CHAPTER 20
Ocular Involvement in Systemic Malignancies
Secondary Tumors of the Eye
Metastatic Carcinoma
Since the first description in 1872 of a metastatic tumor in the eye of a patient with carcinoma, a large body of literature has indicated that the most common type of intraocular or orbital tumor in adults is metastatic. There are several comprehensive studies of ocular metastatic tumors: some have reported the incidence of tumor metastases in a consecutive series in autopsies, some have dealt with tumor incidence in patients with generalized malignancy, and others have used a clinicopathologic approach. As long-term survival from systemic primary malignancy continues to increase, the ophthalmologist will be confronted with a growing incidence of intraocular and orbital metastatic disease requiring prompt recognition and appropriate diagnostic and therapeutic management.
Metastases to the eye are being diagnosed with increasing frequency for various reasons:
increasing incidence of certain tumor types that metastasize to the eye (eg, breast, lung) prolonged survival of patients with certain cancer types (eg, breast cancer)
increasing awareness among medical oncologists and ophthalmologists of the pattern of metastatic disease
Primary tumor sites
The vast majority of metastatic solid tumors to the eye are carcinomas from various organs. Cutaneous melanoma rarely metastasizes to the eye. Table 20-1 shows the most common primary tumors that metastasize to the choroid.
Mechanisms of metastasis to the eye
The mechanism of intraocular metastasis depends on hematogenous dissemination of tumor cells. The anatomy of the arterial blood supply to the eye dictates the predilection of tumor cell deposits within the eye. The posterior choroid, with its rich vascular supply, is the most favored site of intraocular metastases, and it is affected 10–20 times more frequently than is the iris or ciliary body. The retina and optic disc, supplied by the single central retinal artery, are rarely the sole site of involvement. Bilateral ocular involvement has been reported in approximately 25% of cases, and multifocal deposits are frequently seen within the involved eye. Many patients with ocular metastases also have concurrent central nervous system (CNS) metastases.
Table 20-1
Clinical evaluation
The clinical features of intraocular metastases depend on the site of involvement. Metastases to the iris and ciliary body usually appear as white or gray-white gelatinous nodules (Figs 20-1, 20-2, 20-3). The clinical features of anterior uveal metastases may include
iridocyclitis secondary glaucoma rubeosis iridis hyphema
irregular pupil
Figure 20-1 Metastasis to the iris associated with hyphema.
Figure 20-2 Metastasis from breast carcinoma to the iris. (Courtesy of Timothy G. Murray, MD.)
Anterior segment tumors are best evaluated with slit-lamp biomicroscopy coupled with gonioscopy. High-resolution ultrasound imaging may quantify tumor size and anatomical relationships.
Patients with a tumor in the posterior pole commonly complain of loss of vision. Pain and photopsia may be concurrent symptoms. Indirect binocular ophthalmoscopy may reveal a nonrhegmatogenous (ie, exudative) retinal detachment associated with a placoid amelanotic tumor mass (Figs 20-4, 20-5, 20-6). Multiple or bilateral lesions may be present in approximately 25% of cases, highlighting the importance of close evaluation of the fellow eye. These lesions are usually relatively flat and ill defined, often gray-yellow or yellow-white, with secondary alterations at the level of the retinal pigment epithelium (RPE) presenting as clumps of brown pigment (“leopard spotting”; Fig 20-7).
The mushroom configuration frequently seen in primary choroidal melanoma from breakthrough of the Bruch membrane is rarely present in uveal metastases. The retina overlying the metastasis may appear opaque and become detached. Rapid tumor growth with necrosis and uveitis are occasionally observed. Dilated epibulbar vessels may be seen in the quadrant overlying the metastasis. For a differential diagnosis of choroidal metastasis, see Table 20-2.
Figure 20-3 Metastatic cutaneous melanoma to the iris. Note both lesions at periphery.
Figure 20-4 Multiple metastatic lesions to the choroid. Note the pale yellow color and relative flatness.
