Department of Pathology and Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Ann Diagn Pathol. 2024 Oct;72:152321. doi: 10.1016/j.anndiagpath.2024.152321. Epub 2024 May 6.
Retroperitoneal Ewing sarcomas (RES) are very rare and mostly described in case reports. The purpose of this study was to retrospectively analyze the clinicopathology, molecular characteristics, biological behavior, and therapeutic information of 13 cases of primary RES with immunohistochemical staining, fluorescence in situ hybridization, RT-PCR and NGS sequencing detection techniques. The thirteen patients included eight males and five females with a mean age of 34 years. Morphologically, the tumors were comprised of small round or epithelial-like cells with vacuolated cytoplasm (6/13,46 %) arranged in diffuse, nested (8/13,62 %) and perivascular (7/13,54 %) patterns. Unusual morphologic patterns, such as meningioma-like swirling structures and sieve-like structures were relatively novel findings. Immunohistochemical studies showed CD99 (12/13; 92 %), CD56 (11/13; 85 %), NKX2.2 (9/13; 69 %), PAX7 (10/11;91 %) and CD117(6/9;67 %) to be positive.12 cases (92 %) demonstrated EWSR1 rearrangement and 3 cases displayed EWSR1::FLI1 fusion by FISH. ERCC4 splice-site variant, a novel pathogenic variant, was discovered for the first time via RNA sequencing. With a median follow-up duration of 14 months (6 to 79 months), 8/13 (62 %) patients died, while 5/13(38 %) survived. Three cases recurred, and five patients developed metastasis to the liver (2 cases), lung (2 cases) and bone (1 case). RES is an aggressive, high-grade tumor, prone to multiple recurrences and metastases, with distinctive morphologic, immunohistochemical, and molecular genetic features. ERCC4 splicing mutation, which is a novel pathogenic variant discovered for the first time, with possible significance for understanding the disease, as well as the development of targeted drugs.
腹膜后尤文肉瘤（RES）非常罕见，大多在病例报告中描述。本研究旨在通过免疫组织化学染色、荧光原位杂交、RT-PCR 和 NGS 测序检测技术，回顾性分析 13 例原发性 RES 的临床病理、分子特征、生物学行为和治疗信息。13 例患者中，男性 8 例，女性 5 例，平均年龄 34 岁。肿瘤形态上由小圆形或上皮样细胞组成，具有空泡状细胞质（13 例中有 6 例，46%），排列呈弥漫性、巢状（13 例中有 8 例，62%）和血管周围（13 例中有 7 例，54%）模式。不常见的形态模式，如脑膜瘤样漩涡结构和筛状结构是相对较新的发现。免疫组织化学研究显示 CD99（13 例中有 12 例；92%）、CD56（13 例中有 11 例；85%）、NKX2.2（13 例中有 9 例；69%）、PAX7（11 例中有 10 例；91%）和 CD117（9 例中有 6 例；67%）阳性。12 例（92%）显示 EWSR1 重排，3 例通过 FISH 显示 EWSR1::FLI1 融合。首次通过 RNA 测序发现 ERCC4 剪接位点变异，一种新的致病性变异。中位随访时间为 14 个月（6-79 个月），13 例中有 8 例（62%）死亡，5 例（38%）存活。3 例复发，5 例患者发生肝（2 例）、肺（2 例）和骨（1 例）转移。RES 是一种侵袭性、高级别的肿瘤，易多次复发和转移，具有独特的形态、免疫组织化学和分子遗传学特征。ERCC4 剪接突变是首次发现的新的致病性变异，可能对了解疾病以及开发靶向药物具有意义。
