BACKGROUNDAlthough the histologic classification of thymic epithelial tumors has been confusing and controversial, an agreement on the universal classification system for thymic epithelial tumors was achieved by the World Health Organization (WHO) in 1999. The authors previously reported that the WHO histologic classification system reflects invasiveness and immunologic function of thymic epithelial tumors. In this subsequent study, they examined the prognostic significance of this classification system.METHODSClinical features as well as postoperative survival of patients with thymoma, but not thymic carcinoma, were examined with reference to WHO histologic classification based on an experience with 273 patients over a 44‐year period.RESULTSThere were 18 type A tumors, 77 type AB tumors, 55 type B1 tumors, 97 type B2 tumors, and 26 type B3 tumors. In patients with type A, AB, B1, B2, and B3 tumors, the respective proportions of invasive tumor were 11.1%, 41.6%, 47.3%, 69.1%, and 84.6%; the respective proportions of tumors with involvement of the great vessels were 0%, 3.9%, 7.3%, 17.5%, and 19.2%; and the respective 20‐year survival rates were 100%, 87%, 91%, 59%, and 36%. According to the Masaoka staging system, the 20‐year survival rates were 89%, 91%, 49%, 0%, and 0% in patients with Stage I, II, III, IVa, and IVb disease, respectively. By multivariate analysis, the Masaoka staging system and the WHO histologic classification system were significant independent prognostic factors, whereas age, gender, association with myasthenia gravis, completeness of resection, or involvement of the great vessels were not significant independent prognostic factors.CONCLUSIONSThis study showed that histologic appearance reflects the oncologic behavior of thymoma when the WHO classification system is adopted. The WHO classification system may be helpful in clinical practice for the assessment and treatment of patients with thymoma. Cancer 2002;94:624–32. © 2002 American Cancer Society.DOI 10.1002/cncr.10225

This overview of the fifth edition of the WHO classification of thymic epithelial tumors (including thymomas, thymic carcinomas, and thymic neuroendocrine tumors [NETs]), mediastinal germ cell tumors, and mesenchymal neoplasms aims to (1) list established and new tumor entities and subtypes and (2) focus on diagnostic, molecular, and conceptual advances since publication of the fourth edition in 2015. Diagnostic advances are best exemplified by the immunohistochemical characterization of adenocarcinomas and the recognition of genetic translocations in metaplastic thymomas, rare B2 and B3 thymomas, and hyalinizing clear cell carcinomas. Advancements at the molecular and tumor biological levels of utmost oncological relevance are the findings that thymomas and most thymic carcinomas lack currently targetable mutations, have an extraordinarily low tumor mutational burden, but typically have a programmed death-ligand 1 high phenotype. Finally, data underpinning a conceptual advance are illustrated for the future classification of thymic NETs that may fit into the classification scheme of extrathoracic NETs. Endowed with updated clinical information and state-of-the-art positron emission tomography and computed tomography images, the fifth edition of the WHO classification of thymic epithelial tumors, germ cell tumors, and mesenchymal neoplasms with its wealth of new diagnostic and molecular insights will be a valuable source for pathologists, radiologists, surgeons, and oncologists alike. Therapeutic perspectives and research challenges will be addressed as well.

We examined the clinical and functional significance of histologic classification of thymic epithelial neoplasms proposed by the World Health Organization (WHO), based on an analysis of 146 consecutive tumors derived from 141 patients and 47 normal thymuses derived from children ranging in age from 1 to 9 years. Invasive tumors were seen in 12.5%, 38.6%, 40.0%, 69.4%, 80.0%, and 100% of type A, AB, B1, B2, B3, and C primary tumors, respectively. All of six recurrent or metastatic lesions were type B2 tumors. Myasthenia gravis was associated in 0%, 6.8%, 40.0%, 55.6%, 10.0%, and 0% in patients with type A, AB, B1, B2, B3, and C tumors, respectively. The average number (x10(6)) of tumor-associated CD4+CD8+ cells present in 1 g of tumor tissue was 1.5, 391.1, 1041.7, 333.9, 24.5, and 0.2 in type A, AB, B1, B2, B3, and C, respectively, and it was 1168.2 in the normal thymuses. Thus, type B1 tumor retained the function to induce CD4+CD8+ double-positive cells at a level comparable to that of the normal thymic cortical epithelial cells, followed by type AB and type B2 tumors. Type A and B3 tumors had this function at a barely detectable level, and type C tumor was nonfunctional. WHO histologic classification was shown to reflect the clinical features and the T-cell-inducing function of thymic epithelial tumors.