Lymphomas in the Mediastinum
Mediastinal Large B Cell Lymphoma
Mediastinal Large B Cell Lymphoma
CD20 CD30
Immunhistochemische Differentialdiagnose
Nodale DiffuseLarge B Cell Lymphoma
MLBCL
CD20, CD79a +++ +++
IgM, Light chain ++ > ----
CD10 ++ > ---- ----
HLA-DR +++
Bcl-6 +++/-
CD30, CD23 ----/+
----
----
----
+++
Möller, WHO 2004
Mediastinal Large B Cell Lymphoma
Combined Hodgkin Lymphom & MLBCL
CD30+CD15+CD20-
CD30+CD15-CD20+
Hodgkin Lymphoma in a Mediastinal Lymph Node
CD30
Hodgkin Lymphoma in the Thymus
CD30 CK19
CK19
Pseudoepitheliomatous Hyperplasia & Thymic Cysts
Search for Lymphoma, Thymoma, LCH, Metastasis, Germ Cell Neoplasia
Immunhistochemische Differentialdiagnose
Hodgkin Lymphoma(Classical Type; usually NS)
MLBCL
CD30 +++ +++ > ----
CD15 + > ---- -----
CD20 -/+ +++
CD79a ---- +++
PanLeu (CD45) ---- +++
Borderline Cases
between HL and Mediastinal Large B Cell Lymphoma ?
YES !
Distinct Gene Expression Profile of MLBCL (PMBL)
Survival of MLBCL (PMBL) Patients
Conclusions
Distinct gene expression profile of PMBL (molecular diagnosis)
PMBL patients are clinically distinct
Close Relationship of PMBL to Hodgkin Lymphoma
DD between MLBCL and ALCL
CD3 CD30 ALK-1
Immunohistochemical Differential Diagnosis
Anaplastic Large Cell Lymphoma
MLBCL
CD30 +++ +++ > ----
CD15 ---- -----
CD20, CD79a ---- +++
CD3, CD5, CD43, TIA-1 -/++ -----
ALK-1 -/++ -----
T-LBL des Thymus
Infiltration of Mediastinum & Heart; Pleural Effusions; +/- Leukemia
Differential Diagnosis of B1/B2Thymom vs. T-LBL Thymom
T-LBL
Cytokeratin 19 CD1a Ki67
Thymus T-LBLThymoma
DD of Strongly Proliferative Mediastinal Processes
Ki67 not different between Normal Thymus, Thymoma and T-LBL
Lymphocyte Differentiation in the Thymus
WHO, 2004
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
42 Year-old Patient with Sjogren‘s Syndrome
No Cortico-medullary Differentiation, No Capsule
Germinal Center
MALT Lymphoma of the Thymus
CD20+, CD5-, CD10-, CD23-
Cytokeratin 19
LEL
Lymphoepithelial Lesions in MALT-Lymphoma of the Thymus
78 year-old Female, No Symptoms, Progressibe Lymphocytosis
Mediastinal Mass
HC
What is Different Compared to the Previous Case?
HC
No Germinal Centers !
Cytokeratin 19
CD3+, TdT(-)
Ki67 ~10%
Diagnosis : T-Prolymphocytic Leukemia (TPLL)
Conclusion
All Peripheral Lymphomas Can Occur in the Mediastinum
Clinical Relevance of the New WHO Classification?
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)
HistologyStage
Resection Status
OP, RXCHEM
Therapeutic Decisions in Thymoma Patients
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
0/112 Type A-B2 1/28 Type B3 19/24 SCC
ABA
B2 B3 SCC
C-KIT Expression in Thymic Carcinoma
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
Imatinib (-) Imatinib (+)
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
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
