Diagnostic Challenges in Fine-Needle Aspiration Cytology of Mediastinal Tumors and Lesions

Context.--Mediastinal tumors/lesions are frequently encountered in daily cytopathology practice. These lesions are accessible through endoscopic/endobronchial ultrasound-guided or computed tomography-guided fine-needle aspiration cytology and represent a wide range of primary and metastatic tumors. This often poses diagnostic challenges because of the complexity of the mediastinal anatomic structures. Tumors metastatic to mediastinal lymph nodes represent the most common mediastinal lesions and must be differentiated from primary lesions. Objective.--To provide an updated review on the fine-needle aspiration cytology of mediastinal tumors/lesions, with an emphasis on diagnostic challenges. This review encompasses thymic epithelial neoplasms, mediastinal lymphoproliferative disorders, germ cell tumors, neuroendocrine tumors, soft tissue tumors, and metastatic tumors. Differential diagnoses; useful ancillary studies, including targeted immunohistochemical panels; and diagnostic pitfalls are discussed. Data Sources.--Data were gathered from a PubMed search of peer-reviewed literature on mediastinal tumors. Data were also collected from the authors' own practices. Conclusions.--Fine-needle aspiration cytology plays a vital role in evaluation of mediastinal lesions. Being familiar with the clinical and cytomorphologic features of these lesions, appropriately triaging the diagnostic material for ancillary testing, and correlating with radiologic findings are important in arriving at correct diagnoses and guiding management. (Arch Pathol Lab Med. 2022;146:960-974; doi: 10.5858/arpa.2021-0108-RA)