1. Lymphomas in the Mediastinum

2. Mediastinal Large B Cell Lymphoma

3. CD20 CD30

4. Immunhistochemische Differentialdiagnose Nodale Diffuse Large B Cell Lymphoma MLBCL CD20, CD79a +++ +++ IgM, Light chain ++ > ---- CD10 ++ > ---- ---- HLA-DR +++ Bcl-6 +++/- CD30, CD23 ----/+ ---- +++

5. Möller, WHO 2004 Mediastinal Large B Cell Lymphoma

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

7. Hodgkin Lymphoma in a Mediastinal Lymph Node CD30

8. Hodgkin Lymphoma in the Thymus CD30CK19

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

10. Immunhistochemische Differentialdiagnose Hodgkin Lymphoma (Classical Type; usually NS) MLBCL CD30 +++ +++ > ---- CD15 + > ---- ----- CD20 -/+ +++ CD79a ---- +++ PanLeu (CD45) ---- +++

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

12. Distinct Gene Expression Profile of MLBCL (PMBL)

14. Survival of MLBCL (PMBL) Patients

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

17. DD between MLBCL and ALCL CD3 CD30 ALK-1

18. Immunohistochemical Differential Diagnosis Anaplastic Large Cell Lymphoma MLBCL CD30 +++ +++ > ---- CD15 ---- ----- CD20, CD79a ---- +++ CD3, CD5, CD43, TIA-1 -/++ ----- ALK-1 - /++ -----

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

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

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

22. Lymphocyte Differentiation in the Thymus WHO, 2004

23. 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

24. 42 Year-old Patient with Sjogren‘s Syndrome

26. No Cortico-medullary Differentiation, No Capsule

27. Germinal Center

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

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

30. 78 year-old Female, No Symptoms, Progressibe Lymphocytosis Mediastinal Mass

31. HC What is Different Compared to the Previous Case?

32. HC No Germinal Centers !

33. Cytokeratin 19

34. CD3+, TdT(-)

35. Ki67 ~10%

36. Diagnosis : T-Prolymphocytic Leukemia (TPLL)

37. Conclusion All Peripheral Lymphomas Can Occur in the Mediastinum

38. Clinical Relevance of the New WHO Classification?

39. Probability of Survival 1,0,9,8,7,6,5,4 3020100 Stage 1 Stage 2 Stage 3 Stage 4 Survival (Years) 3020100 1,0,9,8,7,6 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 3020100 1,0,9,8,7,6,5,4,3 p < 0.05 R0 resection R 1+2 resection c) Resection status Probability of Survival Survival (Years)

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

41. 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

42. 0/112 Type A-B2 1/28 Type B3 19/24 SCC ABA B2B3SCC C-KIT Expression in Thymic Carcinoma

43. 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 CD117 100 1 5 1 GIST 1 Responder Patient B., A. 100 20 10 100 N.E.J.Med. 2004

44. Imatinib (-)Imatinib (+)

45. 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

46. 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