Clinicopathologic features and genomic analysis of pulmonary blastomatoid carcinosarcoma

Abstract Background: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. Methods: Three cases of pulmonary blastomatoid carcinosarcoma were enrolled in this study. Clinicopathologic informationand 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. Results: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-cateninand 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, PTCH1and LRP1Bwere shared by both epithelial and mesenchymal components. Epithelial component had additional mutations in BCOR, CTNNB1, CTCF, FAT1and DICER1. In patient two, 12 mutations were shared. The epithelial component had BRCA2mutation and the mesenchymal had mutations in CREBBP, ALK, DNMT3A, ASXL2, MYCN andRICTOR. Patient three had 6 shared mutations. The epithelial component had an additional mutation in KAT6Aand the mesenchymal had an additional mutation in APC. Collectively, we observed heterogeneity between epithelial and mesenchymal components of the same tumor. Conclusions: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.