lymphoma;TUMOR

1. Lymphomas in the Mediastinum

2. Mediastinal Large B Cell Lymphoma

3. Mediastinal Large B Cell Lymphoma
CD20 CD30

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

5. Mediastinal Large B Cell Lymphoma
Möller, WHO 2004

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
CD30 CK19

9. Pseudoepitheliomatous Hyperplasia & Thymic Cysts
CK19
Search for Lymphoma, Thymoma, LCH, Metastasis, Germ Cell Neoplasia

10. Immunhistochemische Differentialdiagnose
Hodgkin Lymphoma MLBCL
(Classical Type; usually NS)
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 MLBCL
Lymphoma
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 19 CD1a Ki67

21. DD of Strongly Proliferative Mediastinal Processes
Thymus Thymoma T-LBL
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- κ

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

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

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

32. No Germinal Centers !
HC

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. 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 Survival
Probability 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

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

41. 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, R2
Wait-and-See
W&S ? Rx CHEMO
Rx & Rx

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

43. 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-KIT
100 phospho-AKT 100
1 phospho-BAD 20
5 phospho-MAPK (p42+p44) 10
1 phospho-STAT-1 100
1 phospho-STAT-3
Immunohistochemistry
CD117
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. Acknowledgements
Philipp Ströbel (all in Würzburg) DFG
Masayoshi Inoue & W.-Y. Chuang
Andreas Zettl Deutsche
Hans Konrad Müller-Hermelink Krebshilfe
European Thymoma Network
Peter Rieckmann (Würzburg)
Ralf Gold (Göttingen) EU
Wilfried Nix (Mainz) THYMAIDE
Berthold Schalke (Regensburg)
Reinhard Kiefer (Münster)
Michael Semik (Münster)
Francesco Scaravilli (London)
Nick Willcox, Angela Vincent (Oxford) Alexander
Pärt Peterson (Tartu) von Humboldt
Foundation