Lymphoma

Overview
Concepts, classification, biology
Epidemiology
Clinical presentation
Diagnosis
Staging
Three important types of lymphoma
 Conceptualizing
lymphoma
neoplasms of lymphoid origin, typically
causing lymphadenopathy
leukemia vs lymphoma
lymphomas as clonal expansions of
cells at certain developmental stages
 ALL CLL Lymphomas MM
germinal center
nave

B-lymphocytes

Plasma
Lymphoid cells
progenitor T-lymphocytes

AML Myeloproliferative disorders

Hematopoietic Myeloid Neutrophils
stem cell progenitor

Eosinophils

Basophils

Monocytes

Platelets

Red cells
 B-cell development
memory
B-cell
germinal
stem CLL mature center
cell
naive B-cell
B-cell
lymphoid
progenitor

progenitor-B
MM
ALL
pre-B DLBCL,
immature FL, HL
B-cell plasma cell

Bone marrow Lymphoid tissue

 Classification

Biologically rational Clinically useful

classification classification
Diseases that have distinct Diseases that have distinct
morphology clinical features
immunophenotype natural history
genetic features prognosis
clinical features treatment
 Lymphoma classification
(2001 WHO)
B-cell neoplasms
precursor
mature Non-
Hodgkin
T-cell & NK-cell neoplasms Lymphomas

precursor
mature
Hodgkin lymphoma
 A practical way to think of
lymphoma
Category Survival of Curability To treat or
untreated not to treat
patients

Non- Indolent Years Generally Generally

Hodgkin not curable defer Rx if
lymphoma asymptomatic
Aggressive Months Curable in Treat
some

Very Weeks Curable in Treat

aggressive some

Hodgkin All types Variable Curable in Treat

lymphoma months to most
years
 Mechanisms of
lymphomagenesis
Genetic alterations
Infection
Antigen stimulation
Immunosuppression
 Epidemiology of
lymphomas
5th most frequently diagnosed cancer in
both sexes
males > females
incidence
NHL increasing
Hodgkin lymphoma stable
 Incidence of lymphomas in
comparison with other cancers in
Canada
age adjusted incidence/100,000/yr

70

60 lung
colorectal
50 breast

40
30

20 NHL
10 Hodgkin
lymphoma
0
1985 1990 1995 2000
Year
 Incidence/100,000/annum

0
20
40
60
80
100

0-1
1-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49

Age (years)
50-54
55-59
60-64
65-69
70-74
cases in Canada

75-79
80-84
85+
Age distribution of new NHL
 incidence/100,000/annum

0
1
2
3
4
5
6

0-1
1-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54

Age (years)
55-59
60-64
65-69
70-74
75-79
80-84
85+
lymphoma cases in Canada
Age distribution of new Hodgkin
 Risk factors for NHL
immunosuppression or immunodeficiency
connective tissue disease
family history of lymphoma
infectious agents
ionizing radiation
 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
 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
 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
Staging of lymphoma
Stage I Stage II Stage III Stage IV

A: absence of B symptoms
B: fever, night sweats, weight loss
 Three common
lymphomas
Follicular lymphoma
Diffuse large B-cell lymphoma
Hodgkin lymphoma
 Relative frequencies of
different lymphomas

Non-Hodgkin Lymphomas

Diffuse large B-cell

Hodgkin NHL Follicular
lymphoma
Other NHL

~85% of NHL are B-lineage

 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
 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
 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%
Hodgkin lymphoma

Thomas Hodgkin
(1798-1866)
Classical Hodgkin Lymphoma
 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
Reed-Sternberg cell
 RS cell and variants

classic RS cell lacunar cell popcorn cell

(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
 A possible model of
pathogenesis
transforming loss of apoptosis
event(s)
EBV?

cytokines
germinal
centre RS cell
inflammatory
B cell
response
 Hodgkin lymphoma
Histologic subtypes
Classical Hodgkin lymphoma
nodular sclerosis (most common subtype)
mixed cellularity
lymphocyte-rich
lymphocyte depleted
 Epidemiology
less frequent than non-Hodgkin
lymphoma
overall M>F
peak incidence in 3rd decade
 Associated (etiological?)
factors
EBV infection
smaller family size
higher socio-economic status
caucasian > non-caucasian
possible genetic predisposition
other: HIV? occupation? herbicides?
 Clinical manifestations:
lymphadenopathy
contiguous spread
extranodal sites relatively uncommon
except in advanced disease
B symptoms
Treatment and Prognosis
Stage Treatment Failure- Overall 5
free year
survival survival
I,II ABVD x 4 70-80% 80-90%
& radiation

III,IV ABVD x 6 60-70% 70-80%

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