Despite their rarity, thymic epithelial tumors (TETs) have attracted much interest over the years, leading to an impressive number of histological and staging classifications. At present, TETs are divided by the WHO classification into four main subtypes: type A, type AB, and type B thymomas (subdivided into B1, B2, and B3), and thymic carcinomas, going from the more indolent to the most aggressive ones. Among many debated staging proposals, the TNM and the Masaoka-Koga staging systems have been widely accepted and used in routine practice. The four-tiered histological classification is symmetrically mirrored by the molecular subgrouping of TETs, which identifies an A-like and an AB-like cluster, with frequent GTF2I and HRAS mutations; an intermediate B-like cluster, with a T-cell signaling profile; and a carcinoma-like cluster comprising thymic carcinomas with frequent CDKN2A and TP53 alterations and a high tumor molecular burden. Molecular investigations have opened the way to tailored therapies, such as tyrosine kinase inhibitors targeting KIT, mTOR, and VEGFR, and immune-checkpoints that have been adopted as second-line systemic treatments. In this review, we discuss the crucial events that led to the current understanding of TETs, while disclosing the next steps in this intriguing field.
Keywords: classification; history; staging; therapy; thymic carcinoma; thymic epithelial tumors; thymoma.