CIC 重排肉瘤 (CRS) 是临床上具有侵袭性的未分化圆形细胞肉瘤 (URCS)，通常由 CIC::DUX4 驱动。由于 DUX4 的重复性和融合断点的可变性，分子测试可能会错过 CIC::DUX4 融合。免疫组织化学 (IHC) 染色已作为 CIC::DUX4 融合的替代物进行了研究。我们的目的是评估 DUX4 IHC 在 CRS 检测中的性能及其在非 CRS 圆形细胞或上皮样肿瘤中的表达。纳入了分子证实的 CRS (n = 48) 和非 CRS (n = 105) 病例。 CRS病例中女性35例，男性13例，年龄从不足1岁到67岁不等（中位=41岁）。在分子证实的非 CRS 病例中，在尤文肉瘤（38 例）、肺泡横纹肌肉瘤（18 例）、促结缔组织增生性小圆细胞肿瘤（12 例）和滑膜肉瘤（n = 5）中研究了 C 端 DUX4 表达，如以及非间质肿瘤，例如 SMARCA4/SMARCB1 缺陷型肿瘤（n = 5 例）、原发灶不明的癌（n = 3 例）和血液淋巴肿瘤（4 例）。当超过 50% 的肿瘤细胞中检测到强核表达时，DUX4 IHC 被认为是阳性。当用作 CRS 诊断的替代方法时，DUX4 IHC 的敏感性和特异性分别为 98% 和 100%。只有 1 例 CRS 病例 DUX4 IHC 呈阴性，并具有 CIC::FOXO4 融合。DUX4 IHC 是 CIC::DUX4 融合存在的高度敏感和特异的替代标记物，证明了其在建立 CRS 诊断方面的实用性。© 2024作者。组织病理学由约翰·威利出版

CIC-rearranged sarcomas (CRS) are clinically aggressive undifferentiated round cell sarcomas (URCS), commonly driven by CIC::DUX4. Due to the repetitive nature of DUX4 and the variability of the fusion breakpoints, CIC::DUX4 fusion may be missed by molecular testing. Immunohistochemical (IHC) stains have been studied as surrogates for the CIC::DUX4 fusion. We aim to assess the performance of DUX4 IHC in the work-up of CRS and its expression in non-CRS round cell or epithelioid neoplasms.Cases of molecularly confirmed CRS (n = 48) and non-CRS (n = 105) were included. CRS cases consisted of 35 females and 13 males, with ages ranging from less than 1 year to 67 years (median = 41 years). Among the molecularly confirmed non-CRS cases, C-terminal DUX4 expression was investigated in Ewing sarcomas (38 cases), alveolar rhabdomyosarcomas (18 cases), desmoplastic small round cell tumours (12 cases) and synovial sarcomas (n = five), as well as in non-mesenchymal neoplasms such as SMARCA4/SMARCB1-deficient tumours (n = five), carcinomas of unknown primary (n = three) and haematolymphoid neoplasms (four cases). DUX4 IHC was considered positive when strong nuclear expression was detected in more than 50% of neoplastic cells. When used as a surrogate for the diagnosis of CRS, the sensitivity and specificity of DUX4 IHC was 98 and 100%, respectively. Only one CRS case was negative for DUX4 IHC and harboured a CIC::FOXO4 fusion.DUX4 IHC is a highly sensitive and specific surrogate marker for the presence of CIC::DUX4 fusion, demonstrating its utility in establishing a diagnosis of CRS.© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.