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<p>The <i>EWSR1/FUS::CREB</i> fusion has been increasingly recognized in several histologically and phenotypically dissimilar neoplasms, ranging from low-grade to malignant tumors. However, a group of malignant epithelioid tumors harboring <i>EWSR1/FUS::CREB</i> fusions has been reported as a distinct tumor type that does not fit within well-defined entities. Herein, we report two cases occurring in the uterus with multiple metastatic nodules in the abdomen and pelvis. Morphologically, these tumors showed uniform, medium-sized epithelioid cells with eosinophilic or clear cytoplasm. Keratin AE1/AE3 or epithelial membrane antigen was diffusely positive, with focally positive sex cord-associated markers. Anaplastic lymphoma kinase was positive in Case 1 but not in Case 2. Next-generation sequencing and fluorescence in situ hybridization confirmed the <i>EWSR1 (exon 15)::CREM (exon 6)</i> fusion in both cases. These uterine neoplasms broaden the spectrum of malignant epithelioid neoplasms and should be included in the differential diagnosis of epithelioid neoplasms involving the female reproductive system.</p> Graphical abstract <p></p>

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Clinicopathologic characteristics of uterine malignant epithelioid neoplasms with EWSR1::CREM fusion: Report of 2 cases at a novel site with literature review

  • 期刊论文

  • 发表日期：

    2026年6月26日

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  • Shi-lu Chen,
  • Rong-zhen Luo,
  • Shi-min Zhang,
  • Bao-cheng Lu,
  • Xiao-fang Li,
  • Jia Fu,
  • Yue Li,
  • Li-li Liu

摘要

The EWSR1/FUS::CREB fusion has been increasingly recognized in several histologically and phenotypically dissimilar neoplasms, ranging from low-grade to malignant tumors. However, a group of malignant epithelioid tumors harboring EWSR1/FUS::CREB fusions has been reported as a distinct tumor type that does not fit within well-defined entities. Herein, we report two cases occurring in the uterus with multiple metastatic nodules in the abdomen and pelvis. Morphologically, these tumors showed uniform, medium-sized epithelioid cells with eosinophilic or clear cytoplasm. Keratin AE1/AE3 or epithelial membrane antigen was diffusely positive, with focally positive sex cord-associated markers. Anaplastic lymphoma kinase was positive in Case 1 but not in Case 2. Next-generation sequencing and fluorescence in situ hybridization confirmed the EWSR1 (exon 15)::CREM (exon 6) fusion in both cases. These uterine neoplasms broaden the spectrum of malignant epithelioid neoplasms and should be included in the differential diagnosis of epithelioid neoplasms involving the female reproductive system.

Graphical abstract