The pathology of ocular cancer.

Primary cancers of the eye are rare. These include uveal melanoma, a tumor that preferentially affects the choroid of light-eyed, fair-skinned Europeans, and the pediatric retinal neoplasm retinoblastoma, which is slightly more common worldwide. Uveal melanoma kills about half of affected patients. Most succumb to hepatic metastases, which are unresponsive to current therapy. Factors indicative of poor prognosis include tumor size, ciliary body involvement, epithelioid cells, extraocular extension, lymphocytic and melanophagic infiltration, mitotic activity, vascular mimicry patterns, and most importantly, the detection of monosomy 3 and class 2 gene expression profile in tumor cells using special tests. Most retinoblastomas are caused by sporadic somatic mutations in the RB1 gene, but about one-third arise in infants with germline mutations. The latter tend to develop earlier, are often bilateral and are transmissible to offspring as an autosomal dominant trait. Retinoblastoma displays varying degrees of differentiation including Homer Wright and Flexner-Wintersteiner rosettes and photoreceptor differentiation (fleurettes). Rosettes are more common in eyes enucleated from very young infants. Tumors composed entirely of fleurettes (retinoma/retinocytoma) are thought to be retinoblastoma precursors, and like retinoblastoma, harbor mutations in both copies of the RB1 gene. Retinoblastoma is a major cancer treatment success story in developed countries where most deaths are caused by secondary tumors in germline mutation carriers. High-risk histopathological features that are an indication for adjuvant chemotherapy include massive uveal invasion and retrolaminar optic nerve invasion. Eye-sparing therapies including brachyradiotherapy and systemic and intra-arterial chemotherapy have reduced the number of eyes with retinoblastoma requiring enucleation in recent years.