Understanding Ocular Metastatic Tumors and Simulating Lesions

Ocular metastatic tumors are cancer cells that started elsewhere in the body and spread to the eye via the bloodstream. Because of its abundant vascular supply, the most common site for ocular metastatic disease is the choroid, which provides the avenue for tumor emboli and allows an environment for growth.¹ Approximately 88% of metastases occur in the posterior uvea, namely the choroid, followed by the iris (9%) and the ciliary body (2%).^2,3 Choroidal metastasis is the most common intraocular malignancy in the adult population, with an incidence of approximately 10%.^2,4 It frequently occurs in the later stages of disseminated disease and is considered a poor prognostic sign.¹ This article reviews what you need to know for distinguishing choroidal ocular metastases, and the steps to take once you do so.

APPEARANCE

Choroidal metastatic lesions generally appear as a single (or multiple) yellow subretinal mass that involves the postequatorial region of the eye (Figure 1). Most metastatic tumors are located in the posterior pole and have a domed or plaque-shape appearance. Less frequently, the metastatic tumor may appear orange in color, as in renal cell carcinoma or thyroid cancer, or brown-gray, as in metastatic melanoma. Because of their location, these metastatic tumors are frequently accompanied by subretinal fluid, significant exudative retinal detachment, and the possibility of reduced visual acuity (Figure 2).

Other signs and symptoms, although found less frequently, include diplopia, hyperemia, metamorphopsia, flashes, floaters, peripheral field changes, and pain.^1,2 Up to 11% of patients with metastatic choroidal involvement have no symptoms when they are found upon routine ocular examination.¹

ETIOLOGY

The most common primary source of choroidal metastasis is breast carcinoma, accounting for up to 53% of cases.¹ These tumors were found to be multifocal in 48% of cases and located post equatorially. Lung cancer is the second most common source of choroidal metastasis and is responsible for 29% of cases (Figure 3).^1,5,6 Unilateral and unifocal choroidal lesions are more common with lung cancer.^5,7 Carcinoma of the gastrointestinal tract, prostate, kidney, and skin are less common primary tumors for choroidal metastatic eye disease.^5,6,8 Approximately 65% of patients with choroidal metastasis have a known systemic cancer at the time of eye diagnosis; however, a choroidal metastasis finding may precede the diagnosis of systemic cancer. It is important to note that, in patients without known cancer at the time of diagnosis with choroidal metastasis, the primary tumor sites include lung cancer (7%) and breast cancer (35%). In some instances, the primary site is not found.⁶ When there is no known primary cancer, a thorough systemic workup for cancer should be initiated and coordinated with a medical oncologist. Histopathologically, choroidal metastasis will appear with chords and nests of cancer cells (carcinoma) that infiltrate the choroid virtually from every site in the body.⁹

METASTATIC MECHANISM OF CHOROIDAL METASTASES

Metastatic choroidal tumors survive and thrive on a suitable microenvironment and with ample blood perfusion. The choroid is supplied by the short posterior ciliary arteries, which have multiple branches and high vascularization, thus allowing more tumor emboli to reach the posterior uvea. This may explain why the choroid is more often affected than the ciliary body and sclera.²

DIAGNOSTIC TESTING

When there is no history of a primary malignancy, the diagnosis of a choroidal metastasis can be somewhat difficult. The distinct features of a choroidal metastatic tumor found on indirect ophthalmoscopy can aid in the differential diagnosis. The multimodal imaging options below can be used in-office to detect specific features that indicate the presence of a choroidal metastatic tumor.

• B-Scan Ultrasonography: a medium-high heterogenous echo mass with no choroidal depression and echo attenuation
• Fluorescein Angiography: hypofluorescence in the arterial phase and diffuse fluorescence in the venous phase
• OCT: an uneven or wavy lesion with secondary changes in the retinal pigment epithelium, atrophy of the retinal photoreceptor cell layer, or decreased acoustic reflectance within the tumor or retinal detachment
• OCTA: a lack of blood flow signal and autofluorescence can distinguish a choroidal metastasis from other choroidal tumors and lesions
• Indocyanine Green: a uniform, fluorescent pigment background with a hypofluorescent performance in the arteriovenous phase

In cases of an unidentified primary source and/or indeterminate diagnostic findings, fine needle aspiration biopsy can provide cytological evidence of a metastatic tumor (versus a primary tumor) when needed.^1,2

DIFFERENTIAL DIAGNOSIS

A differential diagnosis list should always include choroidal melanoma, hemangioma, granuloma, osteoma, and sclerochoroidal calcification.¹

Choroidal Melanoma

Choroidal melanoma is the most common primary intraocular neoplasm found in adults. These lesions typically present unilaterally as elevated, darkly pigmented tumors (Figure 4).¹⁰ Choroidal melanomas may also present with subretinal fluid and overlying orange pigment (lipofuscin). Diagnosis is primarily made during clinical examination using indirect ophthalmoscopy and echography. Echographically, choroidal melanomas typically display low internal acoustic reflectivity on A-scan.

Hemangioma

Circumscribed choroidal hemangiomas are benign intraocular tumors that present as round, orange-pink choroidal lesions (Figure 5).¹¹ They typically present in the posterior pole, often near the macula, optic disc, or both. They may remain asymptomatic throughout life; however, if visual symptoms do occur, they are caused by secondary macular edema and/or exudative retinal detachment associated with the hemangioma.

Granuloma

Choridal granulomas are clusters of white blood cells found subretinally and/or within the choroid. They present as amelanotic lesions and may or may not be accompanied by uveitis.¹² These lesions are usually associated with sarcoidosis and tend to respond well to treatment with oral steroids (Figure 6).

Osteoma

Choroidal osteomas (Figure 7) are orange-yellow-white osseous (bony) lesions. Although this is a choroidal lesion, its borders tend to look well-defined. This is caused by overlying retinal pigment epithelial atrophy.

Sclerochoroidal Calcification

Sclerochoroidal calcification tends to present later in life with bilateral, subretinal, yellow-white lesions (Figure 8) that are typically asymptomatic and may be related to an electrolyte imbalance.¹³

TREATMENT

Effective control of these lesions is vital; however, management of choroidal metastasis depends on many factors, including the patient’s systemic status, the number of choroidal tumors, their location, and laterality. In patients with poor systemic status, observation only is preferred. If the metastases are multifocal and bilateral, then systemic chemotherapy, immunotherapy, and hormone therapy (eg, with tamoxifen and aromatase inhibitors) or whole eye plaque radiotherapy are recommended. If a solitary metastasis is found, then radiotherapy, transpupillary radiotherapy, or photodynamic therapy can be performed. Enucleation is reserved for blind, painful eyes.¹

FUTURE OUTLOOK

There are a growing number of chemotherapeutic treatments available to control primary cancer, metastatic tumors, and simulating lesions, leading to longer survival rates for patients with cancer. In order to minimize ocular complications and institute proper referral management and communication, optometrists should make every effort (eg, continuing education, staying current with relevant literature) to identify the disease process as early as possible.