the clinician may use fluorescein angiography to help reveal early hypofluorescence secondary to blockage from the hemorrhage, which is often followed by late hyperfluorescence in the distribution of the choroidal neovascular membrane (Fig 17-12B). Serial observation shows involutional alterations of the evolving disciform lesion.

Choroidal detachments can be hemorrhagic or serous. They are often associated with hypotony and may develop after ophthalmic surgery in the early postoperative period. Hemorrhagic detachments are often dome shaped, involve multiple quadrants, and may be associated with breakthrough vitreous bleeding. Ultrasonographic findings may closely resemble those of melanoma but may reveal absence of intrinsic vascularity and involution of the hemorrhage over time. Observational management is indicated in most cases. MRI with gadolinium contrast may be beneficial in diagnosing suspicious cases.

Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a spontaneously developing, often asymptomatic, peripheral lesion in el derly individuals that resembles a choroidal detachment. It is often associated with suprachoroidal or subretinal bleeding and lipid exudation; associated retinal detachment is uncommon (Fig 17-12C). PEHCR is thought to be analogous to AMD, and the fellow eye often shows a similar or a nonexudative chorioretinal degeneration. PEHCR almost always involutes spontaneously.

Choroidal osteomas are benign, presumably acquired bony tumors that typically arise from the juxtapapillary choroid in young adults (more commonly in women) and are bilateral in 20%–25% of cases. The characteristic lesion appears yellow to orange and has well-defined margins (Fig 17-12D). Ultrasonography reveals a high-amplitude echo corresponding to the bony plate and loss of the normal orbital echoes behind the lesion (acoustic shadowing). CT can reveal calcification but is not needed for diagnosis. Choroidal osteomas typically enlarge slowly over many years and can decalcify with time. If they involve the macula, vision is generally impaired. Subretinal neovascularization is a common complication. The etiology of these lesions is unknown, but chronic low-grade choroidal inflammation has been suspected (see Chapter 12).

Table 17-2 Differential Diagnosis of Amelanotic Choroidal Mass

Choroidal hemangiomas (see Chapter 18) resemble the surrounding fundus in color and may appear to be lightly pigmented or orange. When a slit beam is passed over the lesion, it can appear to glow. These tumors are often better visualized on infrared imaging obtained with OCT than on fundus photographs. In infrared images, choroidal hemangiomas appear dark. Over time, a serous retinal detachment may develop. These lesions, which are often associated with overlying cystic retinal degeneration, are hyperechogenic on ultrasonography and show a characteristic vascular pattern on fluorescein and indocyanine green angiography.

Varix of the vortex vein (Fig 17-12E) is found predominantly in the nasal quadrants and can reach 4–5 mm in diameter. When filled with blood, it appears dark. The clinician can diagnose this condition by observing its coincidence with the vortex vein ampulla and by gently compressing the eye during indirect ophthalmoscopy, which causes the varix to deflate.

Intraocular metastases (Fig 17-12F; see also Chapter 20) are generally amelanotic and thus pale or yellowish, unless they originate from a cutaneous melanoma. Most show moderately high or heterogeneous reflectivity on ultrasonography. Table 17-2 lists additional conditions for consideration in cases with amelanotic choroidal masses.

• Chien JL, Sioufi K, Surakiatchanukul T, Shields JA, Shields CL. Choroidal nevus: a review of prevalence, features, genetics, risks, and outcomes. Curr Opin Ophthalmol. 2017;28(3):228–237.

• Mashayekhi A, Siu S, Shields CL, Shields JA. Slow enlargement of choroidal nevi: a long-term follow-up study. Ophthalmology. 2011;118(2):382–388.

Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.