The 2021 WHO Classification of Tumors of the Thymus and Mediastinum: What Is New in Thymic Epithelial, Germ Cell, and Mesenchymal Tumors?

Abstract

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.

The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors

“…An increased WHO histological grade showed more malignant behavior and was associated with a poor prognosis ( 33 ). We also reviewed our data using the new 2021 WHO histological classification and observed no change in our results because the new classification system did not affect our data on the pathological diagnosis of TETs ( 35 ).…”

Unraveling the Immune Microenvironment of Thymic Epithelial Tumors: Implications for Autoimmunity and Treatment

“…Class C essentially refers to TC and accounts for malignant aggressive neoplasms, usually of squamous differentiation, which demonstrate enhanced invasive and metastatic capacity. The B3 subtype, also termed as atypical thymoma or well-differentiated thymic carcinoma, represents an entity with an intermediate clinicopathological profile and biological characteristics, between the more benign thymomas and class C carcinomas [ 2 , 3 ]. The therapeutic approach for TETs is based predominantly on surgical resection, while platinum-based chemotherapy is the treatment of choice in advanced-stage tumors [ 4 ].…”

“…The different subtypes 2 of 11 are also associated with distinguishing differences in their malignant potential, metastatic capability and prognosis. Thus, TETs are subdivided into six categories: class A, AB, B1, B2, B3 and C (WHO 2021, 5th edition) [2,3]. Tumors of A subtypes are considered as neoplasms of a medullary phenotype, while all B subtypes originate from the thymic cortex.…”

Thymic Epithelial Neoplasms: Focusing on the Epigenetic Alterations

“…The World Health Organization (WHO) histopathological classification further subdivides thymomas into type A, type AB, type B1, type B2 and type B3 based on the morphology of epithelial tumor cells, the relative proportion of the lymphocytic component and the differentiation grade. TC are classified as type C TEN by the WHO [ 2 , 3 , 4 ].…”