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