PowerPoint-Pr

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Lymphomas in the Mediastinum
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Mediastinal Large B Cell Lymphoma
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Mediastinal Large B Cell Lymphoma
CD30
CD20
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Immunhistochemische Differentialdiagnose
Nodale Diffuse Large B Cell Lymphoma
MLBCL
CD20, CD79a

CD30, CD23 ----/


IgM, Light chain gt ----

----
CD10 gt ----
----
HLA-DR

----
Bcl-6 /-

----
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Mediastinal Large B Cell Lymphoma
Möller, WHO 2004
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Combined Hodgkin Lymphom MLBCL
CD30CD15-CD20
CD30CD15CD20-
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Hodgkin Lymphoma in a Mediastinal Lymph Node
CD30
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Hodgkin Lymphoma in the Thymus
CD30
CK19
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Pseudoepitheliomatous Hyperplasia Thymic Cysts
CK19
Search for Lymphoma, Thymoma, LCH, Metastasis,
Germ Cell Neoplasia
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Immunhistochemische Differentialdiagnose
Hodgkin Lymphoma (Classical Type usually NS)
MLBCL
CD30
gt ----
CD15 gt ----
-----
CD20 -/

CD79a ----

PanLeu (CD45) ----

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Borderline Cases between HL and Mediastinal
Large B Cell Lymphoma ?
YES !
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Distinct Gene Expression Profile of MLBCL (PMBL)
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(No Transcript)
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Survival of MLBCL (PMBL) Patients
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(No Transcript)
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Conclusions
Distinct gene expression profile of PMBL
(molecular diagnosis) PMBL patients are
clinically distinct Close Relationship of PMBL
to Hodgkin Lymphoma
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DD between MLBCL and ALCL
CD3
ALK-1
CD30
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Immunohistochemical Differential Diagnosis
Anaplastic Large Cell Lymphoma
MLBCL
CD30
gt ----
CD15 ----
-----
CD20, CD79a ----

CD3, CD5, CD43, TIA-1 -/
-----
ALK-1 -/
-----
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T-LBL des Thymus
Infiltration of Mediastinum Heart Pleural
Effusions /- Leukemia
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Differential Diagnosis of B1/B2Thymom vs. T-LBL
Thymom
T-LBL
Cytokeratin 19
CD1a
Ki67
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DD of Strongly Proliferative Mediastinal Processes
Thymus
T-LBL
Thymoma
Ki67 not different between Normal Thymus, Thymoma
and T-LBL
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Lymphocyte Differentiation in the Thymus
WHO, 2004
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If there is no Abnormal Phenotype of Immature T
cells Loss of CD1a, CD3, CD4, CD5,
CD8 Overexpression of CD34 gt CD10
JH-PCR is monoclonal in 80 of T-LBL Cases
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42 Year-old Patient with Sjogrens Syndrome
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(No Transcript)
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No Cortico-medullary Differentiation, No Capsule
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Germinal Center
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MALT Lymphoma of the Thymus
CD20, CD5-, CD10-, CD23-
k
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Lymphoepithelial Lesions in MALT-Lymphoma of the
Thymus
Cytokeratin 19
LEL
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78 year-old Female, No Symptoms, Progressibe
Lymphocytosis
Mediastinal Mass
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What is Different Compared to the Previous Case?
HC
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No Germinal Centers !
HC
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Cytokeratin 19
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CD3, TdT(-)
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Ki67 10
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Diagnosis T-Prolymphocytic Leukemia (TPLL)
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Conclusion All Peripheral Lymphomas Can Occur in
the Mediastinum
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Clinical Relevance of the New WHO Classification?
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Therapeutic Decisions in Thymoma Patients
a) Masaoka Stage
b) WHO Histotype
c) Resection status
1,0
p lt 0.05
Stage 1
1,0
Type A, AB, B1
,9
,9
Stage 3
,8
,8
Probability of Survival
Probability of Survival
Probability of Survival
R0 resection
Stage 2
,7
,7
,6
Type B2
,6
,5
Type B3
,5
R 12 resection
Type C
,4
Stage 4
,3
,4
30
20
10
0
30
20
10
0
30
20
10
0
Survival (Years)
Survival (Years)
Survival (Years)
JCO
Cancer, 2003 J Clin Oncol, 2004
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Therapeutic Decisions in Thymoma Patients
Histology
Stage
OP, RX CHEM
Resection Status
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Therapeutic Decisions in Thymoma Patients
A, AB, B1 Thymome (50)
B2, B3 Thymomas Thymic Carcinomas (50)
Surgery
Surgery (RO)
Stage III/IV R1, R2
Stage II
Stage I
Wait-and-See
WS ? Rx
Rx
CHEMO Rx
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C-KIT Expression in Thymic Carcinoma
0/112 Type A-B2 1/28 Type B3 19/24
SCC
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Type B3 thymoma
Type B2 thymoma
TSCC KITMUT
TSCC KITWT-1
TSCC KITWT-2
TSCC KITWT-3
TSCC 5
TSCC 6
GIST
Responder Patient B., A.
KIT()
KIT(-)
GIST
100
100
c-KIT
phospho-c-KIT
100
100
phospho-AKT
1
20
phospho-BAD
5
10
phospho-MAPK (p42p44)
1
100
phospho-STAT-1
1
phospho-STAT-3
Immunohistochemistry CD117
N.E.J.Med. 2004
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Imatinib (-)
Imatinib ()
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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

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Acknowledgements
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) Wilfrie
d Nix (Mainz) Berthold Schalke (Regensburg) Reinha
rd Kiefer (Münster) Michael Semik
(Münster) Francesco Scaravilli (London) Nick
Willcox, Angela Vincent (Oxford) Pärt Peterson
(Tartu)
DFG
Deutsche Krebshilfe
EU THYMAIDE
Alexander von Humboldt Foundation