Establishing the diagnosis of mediastinal tumors is viewed as challenging. Why? One reason is that these are relatively rare conditions, meaning that very few physicians have a large experience. This is compounded by the fact that the number of different tumors and conditions is large, thus further segmenting mediastinal tumors into multiple even smaller subgroups. Furthermore, the fundamental nature of mediastinal lesions is quite varied, ranging from fulminant to indolent malignant tumors and from benign conditions with little impact on a patient’s life to life-threatening benign lesions. In addition, the features of a mediastinal lesion that are most useful to suggesting or establishing a diagnosis vary, including clinical presentation, imaging characteristics, and microscopic appearance. There is a strong need from a management perspective to establish the diagnosis with a reasonable degree of confidence before a treatment intervention, yet the optimal approach to obtaining tissue is varied and depends on the suspected diagnosis. Finally, most clinicians lack a structure of how to approach mediastinal tumors, and often explore various avenues (i.e., imaging, biopsy) without a clear understanding of what is at the top of their differential diagnosis list and their rationale for a particular approach (e.g., liquid vs. tissue biopsy).

A structure for approaching mediastinal lesions has been proposed by the International Thymic Malignancy Interest Group (ITMIG), a global multispecialty organization devoted to promoting medical science regarding mediastinal tumors in general, not only thymic tumors [1, 2]. This begins with basic patient characteristics that are known (age, sex), which already focus the differential diagnosis. Sometimes there are particular features that establish a diagnosis with a high degree of certainty (e.g., imaging features that are diagnostic for a substernal goiter or a benign teratoma, the presence of myasthenia gravis or other thymic paraneoplastic syndromes in a patient over 40 with an anterior mediastinal mass). In such cases a biopsy is usually not needed.

More often, a combination of clinical, imaging, and histologic information is needed to establish a diagnosis. The prioritization of the differential diagnosis list, and the relative impact of clinical, imaging and histologic information varies depending on aspects of the case. This highlights the importance of approaching these patients in a multidisciplinary fashion. Unless there are pathognomonic features as mentioned above, a discussion between the clinician, radiologist, and pathologist is tremendously beneficial in aggregating the information, narrowing the diagnostic question, and pointing out the best way to confirm suspected conditions.