Lymphomas in the Mediastinum
Mediastinal Large B Cell Lymphoma
Mediastinal Large B Cell Lymphoma




CD20                    CD30
Immunhistochemische Differentialdiagnose
                   Nodale Diffuse      MLBCL
               Large B Cell Lymphoma

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           MLBCL
           (Classical Type; usually NS)

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    MLBCL
                     Lymphoma

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-              κ
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                                            b) WHO Histotype                                           c) Resection status
                                                                                                                                     1,0
               1,0                                Stage 1                 1,0                                                                                           p < 0.05
                                                                                                      Type A, AB, B1
                                                                                                                                                 ,9



                                                            Probability of Survival




                                                                                                                       Probability of Survival
Probability of Survival




                          ,9

                                                 Stage 3                              ,9                                                         ,8
                          ,8
                                          Stage 2                                                                                                ,7                 R0 resection
                          ,7                                                          ,8
                                                                                                                                                 ,6
                                                                                                       Type B2
                          ,6
                                                                                                                                                 ,5
                                                                                      ,7               Type B3
                          ,5                                                                                                                     ,4               R 1+2 resection
                                                                                                 Type C
                                              Stage 4
                          ,4                                                          ,6                                                         ,3

                               0    10      20        30                                   0     10       20      30                                  0      10         20          30

                                   Survival (Years)                                            Survival (Years)                                           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

  A, AB, B1                 B2, B3 Thymomas &
Thymome (50%)             Thymic Carcinomas (50%)



Surgery (RO)                     Surgery

                Stage I         Stage II      Stage III/IV
                                                R1, R2
Wait-and-See

                W&S ?               Rx         CHEMO
                 Rx                             & Rx
C-KIT Expression in Thymic Carcinoma




 A                       AB




B2                B3              SCC
0/112 Type A-B2    1/28 Type B3     19/24 SCC
ma

                                                                           ma
                                                                      mo

                                                                      mo
                                                                         1

                                                                         2

                                                                        3
                                                   T

                                                                    WT -



                                                                    WT -



                                                                    WT -
                                                  MU




                                                                  thy

                                                                  thy
                                               T




                                                                   T
                                                     IT

                                                                 IT
                                             KI




                                                               KI
                                                   CK

                                                             CK




                                                              B3

                                                              B2
                                                               5
                                                               6
                                            CC




                                                           CC
                                                           CC
                                                           CC
                                       ST




                                                           pe

                                                           pe
                                                    C

                                                           C
                                                                                 Responder




                                            TS

                                                 TS

                                                        TS

                                                        TS
                                                        TS

                                                        TS
                                                        Ty

                                                        Ty
                                    GI
                                                 KIT(+)          KIT(-)
GIST                                                                            Patient B., A.
 100                   c-KIT
                                                                                     100
                phospho-c-KIT


100             phospho-AKT                                                         100
    1            phospho-BAD                                                          20
    5 phospho-MAPK (p42+p44)                                                          10
    1         phospho-STAT-1                                                        100
1             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)                            DFG
Masayoshi Inoue & W.-Y. Chuang
Andreas Zettl                               Deutsche
Hans Konrad Müller-Hermelink                Krebshilfe



European Thymoma Network
Peter Rieckmann (Würzburg)
Ralf Gold (Göttingen)                                    EU
Wilfried Nix (Mainz)                                     THYMAIDE

Berthold Schalke (Regensburg)
Reinhard Kiefer (Münster)
Michael Semik (Münster)
Francesco Scaravilli (London)
Nick Willcox, Angela Vincent (Oxford)   Alexander
Pärt Peterson (Tartu)                   von Humboldt
                                        Foundation

Lymphomas