Molecular pathology of thymoma and thymic carcinoma

Abstract

Thymic epithelial tumors (TETs) comprise a heterogeneous group of epithelial-derived thymic neoplasms with diverse clinical behavior and underlying molecular genetic features. Owing to their rare nature, the molecular classification of TETs has only recently begun to be fully explored. The advent of advanced molecular studies, particularly the ability to sequence the DNA and RNA of tumors in a massively parallel fashion, has led to an increased understanding of the molecular underpinnings of thymic neoplasia. Thymomas, characterized by a heterogeneous group of molecular alterations, tend to have low mutational burdens and various copy number abnormalities including a characteristic loss of chromosomal material in the region of 6q25.2-p25.3, a recurrent, specific point mutation GTF2I p.L424H, and specific expression of certain microRNAs. Thymic carcinomas, in contrast, are generally characterized by increased tumor mutational burdens, multiple copy number alterations, and varied, non-recurrent, somatic mutations. Advances in molecular knowledge of TETs allow for more precise molecular classification of these tumors, and the presence of specific alterations aids in the diagnosis of borderline lesions. In the future, additional molecular studies will better delineate the molecular landscape of these tumors and may one day allow for more targeted treatment algorithms. This review aims to cover the current understanding of the molecular alterations thus far identified in thymomas and thymic carcinomas.