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Lymphoma s. S. Sami Kartı, MD, Prof. Conceptualizing lymphoma. neoplasms of lymphoid origin, typically causing lymphadenopathy. ALL. CLL. Lymphomas. MM. Neutrophils. AML. Myeloproliferative disorders. Myeloid progenitor. Eosinophils. Hematopoietic stem cell. Basophils. Monocytes.

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Lymphoma s

Lymphomas

S. Sami Kartı, MD, Prof.


Conceptualizing lymphoma
Conceptualizing lymphoma

  • neoplasms of lymphoid origin, typically causing lymphadenopathy


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

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


Classification

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


Lymphoma classification 2001 who
Lymphoma classification(2001 WHO)

  • B-cell neoplasms

    • precursor

    • mature

  • T-cell & NK-cell neoplasms

    • precursor

    • mature

  • Hodgkin lymphoma

Non-

Hodgkin

Lymphomas


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

A practical way to think of lymphoma


Mechanisms of lymphomagenesis
Mechanisms of lymphomagenesis

  • Genetic alterations

  • Infection

  • Antigen stimulation

  • Immunosuppression


Epidemiology of lymphomas
Epidemiology of lymphomas

  • 5th most frequently diagnosed cancer in both sexes

  • males > females

  • incidence

    • NHL increasing

    • Hodgkin lymphoma stable


Risk factors for nhl
Risk factors for NHL

  • immunosuppression or immunodeficiency

  • connective tissue disease

  • family history of lymphoma

  • infectious agents

  • ionizing radiation


Clinical manifestations
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
    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 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

    Staging of lymphoma

    A: absence of B symptoms

    B: fever, night sweats, weight loss


    Three common lymphomas
    Three common lymphomas

    • Diffuse large B-cell lymphoma

    • Follicular lymphoma

    • Hodgkin lymphoma


    Relative frequencies of different lymphomas
    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
    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




    Introduction
    Introduction

    • most common type of “aggressive” lymphoma

    • extranodal involvement is common

    • cell of origin: germinal center B-cell


    Clinical presentation
    Clinical presentation

    • Usually presents with one or more rapidly growing tumor masses involving nodal or extranodal sites

    • Not tender

    • Usually not interfere organ function except by compression


    Treatment
    Treatment

    • Chemotherapy

    • Radiotherapy

    • Chemotherapy + radiotherapy

    • Autologous or allogeneic stem cell transplantation in relaps or refractory cases


    Hodgkin lymphoma
    Hodgkin lymphoma

    Thomas Hodgkin

    (1798-1866)



    Hodgkin lymphoma1
    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
    RS cell and variants

    classic RS cell

    lacunar cell

    popcorn cell


    A possible model of pathogenesis
    A possible model of pathogenesis

    loss of apoptosis

    transforming

    event(s)

    EBV?

    cytokines

    germinal

    centre

    B cell

    RS cell

    inflammatory

    response


    Histologic subtypes
    Histologic subtypes

    • Classical Hodgkin lymphoma

      • nodular sclerosis (most common subtype)

      • mixed cellularity

      • lymphocyte-rich

      • lymphocyte depleted


    Epidemiology
    Epidemiology

    • less frequent than non-Hodgkin lymphoma

    • overall M>F

    • peak incidence in 3rd decade


    Associated etiological factors
    Associated (etiological?) factors

    • EBV infection

    • smaller family size

    • higher socio-economic status

    • caucasian > non-caucasian

    • possible genetic predisposition

    • other: HIV? occupation? herbicides?


    Clinical manifestations1
    Clinical manifestations

    • lymphadenopathy

    • extranodal sites relatively uncommon except in advanced disease

    • “B” symptoms



    Long term complications of treatment
    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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