Li Jiezhen, Zeng Qiang, Chen Xin, Huang Haijian
Department of Pathology, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
Department of Pathology, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China.
Virchows Arch. 2024 Dec 9. doi: 10.1007/s00428-024-03989-0.
Soft tissue tumors with EWSR1/FUS fusion to genes encoding the cyclic adenosine monophosphate response element-binding (CREB) transcription factor family (ATF1, CREB1, and CREM) are rare and heterogeneous aggressive tumors, often found in the peritoneal cavity. Here, we report two cases of malignant epithelioid tumors with EWSR1::CREB fusion involving the kidney in females in their 30 s. Both tumors appeared as solitary masses, measuring 5.4 cm and 4.0 cm in diameter. Histologically, the tumors were similar, growing invasively with unclear boundaries and composed of epithelial cells with eosinophilic and clear cytoplasm arranged in sheets, nests, and trabeculae. Immunohistochemically, case 1 showed focal AE1/AE3 positivity, whereas case 2 was negative. Anaplastic lymphoma kinase was diffusely positive in case 1 and focally positive in case 2. Both cases were positive for epithelial membrane antigen, mucin-4, and synaptophysin. High-throughput sequencing identified EWSR1::CREM fusion in case 1, whereas fluorescence in situ hybridization detected EWSR1::CREB1 fusion in case 2. These cases expand the morphological and immunophenotypic characteristics of malignant epithelioid tumors with EWSR1::CREB fusion, highlighting the diagnostic challenges of immunohistochemistry and value of molecular testing for accurate diagnosis.
与编码环磷酸腺苷反应元件结合（CREB）转录因子家族（ATF1、CREB1和CREM）的基因发生EWSR1/FUS融合的软组织肿瘤是罕见的异质性侵袭性肿瘤，常发生于腹腔。在此，我们报告两例30多岁女性发生EWSR1::CREB融合的恶性上皮样肿瘤累及肾脏的病例。两个肿瘤均表现为孤立性肿块，直径分别为5.4厘米和4.0厘米。组织学上，肿瘤相似，呈浸润性生长，边界不清，由具有嗜酸性和透明细胞质的上皮细胞排列成片、巢状和小梁状组成。免疫组化方面，病例1显示局灶性AE1/AE3阳性，而病例2为阴性。间变性淋巴瘤激酶在病例1中弥漫性阳性，在病例2中局灶性阳性。两例上皮膜抗原、粘蛋白-4和突触素均为阳性。高通量测序在病例1中鉴定出EWSR1::CREM融合，而荧光原位杂交在病例2中检测到EWSR1::CREB1融合。这些病例扩展了EWSR1::CREB融合的恶性上皮样肿瘤的形态学和免疫表型特征，突出了免疫组化的诊断挑战以及分子检测对准确诊断的价值。
