Lymphoma and Pseudolymphoma

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1 Lymphoma and Pseudolymphoma Laura B. Pincus, MD Co-Director, Cutaneous Lymphoma Clinic Associate Professor Dermatology and Pathology University of California, San Francisco

2 I HAVE NO RELEVANT RELATIONSHIPS WITH INDUSTRY

3 Willemze R et al. Blood; 2005: 15;105:

4 Outline T-cell lymphoma Mycosis fungoides Sézary syndrome CD30-positive lymphoproliferative disorders B-cell lymphoma Marginal zone Follicle center Diffuse large B-cell lymphoma, leg type B-cell pseudolymphoma

5 Outline T-cell lymphoma Mycosis fungoides Sézary syndrome CD30-positive lymphoproliferative disorders B-cell lymphoma Follicle center Marginal zone Diffuse large B-cell lymphoma, leg type B-cell pseudolymphoma

6 MF: patch stage Patchy to band-like lichenoid infiltrate of CD4+ (usually) lymphocytes Papillary dermal fibrosis Epidermotropism: lymphocytes within the epidermis

7 Collections of lymphocytes (Pautrier s collections) Epidermotropism

8 Lymphocytes align along dermalepidermal junction Epidermotropism

9 Lymphocytes in epidermis with halo Epidermotropism

10 Diagnosis of patch-stage MF often challenging

11 % of cases Epidermotropism in early MF Massone C et al. Am J Surg Pathol. 2005; 29: 550.

12

13 Role for ancillary testing? Loss of pan-t-cell antigens (CD2,5,7) Somewhat controversial Can be found in inflammatory conditions Detection of a T-cell clone Frequency of clones in early MF ~ 70% PLEVA 100%; Contact dermatitis 14% Identical clone at different sites increases sensitivity and specificity Thurber et al. JAAD :

14 Best diagnostic maneuver if first biopsy not diagnostic More biopsies!! Ferrara G, et al J Cutan Path ;35:549.

15 Bottom line At least 2-3 biopsies, broad shaves optimal Consider T-cell clonality testing from two biopsies

16 Histopathology - Plaque Extension of infiltrate into reticular dermis Band-like lymphocytic infiltrate typically denser than in patch-stage disease Both epidermotropism and cytological atypia more evident

17 Histopathology - Tumor Diffuse infiltrate of atypical lymphocytes in diffusely throughout reticular dermis Cytologically atypical features often quite marked

18

19 Outline T-cell lymphoma Mycosis fungoides Sézary syndrome CD30-positive lymphoproliferative disorders B-cell lymphoma Marginal zone Follicle center Diffuse large B-cell lymphoma, leg type B-cell Pseudolymphoma

20 Triad: Sézary syndrome Neoplastic lymphocytes in skin erythroderma Neoplastic lymphocytes in blood Neoplastic lymphocytes in lymph node

21

22 Results %SS %MF tumor Chromosomal alteration Associated gene 75% 23% Gain 8q24 MYC 75% 9% Loss 17p13 p53 15% 59% Gain 7q36 FASTK

23 Skin histopathology Dense band-like infiltrate of lymphocytes, some of which exhibit epidermotropism Some lymphocytes can be large

24

25

26 Caution 40% of patients will not show diagnostic features of Sézary syndrome on skin biopsy Trotter MJ et al. J Cutan Pathol 1997;24:286.

27 Evaluation of blood in Sézary syndrome

28 Blood diagnostic criteria for Sézary syndrome Genotypic analysis: T-cell clone detected AND Flow cytometry: CD4/8 > 10:1 AND/OR CD4+/CD7- > 40% CD4+/CD26- >30% Olsen et al. Blood. 2007;110:

29 Outline T-cell lymphoma Mycosis fungoides Sézary syndrome CD30-positive lymphoproliferative disorders B-cell lymphoma Marginal zone Follicle center Diffuse large B-cell lymphoma, leg type B-cell Pseudolymphoma

