Lymphoma

David Lee MD, FRCPC

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
nave

Lymphomas

MM

B-lymphocytes Plasma cells T-lymphocytes

Lymphoid progenitor

AML
Hematopoietic stem cell Myeloid progenitor

Myeloproliferative disorders
Neutrophils Eosinophils Basophils Monocytes Platelets

Red cells

B-cell development
stem cell lymphoid progenitor
progenitor-B

CLL

mature naive B-cell

germinal center B-cell

memory B-cell

MM DLBCL, FL, HL

ALL
pre-B immature B-cell plasma cell

Classification
Biologically rational classification
Diseases that have distinct morphology immunophenotype genetic features clinical features

Clinically useful classification

Diseases that have distinct clinical features natural history prognosis treatment

Lymphoma classification
(2001 WHO)
B-cell neoplasms
precursor mature
NonHodgkin Lymphomas

T-cell & NK-cell neoplasms

precursor mature

Hodgkin lymphoma

A practical way to think of lymphoma

Category Survival of untreated patients Years Curability To treat or not to treat

NonHodgkin lymphoma

Indolent

Generally not curable

Generally defer Rx if asymptomatic

Aggressive

Months

Curable in some
Curable in some Curable in most

Treat

Very aggressive Hodgkin lymphoma All types

Weeks

Treat

Variable months to years

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

age adjusted incidence/100,000/yr
70 60 50 40 30 20 10 0 1985 1990 1995 Year
NHL Hodgkin lymphoma lung colorectal breast

2000

Incidence/100,000/annum
100 20 40 60 80 0

Age distribution of new NHL cases in Canada

Age (years)

0-1 1-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

incidence/100,000/annum
0 1 2 3 4 5 6

Age distribution of new Hodgkin lymphoma cases in Canada

Age (years)

0-1 1-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+

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 lymphoma NHL Follicular 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
(mixed cellularity)

lacunar cell
(nodular sclerosis)

popcorn cell
(lymphocyte predominance)

A possible model of pathogenesis

transforming event(s) EBV? loss of apoptosis

cytokines

germinal centre B cell

RS cell inflammatory 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 Failurefree survival 70-80% Overall 5 year survival 80-90%

I,II

ABVD x 4 & radiation ABVD x 6

III,IV

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