Figure 20-5 A, Metastatic lesion to the choroid inferiorly, associated with bullous retinal detachment (asterisks). B, Subtle metastatic lesion to the choroid (arrows), near the fovea, associated with serous effusion.
Ancillary tests
Although fluorescein angiography may be helpful in defining the margins of a metastatic tumor, it is typically less useful in differentiating a metastasis from a primary intraocular neoplasm. The double circulation pattern and prominent early choroidal filling often seen in choroidal melanomas are rarely found in metastatic tumors.
Figure 20-6 A, Metastatic carcinoma to the choroid. Vision was reduced to finger counting because of macular involvement. Note irregular pigmentation on surface. B, Same eye, 1 month after radiation therapy. Visual acuity has improved to 20/20. Note increased pigmentation, characteristic of irradiation effects.
Ultrasonography is diagnostically valuable in patients with a metastatic tumor. B-scan shows an echogenic choroidal mass with an ill-defined, sometimes lobulated, outline. Overlying secondary retinal detachment is commonly detected in these cases. A-scan demonstrates moderate to high internal reflectivity.
Fine-needle aspiration biopsy may be helpful in rare cases when the diagnosis cannot be established by noninvasive procedures. Although metastatic tumors may recapitulate the histology of the primary tumor, they are often less differentiated. Special histochemical and immunohistochemical stains assist in the diagnosis of metastatic tumors.
Figure 20-7 Breast metastases, clinical appearance. Note the amelanotic infiltrative choroidal mass with secondary overlying retinal pigment epithelial changes accounting for the characteristic “leopard spots.” (Courtesy of Matthew W. Wilson, MD.)
Table 20-2
Metastases to the optic nerve may produce disc edema, decreased visual acuity, and visual field defects. Because the metastases may involve the parenchyma or the optic nerve sheath, MRI as well as ultrasonography may be valuable in detecting the presence and location of the lesion(s).
Metastases to the retina, which are very rare, appear as white, noncohesive lesions, often distributed in a perivascular location suggestive of cotton-wool spots (Fig 20-8). Because of secondary vitreous seeding of tumor cells, these metastases sometimes resemble retinitis more than they do a true tumor. Vitreous aspirates for cytologic studies may confirm the diagnosis.
Other diagnostic factors
One of the most important diagnostic factors in the evaluation of suspected metastatic tumors is a history of systemic malignancy. More than 90% of patients with uveal metastasis from carcinoma of the breast, for example, have a history of treatment prior to the development of ocular involvement. In the remaining 10% of patients, the primary tumor can usually be diagnosed by breast examination at the time the suspicious ocular lesion is detected. For other patients, however, often there is no prior history of malignancy. This is especially true of patients with ocular metastasis from the lung. A complete systemic evaluation, a family history, and a history of smoking may alert the ophthalmologist to the suspected site of an occult primary tumor. Any patient with an amelanotic fundus mass suspected of being a metastatic focus should have a thorough systemic evaluation, including imaging of the breast, chest, abdomen, and pelvis. PET-CT scanning may help direct a more targeted evaluation.
Figure 20-8 A, Metastatic lung carcinoma to the retina, involving the macula. Vision was reduced to finger counting. B, Same eye, showing characteristic perivascular distribution of metastases. C, Vitreous aspirate from same eye, showing an aggregate of tumor cells, characteristic of adenocarcinoma of the lung.
Prognosis
The diagnosis of tumor metastatic to the uvea implies a poor prognosis, because widespread dissemination of the primary tumor has usually occurred. In one report, the survival time following the diagnosis of metastasis to the uvea ranged from 1 to 67 months, depending on the primary cancer type. Metastatic carcinoid is associated with long survival times. Patients with breast carcinoma metastatic to the uvea survive an average of 9–13 months after the metastasis is recognized, but cases with long-term survival have now been reported. Shorter survival time is typically seen in patients with lung carcinoma and carcinomas arising from the gastrointestinal or genitourinary tracts, in which metastases herald the presence of the primary tumor.