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
naïve

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
stem CLL germinal
cell mature center
naive B-cell
B-cell
lymphoid
progenitor

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

20
40
60
80
100

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

Age (years)
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
Age distribution of new NHL cases in
 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