The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes

Abstract

This overview of the 4th edition of the World Health Organization (WHO) Classification of thymic tumors has two aims. First, to comprehensively list the established and new tumor entities and variants that are described in the new WHO Classification of thymic epithelial tumors, germ cell tumors, lymphomas, dendritic cell and myeloid neoplasms, and soft-tissue tumors of the thymus and mediastinum; second, to highlight major differences in the new WHO Classification that result from the progress that has been made since the 3rd edition in 2004 at immunohistochemical, genetic and conceptual levels. Refined diagnostic criteria for type A, AB, B1-B3 thymomas and thymic squamous cell carcinoma are given, and it is hoped that these criteria will improve the reproducibility of the classification and its clinical relevance. The clinical perspective of the classification has been strengthened by involving experts from radiology, thoracic surgery, and oncology; by incorporating state-of-the-art positron emission tomography/computed tomography images; and by depicting prototypic cytological specimens. This makes the thymus section of the new WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart a valuable tool for pathologists, cytologists, and clinicians alike. The impact of the new WHO Classification on therapeutic decisions is exemplified in this overview for thymic epithelial tumors and mediastinal lymphomas, and future perspectives and challenges are discussed.

Fig. 1

Images of a fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) of a 71-year-old woman with type B3 thymoma. A. Axial CT image at the level of the left main bronchus (B) demonstrates an anterior mediastinal mass (M) and low right paratracheal lympadenopathy. Infiltration of superior recess of the pericardium (arrow). B. Axial fused image at the same level demonstrates that both the primary tumor and the metastasis are FDG avid.

Fig. 2

Cytology of WHO type B2 thymoma (fine needle aspirate). Large tumor cells with elongated or round nuclei and nucleoli intermingled with small lymphocytes.

Fig. 3

Conventional type A thymoma versus atypical type A thymoma variant. A. Conventional type A thymoma exhibiting areas composed of spindle cells (upper half) and polygonal cells (lower half) separated by a broad fibrouis septum. B. and C. Atypical type A thymoma variant showing various degrees of spontaneous necrosis in polygonal cell areas. This tumor invaded the lung and showed a missense mutation (chromosome 7 c.74146970T>A) in the GTF2I gene that is common in type A thymomas but rare in type B thymomas and thymic carcinomas.

Fig. 4

Immunohistochemistry: an important tool for the diagnosis of difficult-to-classify type A versus AB thymomas. A. Abundance of TdT+ immature T cells in type AB thymoma; any such crowding of TdT+ T cells excludes the diagnosis of type A thymoma; B. Moderate numbers of TdT+ immature T cells in a spindle cell thymoma imply a diagnosis of type AB thymoma when occurring in >10% of the tumor: if occurring in ≤10% of the tumor, a diagnosis of type A thymoma should be rendered. C. Near absence of TdT+ immature T cells in type A thymoma.

Fig. 5

Immunohistochemical staining of keratin across the spectrum of type A to B3 thymomas. Of note, among the lymphocyte-rich thymomas a dense epithelial cell networks is typical of type AB and type B2 thymoma, while a delicate network is an obligatory feature of type B1 thymoma.

Fig. 6

Distinct epigenetic profile of mediastinal grey zone lymphoma (MGZL) as assessed by principal component analysis. The methylation data for 1421 CpG targets from various lymphomas and reactive tonsillar B cells (RTB) were subjected to principal component analysis and projected onto the first three principal components. MGZL has a distinct epigenetic profile intermediate between classical Hodgkin lymphoma, nodular sclerosis subtype (CHLNS) and primary mediastinal large B-cell lymphoma (PMLBCL), but different from that of diffuse large B-cell lymphoma (DLBCL) and RTB. Adapted from Haematologica, with permission.