Morphologic Changes in the Thymus Following Chemotherapy for Anterior Mediastinal Germ Cell Tumors: A Study of 91 Cases Emphasizing Pseudoneoplastic Features

Abstract

Context: The interpretation of postchemotherapy resections of anterior mediastinal germ cell tumors plays a critical role in determining future patient management and prognosis. Treatment-related changes in the thymus may mimic residual teratoma or microcystic-pattern yolk sac tumor. There is limited extant information concerning therapy-related pseudoneoplastic thymic alterations. Objective: To provide diagnostic assistance to distinguish nonneoplastic thymic abnormalities secondary to chemotherapy from residual germ cell tumor. Design: We retrospectively reviewed 91 resections of primary anterior mediastinal germ cell tumors with recognizable thymic gland following cisplatin-based chemotherapy. Results: The cohort included 90 men and 1 woman (median age, 29 years). A spectrum of thymic epithelial alterations occurred, including cystic change (macrocysts [n = 21] or microcysts [n = 20]); hyperplasia with reactive atypia (n = 8); ciliated, mucinous, or columnar cell metaplasia (n = 3); and mature squamous metaplasia (n = 2). These changes were similar to so-called acquired multilocular thymic cysts, were often contiguous with and adjacent to normal thymic epithelium, and lacked the neoplastic-type atypia seen in teratomatous elements in this setting. In 1 case, confluent microcysts closely mimicked the appearance of yolk sac tumor but lacked other distinctive features of that neoplasm and its characteristic immunoreactivity. Conclusions: Recognition of therapy-induced thymic changes is important to avoid misinterpretation as residual teratoma or yolk sac tumor. Continuity with and proximity to benign thymic epithelium, absence of neoplastic-type atypia, and awareness of this phenomenon are important in avoiding this pitfall.