The morphologic distinction between
Spitz nevus and
malignant melanoma can be difficult. Because
cyclin D1 has been reported to be overexpressed in
malignant melanomas, but not in common acquired
nevi, we hypothesized that
cyclin D1 might be a useful marker to distinguish Spitz
nevi from
malignant melanoma. Thus, we assessed for
cyclin D1 expression in 11 Spitz
nevi (10 compound and 1 intradermal) and 9
malignant melanomas (4 Clark stages I-III and 5 Clark stages IV-V) using an immunohistochemical method and routinely fixed and processed tissues. The
cyclin D1 results were arbitrarily divided into three groups: 0% to 10%, >10% to 25%, and >25%. We confirmed the observations reported previously by others that
cyclin D1 is expressed in
malignant melanomas but not in common acquired
nevi. Unexpectedly, a relatively high number of
cyclin D1-positive cells (i.
e., >10%) was also found in all cases of
Spitz nevus. However, unlike
malignant melanoma, the
cyclin D1 positivity in Spitz
nevi was present in a
zonal pattern. In other words, the number of
cyclin D1-positive cells decreased as the lesion extended more deeply, with the number of positive cells in the reticular dermis being less than that in the papillary dermis. Fluorescence in situ hybridization methods were used to assess amplification of 11q13, the locus harboring the cyclin D1 gene, in four cases of
Spitz nevus; all were disomic. Using the antibody MIB-1, we compared
cyclin D1 expression to the proliferation rate in Spitz
nevi. Despite the high
cyclin D1 positivity, all Spitz
nevi had a relatively low number of MIB-1-positive cells (mean=3.2%), which was significantly lower than that of
malignant melanomas (mean=15.3%) (p < 0.001). Thus, unlike
malignant melanoma, there appears to be a dissociation between
cyclin D1 overexpression and cell proliferation in Spitz
nevi.