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 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 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. 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.

Correlation between LRP1B Mutations and Tumor Mutation Burden in Gastric Cancer

“…LRP1B expression is reduced in many cancers, and it is a common mutant gene in human cancers [ 15 – 17 ]. Among the studies on LRP1B , it was found that LRP1B plays an important role and may serve as a prognostic marker for cancer during the development of various cancers including gastric cancer [ 18 , 19 ]. In addition, the significant associations between LRP1B mutations and TMB in lung cancer and melanoma have also been reported [ 15 , 20 ].…”

Adult pulmonary blastoma: a case report with spectrum of rare manifestations

“…Thus, a potential genetic link to pediatric pleuropulmonary blastoma was indicated. Recently, MYCN mutation was detected in the micro dissected mesenchymal component based on capture-based targeted next generation sequencing method ( 14 ). In the index case, we came across a pathogenic mutation in the MYCN and ATM genes on NGS where the latter have not been described in the literature as per our best knowledge.…”