Lymphopoietic System-kbk Blok Hematologi

7/30/2019 Lymphopoietic System-kbk Blok Hematologi

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DISORDERS OF

LYMPHOPOIETIC

SYSTEM

KBK SEMESTER IV

BLOK HEMATOLOGI


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LYMPHOPOIETIC SYSTEM :

Circulating B & T lymphocytes

Lymphoid organs : lymph node, spleen,

thymus, MALT


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Lymphocytes : all derived from Bone

Marrow stem cells.

Thymus : T cells BM : B cells


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T lymphocytes

Lymphocytic stem cells migrate to thymus

exposed with thymic hormones

surface receptor (CD 2) as recognize Ag,CD 2 present on membrane + CD 3

marker T cells CD 5, CD 4 (helper)

or CD 8 (suppressor) migrate to

lymph nodes, spleen and peripheralblood.


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B lymphocytes

Acquired repertoire cytoplasmic & cell

surface Ag in bone marrow.

The earliest B cell antigens are CD19,CALLA (common acute leukemia/

lymphoma antigen, CD10) on the cell

membrane, and the nuclear antigen TdT.

Mature genes for immunoglobulin

heavy chains are rearranged

synthesis of IgM molecules .


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In precursor B cells, IgM expressed in

cytoplasm. After activation and clonal

expansion in germinal centers, Blymphocytes migrate B cell-dependt

medullary cords of lymph nodes Ig-

secreting plasma cells or exit lymph

nodes as memory B lymphocytes.


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Mature B cells express surface pan B

cell antigens CD19, CD20, CD22, plus Ig

heavy and light chains.When activated by antigen and

stimulated by an appropriate T helper

cell, B cells develop into plasma cells

that synthesize and exportimmunoglobulins.


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Mature B cells express surface pan B

cell antigens CD19, CD20, CD22, plus Ig

heavy and light chains. When activatedby antigen and stimulated by an

appropriate T helper cell, B cells develop

into plasma cells that synthesize and

export immunoglobulins.


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NATURAL KILLER (NK) AND

CYTOTOXIC CELLSA small proportion of lymphocytes

express neither B nor T cell

differentiation antigens.Act as cytotoxic or natural killer cells (NK

cells.

CD56+, CD3-, and CD8-


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LYMPH NODES

Outer cortex and an inner medulla .

B-cell-dependent cortex :

Inactive follicles (primary follicles)

cohesiveaggregates of small, normal-appearing

lymphocytes.

Active follicles (secondary follicles) Germinal

centers contain large lymphocytes

(centroblasts) and small lymphocytes with

cleaved nuclei (centrocytes) & scattered

macrophages.


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Reactive Hyperplasia of Lymph

Nodes Response to Infections,

Inflammation or Tumors :Acute suppurative or necrotizing

lymphadenitis.

Follicular Hyperplasia : Hyperplasia ofsecondary follicles (germinal centers)

and plasmacytosis of medullary cords

indicate B lymphocyte immunoreactivity

nonspecific reactive follicularhyperplasia etiology not known (viral,

drug/inflammatory), AIDS.


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Interfollicular Hyperplasia Reactivenonspecific interfollicular hyperplasiaviral infections or immunologic reactions mononucleosis, varicella-herpeszoster infection, measles, andcytomegalovirus lymphadenitis, SLE.

Mixed Patterns hyperplasia toxoplasmosis, Cat-scratch disease,lymphogranuloma venereum andtularemia


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Sinus histiocytosis increase tissue

macrophages (histiocytes) of subcap-

sular and trabecular sinuses.


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MALIGNANT LYMPHOMA

Non Hodgkin Lymphoma.

Hodgkin Lymphoma.


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The NHLs are a heterogeneous group oflymphoproliferative malignancies with differing patterns ofbehavior and responses to treatment

Like Hodgkins lymphoma, NHL usually originates in

lymphoid tissues and can spread to other organs.

