Background: Epithelioid haemangioendothelioma (EHE) is an ultra-rare malignant vascular tumour with a prevalence of 1 per 1,000,000. It is typically molecularly characterised by aWWTR1::CAMTA1gene fusion in approximately 90% of cases, or aYAP1::TFE3gene fusion in approximately 10% of cases. EHE cases are typically refractory to therapies, and no anticancer agents are reimbursed for EHE in Australia. Methods: We report a cohort of nine EHE cases with comprehensive histologic and molecular profiling from the Walter and Eliza Hall Institute of Medical Research Stafford Fox Rare Cancer Program (WEHI-SFRCP) collated via nation-wide referral to the Australian Rare Cancer (ARC) Portal. The diagnoses of EHE were confirmed by histopathological and immunohistochemical (IHC) examination. Molecular profiling was performed using the TruSight Oncology 500 assay, the TruSight RNA fusion panel, whole genome sequencing (WGS), or whole exome sequencing (WES). Results: Molecular analysis of RNA, DNA or both was possible in seven of nine cases. TheWWTR1::CAMTA1fusion was identified in five cases. TheYAP1::TFE3fusion was identified in one case, demonstrating unique morphology compared to cases with the more commonWWTR1::CAMTA1fusion. All tumours expressed typical endothelial markers CD31, ERG, and CD34 and were negative for pan-cytokeratin. Cases with aWWTR1::CAMTA1fusion displayed high expression of CAMTA1 and the single case with aYAP1::TFE3fusion displayed high expression of TFE3. Survival was highly variable and unrelated to molecular profile. Conclusions: This cohort of EHE cases provides molecular and histopathological characterisation and matching clinical information that emphasises the molecular patterns and variable clinical outcomes and adds to our knowledge of this ultra-rare cancer. Such information from multiple studies will advance our understanding, potentially improving treatment options.
背景：上皮样血管内皮瘤（EHE）是一种超罕见的恶性血管肿瘤，患病率约为百万分之一。其分子特征通常表现为约90%的病例存在WWTR1::CAMTA1基因融合，约10%的病例存在YAP1::TFE3基因融合。EHE病例通常对治疗不敏感，且在澳大利亚尚无获批用于EHE的抗癌药物获得医保报销。方法：我们通过澳大利亚罕见癌症（ARC）门户网站全国转诊，收集了来自沃尔特与伊丽莎·霍尔医学研究所斯塔福德·福克斯罕见癌症项目（WEHI-SFRCP）的9例EHE病例队列，并进行了全面的组织学和分子特征分析。所有EHE诊断均经组织病理学和免疫组织化学（IHC）检查确认。分子特征分析采用TruSight Oncology 500检测、TruSight RNA融合检测panel、全基因组测序（WGS）或全外显子组测序（WES）进行。结果：在9例病例中，有7例成功进行了RNA、DNA或两者联合的分子分析。其中5例检测到WWTR1::CAMTA1融合，1例检测到YAP1::TFE3融合；与更常见的WWTR1::CAMTA1融合病例相比，该例表现出独特的形态学特征。所有肿瘤均表达典型的内皮标志物CD31、ERG和CD34，且广谱细胞角蛋白呈阴性。具有WWTR1::CAMTA1融合的病例显示CAMTA1高表达，而唯一具有YAP1::TFE3融合的病例显示TFE3高表达。患者生存期差异显著，且与分子特征无关。结论：本EHE病例队列提供了分子与组织病理学特征及匹配的临床信息，强调了该病的分子模式与多变的临床结局，增进了我们对这种超罕见癌症的认识。来自多项研究的此类信息将推动我们的理解，并可能改善治疗选择。
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