Prognostic value of morphometric features and the callender classification in uveal melanomas

Purpose: Cytomorphometric analysis of uveal melanoma has focused on nucleolar characteristics, although nuclear measurements are easier and more reproducible. In this study, we examine a restricted set of nuclear and nucleolar cytomorphometric variables in the search for the most quantifiable and reproducible prognostic parameter among these and discover a means of assessing the malignancy of tumors within the different Callender subgroups. Methods: Uveal melanomas from 94 patients with a minimum follow-up of 5 years underwent nuclear and nucleolar morphometric analysis using a digitized interactive video overlay system. Statistical analysis included univariate and multivariate survival analysis on morphometric variables and classic prognostic parameters (such as Callender cell type, size, etc.). Results: Univariate analysis of cytomorphometric parameters showed the standard deviation of nuclear area (NASD) to be the most significant variable (P < 0.0001; Mantel-Cox, 15.2). This was followed by the difference between nuclear and nucleolar areas (P < 0.002; Mantel-Cox, 9.5), the standard deviation of nucleolar area (SDNA) (P < 0.01; Mantel-Cox, 6.4), and the standard deviation of the shortest nuclear axis (P < 0.02; Mantel-Cox, 6.4). There was a trend for significance with the mean of the ten largest nucleoli (P < 0.07). Multivariate analysis of clinical and cytomorphometric variables showed improvement of prognostic prediction with a combination of the NASD, largest tumor dimension, and glaucoma (P < 0.0001; Mantel-Cox, 26.3). Callender cell type was strongly correlated with the NASD (P < 0.0002), the mean axis ratio of the nuclear area (P < 0.0007), and the mean of the ten largest nucleoli (P < 0.0007). Conclusion: Cytomorphometric analysis of uveal melanoma should include nuclear area and may identify tumors of differing malignancy within the same Callender class.