1. Lymphoma
David Lee MD, FRCPC

2. Overview Concepts, classification, biology Epidemiology
Clinical presentation
Diagnosis
Staging
Three important types of lymphoma

3. Conceptualizing lymphoma
neoplasms of lymphoid origin, typically causing lymphadenopathy
leukemia vs lymphoma
lymphomas as clonal expansions of cells at certain developmental stages

4. Myeloproliferative disorders
ALL MM
CLL
Lymphomas
naïve
germinal center
B-lymphocytes
Plasma
cells
Lymphoid
progenitor
T-lymphocytes
Hematopoietic
stem cell
AML
Myeloproliferative disorders
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloid
progenitor

5. B-cell development Bone marrow Lymphoid tissue CLL MM ALL DLBCL,
memory
B-cell
DLBCL,
FL, HL
ALL
CLL MM
stem
cell
germinal
center
B-cell
mature
naive
B-cell
lymphoid
progenitor
progenitor-B
pre-B
immature
B-cell
plasma cell
Bone marrow
Lymphoid tissue

6. Clinically useful classification Biologically rational classification
Diseases that have distinct
clinical features
natural history
prognosis
treatment
Biologically rational classification
morphology
immunophenotype
genetic features

7. Lymphoma classification (2001 WHO)
B-cell neoplasms
precursor
mature
T-cell & NK-cell neoplasms
Hodgkin lymphoma
Non-
Hodgkin
Lymphomas

8. A practical way to think of lymphoma
Category
Survival of untreated patients
Curability
To treat or not to treat
Non-Hodgkin lymphoma
Indolent
Years
Generally not curable
Generally defer Rx if asymptomatic
Aggressive
Months
Curable in some
Treat
Very aggressive
Weeks
Hodgkin lymphoma
All types
Variable – months to years
Curable in most

9. Mechanisms of lymphomagenesis
Genetic alterations
Infection
Antigen stimulation
Immunosuppression

10. Epidemiology of lymphomas
5th most frequently diagnosed cancer in both sexes
males > females
incidence
NHL increasing
Hodgkin lymphoma stable

11. Incidence of lymphomas in comparison with other cancers in Canada

12. Age distribution of new NHL cases in Canada

13. Age distribution of new Hodgkin lymphoma cases in Canada

14. Risk factors for NHL immunosuppression or immunodeficiency
connective tissue disease
family history of lymphoma
infectious agents
ionizing radiation

15. Clinical manifestations
Variable
severity: asymptomatic to extremely ill
time course: evolution over weeks, months, or years
Systemic manifestations
fever, night sweats, weight loss, anorexia, pruritis
Local manifestations
lymphadenopathy, splenomegaly most common
any tissue potentially can be infiltrated

16. Other complications of lymphoma
bone marrow failure (infiltration)
CNS infiltration
immune hemolysis or thrombocytopenia
compression of structures (eg spinal cord, ureters)
pleural/pericardial effusions, ascites

17. Diagnosis requires an adequate biopsy
Diagnosis should be biopsy-proven before treatment is initiated
Need enough tissue to assess cells and architecture
open bx vs core needle bx vs FNA

18. Staging of lymphoma Stage I Stage II Stage III Stage IV
A: absence of B symptoms
B: fever, night sweats, weight loss

19. Three common lymphomas
Follicular lymphoma
Diffuse large B-cell lymphoma
Hodgkin lymphoma

20. Relative frequencies of different lymphomas
Non-Hodgkin Lymphomas
Diffuse large B-cell
Hodgkin
lymphoma
NHL
Follicular
Other NHL
~85% of NHL are B-lineage

21. Follicular lymphoma most common type of “indolent” lymphoma
usually widespread at presentation
often asymptomatic
not curable (some exceptions)
associated with BCL-2 gene rearrangement [t(14;18)]
cell of origin: germinal center B-cell

22. defer treatment if asymptomatic (“watch-and-wait”)
several chemotherapy options if symptomatic
median survival: years
despite “indolent” label, morbidity and mortality can be considerable
transformation to aggressive lymphoma can occur

23. Diffuse large B-cell lymphoma
most common type of “aggressive” lymphoma
usually symptomatic
extranodal involvement is common
cell of origin: germinal center B-cell
treatment should be offered
curable in ~ 40%

24. Hodgkin lymphoma
Thomas Hodgkin
( )

25. Classical Hodgkin Lymphoma

26. Hodgkin lymphoma cell of origin: germinal centre B-cell
Reed-Sternberg cells (or RS variants) in the affected tissues
most cells in affected lymph node are polyclonal reactive lymphoid cells, not neoplastic cells

27. Reed-Sternberg cell

28. RS cell and variants classic RS cell lacunar cell popcorn cell
(lymphocyte
predominance)
(mixed cellularity)
(nodular sclerosis)

29. A possible model of pathogenesis
loss of apoptosis
transforming
event(s)
EBV?
cytokines
germinal
centre
B cell
RS cell
inflammatory
response

30. Hodgkin lymphoma Histologic subtypes
Classical Hodgkin lymphoma
nodular sclerosis (most common subtype)
mixed cellularity
lymphocyte-rich
lymphocyte depleted

31. Epidemiology less frequent than non-Hodgkin lymphoma overall M>F
peak incidence in 3rd decade

32. Associated (etiological?) factors
EBV infection
smaller family size
higher socio-economic status
caucasian > non-caucasian
possible genetic predisposition
other: HIV? occupation? herbicides?

33. Clinical manifestations:
lymphadenopathy
contiguous spread
extranodal sites relatively uncommon except in advanced disease
“B” symptoms

34. Treatment and Prognosis
Stage
Treatment
Failure-free survival
Overall 5 year survival
I,II
ABVD x 4 & radiation
70-80%
80-90%
III,IV
ABVD x 6
60-70%

35. Long term complications of treatment
infertility
MOPP > ABVD; males > females
sperm banking should be discussed
premature menopause
secondary malignancy
skin, AML, lung, MDS, NHL, thyroid, breast...
cardiac disease

36. Overview Concepts, classification, biology Epidemiology
Clinical presentation
Diagnosis
Staging
Three important types of lymphoma