肉瘤样胸腺瘤是一种罕见的胸腺肿瘤，其特征为Yes Associated Protein 1（YAP1）和Mastermind Like Transcriptional Coactivator 2（MAML2）基因融合，这是由于11号染色体的内部染色体倒位引起的。用针对YAP1 C-terminus 的抗体进行的免疫组织化学研究表明，在YAP1重排的血管性肿瘤、汗腺瘤和汗腺癌中都丧失了YAP1的表达。本研究旨在验证YAP1 C-terminus抗体作为肉瘤样胸腺瘤诊断的辅助免疫组织化学标志物。本研究选取了10例肉瘤样胸腺瘤。使用荧光原位杂交（FISH）、下一代测序（NGS）和逆转录-聚合酶链反应（RT-PCR）分析检测YAP1::MAML2融合。然后，我们进行了免疫组织化学检测，以检测10例肉瘤样胸腺瘤、50例常规胸腺瘤（每种A型胸腺瘤、AB型胸腺瘤、B1型胸腺瘤、B2型胸腺瘤和B3型胸腺瘤各10例）和7例胸腺癌的YAP1 C-terminus表达。所有10例显示了狭窄的分裂信号，距离接近两个信号直径，并且有时在YAP1和MAML2分裂FISH（BA-FISH）中出现假阴性结果。通过融合FISH（F-FISH）分析，在所有10例中观察到了YAP1::MAML2融合的异常共定位信号。8例核酸充足的病例成功测序，所有病例都显示了YAP1::MAML2融合；2例病例通过DNA和RNA测序均检测到融合，6例病例仅通过RNA测序检测到融合。通过RT-PCR在4例病例中鉴定出YAP1::MAML2融合转录本。肉瘤样胸腺瘤在所有10例（100%）中显示了YAP1 C-terminus表达的丧失。所有其他胸腺肿瘤均显示了保留的YAP1 C-terminus表达。YAP1 C-terminus免疫组织化学标记是一种高度敏感和特异性的辅助标志物，可将肉瘤样胸腺瘤与其模仿品区分开来。由于两个基因的接近，分裂FISH（BA-FISH）不能有效检测YAP1::MAML2融合。YAP1 C-terminus表达的丧失是检测肉瘤样胸腺瘤中YAP1::MAML2融合的可靠替代标志。© 2023 John Wiley & Sons Ltd.

Metaplastic thymoma is a rare thymic tumour characterized by Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) gene fusions resulting from an intrachromosomal inversion of chromosome 11. Immunohistochemistry with an antibody directed against the C-terminus of YAP1 has shown loss of expression in YAP1-rearranged vascular neoplasms, poromas, and porocarcinomas. This study aimed to validate an anti-YAP1 C-terminal antibody as an ancillary immunohistochemical marker for the diagnosis of metaplastic thymoma.Ten metaplastic thymomas were selected for the current study. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed to detect YAP1::MAML2 fusions. We then performed immunohistochemistry to detect YAP1 C-terminus expression in 10 metaplastic thymomas, 50 conventional thymomas (10 each of type A thymoma, type AB thymoma, type B1 thymoma, type B2 thymoma, and type B3 thymoma) and seven thymic carcinomas.All 10 cases showed narrow split signals with a distance of nearly two signal diameters and sometimes had false-negative results in YAP1 and MAML2 break-apart FISH (BA-FISH). Abnormal colocalized signals of the YAP1::MAML2 fusion were observed in all 10 cases using fusion FISH (F-FISH) assays. Eight of 10 cases with adequate nucleic acids were successfully sequenced and all showed YAP1::MAML2 fusions; in two cases the fusions were detected by both DNA and RNA sequencing and in six cases by RNA sequencing only. YAP1::MAML2 fusion transcripts were identified in four cases by RT-PCR. Metaplastic thymoma showed loss of YAP1 C-terminus expression in all 10 (100%) cases. All other thymic neoplasms showed retained YAP1 C-terminus expression.YAP1 C-terminus immunohistochemistry is a highly sensitive and specific ancillary marker that distinguishes metaplastic thymoma from its mimics. BA-FISH assays could not effectively detect YAP1::MAML2 fusions due to the proximity of the two genes. Loss of YAP1 C-terminus expression is a reliable surrogate for the detection of YAP1::MAML2 fusions in metaplastic thymoma.© 2023 John Wiley & Sons Ltd.