Loss of expression of the SMARCB1 (INI1/BAF47/SNF5) tumor-suppressor protein, originally identified in pediatric malignant rhabdoid tumors, has been noted in significant percentages of epithelioid sarcomas of classical and proximal-type and in myoepithelial carcinomas. Epithelioid sarcoma and myoepithelial carcinoma are very rare in the vulvar region, and few of these cases have been evaluated for SMARCB1 protein loss by immunohistochemistry (IHC) or for SMARCB1 gene alterations by molecular genetic techniques. We studied the clinicopathologic, IHC, and molecular genetic features of 14 SMARCB1-deficient vulvar neoplasms. All available routinely stained sections were reexamined, and IHC analysis for wide-spectrum cytokeratins, high-molecular weight cytokeratins, epithelial membrane antigen, S100 protein, CD34, smooth muscle actin, desmin, and SMARCB1 was performed. Multiplex ligation-dependent probe amplification and DNA sequencing of the SMARCB1 gene was performed on 12 cases with sufficient available tissue. The 14 vulvar tumors occurred in adult women (mean age 46 y, range 22 to 62 y) and measured 1.1 to 8.8 cm in size (mean 4.7 cm). Tumors were classified as classical-type epithelioid sarcoma (N=1), proximal-type epithelioid sarcoma (N=6), myoepithelial carcinoma (N=4), and "SMARCB1-deficient vulvar sarcoma, not otherwise specified" (N=3) on the basis of combined histopathologic and IHC findings. One myoepithelial carcinoma showed divergent rhabdomyoblastic differentiation. All tested cases showed partial or complete SMARCB1 deletions (homozygous: 9 cases; heterozygous: 3 cases). One case with a heterozygous deletion also showed a c.528delC mutation in exon 5. Fluorescence in situ hybridization for EWSR1 rearrangement was performed for 3 cases classified as myoepithelial carcinoma and was negative. Follow-up (13 patients, range 5 to 72 mo, mean 31 mo) data showed 3 patients dead of disease, 1 alive with unresectable metastatic disease, 1 alive with radiographic evidence of extensive lymph nodal disease, and 8 alive without disease. We conclude that SMARCB1-deficient vulvar neoplasms chiefly comprise epithelioid sarcoma and myoepithelial carcinoma, although some defy easy classification. No association was seen between clinical behavior and the type of SMARCB1 alteration.
肿瘤抑制蛋白SMARCB1（INI1 / BAF47 / SNF5）表达缺失，最初发现于儿童恶性横纹肌样瘤发现，目前在相当部分经典型和近端型上皮样肉瘤及肌上皮癌也有发现。上皮样肉瘤和肌上皮癌很少见于外阴，通过免疫组化（IHC）检测SMARCB1蛋白丢失或分子遗传技术观察SMARCB1基因改变的研究较少。我们研究了14例外阴SMARCB1缺失肿瘤的临床病理特征、免疫组化表达和分子遗传学特点。复习所有病例常规染色切片，并进行广谱细胞角蛋白、高分子量细胞角蛋白、上皮细胞膜抗原、S100蛋白、CD34、平滑肌肌动蛋白、结蛋白和SMARCB1免疫组化染色。对能够获得足够样本的12例进行了SMARCB1基因多重连接探针扩增和DNA测序。14例外阴肿瘤发生于成年女性（平均年龄46岁，从22岁至62岁），病变范围1.1cm至8.8cm（平均4.7cm）。根据组织病理学特征和免疫组化结果分为经典型上皮样肉瘤（n = 1）、近端型上皮样肉瘤（n = 6）、肌上皮癌（n = 4）和“外阴SMARCB1缺乏肉瘤，非特指”（n = 3）。1例肌上皮癌显示不同程度横纹肌母细胞分化。所有检测的病例均显示部分或完全SMARCB1缺失（纯合性缺失：9例；杂合性缺失：3例）。1例杂合缺失还表现有外显子5 的c.528delC突变。3例肌上皮癌还进行了荧光原位杂交检测EWSR1重排，结果为阴性。随访（13例，5-72个月，平均31个月）结果显示，3例死于疾病；1例因肿瘤转移不能手术而带瘤存活；1例存活伴有影像学发现广泛淋巴结转移， 8例无病存活。我们得出结论：虽然有些病例分类困难，外阴SMARCB1缺失肿瘤主要包括上皮样肉瘤和肌上皮癌，临床生物学行为和SMARCB1缺失类型之间无相关性。