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Unusual Tumors Involving the Head and Neck Region

Case 2. Malignant Uveal Melanoma in Ocular Melanocytosis

Helsinki University Central Hospital, Helsinki, Finland

A 49-year-old white woman consulted an ophthalmologist because of discomfort and reduced vision in her right eye for the past 2 months. Her eyes had always been of different color—the right one was dark brown and the left one was greenish (Fig 1, A and B)—but she was not aware of the reason for this. The visual acuity of the right eye was 20/100. It showed typical signs of congenital ocular melanocytosis (OM), including a velvet-like, dark brown iris (Fig 1A), patchy episcleral pigmentation (Fig 1C), and a heavily pigmented choroid. Closer examination revealed engorged episcleral vessels (Fig 1D) feeding a large pigmented choroidal and ciliary body tumor that extended from the lens to the optic disc, as shown by B-scan ultrasonography (Fig 2A: mm, malignant melanoma; on, optic nerve; ret, detached retina). The acoustic reflectivity was low to medium, consistent with uveal melanoma. The left eye had 20/20 vision and a lightly pigmented iris (Fig 1B) and choroid.

View larger version (87K): [in this window] [in a new window]   Fig 1.

View larger version (121K): [in this window] [in a new window]   Fig 2.

Histopathologic examination confirmed the presence of 10-mm-thick choroidal tumor that indented the lens and extended beyond the optic disc to the temporal choroid (Fig 2B). Its anterior part was lightly pigmented and sharply demarcated from the darkly pigmented posterior part. The choroid was intensely pigmented (Fig 2B: ch, choroid). The patchy episcleral pigmentation was heaviest around the optic nerve (Fig 2C). Both parts consisted of spindle and epithelioid melanoma cells (Fig 2D) and contained microvascular loops and networks associated with high metastatic risk.^1,2 Melanosis was observed within the sclera (Fig 2E: scl, sclera), in the chamber angle, within the iris, in the ciliary body (Fig 2F) and choroid, and along ciliary nerves and optic nerve sheaths.

One month after surgery, an abdominal ultrasonograph suggested hepatic metastasis, and the diagnosis of disseminated melanoma was confirmed by abdominal computed tomography scan and fine-needle aspiration biopsy. Results of liver function tests remained normal. Systemic combination chemotherapy was initiated.

Congenital OM is characterized by hyperpigmentation of the episclera, sclera, uveal tract (iris, ciliary body, and choroid), orbital tissues, and, sometimes, of the meninges.³ When periocular skin is affected as well, the condition is termed oculodermal melanocytosis (nevus of Ota).³ Both are usually nonhereditary and unilateral and are estimated to affect about 0.04% of whites,⁴ among whom an association with malignant uveal melanoma is recognized.^3,5 About 1.4% of patients with uveal melanoma have OM, and OM is estimated to increase the risk for uveal melanoma over 20-fold as compared with the general population.⁵ The lifetime risk of developing uveal melanoma, given OM, is calculated to be one in 400.⁶ OM is also fairly common in Asians, but development of uveal melanoma among them is rare.

The excess of melanocytes in the uveal tract may simply underlie the high susceptibility for development of uveal melanoma in patients with OM. Another explanation might be genetic predisposition, although patients with OM do not appear to get uveal melanoma at an earlier age than average.⁶ The frequency of OM among young patients with uveal melanoma, however, is reported to be nine times greater than that among elderly patients with this tumor.⁵

Not all patients with differently colored irides have OM. Other conditions that can cause iris heterochromia, but not episcleral pigmentation, include essential iris atrophy and other forms of iridocorneal endothelial syndromes, Fuchs’s heterochromic iridocyclitis, juvenile xanthogranuloma, melanocytic tumors of the iris, and topical prostaglandin therapy for glaucoma.⁷ Heterochromia can also be hereditary. On the other hand, primary acquired melanosis of the conjunctiva might be confused with OM, but such conjunctival pigmentation is movable over the sclera and unassociated with iris heterochromia and uveal hyperpigmentation.⁸

Patients with congential OM benefit from awareness of their condition and its implications. Any physician can recommend ophthalmologic consultation when he or she notices iris heterochromia. In our case, the patient was unaware of her diagnosis, with a probably fatal outcome. Careful regular follow-up is recommended for early detection of uveal melanoma in OM. It remains challenging, because an incipient tumor may be difficult to recognize from the dark uveal background and because these patients can develop multiple and even orbital melanomas.³

REFERENCES

1. Folberg R, Rummelt V, Parys-Van Ginderdeuren R, et al: The prognostic value of tumor blood vessel morphology in primary uveal melanoma. Ophthalmology 100: 1389-1398, 1993[Medline]

2. Makitie T, Summanen P, Tarkkanen A, et al: Microvascular loops and networks as prognostic indicators in choroidal and ciliary body melanomas. J Natl Cancer Inst 91: 359-367, 1999[Abstract/Free Full Text]

3. Gonder JR, Shields JA, Albert DM, et al: Uveal malignant melanoma associated with ocular and oculodermal melanocytosis. Ophthalmology 89: 953-960, 1982[Medline]

4. Gonder JR, Ezell PC, Shields JA, et al: Ocular melanocytosis: A study to determine the prevalence rate of ocular melanocytosis. Ophthalmology 89: 950-952, 1982[Medline]

5. Singh AD, Shields CL, Shields JA, et al: Uveal melanoma in young patients. Arch Ophthalmol 118: 918-923, 2000[Abstract/Free Full Text]

6. Singh AD, De Potter P, Fijal BA, et al: Lifetime prevalence of uveal melanoma in white patients with oculo(dermal) melanocytosis. Ophthalmology 105: 195-198, 1998[Medline]

7. Green WR: The uveal tract, in Spencer WH (ed): Ophthalmic Pathology: An Atlas and Textbook. Philadelphia, PA, WB Saunders, 1996, pp 1439-2120

8. Folberg R, McLean IW: Primary acquired melanosis and melanoma of the conjunctiva: Terminology, classification, and biologic behavior. Hum Pathol 17: 652-654, 1986[Medline]

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