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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

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Lymphoma l.jpg

Lymphoma

David Lee MD, FRCPC


Overview l.jpg

Overview

  • Concepts, classification, biology

  • Epidemiology

  • Clinical presentation

  • Diagnosis

  • Staging

  • Three important types of lymphoma


Conceptualizing lymphoma l.jpg

Conceptualizing lymphoma

  • neoplasms of lymphoid origin, typically causing lymphadenopathy

  • leukemia vs lymphoma

  • lymphomas as clonal expansions of cells at certain developmental stages


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ALL

CLL

Lymphomas

MM

Neutrophils

AML

Myeloproliferative disorders

Myeloid

progenitor

Eosinophils

Hematopoietic

stem cell

Basophils

Monocytes

Platelets

Red cells

naïve

germinal center

B-lymphocytes

Plasma

cells

Lymphoid

progenitor

T-lymphocytes


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CLL

MM

ALL

DLBCL,

FL, HL

B-cell development

memory

B-cell

germinal

center

B-cell

stem

cell

mature

naive

B-cell

lymphoid

progenitor

progenitor-B

pre-B

immature

B-cell

plasma cell

Bone marrow

Lymphoid tissue


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Biologically rational classification

Clinically useful classification

  • Diseases that have distinct

    • morphology

    • immunophenotype

    • genetic features

    • clinical features

  • Diseases that have distinct

    • clinical features

    • natural history

    • prognosis

    • treatment

Classification


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Lymphoma classification(2001 WHO)

  • B-cell neoplasms

    • precursor

    • mature

  • T-cell & NK-cell neoplasms

    • precursor

    • mature

  • Hodgkin lymphoma

Non-

Hodgkin

Lymphomas


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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

A practical way to think of lymphoma


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Mechanisms of lymphomagenesis

  • Genetic alterations

  • Infection

  • Antigen stimulation

  • Immunosuppression


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Epidemiology of lymphomas

  • 5th most frequently diagnosed cancer in both sexes

  • males > females

  • incidence

    • NHL increasing

    • Hodgkin lymphoma stable


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Incidence of lymphomas in comparison with other cancers in Canada


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Age distribution of new NHL cases in Canada


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Age distribution of new Hodgkin lymphoma cases in Canada


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Risk factors for NHL

  • immunosuppression or immunodeficiency

  • connective tissue disease

  • family history of lymphoma

  • infectious agents

  • ionizing radiation


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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


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    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


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    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


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    Stage I

    Stage II

    Stage III

    Stage IV

    Staging of lymphoma

    A: absence of B symptoms

    B: fever, night sweats, weight loss


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    Three common lymphomas

    • Follicular lymphoma

    • Diffuse large B-cell lymphoma

    • Hodgkin lymphoma


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    Relative frequencies of different lymphomas

    Non-Hodgkin Lymphomas

    Diffuse large B-cell

    Hodgkin

    lymphoma

    NHL

    Follicular

    Other NHL

    ~85% of NHL are B-lineage


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    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


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    • 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


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    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%


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    Hodgkin lymphoma

    Thomas Hodgkin

    (1798-1866)


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    Classical Hodgkin Lymphoma


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    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 l.jpg

    Reed-Sternberg cell


    Rs cell and variants l.jpg

    RS cell and variants

    classic RS cell

    lacunar cell

    popcorn cell

    (lymphocyte

    predominance)

    (mixed cellularity)

    (nodular sclerosis)


    A possible model of pathogenesis l.jpg

    A possible model of pathogenesis

    loss of apoptosis

    transforming

    event(s)

    EBV?

    cytokines

    germinal

    centre

    B cell

    RS cell

    inflammatory

    response


    Hodgkin lymphoma histologic subtypes l.jpg

    Hodgkin lymphomaHistologic subtypes

    • Classical Hodgkin lymphoma

      • nodular sclerosis (most common subtype)

      • mixed cellularity

      • lymphocyte-rich

      • lymphocyte depleted


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    Epidemiology

    • less frequent than non-Hodgkin lymphoma

    • overall M>F

    • peak incidence in 3rd decade


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    Associated (etiological?) factors

    • EBV infection

    • smaller family size

    • higher socio-economic status

    • caucasian > non-caucasian

    • possible genetic predisposition

    • other: HIV? occupation? herbicides?


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    Clinical manifestations:

    • lymphadenopathy

    • contiguous spread

    • extranodal sites relatively uncommon except in advanced disease

    • “B” symptoms


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    Treatment and Prognosis


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    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


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    Overview

    • Concepts, classification, biology

    • Epidemiology

    • Clinical presentation

    • Diagnosis

    • Staging

    • Three important types of lymphoma


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