Alexander Marx, MD, John K. C

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The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes Alexander Marx, MD, John K.C. Chan, MD, Jean-Michel Coindre, MD, Frank Detterbeck, MD, Nicolas Girard, MD, PhD, Nancy L. Harris, MD, Elaine S. Jaffe, MD, Michael O. Kurrer, MD, Edith M. Marom, MD, Andre L. Moreira, MD, Kiyoshi Mukai, MD, Attilio Orazi, MD, Philipp Ströbel, MD Journal of Thoracic Oncology Volume 10, Issue 10, Pages 1383-1395 (October 2015) DOI: 10.1097/JTO.0000000000000654 Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 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 lymphadenopathy. Infiltration of superior recess of the pericardium is indicated by arrow. B. Axial fused image at the same level demonstrates that both the primary tumor and the metastasis are FDG avid. Journal of Thoracic Oncology 2015 10, 1383-1395DOI: (10.1097/JTO.0000000000000654) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Cytology of World Health Organization (WHO) type B2 thymoma (fine needle aspirate). Large tumor cells with elongated or round nuclei and nucleoli intermingled with small lymphocytes. Journal of Thoracic Oncology 2015 10, 1383-1395DOI: (10.1097/JTO.0000000000000654) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 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 fibrous 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.22 Journal of Thoracic Oncology 2015 10, 1383-1395DOI: (10.1097/JTO.0000000000000654) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 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 more than 10% of the tumor, if occurring in less than or equal to 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. Journal of Thoracic Oncology 2015 10, 1383-1395DOI: (10.1097/JTO.0000000000000654) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 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, whereas a delicate network is an obligatory feature of type B1 thymoma. Journal of Thoracic Oncology 2015 10, 1383-1395DOI: (10.1097/JTO.0000000000000654) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 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 (PMBL), but different from that of diffuse large B-cell lymphoma (DLBCL) and RTB. Adapted from Eberle et al.75 with permission. Journal of Thoracic Oncology 2015 10, 1383-1395DOI: (10.1097/JTO.0000000000000654) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions