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Prompted by the well-known difficulties of reliable and objective histologic differentiation between initial malignant melanoma (MM) and benign nevocytic nevi (NN), ultrastructural high-resolution image and multivariate analyses were evaluated for their diagnostic efficiency. Thirty-seven different features describing morphometry (area, circumference, and shape factor), amount of heterochromatin and euchromatin, chromatin homogeneity, and presence of smaller dark chromatin aggregations were determined by a MICROVAX 3500 computer in each of 1840 intraepidermal melanocytic nuclei of 17 MM and 20 NN. A strategy for the classification of cases based on the identification of markedly atypical melanocytic cells (MACS) was developed. MACS, selected in multivariate analysis with a linear combination of the eight most important features for cell classification, were found in 39.4% of the melanoma cells, but only in 0.3% of nevocytic nevus cells. The presence of MACS allowed a clear differentiation between MM and NN. All cases of MM had more than four MACS, whereas 17 cases of nevocytic nevi were MACS negative, and in each of the remaining three cases only one MAC was present. The percentage of MACS detected within intraepidermal parts of MM by using computerized high-resolution image analysis was found to be a highly efficient diagnostic marker. The new classification strategy has the potential of saving considerable time in subsequent studies, because preselected sampling and the calculation of only a few criteria have proven sufficient for correct classification of malignant melanomas.

Frequency of malignant transformation arising in giant congenital nevi is considered to be 4%-5%. More than a half of the patients in which malignant melanoma developed in giant congenital nevi were under the age of 10. It may be hypothesized that dermabrasion of giant congenital nevus may provoke malignant transformation. Some of the cell groups in giant congenital nevus are potentially malignant. Some groups of nevus cells were larger in size than those of other portions of nevus. Electron microscopic observation revealed that nuclei of these larger nevus cells were significantly indented, and melanization of melanosomes was irregular. Coexistence of alpha-like actin with beta- and gamma-actins in giant congenital nevus cells and disappearance of alpha-like actin in malignant melanoma cells were noted.

Proliferative activity and morphometric data have previously been shown to be related with the degree of malignancy in melanocytic skin tumors. In the present study, the proliferative activity, as defined by Ki 67 monoclonal antibody (reactive with all actively cycling cells), has been determined by immunohistologic and morphometric methods in cutaneous melanocytic tumors. Quantitative morphologic features of Ki 67-positive and Ki 67-negative nuclei were separately assessed using computer-assisted image analysis. Comparing morphometric features and proliferative activity, the most significant correlation was found between mean nuclear volume and the percentage of Ki 67-positive nuclei in each lesion (linear regression analysis: r = 0.73; p = less than 0.05). On multidimensional discriminant analysis, tumors with high proliferative activity (more than 5 X 10(3) Ki 67-positive cells per mm3 tumor tissue) were detected at a specificity of 92% and a sensitivity of 75%. Within one lesion, Ki 67-positive nuclei showed an increase in nuclear volume (Wilcoxon test: p = less than 0.05), a more spheroid shape (p = less than 0.05), and a wider dispersion of nuclear volume values (Siegel-Tukey test: p = less than 0.05) than negative nuclei. Discriminant analysis on the basis of nuclear volume density functions facilitated an estimation of the proliferative state (resting or cycling) of a given nucleus. The results are consistent with increased cellular synthetic activity in highly proliferating lesions and particularly in actively cycling cells. The association of proliferative activity and quantitative nuclear features may be helpful in the interpretation of morphometric studies concerning melanocytic skin tumors.

Exposure of cytoskeletal intermediate-sized filaments (ISF) of various cell populations in normal human skin to normal human serum (NHS) results in the deposition of C3 upon these structures; this phenomenon most likely occurs antibody-independently, is initiated by Clq binding to ISF, and is followed by the activation of the classical complement pathway. In the present study we investigated the cytoplasmic C3-binding properties of skin cells undergoing altered differentiation. Incubation of cryostat skin sections of dermal melanocytic nevi with NHS and, subsequently, with fluorescein isothiocyanate-conjugated rabbit antihuman C3 resulted in a bright cytoplasmic staining of the vast majority of nevus cells. Immunoelectron microscopic studies demonstrated that ISF within nevus cells represented the only cytoplasmic C3-binding structures. In contrast, ISF within melanoma cells, basal cell carcinoma cells, and keratinocytes constituting psoriatic lesions lacked C3-binding properties. We propose that changes in structure and subunit protein composition of ISF in certain cells undergoing altered differentiation results in a decrease or loss of their C3-binding capacity.