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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 MM CLL Lymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
naïve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cell
DLBCL,FL, HL
ALL
CLL
MM
germinalcenterB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinct• clinical features• natural history• prognosis• treatment
Biologically rational classification
Diseases that have distinct• morphology• immunophenotype• genetic features• clinical features
Classification
Lymphoma classification(2001 WHO)
• B-cell neoplasms– precursor– mature
• T-cell & NK-cell neoplasms– precursor– mature
• Hodgkin lymphoma
Non-HodgkinLymphomas
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 Curable in some
Treat
Hodgkin lymphoma
All types Variable – months to years
Curable in most
Treat
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
Year
1985 1990 1995 2000
age
adju
sted
inci
denc
e/10
0,00
0/yr
0
10
20
30
40
50
60
70
Hodgkinlymphoma
NHL
breastcolorectallung
Age distribution of new NHL cases in Canada
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e/10
0,00
0/an
num
0
20
40
60
80
100
Age distribution of new Hodgkin lymphoma cases in Canada
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e/10
0,00
0/an
num
0
1
2
3
4
5
6
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
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A: absence of B symptomsB: fever, night sweats, weight loss
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~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
• 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
RS cell and variants
popcorn celllacunar cellclassic RS cell
(mixed cellularity) (nodular sclerosis) (lymphocytepredominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV?
cytokines
Hodgkin lymphomaHistologic subtypes
• Classical Hodgkin lymphoma– nodular sclerosis (most common subtype)– mixed cellularity– lymphocyte-rich– lymphocyte depleted
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-free
survival
Overall 5 year
survival
I,II ABVD x 4 & radiation
70-80% 80-90%
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