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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
slide3
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
slide18
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
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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