MULTIVARIATE DNA CYTOMETRY DISCRIMINATES BETWEEN SPITZ NEVI AND MALIGNANT MELANOMAS BECAUSE LARGE POLYMORPHIC NUCLEI IN SPITZ NEVI ARE NOT ANEUPLOID

To elucidate the reasons for the malignant histologic appearance of me lanocytic nuclei within benign Spitz nevi (SN), we evaluated nuclear D NA distribution and nuclear size using a computerized image analysis s ystem. In each case of 28 SN and 34 malignant melanomas (MM), about 10 0 randomly sampled nuclei were analyzed, prepared as monolayers from p araffin-embedded tissues. Large nuclei in MM (nuclear area > mean nucl ear area of normal melanocytes + 4 sigma) were significantly more like ly to be aneuploid (DNA content greater than or equal to 5c) than larg e nuclei in SN (chi(2) test, p < 0.0001). Only two of 990 large SN nuc lei exhibited DNA values higher than 5c, whereas 236 of 2,024 large MM nuclei were aneuploid or polyploid. Accordingly, in multivariate anal ysis, five features of DNA distribution proved to be most important fo r objective discrimination between MM and SN: 2c deviation index, 5c e xceeding rate, standard deviation of the nuclear DNA content, and both the 85th and the 95th percentiles of DNA distributions. On the basis of these features, we could define a linear discriminant function that allowed a correct diagnosis in 94% of the cases. Our data demonstrate that diagnostically misleading large nuclei in SN are euploid, in con trast to MM. It is thus possible to discriminate SN and MM with high a ccuracy using DNA cytometry. Because paraffin-embedded tissue can be u sed, this technique could be a valuable complement to routine histolog y in equivocal cases.