Fullen Douglas R, Poynter Jenny N, Lowe Lori, Su Lyndon D, Elder James T, Nair Rajan P, Johnson Timothy M, Gruber Stephen B
Department of Pathology, University of Michigan, Ann Arbor, MI 48109-0602, USA.
Mod Pathol. 2006 Oct;19(10):1324-32. doi: 10.1038/modpathol.3800653. Epub 2006 Jun 23.
BRAF mutations are common events in a variety of melanocytic nevi and primary cutaneous melanomas. We have previously found BRAF mutations in 82% of nevi, consisting of congenital, common acquired and dysplastic types, and 33% of primary cutaneous melanomas other than the spitzoid type, similar to other published reports. A small number of studies have evaluated Spitz nevi and have failed to detect any lesions possessing a BRAF mutation. Only one study included categories of atypical Spitz nevus and borderline lesions suspected to be spitzoid melanomas, along with classic Spitz nevi and spitzoid melanomas. We examined a spectrum of spitzoid lesions that included 48 Spitz nevi, some with atypical features, seven atypical (borderline) Spitz tumors, and 13 spitzoid melanomas. BRAF mutations were detected in 12 of 68 spitzoid lesions, of which two were spitzoid melanomas and 10 were Spitz nevi. Five of the 10 Spitz nevi with BRAF mutations were altered by more than usual cytologic atypia and/or architectural atypia overlapping with dysplastic nevi, or irritation/inflammation; one desmoplastic Spitz nevus had a BRAF mutation. These results indicate that a small subset of Spitz nevi, some with atypical histologic features, possess BRAF mutations. Therefore, the BRAF mutational status does not separate all Spitz nevi from spitzoid melanomas and non-Spitz types of melanocytic proliferations, contrary to previous reports.
BRAF突变在多种黑素细胞痣和原发性皮肤黑色素瘤中是常见事件。我们之前发现，在82%的痣（包括先天性、常见获得性和发育异常型）以及33%的非Spitzoid型原发性皮肤黑色素瘤中存在BRAF突变，这与其他已发表的报告相似。少数研究评估了Spitz痣，未检测到任何具有BRAF突变的病变。只有一项研究纳入了非典型Spitz痣和疑似Spitzoid黑色素瘤的交界性病变类别，以及经典Spitz痣和Spitzoid黑色素瘤。我们检查了一系列Spitzoid病变，包括48例Spitz痣（有些具有非典型特征）、7例非典型（交界性）Spitz肿瘤和13例Spitzoid黑色素瘤。在68例Spitzoid病变中的12例检测到BRAF突变，其中2例为Spitzoid黑色素瘤，10例为Spitz痣。10例具有BRAF突变的Spitz痣中有5例伴有比平常更多的细胞学非典型性和/或与发育异常痣重叠的结构非典型性，或伴有刺激/炎症；1例促纤维增生性Spitz痣具有BRAF突变。这些结果表明，一小部分Spitz痣（有些具有非典型组织学特征）存在BRAF突变。因此，与之前的报告相反，BRAF突变状态并不能将所有Spitz痣与Spitzoid黑色素瘤及非Spitz型黑素细胞增生区分开来。
