Thymic epithelial tumors account for approximately 20% of all mediastinal tumors. Nevertheless, they are rare compared with other malignancies, constituting only 0.2% to 1.5% of all solid tumors.1 The WHO classification system distinguishes thymomas (types A, AB, B1, B2, and B3) from thymic carcinomas (type C) based on the morphology of epithelial tumor cells (with increasing degree of atypia along the spectrum from type A to C), proportion of lymphocytic involvement, and resemblance to normal thymic tissue. Clinically, these diseases can also present differently with a large variety of autoimmune disorders, including myasthenia gravis (30%) occurring in patients with thymoma, whereas patients with thymic carcinoma rarely if ever have autoantibody-induced phenomena.2 Surgery continues to be the most important therapeutic modality for early-stage disease, and a multidisciplinary approach incorporating surgery, radiation, and chemotherapy is recommended in advanced or recurrent disease. Research, however, has been hampered by the rarity of these tumors, which has led to a lack of international consensus surrounding appropriate histopathologic and staging criteria. Much debate has occurred regarding the limitations of the current histologic classifications with regard to both subtype definitions and consistency of diagnosis. The lack of established cell lines and animal models has hindered laboratory investigations, resulting in limited improvements in understanding of tumor biology. In the past decade, newer techniques such as comparative genomic hybridization (CGH), expression array analysis, and next-generation sequencing have resulted in incremental improvements in the understanding of these highly heterogenous tumors. This article focuses on the biological differences between thymomas and thymic carcinomas that may impact treatment decisions, and discusses targeted therapy trials performed to date in the advanced disease setting.
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