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Since advanced melanoma remains practically incurable, early detection is an important step toward a reduction in mortality. High expectations are entertained for a technique known as dermoscopy or epiluminescence light microscopy; however, evaluation of pigmented skin lesions by this method is often extremely complex and subjective. To obviate the problem of qualitative interpretation, methods based on mathematical analysis of pigmented skin lesions, such as digital dermoscopy analysis, have been developed. In the present study, we used a digital dermoscopy analyzer (DBDermo-Mips system) to evaluate a series of 588 excised, clinically atypical, flat pigmented skin lesions (371 benign, 217 malignant). The analyzer evaluated 48 parameters grouped into 4 categories (geometries, colors, textures and islands of color), which were used to train an artificial neural network. To evaluate the diagnostic performance of the neural network and to check it during the training process, we used the error area over the receiver operating characteristic curve. The discriminating power of the digital dermoscopy analyzer plus artificial neural network was compared with histologic diagnosis. A feature selection procedure indicated that as few as 13 of the variables were sufficient to discriminate the 2 groups of lesions, and this also ensured high generalization power. The artificial neural network designed with these variables enabled a diagnostic accuracy of about 94%. In conclusion, the good diagnostic performance and high speed in reading and analyzing lesions (real time) of our method constitute an important step in the direction of automated diagnosis of pigmented skin lesions. © 2002 Wiley-Liss, Inc.

A variable fraction of anaplastic large-cell lymphomas (ALCLs) exhibits a t(2;5)(p23;q35) translocation that results in expression of the chimeric hyperphosphorylated protein NPM-ALK (p80). Tumor cells expressing NPM-ALK exhibit markedly enhanced proliferative activity, but comparative cellular kinetic studies on ALK⁺ (ALK lymphomas) and ALK^– lymphomas are lacking. The present study showed that ALK⁺ lymphomas, detected with the monoclonal antibody ALKc (n = 17), had significantly higher average values for the proliferation-associated parameters mitotic index, ana/telophase index, growth index (x × mitotic index – apoptotic index, assuming x = 3), percentages of Ki-67⁺ cells and fraction of cells expressing cyclin A or B or the cell cycle–regulatory protein p34^cdc2 than did ALK^– ALCLs (n = 15). Whether this intense proliferative activity contributes to the good response to chemotherapy and favorable outcome of ALK⁺ ALCLs remains to be assessed in a larger series of patients. Our findings support the notion that ALK⁺ and ALK^– ALCLs are 2 distinct disease entities. Int. J. Cancer 86:777–781, 2000. © 2000 Wiley-Liss, Inc.

In view of recent knowledge on proteins regulating the cell cycle, we re-evaluated proliferative features of 98 diffusely growing non-Hodgkin's lymphomas. The combined use of 5 proliferation–associated variables (mitotic indices and percentages of Ki-67⁺, p34^cdc2+, cyclin A⁺ and cyclin B⁺ cells) and their entry into a multivariate cluster analysis separated, without overlaps, the entire cohort into 3 groups (clusters) with (1) low, (2) intermediate and (3) high proliferative activity. Conversely, bivariate plots exposed considerable cluster overlaps. Multivariate stepwise discriminant analysis of all cases revealed a decreasing order of discriminant power for % Ki-67⁺ cells > % p34^cdc2+ cells > mitotic index > % cyclin A⁺ cells > % cyclin B⁺ cells. The combined use of 2 variables only, mitotic index and % p34^cdc2+ cells, allowed a clear-cut separation of clusters 2 and 3. In bivariate plots, correlations were best between % Ki-67⁺ cells and % cyclin A⁺ cells and between mitotic indices and % cyclin B⁺ cells. Except for chronic lymphocytic leukemias, immunocytomas and marginal zone lymphomas (all in cluster 1), individual lymphoma entities were distributed among at least 2 clusters. There was, however, a marked preponderance of mantle cell lymphomas and diffuse follicular center lymphomas in cluster 1 and of diffuse large B-cell lymphomas and peripheral T-cell lymphomas in cluster 2. Anaplastic large-cell lymphomas predominated in cluster 3 and responded best to therapy. Int. J. Cancer 83:203–209, 1999. © 1999 Wiley-Liss, Inc.

Our study was designed to compare cellular kinetic parameters of classical Hodgkin's disease (HD) with those of anaplastic large cell lymphomas (ALCL-C, common type; and ALCL-HL, Hodgkin's like), with a particular focus on the G2/M transition. These disorders share some phenotypic properties, e.g., CD30 positivity of putative neoplastic cells. The percentages of cells expressing p34^cdc2 (p34) and cyclin B-1 (cyclin-B), which form a complex (maturation/mitosis promoting factor, MPF) regulating the G2-M phases of the cell cycle, were also registered. Highly significant differences between HD and ALCL-C were recognized: a) in HD, evidence for abortive mitosis (i.e., difficulty to proceed beyond the metaphase stage) and consequent multinucleation and/or deletion of CD30⁺ cells was prominent, in contrast to ALCL-C. This was associated with a markedly lower fraction of large atypical cells (LAC) expressing cyclin-B in the cytoplasm and the nucleus (C + N) in HD than in ALCL-C; b) the extent of multinucleation of CD30⁺ cells in HD, but not in ALCL-C, was correlated with the %p34⁺ LAC; c) the proportions of LAC expressing p34 and/or cyclin-B (C) were positively related to the percentages of cyclin-B (C + N)⁺ LAC in ALCL-C but not in HD; d) in HD, in contrast to ALCL-C, the size of the fraction of cyclin-B (C + N)⁺ LAC did not correlate with the ana/telophase indices (ATI, reflecting successful completion of mitosis) and the magnitude of cell loss; e) in ALCL-C, the percentages of p34⁺ LAC were positively correlated with ATI or the degree of CD30⁺ cell deletion, but inversely in HD. With regard to all parameters mentioned above, ALCL-HL tended to take an intermediate position between HD and ALCL-C, but sided more with the latter. In conclusion, our present results suggest a derangement of MPF kinetics and functions that is more profound in HD than in ALCL-C. Int. J. Cancer 77:408–414, 1998. © 1998 Wiley-Liss, Inc.