Challenges and Controversies in the Diagnosis and Management of Thymic Epithelial Tumors from the Thymic Tumor Subcommittee of the International Association for the Study of Lung Cancer Rare Tumors Committee.

Thymic epithelial tumors (TETs), comprising thymomas, thymic carcinomas, and thymic neuroendocrine neoplasms, are rare prevascular (anterior) mediastinal malignancies characterized by histologic and clinical heterogeneity. Their management is complex because of overlapping pathologic features, variable clinical behavior, frequent associations with autoimmune conditions, and lack of standardized therapeutic algorithms. This review addresses current challenges across the diagnosis, management, and treatment of TETs. We outline diagnostic difficulties, including distinguishing TETs from histologic mimickers, and highlight the utility of immunohistochemical and molecular markers. Surgical considerations for early-stage disease are explored, debating thymomectomy versus complete thymectomy and optimal minimally invasive approaches, while also discussing the role of lymph node dissection and adjuvant therapy. Furthermore, this review delves into the evolving roles of immunotherapy and targeted therapy in TETs, acknowledging their potential while addressing challenges such as high rates of autoimmune disease recurrence and adverse events. The promising, albeit largely retrospective, applications of artificial intelligence in TETs, spanning diagnosis, target discovery, and prognostic modeling, are also explored as a critical area for future integration into clinical practice.