Choroidal and Retinal Metastasis

Introduction

In the 2008 annual report to the nation on the status of cancer in America from the collaborative work of the National Cancer Institute (NCI), American Cancer Society, Centers for Disease Control and Prevention (CDC), and the North American Association of Central Cancer Registries (NAACR), it was documented that

C.L. Shields, M.D.( ) • J.A. Shields, M.D. Wills Eye Institute, Thomas Jefferson University

Hospital, 840 Walnut Street, Suite 1440, Philadelphia, PA 19107, USA

e-mail: carol.shields@shieldsoncology.com; jerry.shields@shieldsoncology.com

the incidence and death rates from all cancers combined decreased significantly [1]. These decreases were driven by declines in incidence and death rate for the three most common cancers in men including lung, colorectum, and prostate cancers. Additionally, two of the three leading cancers in women declined including breast and colorectum cancers. The lung cancer death rate in women leveled off. They emphasized that even though the overall lung cancer death rate had stabilized, this finding varied by region as in areas of high cigarette smoking prevalence, such as the southern and midwestern states, the death rate actually increased. They advised improvement in state tobacco control programs.

Systemic cancers can metastasize to the eye. The most common cancers to spread to the ocular structures include breast and lung cancer [2]. The decreasing incidence of these cancers could impact the frequency of ocular metastasis.

Historically, metastatic tumors to the eye were believed to be rare. A classic ophthalmic textbook in 1966 stated that few surgeons had observed more than one case of ocular metastasis [3]. Later, it was realized that ocular metastases were more common, and over the past 50 years, there have been several reports on the incidence and prognosis of patients with metastatic tumors to the eye [4–12]. Albert and associates found that 2% of 213 patients with known systemic cancer and metastases had choroidal metastases [5]. Bloch and Gartner reported that 8% of eyes in 230 patients with autopsy-proven carcinomas had histologically confirmed uveal metastatic foci [7]. Nelson and coworkers found in an autopsy study that 4% of patients dying of carcinoma had ocular metastases [10]. They estimated that in the year 1983, 22,000 patients who died of cancer had ocular metastatic disease [10].

Most reports on ocular metastases come from pathology laboratories or from general cancer centers where patients have had known primary cancers and/or metastatic disease and the eyes were subsequently examined. These studies have focused on the source of the primary tumor, as well as on general clinical and histopathologic features of the tumor (derived from autopsy or pathology reports in some instances) [4–8, 10]. Ocular metastases on file at the Armed Forces Institute of Pathology were reviewed by Hart in 1962 [4] and Ferry and Font in 1974 [8].

There are only a few comprehensive reports on the clinical features of ocular metastases from an ophthalmologic point of view. In 1979, Stephens and Shields reviewed 70 cases of uveal metastases and provided general details on the clinical findings of these tumors [9]. In 1997, Shields and coworkers reported extensive detail on the clinical features and management of uveal metastases in a large group of 420 consecutive patients [2]. Later, findings on the features of metastasis to the optic disk were reported [13].

Others have focused on the features of uveal metastases from specific primary sites such as breast [14–20], prostate [21], skin [22–25], and carcinoid tumors [26]. In 1987, Freedman and Folk reported on the clinical aspects of metastatic tumors to the choroid in 61 patients, and they addressed specifically the factors affecting the median survival time after ocular diagnosis [11]. Later, Shields and Shields summarized their experience with clinical features, diagnostic techniques, and management of intraocular metastases in a textbook and comprehensive atlas on ocular tumors [27, 28].

Primary Cancer Sites Leading to Intraocular Metastasis

Metastatic tumors generally spread to the ocular region via hematogenous dissemination. Metastases can occur in the intraocular structures such as the uvea, retina, optic disk, or vitreous cavity, and they can manifest in the adnexal structures like the eyelid, conjunctiva, or orbit [1, 2]. The great majority of ocular metastases are detected in the uvea. In an analysis of 950 individual uveal metastases, metastatic tumors most often occurred in the choroid (88%) and less frequently in the iris (9%) or ciliary body (2%) [2, 29] (Fig. 14.1). Rarely, ocular metastases are found in the retina, optic disk, or vitreous [13, 27, 28].

Uveal metastases most commonly originate from primary cancers in the breast (47%), lung (21%), gastrointestinal tract (4%), kidney (2%), skin (melanoma) (2%), prostate gland (2%), and other sites (4%) [2] (Table 14.1) (Fig. 14.2). In approximately 17% of all patients, the primary tumor site remains unknown. At the time of presentation with a uveal metastasis, approximately 30% of patients have no known history of primary cancer [2]. Subsequent evaluation of these patients reveals a primary tumor most commonly in the lung (35%) and less frequently in the breast (7%) and others sites (6%) (Fig. 14.3). Despite repeated evaluation, the primary site in these select patients who present without a history of cancer remains unknown in 51% of patients.

Nearly one-half of such patients with no detectable primary site die of diffuse metastatic disease shortly after the ocular diagnosis [2].

Patient Profile

Breast cancer is by far the most common malignancy to metastasize to the uvea, accounting for 39–49% of all uveal metastasis [2, 5–12]. In a review of 3,802 breast cancer patients, Kamby and coworkers reported the five most common sites of metastasis from breast cancer were the lung (71%), bone (71%), lymph nodes (67%), liver (62%), and pleura (50%) [30]. Ocular metastasis from breast cancer occurs in 9–37% of patients depending on the source of the study [7, 10, 16]. Uveal metastases represent the smallest detectable lesions of systemic dissemination of breast cancer and occur at a median of 3 years following diagnosis of the primary tumor [16].

Uveal metastases are more commonly found in women, primarily due to the high frequency of breast cancer metastatic to the eye. In an analysis of 450 patients with uveal metastases from all primary cancer sites, the tumor was found in men in 33% and women in 67% [2]. Uveal metastases in men originated from cancer of the lung (40%), gastrointestinal tract (9%), kidney (6%), skin (melanoma) (4%), prostate gland (6%), breast (1%), others (4%), and unknown primary site (29%) [2]. Single cases of breast cancer metastatic to the eye in men have been published (see Table 14.1) [31, 32]. Uveal metastases in women were from cancer of the breast (68%), lung (12%), gastrointestinal tract (2%), kidney (<1%), skin (melanoma) (1%), others (4%), and unknown (12%) [2]. In an analysis of 264 patients with uveal metastases from breast cancer, the primary tumor was found in women in 99% and men in 1% [17].