Systemic treatment of advanced thymic malignancies.

The rarity of thymic malignancies prevents us from performing large randomized clinical trials. As a result, systemic treatment decisions are often guided by a small amount of prospective trial data, retrospective series, and individual case reports. In recent years, we have begun to unravel the molecular biology of thymic tumors. It is becoming more apparent as a result of gene expression profiling and genomic clustering studies that the subclassifications of type A, AB, B1, B2, B3, and thymic carcinoma have different molecular features that may be clinically relevant. Genomic profiling distinguishes type B3 thymoma and thymic carcinoma as distinct entities from type A and type B2 thymoma. Furthermore, type B2 thymomas can be separated from other subgroups in that it has a more distinct lymphocytic component than the other groups where epithelial cells predominate. Next generation RNA sequencing has recently identified a large microRNA cluster on chromosome 19q13.42 in types A and AB thymomas, which is absent in type B thymomas and thymic carcinomas. This cluster has been shown to result in activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway, which suggests a possible role for PI3K inhibitors in these subtypes. The presence of KIT mutations in thymic carcinomas is also well described. Herein we discuss the chemotherapeutic and targeted treatment options for advanced thymic malignancies and highlight important advances in our understanding of the molecular biology of these rare tumors.