间皮瘤是一种罕见的、侵袭性的间皮细胞恶性肿瘤，偶尔会出现复发性融合。 EWSR1/FUS-CREB、YY1、MAP3K8、NR4A3 和 ALK 重排增殖已在有限的系列中报道，没有明确的组织学或临床相关性，限制了临床医生评估预后并将这些新实体整合到治疗决策中的能力。本研究的目的是从组织学、分子学和临床上更好地表征这些重排的增殖。收集每个病例的临床、病理和全面的转录组和突变数据。总共包括 41 个肿瘤，包括 7 个 ALK、10 个 MAP3K8、 4 个 NR4A3、8 个 ESWR1/FUS::ATF1、8 个 EWSR1::YY1 和 4 个 SUFU 融合病例。我们发现，除了携带 NR4A3 和 SUFU 的病例外，女性占主导地位；大多数患者年龄在 60 岁左右，但携带 ALK 或 EWSR1/FUS::ATF1 基因融合的患者更年轻。每组都表现出不同的组织学、免疫组织化学、分子特征和肿瘤学过程。具体来说，MAP3K8和ALK呈现PAX8乳头状增殖，ESWR1/FUS::ATF1和EWSR1::YY1呈现血管瘤样纤维组织细胞瘤样模式，而SUFU呈现“组织培养”样梭形细胞增殖。不良预后因素包括胸膜部位、男性、Ki67 ≥10% 以及 ESWR1/FUS::ATF1 或 SUFU 基因融合。这项研究显着拓宽了与融合相关的间皮肿瘤的范围，为新的上皮样（间皮）增殖提供了见解。具有独特的组织学外观、分子特征和预后，以指导患者的适应性治疗。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Mesothelioma is a rare and aggressive malignant neoplasm arising from mesothelial cells, which occasionally manifests recurrent fusions. EWSR1/FUS-CREB, YY1, MAP3K8, NR4A3, and ALK-rearranged proliferations have been reported in limited series with no clear histological or clinical correlations, limiting clinicians' ability to assess prognosis and integrate these new entities into therapeutic decisions. The aim of this study was to better characterize these rearranged proliferations histologically, molecularly, and clinically.Clinical, pathological, and comprehensive transcriptome and mutation data were collected for each case.A total of 41 tumors were included, encompassing 7 ALK, 10 MAP3K8, 4 NR4A3, 8 ESWR1/FUS::ATF1, 8 EWSR1::YY1, and 4 SUFU-fused cases. We found a female predominance, except for cases harboring NR4A3 and SUFU; and most patients were around 60 years of age, but those harboring ALK or EWSR1/FUS::ATF1 gene fusions were younger. Each group exhibited distinct histological, immunohistochemical, molecular features, and oncological courses. Specifically, MAP3K8 and ALK presented PAX8+ papillary proliferations, ESWR1/FUS::ATF1 and EWSR1::YY1 displayed angiomatoid fibrous histiocytoma-like patterns, while SUFU showcased 'tissue culture'-like spindle cell proliferation. Poor prognosis factors were the pleural site, male sex, Ki67 ≥10%, and ESWR1/FUS::ATF1 or SUFU gene fusions.This study significantly broadens the spectrum of mesothelial tumors associated with fusions, offering insight into novel epithelioid (mesothelial) proliferations with distinctive histological appearances, molecular profiles, and prognoses to guide adapted treatments for patients.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.