title: Intralesional and metastatic heterogeneity in malignant melanomas demonstrated by stereologic estimates of nuclear volume.
abstract: Regional variability of nuclear 3-dimensional size can be estimated objectively using point-sampled intercepts obtained from different, defined zones within individual neoplasms. In the present study, stereologic estimates of the volume-weighted mean nuclear volume, nuclear vv, within peripheral and central zones of cutaneous, primary, and secondary malignant melanomas were obtained. For comparisons, estimates of nuclear vv were also obtained from primary and metastatic melanomas, based on stereologic measurements taking the whole tumor sectional areas into consideration. Estimates of nuclear vv were on average larger in the peripheral zones of primary melanomas, than nuclear vv in central zones (2p = 6.7 x 10(-4), whereas no zonal differences were demonstrated in metastatic lesions (2p = 0.21). A marked intraindividual variation was demonstrated between primary and corresponding secondary melanomas (2p = 1.7 x 10(-39). These results do not necessarily indicate clonal heterogeneity, but are in agreement with the hypothesis of polyclonal and monoclonal composition of primary and metastatic neoplasms, respectively. Estimates of nuclear vv based on measurements of whole sectional areas of primary melanomas showed large interindividual variation. This finding emphasizes that unbiased estimates of nuclear vv are robust to regional heterogeneity of nuclear volume and thus suitable for purposes of objective, quantitative malignancy grading of melanomas.
authors.affiliation: Stereological Research Laboratory, University Institute of Pathology, Aarhus, Denmark.
authors.forename: F B
authors.initials: FB
authors.lastname: Sørensen
authors.forename: M
authors.initials: M
authors.lastname: Erlandsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000473:pathology* / Q000556:secondary / Q000648:ultrastructure; D008875:Middle Aged; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000473:pathology* / Q000648:ultrastructure