Quantitative evaluation of the progressive nuclear abnormalities in urothelial papillary lesions

The natural history of noninvasive urothelial papillary carcinomas is characterized by structural and nuclear abnormalities of the epithelial lining in the three grades. Morphometry is applied to measure nuclear-related quantitative parameters from the lower (L) and upper (U) halves of urothelial thickness, i.e. perimeter, area and roundness factor. Their mean and SD as well as the derived parameters have values steadily higher from normal-looking urothelium to G3, whereas the relative frequency distribution shows over-lapping among the grades. The multivariate analysis is then applied. First of all the smallest number of least correlated and most discriminant features is selected: SD of nuclear area log (L), percentage of round nuclei (L), mean of the 10 largest values of nuclear area (L) and mean nuclear perimeter (L). The results of the pattern recognition analysis based on these features show the following percentages of agreement between histopathological and computer classifications: 94% in the training set and 80% in the test set. The calculation of the classification probability and the adoption of a threshold approach of 0.25 less than P less than 0.75 are helpful in identifying the 'in-between' cases, i.e., those in the 'intermediate' position between G1 and G2 and between G2 and G3. Morphometry and multivariate analysis allow us to quantify the nuclear abnormalities of urothelial papillary carcinomas and show a progressive and continuous spectrum of modifications.