T cell lymphoma diagnostics and differential diagnosis to Hodgkin lymphoma

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1 T cell lymphoma diagnostics and differential diagnosis to Hodgkin lymphoma Sylvia Hartmann Dr. Senckenberg Institute of Pathology Goethe University Frankfurt

2 Overview Borderline ALCL classical HL Borderline AITL and FTCL classical HL/NLPHL

3 Case 1 28 year-old patient enlarged cervical lymph node

4

5 CD30 PAX5

6 TIA1 ALK

7 ALK+ anaplastic large cell lymphoma, Hodgkin-like variant In PAX5-negative Hodgkin lymphoma (or cases with strong lymphohistiocytic infiltrate) -> always stain ALK!

8 Case 2 59 year-old patient Enlarged inguinal lymph node

9

10 CD30

11 CD30

12 CD30

13 PAX5

14 Granzyme B chl with cytotoxic phenotype? or ALK- ALCL?

15 Features in favor of ALK- ALCL Adult/elderly patients Morphology of hallmark cells, no eosinophilic nucleoli PAX5-negativity of tumor cells Sinusoidal expansion Stronger CD30 expression Expression of cytotoxic molecules Eosinophilia but usually less reactive lymphocytes

16 ALK- ALCL Classical Hodgkin Lymphoma

17 CD30 PAX5 ALK- ALCL Classical Hodgkin lymphoma

18 T gamma Clonality VH

19 ALK- Anaplastic large cell lymphoma In WHO revision 2016 definite entity that includes cytogenetic subsets that appear to have prognostic implications (eg, 6p25 rearrangments at IRF4/DUSP22 locus).

20 Brune et al., J Exp Med 2008 Eckerle et al., Leukemia 2009 chl ALCL

21 chl ALK- ALCL CD83 CCL22 STAT3 TUBB2B

22 Döring et al., Mod Pathol

23 Am J Surg Pathol May;36(5): CD15 CD30

24 In our patient: History of cutaneous CD30+ ALCL -> nodal relapse of primary cutaneous ALCL

25 Case 3 60 year-old female patient Generalized lymphadenopathy B symptoms, splenomegaly

26

27

28 CD30 LMP1

29 CD20 EBV-infected blastoid B cells HRS cells or HRS-like cells?

30 CD20

31 Follicular T Helper cell markers PD1 CD10

32 FDC (CD23) Angioimmunoblastic T cell lymphoma (AITL) with (clonal) EBV-infected CD30+ blasts

33 First description of EBV-infected HRS-like cells in AITL: Quintanilla-Martinez et al., Am J Surg Pathol 1999 J Pathol 2017

34 Naive B cells, mainly polyclonal

35 Diagnostic features of angioimmunoblastic T cell lymphoma (AITL) Open sinuses Expansion to perinodal tissue B cell rim along sinuses Mixed, epitheloid cell rich infiltrate Clear cells Regressive germinal centers Scattered B blasts CD30+/- and EBV+/- Expansion of FDC networks

36 CD3

37 PTCL of T FH phenotype show an aberrant CD3 -/dim CD4 + population 90% of follicular TCL 73.3% of AITL Alikhan et al., Mod Pathol 2016

38 WHO revision 2016 Nodal peripheral T-cell lymphoma with TFH phenotype which includes angioimmunoblastic T cell lymphoma Follicular T cell lymphoma

39 Case 4 54 year-old patient Single enlarged inguinal lymph node

40 chl with HRS cells or TCL with HRS-like cells??

41 Immunophenotype of HRS/HRS-like cells CD30 CD15

42 Immunophenotype of HRS/HRS-like cells CD20 PAX5 EBER

43 Immunophenotype of surrounding T cells PD1 CD10

44 Immunophenotype of surrounding T cells CXCL13 ICOS

45 Follicular T cell lymphoma (with HRS-like cells) New provisional entity in WHO revision Follicular, perifollicular or NLPHL-like pattern First described by Rüdiger et al. Am J Surg Pathol, 2000 Frequently HRS-like cells

46 Own experience of FTCL Neoplastic cells positive CD10 11/11 PD1 11/11 BCL6 11/11 ICOS 10/10 CXCL13 9/11

47 Own experience of FTCL: HRS-like cells in 11/11 cases Neoplastic T cells rosetting around HRS-like cells in 6/11 cases CD30 11/11 CD20 5/11 LMP1 7/11 CD15 2/11 PAX5 11/11 MUM1 11/11 Immunophenotype of HRS-like cells

48 HRS-like cells in 57 cases of different types of PTCL CD30 100% CD20 64% EBV 91% CD15 80% PAX5 100% Immunophenotype of HRS-like cells Nicolae et al. Am J Surg Pathol 2013

49 Delineation classical HL and T cell lymphomas with TFH phenotype chl HRS cells clonal + HRS-like cells T cell lymphomas + HRS-like cells (EBV-infected) B cells polyclonal or monoclonal T cells polyclonal T cells monoclonal Quintanilla-Martinez et al. Am J Surg Path 1999 Moroch et al., Am J Surg Path 2012 Eladl et al., Am J Surg Path 2017

50 Case 5 50-year old patient Stereotactic brain biopsy

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52

53 CD3 CD20 PAX5 CD79

54 CD4 CD8

55 TCR gamma PCR polyclonal

56 IgH Framework I III monoclonal!

57 HHV8 MUM1 CD138 HHV8-associated plasmablastic lymphoma with aberrant CD3- expression

58 CD20 negative or only focally positive in 13/21 samples Cytoplasmic CD3 localization Other T cell antigens negative Frequent extranodal localization

59 Summary T cell lymphomas frequently contain Hodgkinlike cells Hodgkin-like cells can be part of the neoplastic clone (T cells in ALCL) or reactive bystander cells (B cells in T FH type lymphomas) Immunophenotype can be misleading

60 Kiitos! Frankfurt Martin-Leo Hansmann Claudia Döring Markus Schneider Ralf Lieberz Yvonne Michel Elena Hartung Susanne Hansen Essen Ralf Küppers Marc Weniger Anna Lollies Friederike Schwartz Tampere Martine Vornanen Bologna Stefano Pileri Claudio Agostinelli Brescia Fabio Facchetti Helsinki Marja-Liisa Karjalainen- Lindsberg Mikko Mäyränpää Oulu Saila Kauppila Outi Kuittinen Pyry Uotila