Lymphomas in the Mediastinum
Mediastinal Large B Cell Lymphoma
Mediastinal Large B Cell Lymphoma
CD20
CD30
Immunhistochemische Differentialdiagnose
Nodale Diffuse
Large B Cell Lymphoma
MLBCL
CD20, CD79a
+++
+++
CD30, CD23
----/+
+++
IgM, Light chain
++ > ----
----
CD10
++ > ----
----
HLA-DR
Bcl-6
+++
----
+++/-
----
Mediastinal Large B Cell Lymphoma
Möller, WHO 2004
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
Pseudoepitheliomatous Hyperplasia & Thymic Cysts
CK19
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
DD of Strongly Proliferative Mediastinal Processes
Thymus
Thymoma
T-LBL
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-
k
Lymphoepithelial Lesions in MALT-Lymphoma of the Thymus
Cytokeratin 19
LEL
78 year-old Female, No Symptoms, Progressibe Lymphocytosis
Mediastinal Mass
What is Different Compared to the Previous Case?
HC
No Germinal Centers !
HC
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?
Therapeutic Decisions in Thymoma Patients
a) Masaoka Stage
1,0
b) WHO Histotype
Stage 1
c) Resection status
1,0
1,0
p < 0.05
Stage 3
,8
Stage 2
,7
Probability of Survival
,9
Probability of Survival
Probability of Survival
Type A, AB, B1
,9
,8
Type B2
,6
,5
0
10
20
Survival (Years)
30
,6
R 1+2 resection
,3
,6
,4
R0 resection
,7
,4
Type C
Stage 4
,8
,5
Type B3
,7
,9
0
10
20
Survival (Years)
30
0
10
20
30
Survival (Years)
JCO
Cancer, 2003; J Clin Oncol, 2004
Therapeutic Decisions in Thymoma Patients
Stage
Histology
OP, RX
CHEM
Resection Status
Therapeutic Decisions in Thymoma Patients
B2, B3 Thymomas &
Thymic Carcinomas (50%)
A, AB, B1
Thymome (50%)
Surgery
Surgery (RO)
Stage I
Stage II
Stage III/IV
R1, R2
Wait-and-See
W&S ?
Rx
Rx
CHEMO
& Rx
C-KIT Expression in Thymic Carcinoma
A
B2
0/112 Type A-B2
AB
B3
1/28 Type B3
SCC
19/24 SCC
GIST
100
KIT(+)
c-KIT
KIT(-)
Responder
Patient B., A.
100
phospho-c-KIT
100
phospho-AKT
100
1
phospho-BAD
20
5 phospho-MAPK (p42+p44)
10
1
1
phospho-STAT-1
100
phospho-STAT-3
Immunohistochemistry
CD117
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
Acknowledgements
Philipp Ströbel (all in Würzburg)
Masayoshi Inoue & W.-Y. Chuang
Andreas Zettl
Hans Konrad Müller-Hermelink
DFG
Deutsche
Krebshilfe
European Thymoma Network
Peter 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)
EU
THYMAIDE
Alexander
von Humboldt
Foundation