Background/Objectives: Mediastinal tumors, regardless of their location, can grow to significant sizes, causing compression-related symptoms. The term “giant” mediastinal tumor is inconsistently defined in the literature. This study presents a new clinical–radiological classification (CRC) for mediastinal tumors and evaluates its applicability through a systematic review and a detailed case analysis of a giant thymolipoma. Methods: A systematic review of the literature from the past decade was conducted using PubMed to identify relevant studies on “giant” mediastinal tumors. The inclusion criteria focused on studies involving adult patients with documented tumor size and symptomatology. The review identified 22 studies, with most anterior mediastinal tumors classified as CRC 3 (81%), indicating “giant” tumors. Thymolipomas accounted for 58% of these cases. Tumor volume and weight correlated with symptom severity, guiding surgical approaches. The proposed CRC effectively standardized the definition of “giant” tumors. The case analysis of a 6.84 kg thymolipoma highlighted the challenges of surgical resection, confirming the importance of tailored surgical strategies for large tumors. Conclusions: The novelty of the study lies mainly in the new clinical–radiological classification (CRC) of mediastinal tumors. This classification integrates clinical presentation and cross-sectional imaging findings, offering a standardized framework for tumor reporting. In addition, it provides a precise definition of “giant” mediastinal tumors. The findings emphasize the need for early surgical intervention to prevent severe symptoms and complications. This study also showcases the largest enbloc-resected thymolipoma reported in the recent literature, supporting the utility of the proposed classification in clinical practice.
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