Uveal melanoma: A pathologist's perspective and review of translational developments

The eye and periorbital soft tissue are derived from the neuroectodermal neural crest, leading to a wide range of tumor types that arise at this site. The uveal tract (iris, ciliary body, and choroid) normally contains melanocytes, and thus both benign nevi and malignant melanoma can arise there, the choroid being the most frequent site. Uveal melanoma (UM) in adults and retinoblastoma (in young children) are the 2 most common primary intraocular malignancies. Retinoblastoma is the most common eye cancer worldwide, but the most common ocular cancer in the United States and Europe is UM. This review will focus on UM and will include the epidemiology, pathologic findings, prognosis and treatment, and review of ongoing molecular discoveries aimed at elucidating the pathways that could lead to adjuvant therapy. These tumors are not uncommon to dedicated ocular pathologists and may occasionally be encountered by general pathologists as well. First, a short word about metastases to the uveal tract is in order, because of its importance in the differential diagnosis. Although the most common primary malignancy in the adult eye is UM, the most frequent adult intraocular malignancy identified in autopsy studies is metastatic carcinoma to the uveal tract. Metastases usually occur late, and the eye is thus rarely enucleated in this setting. However it is important to be aware of this as sometimes, the ophthalmologist cannot determine clinically if an amelanotic tumor represents melanoma or metastasis, possibly from an unknown primary. Shields and colleagues reported on their experience and found that the most common primary sites for uveal metastasis are breast, followed by lung, and then the gastrointestinal tract. Immunohistochemical stains for cytokeratin or more specific markers such as CK7, CK20, TTF-1, BRST-2, CDX2, and PSA may be helpful if there is no known primary. Metastases to the eye also occur in the orbit, eyelid, and rarely to the retina.