Alnaqshanbandi Sarah M, McAfee John L, Ko Jennifer S, Billings Steven D, Ronen Shira
Pathology & Laboratory Medicine Institute, Cleveland Clinic, OH.
Am J Surg Pathol. 2024 Dec 1;48(12):1543-1550. doi: 10.1097/PAS.0000000000002316. Epub 2024 Oct 8.
Pilomatrical skin tumors harbor mutations in CTNNB1 , which encodes for β-catenin, a downstream effector of the Wnt signaling pathway responsible for the differentiation, proliferation, and adhesion of epithelial stem cells. Therefore, downstream molecules, such as CDX2, LEF-1, and SATB2, in the Wnt signaling pathway could be useful diagnostic markers. Here, we sought to investigate the potential of immunohistochemistry (IHC) to differentiate between pilomatricoma and pilomatrical carcinoma, as well as from other cutaneous adnexal tumors. We studied 88 cases of cutaneous tumors (14 pilomatrical carcinomas, 18 pilomatricomas, 13 basal cell carcinomas, 12 squamous cell carcinomas, 12 sebaceous carcinomas, 10 Merkel cell carcinomas, 7 trichoblastomas, and 2 hidradenocarcinomas) using a broad panel of IHC markers: β-catenin, SATB2, CDX2, LEF1, Ber-EP4, and PRAME. Pilomatricoma and pilomatrical carcinoma displayed >75% nuclear staining for β-catenin. CDX2 also strongly stained pilomatrical tumors; however, the staining distribution was limited in pilomatricoma and more widespread in pilomatrical carcinoma. But, overall, it was less than β-catenin. SATB2 and Ber-EP4 expressions were noted only in a subset of both pilomatrical carcinoma and pilomatricoma, whereas LEF-1 showed strong, diffuse nuclear positivity in both pilomatricoma and pilomatrical carcinoma. Among the IHC markers evaluated, none could distinguish between pilomatricoma and pilomatrical carcinoma. However, the combined use of β-catenin with CDX2 markers may assist in not only confirming the pilomatrical nature of the proliferation but also in differentiating benign from malignant cases when there is a significant presence of CDX2 staining. Despite these findings, the diagnosis should continue to primarily depend on a thorough histopathologic examination.
毛母质皮肤肿瘤存在CTNNB1基因突变，CTNNB1编码β-连环蛋白，它是Wnt信号通路的下游效应因子，负责上皮干细胞的分化、增殖和黏附。因此，Wnt信号通路中的下游分子，如CDX2、LEF-1和SATB2，可能是有用的诊断标志物。在此，我们试图研究免疫组织化学（IHC）在鉴别毛母质瘤和毛母质癌以及与其他皮肤附属器肿瘤方面的潜力。我们使用了一系列广泛的IHC标志物：β-连环蛋白、SATB2、CDX2、LEF1、Ber-EP4和PRAME，对88例皮肤肿瘤（14例毛母质癌、18例毛母质瘤、13例基底细胞癌、12例鳞状细胞癌、12例皮脂腺癌、10例默克尔细胞癌、7例毛母细胞瘤和2例汗腺癌）进行了研究。毛母质瘤和毛母质癌显示β-连环蛋白核染色>75%。CDX2也强烈染色毛母质肿瘤；然而，染色分布在毛母质瘤中有限，在毛母质癌中更广泛。但是，总体而言，其染色程度低于β-连环蛋白。SATB2和Ber-EP4的表达仅在部分毛母质癌和毛母质瘤中观察到，而LEF-1在毛母质瘤和毛母质癌中均显示强的、弥漫性核阳性。在所评估的IHC标志物中，没有一种能够区分毛母质瘤和毛母质癌。然而，联合使用β-连环蛋白和CDX2标志物不仅有助于确认增殖的毛母质性质，而且当CDX2染色显著时，有助于区分良性和恶性病例。尽管有这些发现，诊断仍应主要依赖于全面的组织病理学检查。
