PDF(Pubmed)
Abstract：
Uterine adenosarcoma (AS) is a rare biphasic neoplasm composed of a malignant, usually low-grade stromal component and benign epithelial component, usually endometrioid. Pathogenesis is unknown; some cases are undoubtably associated with tamoxifen use. Endometrial clear cell carcinoma (CCC) is an aggressive subtype of endometrial cancer, accounting for less than 10% of all uterine carcinomas. The etiology is unknown but can rarely be associated with Lynch syndrome and tamoxifen administration. The development of a composite neoplasm consisting of adenocarcinoma in AS is extremely rare. Endometrioid carcinoma typically represents the epithelial component of the composite tumor. Here we present the very first case of composite tumor, namely, AS with CCC in which next-generation sequencing was performed. Patient was an 85-year-old woman treated with tamoxifen for 5 years. To better understand the pathobiology of two tumors, a targeted genomic analysis of both components was performed. We found seven identical somatic variants in the samples of both tumors, indicating that the tumors have a high probability of having the same origin. Dual amplification of CDK4 and MDM2 was the most likely primary cause of tumor formation, but also one driver variant in the DHX15 gene that was present in both tumor components, suggesting that DHX15 may play an important role in the initiation and development of sarcoma and carcinoma. The patient is followed by regular clinical controls and is alive without signs of disease recurrence 18 months after surgery.
摘要：
子宫腺肉瘤（AS）是一种罕见的双相肿瘤，由恶性，通常是低级别的基质成分和良性上皮成分，通常是子宫内膜样。发病机制未知；某些病例无疑与他莫昔芬的使用有关。子宫内膜透明细胞癌（CCC）是子宫内膜癌的侵袭性亚型，占所有子宫癌的不到10％。病因未知，但很少与Lynch综合征和他莫昔芬给药有关。在AS中，由腺癌组成的复合肿瘤的发展极为罕见。子宫内膜样癌通常代表复合肿瘤的上皮成分。这里我们介绍了第一例复合肿瘤，即,AS与CCC一起进行了下一代测序。患者是用他莫昔芬治疗5年的85岁女性。为了更好地了解两种肿瘤的病理学，我们对这两种成分进行了靶向基因组分析.我们在两种肿瘤的样本中发现了七个相同的体细胞变异，表明肿瘤具有相同起源的可能性很高。CDK4和MDM2的双重扩增是肿瘤形成的最可能的主要原因，但DHX15基因中的一个驱动变异也存在于两个肿瘤成分中，提示DHX15可能在肉瘤和肿瘤的发生发展中起重要作用。患者随后进行定期临床对照，并且在手术后18个月存活，没有疾病复发的迹象。
