Stereological estimation of nuclear volume in benign melanocytic lesions and cutaneous malignant melanomas

Recent developments in stereology have made it possible to obtain unbiased, objective estimates of the volume weighted mean nuclear volume (vV) from ordinary histological sections, without any assumptions concerning nuclear shape. The aim of this study was to gather baseline data of nuclear vV in melanocytic cutaneous tumors and to compare these with estimates of nuclear volume fraction and with traditional two-dimensional morphometric estimates of nuclear profile area, nuclear density, and mitotic index. Routinely processed, paraffin embedded tissue specimens from 47 malignant melanomas and 76 noninvasive melanocytic cutaneous tumors were investigated retrospectively. vV clearly distinguished between noninvasive (average vV = 122 microns 3) and invasive lesions (average vV = 246 microns 3). Most of the patients with malignant melanomas showing an overlap of nuclear vV with benign lesions had a favorable prognosis. No significant differences in vV could be demonstrated among different noninvasive tumor types. Two-dimensional estimates only distinguished benign from malignant tumors with considerable overlap and with significantly varying influence from other factors among different benign lesional types. The variance associated with estimates of vV disclosed a linear relationship to vV, whereas the relative variation seemed to be constant. Tumor heterogeneity was without significant influence on estimates of nuclear vV. It is concluded that nuclear vV is a superior, efficient, and sensitive estimator for distinguishing between melanocytic cutaneous tumors showing different biological behavior, well-suited for objective malignancy grading.