The Morphologic Spectrum of Mediastinal Yolk Sac Tumors: Diagnostic Challenges and Pitfalls

Pure mediastinal yolk sac tumor is an uncommon and aggressive malignant germ cell neoplasm that presents considerable diagnostic difficulties owing to its pronounced clinical and morphological variability. Mediastinal yolk sac tumors, in contrast to their gonadal equivalents, typically occur at later stages, are typically associated with mixed germ cell components, and have a diverse array of histologic patterns that may resemble both germ cell and somatic malignancies. Accurate identification of these types of cancer is essential since diagnostic misclassification may significantly impact treatment and prognosis. This review provides a comprehensive overview of the morphologic spectrum of mediastinal yolk sac tumor, with emphasis on both classic and variant histologic patterns, including reticular, solid, glandular, papillary, hepatoid, and other less common growth forms. The immunohistochemical correlations of these patterns and their role in resolving diagnostic dilemmas are discussed, along with key differential diagnoses encountered in small mediastinal biopsy specimens. Particular attention is given to the limitations of limited tissue sampling, the impact of post-chemotherapy morphologic changes, and the potential for misinterpretation in this challenging anatomic site. By integrating morphologic features with clinical, radiologic, and laboratory findings, this review aims to enhance diagnostic accuracy and improve recognition of mediastinal yolk sac tumor across its diverse presentations.