Tumor progression in uveal melanoma

Ophthalmic melanomas can be divided in extra-ocular (conjunctiva, caruncle) and intraocular uveal melanomas (iris, ciliary body and choroid). Uveal melanomas account for 95% of ocular melanomas, while only 5% are conjunctival in origin. The extra-ocular and intra-ocular melanomas differ in biological behavior. Melanocytes originate from the neural crest and are normally present in the uveal stroma, similar to dermal melanocytes. Intraepithelial precursor lesions of invasive melanoma occur in the conjunctiva and the caruncle but within the eye an intra-epithelial (retinal pigment epithelium) precursor lesion has not betH demonstrated. Therefore a radial and vertical growth phase, as is recognized in cutaneOUI> and conjunctival melanomas, is not evident in intra-ocular melanoma. Because uveal melanomas are not easily accessible for incisional biopsy (without disruption of vision), only two lesions of melanocytic origin are defined clinically: nevus and melanoma. Progression in melanoma is clinically associated with tumor size. Most malignant melanomas of the choroid can be diagnosed by ophthalmoscopy and ultrasonography, and evidence of growth is best established by serial photography of the fundus. The uvea consists of highly vascularized tissue. There are no demonstrated lymphatics within the uveal tract, or in the posterior orbit. This explains the difference in biological behavior of ophthalmic melanomas: conjunctival melanomas spread first to regional lymph nodes whereas choroidal and ciliary body melanomas metastasize hematogenously and preferentially first to the liver. Strikingly, another intra-ocular tumor, the retinoblastoma usually does not metastasize until after it has invaded the orbit. From the orbit it gains access to lymphatic vessels in the anterior orbit. Unlike uveal melanoma, the initial metastases from retinoblastoma are often to regional lymph nodes. Uveal melanoma metastasize relatively late: the 5, 10 and 15-year survival rates based on tumorrelated deaths vary from 65%, 52% and 46%, respectively;'" to 72%, 59% and 53%, respectively, in recent series. The estimated 5-year-survival rate of cutaneous melanoma varies between 70_80%.7.8 Once the diagnosis of hepatic metastasis from uveal melanoma has clinically been made) the median survival is extremely poor: between two 9,10 and seven months, II The median survival time in patients in whom the liver was either not involved at all, or not among the first sites of dissemination is 19 months.

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