Long-term Survival in a Patient With Uveal Melanoma and Liver Metastasis FREE

Uveal melanoma¹ is the most commonprimary ocular malignancy in whites and represents 70% of all primary ocularmalignancies. In patients with metastatic uveal melanoma, the prognosis forthose with initial metastasis to the liver is particularly poor. The mediansurvival of patients who first develop liver metastasis from uveal melanomais 5 to 7 months, as compared with 18 months for other initial sites of metastasis.^{2 - 4} This poor prognosiscontinues despite treatment modalities such as chemoembolization.^{5 - 6} We report a case of uveal melanomawith initial metastasis to the liver in a patient who survived for more than5 years after diagnosis of liver metastasis.

Possible uveal melanoma in the left eye was diagnosed in a 74-year-oldwhite woman with a history of hypertension. The melanoma was discovered aftershe sought evaluation for decreased visual acuity in that eye. The patientwas seen at the Wilmer Eye Institute, Baltimore, Md, September 13, 1993. Examinationrevealed best-corrected visual acuity 20/30 OD and counting fingers OS. Therewas a mild afferent pupillary defect with esotropia in the left eye. Examinationof the left eye revealed a pigmentary ciliochoroidal lesion growing into thelens. The iris was bowed forward temporally. Dilated fundus examination discloseda cap of retinal detachment over the lesion. Ultrasonography disclosed a large,solid, dome-shaped lesion temporally, which was anterior to the equator, withextension into the ciliary body. The lesion displayed low internal reflectivity.The basal diameter measured 18 × 17 mm, with a maximal elevation of12.8 mm. Malignant melanoma was diagnosed. As a participant in the CollaborativeOcular Melanoma Study for large-lesion melanoma, she was randomized to undergoenucleation without prior irradiation. The procedure was performed September24, 1993.

Gross examination of the globe disclosed a mottled gray tumor involvingthe choroid, ciliary body, and iris periphery. The tumor measured 17 mm atits base and 11 mm in maximum height. Posteriorly, the tumor extended to within9 mm from the margin of the disc. The lens was molded by the tumor and showedcortical changes. The retina was detached.

Microscopic examination of serial sections disclosed a lightly pigmentedtumor of the choroid and ciliary body that invaded the iris leaf and trabecularmeshwork (Figure 1). According tothe 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. Tumorcells 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 moderateinflammation with lymphocytes at the base of the tumor and within the tumor.Some foci of necrosis, focal hemorrhages, and balloon cells were present withinthe tumor. Numerous corpora arenacea were seen in the arachnoid surroundingthe optic nerve. The final diagnosis was spindle cell melanoma of the choroid,ciliary body, and iris, with invasion of the trabecular meshwork and correspondingretinal detachment.

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

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

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

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

The prognosis for patients with metastatic choroidal melanoma is poor.Survival from time of development of systemic metastasis ranged from 1 to31 months in 1 study.² The liver is themost common site of metastasis in choroidal melanoma.⁷ Theprognosis is particularly poor for patients with initial metastasis to theliver.^{2 - 4} Thisfinding remains true despite various therapeutic strategies, such as chemoembolization^{5 - 6} and hepatic perfusion with melphalanwith or without tumor necrosis factor.⁸

In our case, the patient survived more than 7 years after diagnosisof the primary uveal melanoma and more than 5 years after development of metastaticmelanoma to the liver. This patient underwent 1 course of chemoembolizationof liver metastases, which was performed when CT studies demonstrated metastaticspread within the liver. Subsequent CT demonstrated stability of the livermetastases and prompted speculation about the development of an immune responseto the malignancy. The patient developed vitiligo. Only a few cases have beenreported of patients with choroidal melanoma and vitiligo.⁹ Thisdisorder, thought to have an autoimmune cause, may confer a favorable prognosisfor patients with cutaneous melanomas.¹⁰ Thepatient did not undergo any other therapy for melanoma, although she did undergosurgery for adenocarcinoma of the sigmoid colon. The long-term survival ofthis patient reinforces the concept that patient-specific factors, such asthe possible development of an immune response, can affect the course of uvealmelanoma.

The authors have no relevant financial interest in this article.

Corresponding author: Elia J. Duh, MD, 600 N Wolfe St, Jefferson3-109, Baltimore, MD 21287 (e-mail: eduh@jhmi.edu).