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.

中文翻译：

---

子宫 MEIS1::NCOA2 融合肉瘤伴肺转移：病例报告和文献综述。

MEIS1::NCOA1/2 融合肉瘤是最近描述的一种新实体，产生于多个部位，尤其好发于泌尿生殖道和妇科器官。尽管存在多次局部区域复发，但这些肿瘤被认为表现为低度恶性。在此，我们报告一例子宫 MEIS1::NCOA2 融合肉瘤伴肺转移。患者为47岁女性，有异常子宫出血病史，发现子宫肌层肿块，经病理证实为子宫肉瘤。肿瘤主要由单调的梭形细胞组成，细胞质稀少，细胞核拥挤，有丝分裂活动活跃，呈束状和流状生长。形态学和免疫表型特征是非特异性的，并且诊断为高级别子宫肉瘤，并具有平滑肌肉瘤与高级别子宫内膜间质肉瘤的区别。在 27 个月的随访中，患者发现肺部转移，由单调圆形细胞肉瘤组成。对原发性子宫肉瘤进行基于 RNA 和 DNA 的回顾性下一代测序揭示了 MEIS1::NCOA2 基因融合、CTNNB1 基因、HMGA2 和 CDK4 基因外显子 3 中的 c.94G>C/p.D32H 突变扩增，以及中等/边缘水平的 MDM2 基因扩增。基于聚合酶链反应的分子分析进一步表明，肺转移中也存在MEIS1::NCOA2基因融合和CTNNB1体细胞突变。该病例是首例此类远处（肺）转移的妇科肉瘤病例，也是所有报道的 MEIS1::NCOA1/2 融合肉瘤中的第二例转移病例，凸显了这一新兴实体的恶性转移潜力。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发生的遗传事件。