Abstract:
Mesonephric-type (or -like) adenocarcinomas (MAs) of the ovary are an uncommon and aggressive histotype. They appear to arise through transdifferentiation from Müllerian lesions creating diagnostic challenges. Thus, we aimed to develop a histologic and immunohistochemical (IHC) approach to optimize the identification of MA over its histologic mimics, such as ovarian endometrioid carcinoma (EC). First, we screened 1,537 ovarian epithelial neoplasms with a four-marker IHC panel of GATA3, TTF1, ER, and PR followed by a morphological review of EC to identify MA in retrospective cohorts. Interobserver reproducibility for the distinction of MA versus EC was assessed in 66 cases initially without and subsequently with IHC information (four-marker panel). Expression of PAX2, CD10, and calretinin was evaluated separately, and survival analyses were performed. We identified 23 MAs from which 22 were among 385 cases initially reported as EC (5.7%) and 1 as clear cell carcinoma. The interobserver reproducibility increased from fair to substantial (κ = 0.376-0.727) with the integration of the four-marker IHC panel. PAX2 was the single most sensitive and specific marker to distinguish MA from EC and could be used as a first-line marker together with ER/PR and GATA3/TTF1. Patients with MA had significantly increased risk of earlier death from disease (hazard ratio = 3.08; 95% CI, 1.62-5.85; p < 0.0001) compared with patients with EC, when adjusted for age, stage, and p53 status. A diagnosis of MA has prognostic implications for stage I disease, and due to the subtlety of morphological features in some tumors, a low threshold for ancillary testing is recommended.
摘要:
卵巢的中肾型(或类似)腺癌(MAs)是一种罕见且侵袭性的组织型。它们似乎是通过苗勒氏病变的转分化而产生的,这给诊断带来了挑战。因此,我们旨在开发一种组织学和免疫组织化学(IHC)方法,以优化MA的组织学模拟物的鉴定,如卵巢子宫内膜样癌(EC)。首先,我们用GATA3、TTF1、ER、和PR,然后对EC进行形态学回顾,以确定回顾性队列中的MA。在66例最初没有IHC信息并随后使用IHC信息(四标记组)的病例中,评估了MA与EC区别的观察者间再现性。分别评估PAX2、CD10和钙视网膜素的表达,并进行生存分析。我们确定了23个MA,其中385例最初报告为EC(5.7%)和1例透明细胞癌。通过整合四标记IHC面板,观察者间的可重复性从一般增加到实质性(κ=0.376-0.727)。PAX2是区分MA和EC的唯一最敏感和最特异的标记,可以与ER/PR和GATA3/TTF1一起用作一线标记。与EC患者相比,MA患者早期死亡的风险显著增加(风险比=3.08;95%CI,1.62-5.85;p<0.0001)。当调整年龄时,舞台,和p53状态。MA的诊断对I期疾病具有预后意义,由于某些肿瘤的形态特征微妙,建议辅助测试的门槛较低。