A primary thymic adenocarcinoma with two components that traced distinct evolutionary trajectories

Even though it is a rare subtype, identifying the genetic features of thymic adenocarcinoma is valuable for a multifaceted understanding of thymic epithelial tumors. We experienced a female patient with thymic adenocarcinoma associated with thymic cysts. The tumor consisted of a solid whitish lesion (lesion‐1) and a large cystic lesion with small papillary nodules (lesion‐2). Microscopically, lesion‐1 exhibited poorly differentiated adenocarcinoma accompanying numerous inflammatory cell infiltrates, and lesion‐2 (the nodules within the cystic lesion) exhibited enteric‐type adenocarcinoma. Consistent with the histological difference, whole‐exome sequencing revealed that these two components exhibited distinct genetic features, except for only a few shared mutations, including CDKN2A truncation. Lesion‐1 exhibited microsatellite instability‐high signature with high mutation burden, for which immune checkpoint inhibitors might apply; and lesion‐2 exhibited whole‐genome doubling with KRAS hotspot mutation. Our case presents novel genetic features of thymic adenocarcinoma and demonstrates that distinct mutational processes can be operative within a single tumor.