Lymphomas

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lymphoma;TUMOR

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Lymphomas

  1. 1. Lymphomas in the Mediastinum
  2. 2. Mediastinal Large B Cell Lymphoma
  3. 3. Mediastinal Large B Cell LymphomaCD20 CD30
  4. 4. Immunhistochemische Differentialdiagnose Nodale Diffuse MLBCL Large B Cell LymphomaCD20, CD79a +++ +++CD30, CD23 ----/+ +++IgM, Light chain ++ > ---- ----CD10 ++ > ---- ----HLA-DR +++ ----Bcl-6 +++/- ----
  5. 5. Mediastinal Large B Cell Lymphoma Möller, WHO 2004
  6. 6. Combined Hodgkin Lymphom & MLBCL CD30+CD15-CD20+CD30+CD15+CD20-
  7. 7. Hodgkin Lymphoma in a Mediastinal Lymph Node CD30
  8. 8. Hodgkin Lymphoma in the ThymusCD30 CK19
  9. 9. Pseudoepitheliomatous Hyperplasia & Thymic Cysts CK19Search for Lymphoma, Thymoma, LCH, Metastasis, Germ Cell Neoplasia
  10. 10. Immunhistochemische Differentialdiagnose Hodgkin Lymphoma MLBCL (Classical Type; usually NS)CD30 +++ +++ > ----CD15 + > ---- -----CD20 -/+ +++CD79a ---- +++PanLeu (CD45) ---- +++
  11. 11. Borderline Casesbetween HL and Mediastinal Large B Cell Lymphoma ? YES !
  12. 12. Distinct Gene Expression Profile of MLBCL (PMBL)
  13. 13. Survival of MLBCL (PMBL) Patients
  14. 14. ConclusionsDistinct gene expression profile of PMBL(molecular diagnosis)PMBL patients are clinically distinctClose Relationship of PMBL to HodgkinLymphoma
  15. 15. DD between MLBCL and ALCL CD3 CD30 ALK-1
  16. 16. Immunohistochemical Differential Diagnosis Anaplastic Large Cell MLBCL LymphomaCD30 +++ +++ > ----CD15 ---- -----CD20, CD79a ---- +++CD3, CD5, CD43, TIA-1 -/++ -----ALK-1 -/++ -----
  17. 17. T-LBL des ThymusInfiltration of Mediastinum & Heart; Pleural Effusions; +/- Leukemia
  18. 18. Differential Diagnosis of B1/B2Thymom vs. T-LBL Thymom T-LBL Cytokeratin 19 CD1a Ki67
  19. 19. DD of Strongly Proliferative Mediastinal Processes Thymus Thymoma T-LBLKi67 not different between Normal Thymus, Thymoma and T-LBL
  20. 20. Lymphocyte Differentiation in the Thymus WHO, 2004
  21. 21. 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
  22. 22. 42 Year-old Patient with Sjogren‘s Syndrome
  23. 23. No Cortico-medullary Differentiation, No Capsule
  24. 24. Germinal Center
  25. 25. MALT Lymphoma of the ThymusCD20+, CD5-, CD10-, CD23- κ
  26. 26. Lymphoepithelial Lesions in MALT-Lymphoma of the Thymus Cytokeratin 19 LEL
  27. 27. 78 year-old Female, No Symptoms, Progressibe Lymphocytosis Mediastinal Mass
  28. 28. What is Different Compared to the Previous Case? HC
  29. 29. No Germinal Centers !HC
  30. 30. Cytokeratin 19
  31. 31. CD3+, TdT(-)
  32. 32. Ki67 ~10%
  33. 33. Diagnosis : T-Prolymphocytic Leukemia (TPLL)
  34. 34. ConclusionAll Peripheral Lymphomas Can Occur in the Mediastinum
  35. 35. Clinical Relevance of the New WHO Classification?
  36. 36. Therapeutic Decisions in Thymoma Patients a) Masaoka Stage b) WHO Histotype c) Resection status 1,0 1,0 Stage 1 1,0 p < 0.05 Type A, AB, B1 ,9 Probability of Survival Probability of SurvivalProbability of Survival ,9 Stage 3 ,9 ,8 ,8 Stage 2 ,7 R0 resection ,7 ,8 ,6 Type B2 ,6 ,5 ,7 Type B3 ,5 ,4 R 1+2 resection Type C Stage 4 ,4 ,6 ,3 0 10 20 30 0 10 20 30 0 10 20 30 Survival (Years) Survival (Years) Survival (Years) JCO Cancer, 2003; J Clin Oncol, 2004
  37. 37. Therapeutic Decisions in Thymoma Patients Stage Histology OP, RX CHEM Resection Status
  38. 38. Therapeutic Decisions in Thymoma Patients A, AB, B1 B2, B3 Thymomas &Thymome (50%) Thymic Carcinomas (50%)Surgery (RO) Surgery Stage I Stage II Stage III/IV R1, R2Wait-and-See W&S ? Rx CHEMO Rx & Rx
  39. 39. C-KIT Expression in Thymic Carcinoma A ABB2 B3 SCC0/112 Type A-B2 1/28 Type B3 19/24 SCC
  40. 40. ma ma mo mo 1 2 3 T WT - WT - WT - MU thy thy T T IT IT KI KI CK CK B3 B2 5 6 CC CC CC CC ST pe pe C C Responder TS TS TS TS TS TS Ty Ty GI KIT(+) KIT(-)GIST Patient B., A. 100 c-KIT 100 phospho-c-KIT100 phospho-AKT 100 1 phospho-BAD 20 5 phospho-MAPK (p42+p44) 10 1 phospho-STAT-1 1001 phospho-STAT-3 Immunohistochemistry CD117 N.E.J.Med. 2004
  41. 41. Imatinib (-) Imatinib (+)
  42. 42. 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
  43. 43. AcknowledgementsPhilipp Ströbel (all in Würzburg) DFGMasayoshi Inoue & W.-Y. ChuangAndreas Zettl DeutscheHans Konrad Müller-Hermelink KrebshilfeEuropean Thymoma NetworkPeter Rieckmann (Würzburg)Ralf Gold (Göttingen) EUWilfried Nix (Mainz) THYMAIDEBerthold Schalke (Regensburg)Reinhard Kiefer (Münster)Michael Semik (Münster)Francesco Scaravilli (London)Nick Willcox, Angela Vincent (Oxford) AlexanderPärt Peterson (Tartu) von Humboldt Foundation

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