Nagasaka T, Lai R, Medeiros L J, Brynes R K, McCourty A, Harada T, Saddik M
Division of Pathology, Nagoya University Hospital, Japan.
Am J Dermatopathol. 1999 Apr;21(2):115-20. doi: 10.1097/00000372-199904000-00001.
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.
鉴别Spitz痣与恶性黑色素瘤的形态学差异可能具有挑战性。由于有报道称细胞周期蛋白D1在恶性黑色素瘤中过表达，但在常见的获得性痣中则不然，我们推测细胞周期蛋白D1可能是区分Spitz痣与恶性黑色素瘤的有用标志物。因此，我们采用免疫组织化学方法，对11例Spitz痣（10例复合痣和1例皮内痣）和9例恶性黑色素瘤（4例Clark分期I - III期和5例Clark分期IV - V期）以及常规固定和处理的组织进行细胞周期蛋白D1表达评估。细胞周期蛋白D1的结果被任意分为三组：0%至10%、>10%至25%以及>25%。我们证实了其他人之前报道的观察结果，即细胞周期蛋白D1在恶性黑色素瘤中表达，但在常见的获得性痣中不表达。出乎意料的是，在所有Spitz痣病例中也发现了相对较高数量的细胞周期蛋白D1阳性细胞（即>10%）。然而，与恶性黑色素瘤不同，Spitz痣中的细胞周期蛋白D1阳性呈带状分布。换句话说，随着病变向深部扩展，细胞周期蛋白D1阳性细胞数量减少，网状真皮中的阳性细胞数量少于乳头真皮中的阳性细胞数量。采用荧光原位杂交方法评估4例Spitz痣中含有细胞周期蛋白D1基因的11q13位点的扩增情况；所有病例均为二倍体。我们使用抗体MIB - 1比较了Spitz痣中细胞周期蛋白D1的表达与增殖率。尽管细胞周期蛋白D1阳性率较高，但所有Spitz痣中MIB - 1阳性细胞数量相对较少（平均值 = 3.2%），显著低于恶性黑色素瘤（平均值 = 15.3%）（p < 0.001）。因此，与恶性黑色素瘤不同，Spitz痣中细胞周期蛋白D1过表达与细胞增殖之间似乎存在分离。
