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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


B cell development l.jpg

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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Risk factors for NHL Canada

  • immunosuppression or immunodeficiency

  • connective tissue disease

  • family history of lymphoma

  • infectious agents

  • ionizing radiation


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Clinical manifestations Canada

  • 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 l.jpg
    Other complications of lymphoma Canada

    • 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 Canada

    • 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 l.jpg

    Stage I Canada

    Stage II

    Stage III

    Stage IV

    Staging of lymphoma

    A: absence of B symptoms

    B: fever, night sweats, weight loss


    Three common lymphomas l.jpg
    Three common lymphomas Canada

    • Follicular lymphoma

    • Diffuse large B-cell lymphoma

    • Hodgkin lymphoma


    Relative frequencies of different lymphomas l.jpg
    Relative frequencies of different lymphomas Canada

    Non-Hodgkin Lymphomas

    Diffuse large B-cell

    Hodgkin

    lymphoma

    NHL

    Follicular

    Other NHL

    ~85% of NHL are B-lineage


    Follicular lymphoma l.jpg
    Follicular lymphoma Canada

    • 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


    Slide22 l.jpg


    Diffuse large b cell lymphoma l.jpg
    Diffuse large B-cell lymphoma Canada

    • 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 l.jpg
    Hodgkin lymphoma Canada

    Thomas Hodgkin

    (1798-1866)



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    Hodgkin lymphoma Canada

    • 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 l.jpg
    RS cell and variants Canada

    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 Canada

    loss of apoptosis

    transforming

    event(s)

    EBV?

    cytokines

    germinal

    centre

    B cell

    RS cell

    inflammatory

    response


    Hodgkin lymphoma histologic subtypes l.jpg
    Hodgkin lymphoma CanadaHistologic subtypes

    • Classical Hodgkin lymphoma

      • nodular sclerosis (most common subtype)

      • mixed cellularity

      • lymphocyte-rich

      • lymphocyte depleted


    Epidemiology l.jpg
    Epidemiology Canada

    • less frequent than non-Hodgkin lymphoma

    • overall M>F

    • peak incidence in 3rd decade


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    Associated (etiological?) factors Canada

    • EBV infection

    • smaller family size

    • higher socio-economic status

    • caucasian > non-caucasian

    • possible genetic predisposition

    • other: HIV? occupation? herbicides?


    Clinical manifestations33 l.jpg
    Clinical manifestations: Canada

    • lymphadenopathy

    • contiguous spread

    • extranodal sites relatively uncommon except in advanced disease

    • “B” symptoms



    Long term complications of treatment l.jpg
    Long term complications of treatment Canada

    • infertility

      • MOPP > ABVD; males > females

      • sperm banking should be discussed

      • premature menopause

    • secondary malignancy

      • skin, AML, lung, MDS, NHL, thyroid, breast...

    • cardiac disease


    Overview36 l.jpg
    Overview Canada

    • Concepts, classification, biology

    • Epidemiology

    • Clinical presentation

    • Diagnosis

    • Staging

    • Three important types of lymphoma


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