1. Leukopenia, leukocytosis

2. Follicular hyperplasia

3. NEOPLASTIC PROLIFERATIONS OF WHITE CELLS
Lymphoid neoplasms
The phenotype of the tumor cells resembles that of normal counterparts
Myeloid neoplasms
Origin of hematopoietic stem cells that give rise to cells of the myeloid lineage
Histiocytoses
Proliferative lesions of macrophages and dendritic cells

4. Etiology and pathogenetic factors in white cell neoplasia
Chromosomal translocations and oncogenes
Inherited genetic factors
Virus
Environmental agents
Iatrogenic factors

5. Definition of lymphoid neoplasms
Lymphoma
Lymphoid neoplasms present predominantly as solid masses
Leukemia (lymphoid leukemia)
Lymphoid neoplasms involve mainly in bone marrow and usually in peripheral blood

6. Histology of a lymph node

7. Secondary Lymphoid Follicle (B-cell)
Interfollicular
zone (T-cell)
Mantle zone
Germinal
center
Dark zone
Light zone
Centrocyte
Centroblast

8. Development of Lymphocytes

9. Normal Counterpart of B-cell Neoplasms

11. Lymphoma Classification
“Revised European-American Classification of Lymphoid Neoplasms” (REAL) proposed by ILSG in 1994
World Health Organization (WHO) classification
Why classification?

12. Three major categories of lymphoid neoplasms
B cell lymphomas
Precursor vs. peripheral
T and NK cell lymphomas
Hodgkin lymphoma (HL)
Lymphoma vs. leukemia
Small lymphocyte, lymphoblast, Burkitt

13. The WHO Classification of the Lymphoid Neoplasms
I. Precursor B-Cell Neoplasms
Precursor-B lymphoblastic leukemia/lymphoma
II. Peripheral B-Cell Neoplasms
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
B-cell prolymphocytic leukemia
Lymphoplasmacytic lymphoma (LPL)
Splenic and nodal marginal zone lymphomas
Extranodal marginal zone lymphoma
Mantle cell lymphoma (MCL)
Follicular lymphoma (FL)
Marginal zone lymphoma (MZL)
Hairy cell leukemia
Plasmacytoma/plasma cell myeloma
Diffuse large B-cell lymphoma (DLBCL)
Burkitt lymphoma (BL)

14. III. Precursor T-Cell Neoplasms
Precursor-T lymphoblastic leukemia/lymphoma
IV. Peripheral T-Cell and NK-Cell Neoplasms
T-cell prolymphocytic leukemia
Large granular lymphocytic leukemia
Mycosis fungoides/Sézary syndrome
Peripheral T-cell lymphoma, unspecified (PTCL, NOS)
Anaplastic large cell lymphoma (ALCL)
Angioimmunoblastic T-cell lymphoma
Enteropathy-associated T-cell lymphoma
Panniculitis-like T-cell lymphoma
Hepatosplenic γ/δ T-cell lymphoma
Adult T-cell leukemia/lymphoma
NK/T-cell lymphoma, nasal type
NK-cell leukemia

15. V. Hodgkin Lymphoma
Classical subtypes
Nodular sclerosis (NS)
Mixed cellularity (MC)
Lymphocyte-rich (LRC)
Lymphocyte depletion (LD)
Lymphocyte predominance (LP)

16. Summary of Major Types of Lymphoid Neoplasms
Diagnosis
Cell of Origin
Genotype
Salient Clinical Features BL
Germinal center B-cell; CD10 expression usually seen
Translocations involving c-myc and Ig loci; usually t(8;14), but also t(2;8) or t(8;22). African (endemic) cases latently infected with EBV
Adolescents or young adults with jaw or extranodal abdominal masses; uncommonly presents as a "leukemia"; aggressive

17. SLL/CLL

18. Prolymphocyte

19. CLL

20. SLL/CLL

21. FL

22. Centrocyte & centroblast

23. FL (spleen)

24. Bcl-2 expression in reactive and neoplastic follicles

25. DLBCL

26. DLBCL (spleen)

28. BL

29. BL

31. LPL

32. MCL

33. MCL

35. Mucosa-associated lymphoid tissue (MALT) type-lymphoma
Extranodal marginal zone lymphoma
Postgerminal center memory B-cell
Trisomy 18, t(11;18), t(1;14); latter create MALT1-IAP2 and BCL10-IgH fusion genes, respectively
Arises at extranodal sites in adults with chronic inflammatory diseases; may remain localized; indolent

