Gross examination of the globe disclosed a mottled gray tumor involving the choroid, ciliary body, and iris periphery. The tumor measured 17 mm at its base and 11 mm in maximum height. Posteriorly, the tumor extended to within 9 mm from the margin of the disc. The lens was molded by the tumor and showed cortical changes. The retina was detached.

Microscopic examination of serial sections disclosed a lightly pigmented tumor of the choroid and ciliary body that invaded the iris leaf and trabecular meshwork (Figure 1). According to the Armed Forces Institute of Pathology modification of the Callendar classification, this was a spindle cell malignant melanoma (Figure 2). A count of 40 high-power fields revealed no mitotic figures. The tumor ruptured the Bruch membrane and invaded the peripheral retina. Tumor cells were not seen in the vitreous. There was invasion along a ciliary nerve, with tumor extending close to the surface of the sclera. There was moderate inflammation with lymphocytes at the base of the tumor and within the tumor. Some foci of necrosis, focal hemorrhages, and balloon cells were present within the tumor. Numerous corpora arenacea were seen in the arachnoid surrounding the optic nerve. The final diagnosis was spindle cell melanoma of the choroid, ciliary body, and iris, with invasion of the trabecular meshwork and corresponding retinal detachment.

View larger version (77K): [in this window] [in a new window] Figure 1. Microscopic examination of the globe disclosed a large basophilic tumor (single arrow) arising from the uveal tract, which indented the lens (asterisk) and induced retinal detachment with surrounding subretinal fluid (double arrow) (hematoxylin-eosin).

View larger version (178K): [in this window] [in a new window] Figure 2. Photomicrograph of melanoma cells revealed a dense collection of cohesive spindle-shaped cells with poorly defined cell borders. Some of the cells exhibited the nuclear folds of the spindle A type (single arrow), while other cells had more distinct nucleoli typical of the spindle B type (double arrow) (hematoxylin-eosin, original magnification x200).

Follow-up during the next few years disclosed no evidence of local recurrence. In April 1996, physical examination revealed hepatomegaly despite the patient being asymptomatic. Liver function test results were within normal limits, but computed tomography (CT) demonstrated multiple lesions in the lower portions of the liver. Fine-needle biopsy of the liver was performed May 3, 1996. Histopathological analysis disclosed spindle-shaped, melanin-containing cells diagnostic of metastatic malignant melanoma (Figure 3). Dense aggregates of lymphocytes were also observed. Immunohistochemical staining was positive for HMB-45.

View larger version (206K): [in this window] [in a new window] Figure 3. Fine-needle biopsy and histopathologic analysis of liver cells disclosed spindle-shaped cells that replaced normal liver architecture and were diagnostic of melanoma. Focal mitotic figures were seen within the melanoma cells. A dense lymphocytic infiltrate was adjacent to the metastatic lesion (hematoxylin-eosin, original magnification x200).

Observation was elected. In October 1996, CT showed an increase in metastasis to the rest of the liver. The patient therefore underwent 1 course of chemoembolization. Follow-up CT, including scanning performed in June 1998, disclosed no substantial change in the liver lesions; liver function test results remained within normal limits.

The patient was seen in January 1999 at the Wilmer Eye Institute, where she commented on the loss of skin pigment of the scalp and arms; this was thought to be due to an autoimmune reaction to pigment. There was no sign of local tumor recurrence in the left eye.

On September 30, 1999, the patient underwent sigmoid colectomy, small-bowel resection, cholecystectomy, and liver biopsy at Johns Hopkins Hospital, Baltimore, Md, primarily for removal of adenocarcinoma. Pathological examination results revealed moderately differentiated adenocarcinoma of the sigmoid colon, with lymph nodes negative for cancer and metastatic melanoma of the left and right lobes of the liver. Cholecystitis and cholelithiasis were confirmed. No evidence of small-bowel tumor involvement was found. The patient died June 30, 2001.

Comment.
The prognosis for patients with metastatic choroidal melanoma is poor. Survival from time of development of systemic metastasis ranged from 1 to 31 months in 1 study.² The liver is the most common site of metastasis in choroidal melanoma.⁷ The prognosis is particularly poor for patients with initial metastasis to the liver.^2-4 This finding remains true despite various therapeutic strategies, such as chemoembolization^5-6 and hepatic perfusion with melphalan with or without tumor necrosis factor.⁸

In our case, the patient survived more than 7 years after diagnosis of the primary uveal melanoma and more than 5 years after development of metastatic melanoma to the liver. This patient underwent 1 course of chemoembolization of liver metastases, which was performed when CT studies demonstrated metastatic spread within the liver. Subsequent CT demonstrated stability of the liver metastases and prompted speculation about the development of an immune response to the malignancy. The patient developed vitiligo. Only a few cases have been reported of patients with choroidal melanoma and vitiligo.⁹ This disorder, thought to have an autoimmune cause, may confer a favorable prognosis for patients with cutaneous melanomas.¹⁰ The patient did not undergo any other therapy for melanoma, although she did undergo surgery for adenocarcinoma of the sigmoid colon. The long-term survival of this patient reinforces the concept that patient-specific factors, such as the possible development of an immune response, can affect the course of uveal melanoma.

The authors have no relevant financial interest in this article.