This study was designed to investigate the clinicopathologic features of pulmonary blastomatoid carcinosarcoma and explore the genomic profiles of epithelial and mesenchymal components in this tumor. Three cases of pulmonary blastomatoid carcinosarcoma were enrolled in this study. Clinicopathologic information and prognostic data were retrospectively reviewed. Diagnostic immunohistochemistry was performed. The epithelial and mesenchymal components were microdissected to investigate the genomic profiles by performing capture-based targeted next generation sequencing. The epithelial components in patient one consisted of low-grade and high-grade fetal lung adenocarcinoma. Low-grade epithelial cells showed nuclear expression of β-catenin and missense mutation of CTNNB1. The epithelial components in another two patients consisted of high-grade fetal lung adenocarcinoma/enteric adenocarcinoma. The epithelial cells showed membrane staining of β-catenin and harbored no mutation of CTNNB1. The mesenchymal components in all three tumors were composed of primitive round/spindle cells without definite differentiation and showed cytoplasmic dot positive of β-catenin and no corresponding mutation. Within a tumor, both components exhibited relatively comparable molecular profile. In patient one, 4 mutations: RB1, FAT3, PTCH1 and LRP1B were shared by both epithelial and mesenchymal components. Epithelial component had additional mutations in BCOR, CTNNB1, CTCF, FAT1 and DICER1. In patient two, 12 mutations were shared. The epithelial component had BRCA2 mutation and the mesenchymal had mutations in CREBBP, ALK, DNMT3A, ASXL2, MYCN and RICTOR. Patient three had 6 shared mutations. The epithelial component had an additional mutation in KAT6A and the mesenchymal had an additional mutation in APC. Collectively, we observed heterogeneity between epithelial and mesenchymal components of the same tumor. Blastomatoid carcinosarcoma showed characteristic morphology and immunophenotype. Parallel detection of genetic abnormalities in epithelial and mesenchymal components could provide further evidence for tumor differentiation, molecular targeting and differential diagnosis.

中文翻译：

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肺母细胞瘤样癌肉瘤的临床病理特征及基因组分析

本研究旨在探讨肺母细胞样癌肉瘤的临床病理特征，并探讨该肿瘤上皮和间质成分的基因组谱。本研究纳入了 3 例肺母细胞样癌肉瘤病例。回顾性分析临床病理学信息和预后数据。进行了诊断性免疫组织化学检查。对上皮和间质成分进行显微解剖，通过执行基于捕获的靶向下一代测序来研究基因组图谱。1号患者的上皮成分包括低级别和高级别胎儿肺腺癌。低级别上皮细胞显示β-连环蛋白的核表达和CTNNB1的错义突变。另外两名患者的上皮成分为高级别胎儿肺腺癌/肠腺癌。上皮细胞显示β-连环蛋白的膜染色，并且没有CTNNB1突变。三个肿瘤的间质成分均由原始圆形/梭形细胞组成，未明确分化，胞浆内β-连环蛋白点阳性，无相应突变。在肿瘤内，两种成分都表现出相对可比的分子特征。在 1 号患者中，上皮和间质成分共有 4 个突变：RB1、FAT3、PTCH1 和 LRP1B。上皮成分在 BCOR、CTNNB1、CTCF、FAT1 和 DICER1 中存在其他突变。在二号患者中，共有 12 个突变。上皮成分有BRCA2突变，间质成分有CREBBP、ALK、DNMT3A、ASXL2、MYCN和RICTOR突变。三号患者有 6 个共同突变。上皮成分在 KAT6A 上有一个额外的突变，间质成分在 APC 上有一个额外的突变。总的来说，我们观察到同一肿瘤的上皮成分和间质成分之间的异质性。母细胞样癌肉瘤表现出特征性的形态和免疫表型。并行检测上皮和间质成分的遗传异常可以为肿瘤分化、分子靶向和鉴别诊断提供进一步的证据。