Incidence and Mortality
Melanoma of the uveal tract (iris, ciliary body, and choroid), though rare, is the most common primary intraocular malignancy in adults. The mean age-adjusted incidence of uveal melanoma in the United States is approximately 4.3 new cases per million people, with no clear variation by latitude. Males have a higher incidence than females (4.9 vs. 3.7 per million). The age-adjusted incidence of this cancer has remained stable since at least the early 1970s.[1,2] U.S. incidence rates are low compared with the rates of other reporting countries, which vary from about 5.3 to 10.9 cases per million. Some of the variation may be the result of differences in inclusion criteria and methods of calculation.
Uveal melanoma is diagnosed mostly at older ages, with a progressively rising, age-specific, incidence rate that peaks near the age of 70 years.
In view of these susceptibility factors, numerous observational studies have attempted to explore the relationship between sunlight exposure and risk of uveal melanoma. To date, these studies have found only weak associations or yielded contradictory results. Similarly, there is no consistent evidence that occupational exposure to UV light or other agents is a risk factor for uveal melanoma.[3,5]
Uveal melanomas can arise in the anterior (iris) or the posterior (ciliary body or choroid) uveal tract. Iris melanomas have the best prognosis, whereas melanomas of the ciliary body have the least favorable prognosis. Most uveal tract melanomas originate in the choroid. The ciliary body is less commonly a site of origin, and the iris is the least common. The comparatively low incidence of iris melanomas has been attributed to the characteristic features of these tumors, i.e., they tend to be small, slow growing, and relatively dormant in comparison with their posterior counterparts. Iris melanomas rarely metastasize. Melanomas of the posterior uveal tract generally have a more malignant, histologic appearance; are detected later; and metastasize more frequently than iris melanomas. The typical choroidal melanoma is a brown, elevated, dome-shaped subretinal mass. The degree of pigmentation ranges from dark brown to totally amelanotic.
Most uveal melanomas are initially completely asymptomatic. As the tumor enlarges, it may cause distortion of the pupil (iris melanoma), blurred vision (ciliary body melanoma), or markedly decreased visual acuity caused by secondary retinal detachment (choroidal melanoma). Serous detachment of the retina may occur. If extensive detachment occurs, secondary angle-closure glaucoma occasionally develops. Clinically, several lesions simulate uveal melanoma, including metastatic carcinoma, posterior scleritis, and benign tumors, such as nevi and hemangiomas.
Anatomy of the eye.
Careful examination by an experienced clinician remains the most important test to establish the presence of intraocular melanoma. It is not possible to distinguish a small uveal melanoma from a nevus. Small uveal lesions are often observed for growth to make a diagnosis of melanoma. Clinical findings that may help to identify melanoma include:
- Tumor thickness of more than 2 mm.
- Subretinal fluid.
- Visual symptoms.
- Orange pigment on the tumor surface.
- A tumor margin touching the optic disc.
Ancillary diagnostic testing, including fluorescein angiography and ultrasonography, can be extremely valuable in establishing and/or confirming the diagnosis. In a large, retrospective, single-center series of 2,514 consecutive patients with choroidal nevi, the progression rates to melanoma at 5, 10, and 15 years were 8.6%, 12.8%, and 17.3%, respectively.
A number of factors influence prognosis. The most important factors include the following:
- Cell type. (Refer to the Cellular Classification of Intraocular [Uveal] Melanoma section of this summary for more information).
- Tumor size.
- Location of the anterior margin of the tumor.
- Degree of ciliary body involvement.
- Extraocular extension.
Several additional microscopic features can affect the prognosis of intraocular melanoma, including:
- Mitotic activity.
- Lymphocytic infiltration.
- Fibrovascular loops (possibly).
Cell type is the most commonly used predictor of outcome following enucleation, with spindle-A cell melanomas carrying the best prognosis and epithelioid cell melanomas carrying the least favorable prognosis.[1,4,9] Nevertheless, most tumors have an admixture of cell types, and there is no clear consensus regarding the proportion of epithelioid cells that constitutes designation of a tumor as mixed or epithelioid.
Extraocular extension, recurrence, and metastasis are associated with an extremely poor prognosis, and long-term survival cannot be expected. The 5-year mortality rate associated with metastasis from ciliary body or choroidal melanoma is approximately 30%, compared with a rate of 2% to 3% for iris melanomas.
- Singh AD, Topham A: Incidence of uveal melanoma in the United States: 1973-1997. Ophthalmology 110 (5): 956-61, 2003.
- Inskip PD, Devesa SS, Fraumeni JF Jr: Trends in the incidence of ocular melanoma in the United States, 1974-1998. Cancer Causes Control 14 (3): 251-7, 2003.
- Singh AD, Bergman L, Seregard S: Uveal melanoma: epidemiologic aspects. Ophthalmol Clin North Am 18 (1): 75-84, viii, 2005.
- Weis E, Shah CP, Lajous M, et al.: The association between host susceptibility factors and uveal melanoma: a meta-analysis. Arch Ophthalmol 124 (1): 54-60, 2006.
- Harris RB, Griffith K, Moon TE: Trends in the incidence of nonmelanoma skin cancers in southeastern Arizona, 1985-1996. J Am Acad Dermatol 45 (4): 528-36, 2001.
- Malignant melanoma of the uvea. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 547-59.
- Yap-Veloso MI, Simmons RB, Simmons RJ: Iris melanomas: diagnosis and management. Int Ophthalmol Clin 37 (4): 87-100, 1997 Fall.
- Eye and ocular adnexa. In: Rosai J: Ackerman's Surgical Pathology. 8th ed. St. Louis, Mo: Mosby, 1996, pp 2449-2508.
- Albert DM, Kulkarni AD: Intraocular melanoma. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 2090-8.
- Shields CL, Furuta M, Berman EL, et al.: Choroidal nevus transformation into melanoma: analysis of 2514 consecutive cases. Arch Ophthalmol 127 (8): 981-7, 2009.
- Gragoudas ES, Egan KM, Seddon JM, et al.: Survival of patients with metastases from uveal melanoma. Ophthalmology 98 (3): 383-9; discussion 390, 1991.
- Introduction to melanocytic tumors of the uvea. In: Shields JA, Shields CL: Intraocular Tumors: A Text and Atlas. Philadelphia, Pa: Saunders, 1992, pp 45-59.