Lymphomas in the Mediastinum. Mediastinal Large B Cell Lymphoma.
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Transcript of Lymphomas in the Mediastinum. Mediastinal Large B Cell Lymphoma.
![Page 1: Lymphomas in the Mediastinum. Mediastinal Large B Cell Lymphoma.](https://reader036.fdocuments.in/reader036/viewer/2022081512/56649c7e5503460f9493340c/html5/thumbnails/1.jpg)
Lymphomas in the Mediastinum
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Mediastinal Large B Cell Lymphoma
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Mediastinal Large B Cell Lymphoma
CD20 CD30
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Immunhistochemische Differentialdiagnose
Nodale DiffuseLarge B Cell Lymphoma
MLBCL
CD20, CD79a +++ +++
IgM, Light chain ++ > ----
CD10 ++ > ---- ----
HLA-DR +++
Bcl-6 +++/-
CD30, CD23 ----/+
----
----
----
+++
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Möller, WHO 2004
Mediastinal Large B Cell Lymphoma
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Combined Hodgkin Lymphom & MLBCL
CD30+CD15+CD20-
CD30+CD15-CD20+
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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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CK19
Pseudoepitheliomatous Hyperplasia & Thymic Cysts
Search for Lymphoma, Thymoma, LCH, Metastasis, Germ Cell Neoplasia
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Immunhistochemische Differentialdiagnose
Hodgkin Lymphoma(Classical Type; usually NS)
MLBCL
CD30 +++ +++ > ----
CD15 + > ---- -----
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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Survival of MLBCL (PMBL) Patients
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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 CD30 ALK-1
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Immunohistochemical Differential Diagnosis
Anaplastic Large Cell Lymphoma
MLBCL
CD30 +++ +++ > ----
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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Thymus T-LBLThymoma
DD of Strongly Proliferative Mediastinal Processes
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 > CD10
JH-PCR is monoclonal in ~ 80% of T-LBL Cases
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42 Year-old Patient with Sjogren‘s Syndrome
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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-
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Cytokeratin 19
LEL
Lymphoepithelial Lesions in MALT-Lymphoma of the Thymus
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78 year-old Female, No Symptoms, Progressibe Lymphocytosis
Mediastinal Mass
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HC
What is Different Compared to the Previous Case?
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HC
No Germinal Centers !
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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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Pro
bab
ility
of
Sur
viva
l
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
Pro
bab
ility
of
Sur
viva
l
Survival (Years)
a) Masaoka Stage b) WHO Histotype
Type A, AB, B1
Type B2
Type B3
Type C
JCOCancer, 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
Pro
bab
ility
of
Sur
viva
lSurvival (Years)
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HistologyStage
Resection Status
OP, RXCHEM
Therapeutic Decisions in Thymoma Patients
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A, AB, B1 Thymome (50%)
B2, B3 Thymomas &Thymic Carcinomas (50%)
Wait-and-See
Surgery (RO) Surgery
Stage I Stage II Stage III/IVR1, R2
W&S ?Rx
Rx CHEMO& Rx
Therapeutic Decisions in Thymoma Patients
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0/112 Type A-B2 1/28 Type B3 19/24 SCC
ABA
B2 B3 SCC
C-KIT Expression in Thymic Carcinoma
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Type
B3
thym
oma
Type
B2
thym
oma
GIS
T
TSC
C K
ITM
UT
TSC
C K
ITW
T-1
TSC
C K
ITW
T-2
TSC
C K
ITW
T-3
TSC
C 5
TSC
C 6
phospho-MAPK (p42+p44)
c-KIT
phospho-c-KIT
phospho-AKT
phospho-BAD
phospho-STAT-1
phospho-STAT-3
KIT(+) KIT(-)
ImmunohistochemistryCD117
100
100
1
5
1
GIST
1
ResponderPatient B., A.
100
100
20
10
100
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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Philipp Ströbel (all in Würzburg)Masayoshi Inoue & W.-Y. ChuangAndreas ZettlHans Konrad Müller-Hermelink
European Thymoma NetworkPeter 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
DeutscheKrebshilfe
EUTHYMAIDE
Alexandervon HumboldtFoundation