So-called primary yolk sac tumors of the vulva are very rare and often have an aggressive disease course. Their molecular features have not been previously characterized. There is also a well-documented group of SMARCB1 (INI-1)-deficient vulvar neoplasms, which includes proximal-type epithelioid sarcoma and myoepithelial carcinoma. Until now, “vulvar yolk sac tumors” and SMARCB1-deficient neoplasms were considered unrelated diseases. After reviewing an index case of a vulvar yolk sac tumor with loss of SMARCB1 by immunohistochemistry, we retrospectively identified 2 additional cases diagnosed as vulvar yolk sac tumors. Patient ages were 34, 32, and 25 years old, and 2 tumors were associated with a pregnancy. All 3 cases showed morphology typical of a yolk sac tumor, and by immunohistochemistry all were positive for SALL4, glypican-3, keratins, and lacked CD34 positivity. All tumors also demonstrated loss of SMARCB1 in tumor cells. Targeted molecular profiling was performed in 2 cases and identified 2 copy deletion of SMARCB1, without genomic alterations typically seen in gonadal yolk sac tumors. In the third case, isochromosome 12p was not identified by fluorescence in situ hybridization. All 3 patients had either local recurrences or distant metastases, and 2 died of disease. One patient had progressive disease while receiving the enhancer of zeste homolog 2 inhibitor tazemetostat. Overall, these findings suggest that vulvar tumors with pure yolk sac-like morphology may represent morphologic variants of SMARCB1-deficient tumors and not veritable germ cell neoplasia. This potential reclassification may have both prognostic and treatment implications and warrants study of additional extragonadal yolk sac tumors.

所谓的外阴原发性卵黄囊肿瘤非常罕见，并且通常具有侵袭性病程。它们的分子特征此前尚未被表征。还有一组有据可查的 SMARCB1 (INI-1) 缺陷型外阴肿瘤，其中包括近端型上皮样肉瘤和肌上皮癌。到目前为止，“外阴卵黄囊肿瘤”和 SMARCB1 缺陷肿瘤被认为是不相关的疾病。在通过免疫组织化学检查了 1 例 SMARCB1 缺失的外阴卵黄囊肿瘤指标病例后，我们回顾性地鉴定了另外 2 例被诊断为外阴卵黄囊肿瘤的病例。患者年龄分别为 34 岁、32 岁和 25 岁，其中 2 例肿瘤与妊娠有关。所有 3 例病例均表现出典型的卵黄囊肿瘤形态，免疫组织化学检测均为 SALL4、磷脂酰肌醇蛋白聚糖 3、角蛋白阳性，但缺乏 CD34 阳性。所有肿瘤都显示肿瘤细胞中 SMARCB1 缺失。对 2 例病例进行了靶向分子分析，发现SMARCB1存在 2 个拷贝缺失，而没有在性腺卵黄囊肿瘤中常见的基因组改变。在第三种情况下，荧光原位杂交未鉴定出同染色体 12p。3名患者均出现局部复发或远处转移，其中2名患者死亡。一名患者在接受 zeste 同源物 2 抑制剂 tazemetostat 增强剂治疗时出现疾病进展。总的来说，这些发现表明具有纯卵黄囊样形态的外阴肿瘤可能代表 SMARCB1 缺陷型肿瘤的形态变异，而不是真正的生殖细胞肿瘤。这种潜在的重新分类可能具有预后和治疗意义，并值得对其他性腺外卵黄囊肿瘤进行研究。