Clear Cell Carcinoma Arising in Low-Grade Mullerian Adenosarcoma: First Reported Case with Insight into Molecular Profile

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.

Keywords

• uterus
• adenosarcoma
• clear cell carcinoma
• immunohistochemistry
• next-generation sequencing