Lymphomas in the Mediastinum

Mediastinal Large B Cell Lymphoma

CD20 CD30

Immunhistochemische Differentialdiagnose Nodale Diffuse Large B Cell Lymphoma MLBCL CD20, CD79a IgM, Light chain ++ > ---- CD10 ++ > HLA-DR +++ Bcl-6 +++/- CD30, CD /

Möller, WHO 2004 Mediastinal Large B Cell Lymphoma

Combined Hodgkin Lymphom & MLBCL CD30+CD15+CD20- CD30+CD15-CD20+

Hodgkin Lymphoma in a Mediastinal Lymph Node CD30

Hodgkin Lymphoma in the Thymus CD30CK19

Pseudoepitheliomatous Hyperplasia & Thymic Cysts Search for Lymphoma, Thymoma, LCH, Metastasis, Germ Cell Neoplasia

Immunhistochemische Differentialdiagnose Hodgkin Lymphoma (Classical Type; usually NS) MLBCL CD > ---- CD15 + > CD20 -/+ +++ CD79a PanLeu (CD45)

Borderline Cases between HL and Mediastinal Large B Cell Lymphoma ? YES !

Distinct Gene Expression Profile of MLBCL (PMBL)

Survival of MLBCL (PMBL) Patients

Conclusions Distinct gene expression profile of PMBL (molecular diagnosis) PMBL patients are clinically distinct Close Relationship of PMBL to Hodgkin Lymphoma

DD between MLBCL and ALCL CD3 CD30 ALK-1

Immunohistochemical Differential Diagnosis Anaplastic Large Cell Lymphoma MLBCL CD > ---- CD CD20, CD79a CD3, CD5, CD43, TIA-1 -/ ALK-1 - /

T-LBL des Thymus Infiltration of Mediastinum & Heart; Pleural Effusions; +/- Leukemia

Differential Diagnosis of B1/B2Thymom vs. T-LBL Thymom T-LBL Cytokeratin 19CD1aKi67

ThymusT-LBLThymoma DD of Strongly Proliferative Mediastinal Processes Ki67 not different between Normal Thymus, Thymoma and T-LBL

Lymphocyte Differentiation in the Thymus WHO, 2004

If there is no Abnormal Phenotype of Immature T cells Loss of CD1a, CD3, CD4, CD5, CD8 Overexpression of CD34 > CD10 JH-PCR is monoclonal in ~ 80% of T-LBL Cases

42 Year-old Patient with Sjogren‘s Syndrome

No Cortico-medullary Differentiation, No Capsule

Germinal Center

MALT Lymphoma of the Thymus CD20+, CD5-, CD10-, CD23- 

Cytokeratin 19 LEL Lymphoepithelial Lesions in MALT-Lymphoma of the Thymus

78 year-old Female, No Symptoms, Progressibe Lymphocytosis Mediastinal Mass

HC What is Different Compared to the Previous Case?

HC No Germinal Centers !

Cytokeratin 19

CD3+, TdT(-)

Ki67 ~10%

Diagnosis : T-Prolymphocytic Leukemia (TPLL)

Conclusion All Peripheral Lymphomas Can Occur in the Mediastinum

Clinical Relevance of the New WHO Classification?

Probability of Survival 1,0,9,8,7,6,5, Stage 1 Stage 2 Stage 3 Stage 4 Survival (Years) ,0,9,8,7,6 Probability of Survival Survival (Years) a) Masaoka Stageb) WHO Histotype Type A, AB, B1 Type B2 Type B3 Type C JCO Cancer, 2003; J Clin Oncol, 2004 Therapeutic Decisions in Thymoma Patients ,0,9,8,7,6,5,4,3 p < 0.05 R0 resection R 1+2 resection c) Resection status Probability of Survival Survival (Years)

HistologyStage Resection Status OP, RX CHEM Therapeutic Decisions in Thymoma Patients

A, AB, B1 Thymome (50%) B2, B3 Thymomas & Thymic Carcinomas (50%) Wait-and-See Surgery (RO) Surgery Stage I Stage II Stage III/IV R1, R2 W&S ? Rx CHEMO & Rx Therapeutic Decisions in Thymoma Patients

0/112 Type A-B2 1/28 Type B3 19/24 SCC ABA B2B3SCC C-KIT Expression in Thymic Carcinoma

Type B3 thymomaType B2 thymoma GIST TSCC KIT MUT TSCC KIT WT -1TSCC KIT WT -2TSCC KIT WT -3 TSCC 5TSCC 6 phospho-MAPK (p42+p44) c-KIT phospho-c-KIT phospho-AKT phospho-BAD phospho-STAT-1 phospho-STAT-3 KIT(+)KIT(-) Immunohistochemistry CD GIST 1 Responder Patient B., A N.E.J.Med. 2004

Imatinib (-)Imatinib (+)

Summary The new WHO Thymoma Classification describes histological, genetic und clinical entities In addition to tumor stage and resection status, the histological thymoma subtype according to WHO criteria contributes significantly to therapeutic decisions in thymoma patients Type A, AB and probably B1 thymomas even at stage II do not require any adjuvant treatment after R0-Resection

Philipp Ströbel (all in Würzburg) Masayoshi Inoue & W.-Y. Chuang Andreas Zettl Hans Konrad Müller-Hermelink European Thymoma Network Peter Rieckmann (Würzburg) Ralf Gold (Göttingen) Wilfried Nix (Mainz) Berthold Schalke (Regensburg) Reinhard Kiefer (Münster) Michael Semik (Münster) Francesco Scaravilli (London) Nick Willcox, Angela Vincent (Oxford) Pärt Peterson (Tartu) Acknowledgements DFG Deutsche Krebshilfe EU THYMAIDE Alexander von Humboldt Foundation