Xing Deyin, Meyer Christian F, Gross John M, Argani Pedram, Hung Chien-Fu, Wu T-C, Vang Russell, Armstrong Deborah K, Gaillard Stéphanie L
Int J Gynecol Pathol. 2024 Jan 1;43(1):47-55. doi: 10.1097/PGP.0000000000000951. Epub 2023 Mar 13.
MEIS1::NCOA1/2 fusion sarcomas are a recently described novel entity arising in a variety of locations with a predilection for the genitourinary tract and gynecologic organs. Despite multiple locoregional recurrences, these tumors are thought to behave in a low-grade malignant manner. Here we report a uterine MEIS1::NCOA2 fusion sarcoma with lung metastasis. The patient was a 47-yr-old woman with a history of abnormal uterine bleeding who was found to have a myometrial mass confirmed by pathology to be uterine sarcoma. The tumor was predominantly composed of monotonous spindle cells with scant cytoplasm, crowded nuclei, and brisk mitotic activity, growing in a fascicular and streaming pattern. The morphologic and immunophenotypic features were nonspecific and a diagnosis of high-grade uterine sarcoma with a differential of leiomyosarcoma versus high-grade endometrial stromal sarcoma was rendered. At the 27-mo follow-up, the patient was found to have a lung metastasis consisting of a monotonous round cell sarcoma. A retrospective RNA-based and DNA-based next-generation sequencing of the primary uterine sarcoma revealed a MEIS1::NCOA2 gene fusion, a c.94G>C/p.D32H mutation in exon 3 of CTNNB1 gene, HMGA2 , and CDK4 gene amplification, and an intermediate/marginal level of MDM2 gene amplification. Polymerase chain reaction-based molecular analysis further demonstrated that the MEIS1::NCOA2 gene fusion and CTNNB1 somatic mutation were also present in the lung metastasis. This case represents the first case of such gynecologic sarcoma with distant (lung) metastasis, and the second metastatic case among all reported MEIS1::NCOA1/2 fusion sarcomas, highlighting the malignant metastatic potential of this emerging entity. Our case also indicates that HMGA2/CDK4/MDM2 region amplification and CTNNB1 somatic mutation might be recurrent genetic events in this rare sarcoma subtype.
MEIS1::NCOA1/2融合肉瘤是一种最近被描述的新型肿瘤，可发生于多种部位，尤其好发于泌尿生殖道和妇科器官。尽管有多次局部复发，但这些肿瘤被认为具有低度恶性行为。在此，我们报告一例发生肺转移的子宫MEIS1::NCOA2融合肉瘤。患者为一名47岁女性，有子宫异常出血病史，经病理证实子宫肌层肿物为子宫肉瘤。肿瘤主要由胞质稀少、核拥挤且有活跃核分裂象的单一梭形细胞组成，呈束状和流水状生长。形态学和免疫表型特征不具有特异性，诊断为高级别子宫肉瘤，鉴别诊断包括平滑肌肉瘤和高级别子宫内膜间质肉瘤。在27个月的随访中，发现患者出现了由单一圆形细胞肉瘤组成的肺转移。对原发性子宫肉瘤进行的基于RNA和DNA的回顾性二代测序显示存在MEIS1::NCOA2基因融合、CTNNB1基因第3外显子的c.94G>C/p.D32H突变、HMGA2和CDK4基因扩增以及MDM2基因的中等/边缘水平扩增。基于聚合酶链反应的分子分析进一步表明，肺转移灶中也存在MEIS1::NCOA2基因融合和CTNNB1体细胞突变。该病例代表了首例发生远处（肺）转移的此类妇科肉瘤，也是所有已报道的MEIS1::NCOA1/2融合肉瘤中的第二例转移病例，突出了这种新出现实体的恶性转移潜能。我们的病例还表明，HMGA2/CDK4/MDM2区域扩增和CTNNB1体细胞突变可能是这种罕见肉瘤亚型中反复出现的遗传事件。