NHL, however, is much less predictable than Hodgkinslymphoma and has a far greater predilection todisseminate to extra nodal sites.

The prognosis depends on the histological type, stage,

and treatment.


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EPIDEMIOLOGY

4-5% of cancer in US

2005: 58 875 cases, 18 840 will die

Both adults & children Men are more common than women

White > african & asian american

Risk of getting NHL during lifetime :

- Men : 1/46- Women : 1/55

Risk of dying : 1/100


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RISK FACTOR

Men > Women

Age , Risk

Weakened Immuned system

- inherited disease

- autoimmune disease

- human immunodeficiency virus (HIV)

- drugs given because you had an organ

transplant.


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infected with

- HTLV-1

- EBV

- Helicobacter pylori exposed to certain chemicals

- ingredients in pesticides

- herbicides

- solvents- fertilizers


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SIGNS & SYMPTOMS

Most common : painless swelling of the lymph nodes in the neck,underarm (axilla), or groin.

Other :

- Unexplained fever

- Night sweats- Constant fatigue

- Unexplained weight loss and anorexia (poor appetite)

- Itchy skin (pruritus)

- Reddened patches on the skin

Symptoms above cant 100% determine NHL- flu, other infection

- only doctor can make diagnosis
http://en.wikipedia.org/wiki/Feverhttp://en.wikipedia.org/wiki/Night_sweatshttp://en.wikipedia.org/wiki/Fatiguehttp://en.wikipedia.org/wiki/Weight_losshttp://en.wikipedia.org/wiki/Anorexiahttp://en.wikipedia.org/wiki/Itchhttp://en.wikipedia.org/wiki/Itchhttp://en.wikipedia.org/wiki/Anorexiahttp://en.wikipedia.org/wiki/Weight_losshttp://en.wikipedia.org/wiki/Fatiguehttp://en.wikipedia.org/wiki/Night_sweatshttp://en.wikipedia.org/wiki/Fever


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Swollen Lymph Node


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DIAGNOSIS Physical examination Medical history

Biopsy

- excisional

- incisional

- fine needle aspiration

Imaging studies

- chest x-ray

- computed tomography (CT) scan

- PET scan- MRI

- Lymphangiogram:
http://www.seattlecca.org/patientsandfamilies/adultCare/clinicalProgs/lymphoma/Definitions.htmhttp://www.seattlecca.org/patientsandfamilies/adultCare/clinicalProgs/lymphoma/Definitions.htmhttp://en.wikipedia.org/wiki/Lymphangiogramhttp://en.wikipedia.org/wiki/Lymphangiogramhttp://www.seattlecca.org/patientsandfamilies/adultCare/clinicalProgs/lymphoma/Definitions.htmhttp://www.seattlecca.org/patientsandfamilies/adultCare/clinicalProgs/lymphoma/Definitions.htm


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To diagnose whether the cancer has spread

around the lymph system or to other areas.

- CBC- Blood chemistry analysis

- Lumbar puncture

- Bone marrow test


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Biopsy


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TREATMENT

Chemotherapy

Radiation Therapy

Bone Marrow Transplantation Biological Therapy


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Chemotherapy

Uses drugs to kill cancer cell

Enter bloodstream & travel through body

Disadvantages kill healthy cell

Drug combination in cycle Given alone or with radiation therapy

Vein or mouth

Side effect :

- Nausea and vomiting

- Fatigue or tiredness- Hair loss

- Esophagitis or irritation of the swallowing tube


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Radiation Therapy

External beam

Linear accelerator

Short burst of x-ray

Square-shaped manner

Also kill other cell


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Bone Marrow Transplantation

injection of healthy stem cells from a

donor's bone marrow into your vein

The new stem cells travel through thebloodstream to your bone cavities.

Stem cells are cells that can produce red

blood cells, white blood cells, and

platelets.


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Biological Therapy

using medications or substances made

by the body to increase or restore your

body's natural defenses against cancer It is also called immunotherapy

Monoclonal antibodies and interferon are

examples of biological therapy used to

treat some types of lymphoma.


