DNA‐index and stereological estimation of nuclear volume in primary and metastatic malignant melanomas: A comparative study with analysis of heterogeneity

The aim of this study was to investigate the relationship between physical nuclear volume and ploidy level in malignant melanomas, and to analyse the heterogeneity of these two parameters among primary and corresponding secondary tumours. Unbiased stereological estimates of nuclear volume can be obtained objectively by point-sampled intercepts. Using this approach, the volume-weighted mean nuclear volume, nuclear vv, was estimated in ordinary histological sections from 34 primary cutaneous malignant melanomas and their corresponding 62 metastatic lesions. For comparison, DNA-indices (DI) were determined by flow cytometry in adjacent sections from the same paraffin-embedded tumours. Only a poor correlation was found between nuclear vv and DI (Kendall's tau = +0.21). The variability of nuclear vv among metastatic lesions was increased as compared to primary melanomas, whereas averaged mean values of nuclear vv did not differ significantly between the two types of neoplasms. Aneuploidy was not significantly associated with increased nuclear vv. Pronounced intra-patient heterogeneity of nuclear vv was disclosed among metastases and between the primary melanoma and the metastatic lesions. Likewise, no significant association between DI of primary and metastatic melanomas was demonstrated. Heterogeneity of nuclear vv and DI in malignant melanomas is in agreement with the theory of polyclonality.