A Mutational Profile in Multiple Thymic Squamous Cell Carcinoma

Background: Multiple thymic squamous cell carcinoma (TSCC) is a rare thymic epithelial tumor with a dismal prognosis. Mutational profiles of multiple TSCC may expand our understanding of tumorigenesis and treatment options for these tumors.

Methods: We sequenced the whole exomes of 3 TSCC nodules from a multiple TSCC patient and a paired peripheral blood sample and identified single-nucleotide variants and small insertions and deletions, and also performed gene ontological and pathway analyses.

Results: The 3 TSCC nodules were subjected to hematoxylin-eosin staining, and the results showed that these 3 nodules were highly similar with respect to histology. We identified 116, 94 and 98 non-synonymous somatic mutations in the 3 TSCC nodules, and 34 mutations, including mutations in and , among others, were present in all 3 TSCC nodules. We then performed immunohistochemistry to assess two selected genes, and , and found that the 3 TSCC nodules expressed similar levels of and . Further gene ontological analysis and pathway analysis revealed that the 3 TSCC nodules also had similar significantly enriched pathways based on the identified genetic alterations. These results demonstrated that the 3 multiple TSCC nodules were spatially independent of each other but were highly similar with respect to histological sources and genetic characteristics, suggesting that 2 TSCC nodules were likely metastases of the third nodule.

Conclusions: These findings suggest that TSCC cells can be transferred to other sites inside the thymus and that total thymectomy is a good treatment option for thymic epithelial tumors.