36. Mature B cell lymphomas
Epidemiology
Median age: 6th~7th decades
Mediastinal large B-cell lymphoma: 37
Burkitt lymphoma: 30
In children
Burkitt lymphoma (BL)
Diffuse large B-cell lymphoma (DLBCL)
M>F: mantle cell lymphoma
F>M: mediastinal large B-cell lymphoma

37. Risk factors Abnormality of the immune system
Immunodeficiency (HIV, recipient of transplantation)
BL, DLBCL
Autoimmune disease
MALT lymphoma

38. Etiology-- Infectious agents
EBV
BL (100% in endemic, 40% in others)
lymphomas in immunosuppressed patients
HHV8
primary effusion lymphoma
Hepatitis C virus
lymphoplasmacytic lymphoma
Bacteria
MALT lymphoma (stomach, skin, intestine)

40. Genetics Mantle cell lymphoma (MCL) Follicular lymphoma (FL)
t(11;14): Cyclin D1/Bcl-1
Follicular lymphoma (FL)
t(14;18): Bcl-2
Burkitt lymphoma (BL)
t(8;14), t(2;8), t(8;22): c-myc
MALT lymphoma
t(11;18): API-2

41. Clinical Presentations
Predominantly disseminated (leukemia)
SLL/CLL, LPL, hairy cell leukemia (HCL), splenic marginal zone lymphoma, myeloma
Primary extranodal
MALT lymphoma
Predominantly nodal
Follicular lymphoma, mantle cell lymphoma, nodal marginal zone lymphoma

42. Clinical features and survival
Indolent & incurable
SLL/CLL, FL: median survival > 5 yrs
Indolent & curable
MALT lymphoma
Incurable & aggressive
MCL: median survival 3 yrs
Aggressive but curable
DLBCL (40% cure rate), BL

43. Mature T- and NK-cell neoplasms
Incidence
12% in the Western world
Peripheral T-cell lymphoma, unspecified (PTCL-U)
Anaplastic large cell lymphoma (ALCL)
39% in Taiwan
Nasal and nasal-type NK/T-cell lymphoma
Why?
Lower B lymphoma, virus, racial predisposition

44. Etiology Virus unknown EBV NK/T-cell lymphoma NK/T-cell leukemia
HTLV-1
Adult T-cell leukemia/lymphoma
unknown

45. PTCL, unspecified

46. ALCL-hallmark (horseshoe) cells

47. ALK expression in ALCL

49. Nasal type NK/T-cell lymphoma
Natural killer cell (common) or cytotoxic T-cell (rare)
No specific chromosomal abnormality; uniformly EBV associated
Adults with destructive extranodal masses, most commonly sinonasal; often accompanied by hemophagocytic syndrome; aggressive

50. Reed-Sternberg (RS) cell

51. Characteristics About 30% of all lymphomas
Usually arise in cervical lymph nodes
The majority in young adults
Typically localized at presentation
Scattered tumor cells in a background of inflammatory cells
The tumor cells are usually ringed by T-cells in a rosette-like manner

52. Mononuclear variant of RS cell

53. Lacunar variant

54. Lymphohistiocytic (L&H) variant

55. Subclassification Nodular lymphocyte predominant (NLPHL)
5% of all HL
30~50 y/o male
Most stage I/II
Develop slowly
Frequent relapses
Responsive to Tx
Rarely being fatal
10 yr survival rate >90%
Classical (CHL)
95% of all HL
15~35 & late adult
Neck, mediastinum
55% stage I/II
40% systemic symptoms
EBV association
Curable in the majority
5 yr survival >85%

56. NS type

57. MC type

58. NLP type

59. Signals mediate cross-talk between RS and surrounding normal cells

60. Clinical Differences Between Hodgkin and Non-Hodgkin Lymphomas
More often localized to a single axial group of nodes (cervical, mediastinal, para-aortic)
More frequent involvement of multiple peripheral nodes
Orderly spread by contiguity
Noncontiguous spread
Mesenteric nodes and Waldeyer ring rarely involved
Waldeyer ring and mesenteric nodes commonly involved
Extranodal involvement uncommon
Extranodal involvement common

61. THANK YOU

62. HCL

63. HCL