Department of Pathology, University of California San Diego, San Diego, CA, USA.
Department of Pathology, University of Alabama, Birmingham, AL, USA.
Mod Pathol. 2019 Dec;32(12):1847-1860. doi: 10.1038/s41379-019-0341-6. Epub 2019 Aug 2.
Uterine yolk sac tumors have gained increased recognition in recent years. The current study is a multi-faceted examination of yolk sac tumor-like phenotypes in endometrial tumors, based on an analysis of 3 groups of uterine tumors: Group 1: 9 endometrial tumors that had been classified as yolk sac tumor, or as having a yolk sac tumor component, were assessed with a 35-marker immunohistochemical panel, with the goal of defining their immunophenotypic spectrum; Group 2, comprised of 70 endometrial carcinomas of various histotypes, were analyzed for their expression of SALL4, Glypican-3, and AFP, to assess the specificity of these markers for yolk sac tumors relative to endometrial carcinomas; Group 3, comprised of 626 archived cases of endometrial carcinoma/carcinosarcoma, reviewed to define the frequency of yolk sac tumor-like morphology therein. Yolk sac tumor areas in the Group 1 cases were consistently immunoreactive for SALL4 and Glypican-3; variably positive for AFP (89%), Villin (89%), PLAP (78%), 34βE12 (67%), CAM 5.2 (62.5%), EMA (56%), CD117 (50%), p16 (50%), CDX2 (44%), p53 (44% aberrant), MOC31 (37.5%), CK7 (33%), GATA3 (33%), CK5 (25%), and PAX8 (11%); and were negative for CD30, Napsin A, OCT4, estrogen, androgen, and progesterone receptors. 29 (41%) of the 70 group-2 cases expressed at least one of the 3 markers, and 96% of the positive cases was a high-grade histotype. Glypican-3, SALL4, and AFP were positive in 30, 20, and 2.8% of group-2 cases respectively; however, co-expression of any 2, or all 3 markers was uncommon (<9 and 1.4% of cases respectively). Potential yolk sac tumor-like morphology was identified in 5 (0.8%) of 626 group-3 cases, and three were ultimately deemed to be true yolk sac tumor phenotypes based on their morphologic and immunophenotypic similarity to the group 1 cases. These findings highlight the broad immunophenotypic spectrum of uterine yolk sac tumors, the potential pitfalls associated with using immunophenotypes alone to define yolk sac tumor differentiation in endometrial carcinoma, and the utility and limitations of morphologic assessment to identify yolk sac tumors at this site.
近年来，人们对子宫卵黄囊瘤的认识逐渐增加。本研究通过对三组子宫肿瘤进行分析，对子宫内膜肿瘤中的卵黄囊瘤样表型进行了多方面的研究：第 1 组：9 例被归类为卵黄囊瘤或具有卵黄囊瘤成分的子宫内膜肿瘤，使用 35 种免疫标志物进行评估，旨在确定其免疫表型谱；第 2 组：70 例不同组织学类型的子宫内膜癌，分析其 SALL4、Glypican-3 和 AFP 的表达，以评估这些标志物相对于子宫内膜癌对卵黄囊瘤的特异性；第 3 组：626 例存档的子宫内膜癌/癌肉瘤病例，回顾其卵黄囊瘤样形态的频率。第 1 组病例中的卵黄囊瘤区域始终对 SALL4 和 Glypican-3 呈免疫反应性；对 AFP（89%）、Villin（89%）、PLAP（78%）、34βE12（67%）、CAM 5.2（62.5%）、EMA（56%）、CD117（50%）、p16（50%）、CDX2（44%）、p53（44%异常）、MOC31（37.5%）、CK7（33%）、GATA3（33%）、CK5（25%）和 PAX8（11%）呈可变阳性；对 CD30、Napsin A、OCT4、雌激素、雄激素和孕激素受体呈阴性。第 2 组 70 例中有 29 例（41%）至少表达了 3 种标志物中的 1 种，阳性病例中 96%为高级别组织学类型。Glypican-3、SALL4 和 AFP 在第 2 组病例中的阳性率分别为 30%、20%和 2.8%；然而，任何 2 种或 3 种标志物的共同表达并不常见（分别为<9%和 1.4%的病例）。第 3 组 626 例中有 5 例（0.8%）发现潜在的卵黄囊瘤样形态，其中 3 例最终根据其与第 1 组病例相似的形态学和免疫表型被认为是真正的卵黄囊瘤表型。这些发现强调了子宫卵黄囊瘤广泛的免疫表型谱，单独使用免疫表型来定义子宫内膜癌中的卵黄囊瘤分化所涉及的潜在陷阱，以及形态评估在该部位识别卵黄囊瘤的实用性和局限性。
