Department of Pathology, Institut de Pathologie Multisite, Lyon-Sud University Hospital, Hospices Civils de Lyon, Pierre-Bénite; CICLY - EA3738, Université Claude Bernard Lyon 1, Lyon.
Department of Pathology, Gustave Roussy Institute, Villejuif.
ESMO Open. 2024 Aug;9(8):103644. doi: 10.1016/j.esmoop.2024.103644. Epub 2024 Jul 25.
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.
间皮瘤是一种罕见且侵袭性的恶性肿瘤，来源于间皮细胞，偶尔会出现反复融合。已有有限的系列研究报道了 EWSR1/FUS-CREB、YY1、MAP3K8、NR4A3 和 ALK 重排增殖，但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和将这些新实体纳入治疗决策的能力。本研究旨在从组织学、分子和临床方面更好地描述这些重排增殖。
为每个病例收集了临床、病理和全面的转录组和突变数据。
共纳入 41 例肿瘤，包括 7 例 ALK、10 例 MAP3K8、4 例 NR4A3、8 例 EWSR1/FUS::ATF1、8 例 EWSR1::YY1 和 4 例 SUFU 融合病例。我们发现女性居多，除了 NR4A3 和 SUFU 病例；大多数患者年龄在 60 岁左右，但携带 ALK 或 EWSR1/FUS::ATF1 基因融合的患者年龄较小。每个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。具体而言，MAP3K8 和 ALK 呈现 PAX8+乳头状增殖，EWSR1/FUS::ATF1 和 EWSR1::YY1 显示出类似血管瘤样纤维组织细胞瘤的模式，而 SUFU 则表现出“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 EWSR1/FUS::ATF1 或 SUFU 基因融合。
本研究显著拓宽了与融合相关的间皮瘤谱，为具有独特组织学表现、分子谱和预后的新型上皮（间皮）增殖提供了深入了解，以指导为患者提供适应性治疗。
