Woman referred for peripheral retinal abnormality

Exudative detachment, telangiectasias in a pigmented peripheral retinal lesion were seen in the left eye.

Jeffrey Chang

Vivek Chaturvedi

A 50-year-old white woman with a history of lupus diagnosed 7 years ago was referred to the retina service of the New England Eye Center after a routine eye examination revealed a peripheral retinal abnormality in her left eye.

She had noticed an occasional floater and intermittent photopsias in the left eye for more than 4 years, but had not noticed any changes to her peripheral vision or new metamorphopsia.

Her medical history was significant for lupus, which had been treated with Plaquenil (hydroxychloroquine, Sanofi-Aventis) for 5 years. She suffered bilateral jugular vein thromboses in 2004, thought to be due to her lupus, and was also on Coumadin (warfarin sodium tablets, Bristol-Myers Squibb) for atrial fibrillation.

Examination

On examination, the patient’s visual acuity was 20/20 in the right and left eyes. IOP by applanation was 15 mm Hg in the right eye and 13 mm Hg in the left eye. Pupillary exam, confrontation visual fields and color vision testing were normal. Slit lamp examination was unremarkable in both eyes. Dilated fundus examination revealed slightly tortuous retinal arteries in both eyes. The right inferior fundus showed a shallow peripheral elevation of the retina inferiorly consistent with retinoschisis. The left fundus showed a 10.4 mm × 6.1 mm flat choroidal nevus extending from 1 to 6 o’clock peripherally, with a small, localized accompanying exudative retinal detachment, telangiectasias and scattered areas of hemorrhage temporally (Figure 1). There was no vitreous cell or vascular sheathing seen in either eye.

Figure 1. A peripheral, flat choroidal nevus in the temporal retina with accompanying exudative retinal detachment, telangiectasias and scattered areas of hemorrhage.

Figure 2. Mid-phase fluorescein angiogram of the temporal retina showing capillary nonperfusion inferotemporally. Images: Chen J, Duker JS

On fluorescein angiogram, there was capillary nonperfusion inferotemporally (Figure 2), and in the area of the exudative detachment, there was hyperfluorescence and late leakage. On B-scan, the nevus was flat with an area of exudative detachment noted.

What is your diagnosis?

Exudative detachment, choroidal nevus

Due to the appearance of the peripheral retinal capillary nonperfusion and exudative detachment, familial exudative vitreoretinopathy was considered as a possible diagnosis. However, the patient’s son and daughter were subsequently examined and were clear of retinal abnormalities. In addition, peripheral retinal vessels in familial exudative vitreoretinopathy should appear straightened, which was not the case in this patient.

Coats’ disease was considered due to the patient’s peripheral telangiectatic vessels, exudative detachment and capillary nonperfusion, but the clinical appearance was not classic. Vasculitis from lupus may cause retinal nonperfusion, but there was no evidence of retinal vasculitis on exam. Blood dyscrasias, diabetic retinopathy and retinal vascular occlusions may also produce capillary nonperfusion.

Given the large choroidal nevus, choroidal melanoma was also considered in the differential diagnosis. Peripheral exudative hemorrhagic chorioretinopathy, a bilateral extramacular degenerative process of the eyes that can simulate choroidal melanoma, can be associated with peripheral subretinal or sub-RPE blood or exudation. However, these lesions are often bilateral, and there was no evidence of peripheral retinal degeneration in the right eye.

Diagnosis

As there was no evidence of vision-threatening exudation or growth, observation was recommended and the patient was monitored on a 3-month basis. A hemoglobin electrophoresis was drawn, which was normal. On her third visit, the exam revealed the base of the nevus had grown in size posteriorly, and in addition, a repeat B-scan ultrasound showed an increase in the thickness of the lesion to 3 mm.

Figure 3. Hematoxylin and eosin stain showing mixed cellularity malignant melanoma.

Figure 4. Mosaic fundus photo after gamma knife radiation.

Because of concern for a slow-growing choroidal melanoma, a vitrectomy and fine needle aspiration biopsy were performed. The biopsy showed malignant melanoma with a mixture of spindle and epithelioid cells (Figure 3). Fluorescent in situ hybridization was performed and demonstrated a monosomy 3 genotype. Upon the diagnosis of choroidal melanoma, a complete evaluation and a metastatic work-up including a liver CT and a PET scan were performed. Soon after, the patient received radiation therapy. Gamma knife radiation was selected due the relatively diffuse nature of the melanoma and the patient’s preference for no further surgery. Over a 6-month follow-up, the lesion has since remained stable with no growth and no evidence of systemic metastases (Figure 4).

Discussion

Choroidal melanomas are the most common primary intraocular tumors in adults, with an estimated incidence in the U.S. of 0.6 cases per 100,000 people and a higher incidence in northern European countries.

Choroidal melanomas can assume various shapes, but are usually domed-shaped and can have a mushroom-like appearance if there is a break in Bruch’s membrane. Melanomas can also appear multilobular or, in the case of this patient, diffuse in shape. Diffuse choroidal melanomas are rare, occurring in about 5% of cases, and can grow throughout the choroid with minimal elevation. Choroidal melanomas may also vary in coloration from amelanotic to darkly pigmented. Significant findings on clinical exam that suggest malignancy include lesions with a basal diameter larger than 10 mm, thickness more than 2 mm, subretinal fluid, orange pigment overlying the lesion and margins within 3 mm of the optic disc. Subjective symptoms such as metamorphopsia, photopsias and visual field loss can signal an enlargement of the melanocytic lesion.

Although our patient did not have the typical appearance of choroidal melanoma on fundus exam and fluorescein angiogram initially, the growth pattern and eventual pathology and cytogenetic studies were able to confirm the presence of melanoma. Fine needle biopsy is not usually required to make the diagnosis, but may be valuable in difficult cases.

There have been several chromosomal mutations associated with uveal melanoma based on cytogenetic studies, including the loss of chromosome 3 and a gain in chromosome 8q. Chromosome 3 monosomy is associated with a poor prognosis and greater metastatic potential. Prescher and colleagues analyzed tissue from patients with primary enucleation for malignant uveal melanoma and showed that 57% of cases with monosomy 3 relapsed with metastatic disease within a median follow-up period of 3.4 years. None of the patients who retained both chromosomes 3 developed metastatic disease.

References:

• Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jöckel KH, Becher R. Prognostic implications of monosomy 3 in uveal melanoma. Lancet. 1996;347(9010):1222-1225.
• Reese AB, Howard GM. Flat uveal melanomas. Am J Ophthalmol. 1967;64(6):1021-1028.
• Shields CL, Salazar PF, Mashayekhi A, Shields JA. Peripheral exudative hemorrhagic chorio-retinopathy simulating choroidal melanoma in 173 eyes. Ophthalmology. 2009;116(3):529-535.
• Singh AD, Topham A. Incidence of uveal melanoma in the United States: 1973-1997. Ophthalmology. 2003;110(5):956-961.

• John Chen, MD, and Jay S. Duker, MD, can be reached at Tufts Medical Center, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.

• Edited by Jeffrey Chang, MD, and Vivek Chaturvedi, MD. Drs. Chang and Chaturvedi can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.