An alternative hypothesis for observed mortality rates due to metastasis after treatment of choroidal melanomas of different sizes

Purpose: To propose an alternative hypothesis for the observed differential survival of patients with small, medium, and large choroidal melanomas based on recently uncovered cytogenetic evidence about melanocytic choroidal tumors. Methods: Review and analysis of published data. Results: Recent evidence has shown that recurring nonrandom cytogenetic abnormalities are present within virtually all cytomorphologically malignant cells that compose choroidal melanomas and that certain individual cytogenetic abnormalities and combinations of these abnormalities are important prognostic factors for metastasis and metastatic death. Although these cytogenetic abnormalities are strongly correlated with recognized clinical prognostic factors (tumor size, intraocular tumor location) and histomorphologic prognostic factors (melanoma cell type, vascular mimicry pattern) for metastasis, most laboratories have found these cytogenetic abnormalities to be much more robust indicators that metastasis will or will not develop than these clinical and histopathologic factors. In most series of uveal melanomas evaluated by current cytogenetic methods, approximately 30% to 60% of the tumors have cytogenetic abnormalities indicative of high likelihood of metastasis posttreatment. Evidence suggests that these abnormalities are more frequent in larger tumors than in smaller ones. Survival analyses of uveal melanoma patients whose tumors have been evaluated cytogenetically have shown rates of metastasis that approach 100% for patients with a tumor exhibiting monosomy 3 or a class 2 gene expression profile but are very low for those with a tumor that did not exhibit these cytogenetic abnormalities. Conclusion: The better prognosis of patients with smaller choroidal melanomas is likely to be attributable to a lower probability of cytogenetic abnormalities indicative of metastatic capability among smaller tumors and not to effectiveness of treatment at preventing metastasis.