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. Clinic-pathologic 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. Results: The epithelial component in patient one was consistent of low-grade and high-grade fetal lung adenocarcinoma and displayed aberrant nuclear expression of β-catenin and missense mutation of CTNNB1 in its low-grade epithelial. The epithelial component in another two patients were consistent of high-grade fetal lung adenocarcinoma/enteric adenocarcinoma and harbored no mutation of CTNNB1. The mesenchymal components in all three tumors were primitive round/spindle cells in morphology 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 had additional mutations in BCOR, CTNNB1, CTCF, FAT1 and DICER1. In patient two, 12 mutations were shared. The epithelial had BRCA2 mutations and the mesenchymal had mutations in CREBBP, ALK, DNMT3A, ASXL2, MYCN andRICTOR. Patient three had 6 shared mutations. The epithelial 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. Conclusions: Parallel detection of genetic abnormalities in epithelial and mesenchymal components of blastomatoid carcinosarcoma could provide evidence for tumor differentiation, molecular targeting and further distinguish them from conventional pulmonary blastoma and carcinosarcoma.