30 CD30-positive lymphoproliferative disorders Group of primary cutaneous T-cell lymphomas with expression of CD30 Lymphomatoid papulosis (LyP) Primary cutaneous anaplastic large cell lymphoma (ALCL)

31 Lymphomatoid Papulosis (LyP) 5 histopathologic types: A, B, C, D, E

32 LyP

33

34 Lymphomatoid papulosis (LyP) Type A Wedge-shaped infiltrate +/-Epidermotropism Clusters of or scattered large atypical lymphocytes CD4+ Admixed neutrophils, eosinophils, small lymphocytes

35

36

37

38 CD30

39 Type D LyP Saggini A et al. Am J Surg Pathol 2010;34:1168

40 Histopathology Typical LyP Marked epidermotropism Immunophenotype CD8+/CD30+/CD3+ Type D LyP Saggini A et al. Am J Surg Pathol 2010;34:1168

41

42

43 CD30

44 Anaplastic large cell lymphoma (ALCL)

45 ALCL Histopathology: Diffuse sheets of large and atypical lymphocytes

46

47 CD30

48 Outline T-cell lymphoma Mycosis fungoides Sézary syndrome CD30-positive lymphoproliferative disorders B-cell lymphoma Marginal zone Follicle center Diffuse large B-cell lymphoma, leg type B-cell Pseudolymphoma

49 Primary cutaneous marginal zone lymphoma

50 Primary cutaneous marginal zone lymphoma: Histopathology Dermal-based infiltrate, epidermal spared Reactive lymphoid follicles, often Neoplastic cells at periphery Plasma cells and plasmacytoid lymphocytes

51

52

53

54 Primary cutaneous marginal zone lymphoma Normal kappa/lambda ratio 2:1 Kappa or lambda skewed ratio Kappa:lambda > 10:1 Lambda>kappa

55 Kappa Lambda

56 Outline T-cell lymphoma Mycosis fungoides Sézary syndrome CD30-positive lymphoproliferative disorders B-cell lymphoma Marginal zone Follicle center Diffuse large B-cell lymphoma, leg type B-cell Pseudolymphoma

57

58 Primary cutaneous follicle center lymphoma Follicular pattern Nodules within the dermis composed of neoplastic lymphoid follicles Reduced or absent mantle zones Lack of tingible body macrophages

59

60 Bcl-6 CD21 Ki-67

61 Outline T-cell lymphoma Mycosis fungoides Sézary syndrome CD30-positive lymphoproliferative disorders B-cell lymphoma Marginal zone Follicle center Diffuse large B-cell lymphoma, leg type B-cell Pseudolymphoma

62 Diffuse large B-cell lymphoma, leg type

63

64 CD20 bcl2 MUM1

65 Outline T-cell lymphoma Mycosis fungoides Sézary syndrome CD30-positive lymphoproliferative disorders B-cell lymphoma Marginal zone Follicle center Diffuse large B-cell lymphoma, leg type B-cell pseudolymphoma

66 B-cell pseudolymphoma Cutaneous lymphoid hyperplasia, most common type Nodules of reactive lymphoid follicles Intact mantles Tingible body macrophages High Ki-67 rate of proliferation Bcl-6 staining only in CD21-positive foci

67 Cutaneous lymphoid hyperplasia

68

69 Ki67 Bcl-6 CD21

70 Cutaneous lymphoid hyperplasia Follicle center lymphoma CD21 CD21 Ki67 Ki67 Bcl-6 Bcl-6

71 Review T-cell lymphoma Mycosis fungoides Sézary syndrome CD30-positive lymphoproliferative disorders B-cell lymphoma Marginal zone Follicle center Diffuse large B-cell lymphoma, leg type B-cell pseudolymphoma

72 Acknowledgements Beth Ruben, MD Weiyun Ai, MD Sue Yom, MD Timothy McCalmont, MD Thaddeus Mully, MD Philip LeBoit, MD Iwei Yeh, MD Jeffrey North, MD

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