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CLASSIFICATION

Morphologic

Immune-Based

The Working FormulationUpdated REAL / WHO


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Morphologic Classification

type of involvement

1956 Rappaport Classification

Simple, separate more aggressive & lessaggressive


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Immune-Based Classification

Luke & Collins (1974) US

Kiel Classification Europe

Fits theoretic concepts of development of

lymphoid cell

Not gained universal acceptance bcoz :

- their complexity

- need ancillary test to reach precise diagnoses


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Working Formulation

Classification

1975, NCI develop The Working

Formulation of Non-Hodgkins

Lymphoma for Clinical UsageCurrently used in US


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Working Formulation Rappaport Classification

Low-grade

A. Small lymphocytic, consistent with chronic

lymphocytic leukemia (SL)

B. Follicular, predominantly small-cleaved cell

(FSC)

C. Follicular, mixed small-cleaved and large

cell (FM)

Intermediate-gradeD. Follicular, predominantly large cell (FL)

E. Diffuse, small-cleaved cell (DSC)

F. Diffuse mixed, small and large cell (DM)

G. Diffuse, large cell, cleaved or noncleaved

cell (DL)

High-grade

H. Immunoblastic, large cell (IBL)

I. Lymphoblastic, convoluted or

nonconvoluted cell (LL)

J. Small noncleaved-cell, Burkitt's or

non-Burkitt's (SNC)

- Diffuse lymphocytic, well-differentiated (DLWD)

- Nodular lymphocytic,poorly differentiated (NLPD)

- Nodular mixed, lymphocytic and histiocytic (NM)

- Nodular histiocytic (NH)- Diffuse lymphocytic, poorly differentiated (DLDP)

- Diffuse mixed, lymphocytic and histiocytic (DM)

- Diffuse histiocytic (DH)

- Diffuse histiocytic (DH)

- Diffuse lymphoblastic (DL)

- Diffuse undifferentiated Burkitt's or non-Burkitt's

(DU)


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Updated REAL / WHO

Classification

Working formulation became outdated

Since 1995, members of the European and AmericanHematopathology societies have been collaborating on anew World Health Organization (WHO) classification,

which represents an updated version of the REALsystem.

3 major categories of lymphoid malignancies based onmorphology and cell lineage:

- B-cell neoplasms

- T-cell/natural killer (NK)-cell neoplasms

- Hodgkins lymphoma


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I. B-cell neoplasm

IA Precursor B-cell neoplasm:

precursor B-acute lymphoblast

leukemia/lymphoblast lymphoma

(B-ALL, LBL).

IB Peripheral B-cell neoplasms.

1. B-cell chronic lymphocyticleukemia/small lymphocytic lymphoma.

2. B-cell prolymphocytic leukemia.

3. Lymphoplasmacyticlymphoma/immunocytoma.

4. Mantle cell lymphoma.

5. Follicular lymphoma.

6. Extranodal marginal zone B-celllymphoma of MALT type.

7. Nodal marginal zone B-cell lymphoma (monocytoid B-cells).

8. Splenic marginal zone lymphoma (villous lymphocytes).

9. Hairy cell leukemia.

10. Plasmacytoma/plasma cell myeloma.

11. Diffuse large B-cell lymphoma.

12. Burkitt's lymphoma.

II. T-cell and putative NK-cell neoplasm

IIA.Precursor T-cell neoplasm: precursor

T-acute lymphoblast

leukemia/lymphoblast lymphoma

(T- ALL, LBL).

IIB. Peripheral T-cell and NK-cell

neoplasms.

1. T-cell chronic lymphocyticleukemia/prolymphocytic leukemia.

2. T-cell granular lymphocytic leukemia.

3. Mycosis fungoides/Szary syndrome.

4. Peripheral T-cell lymphoma, nototherwise characterized.

5. Hepatosplenic gamma/delta T-celllymphoma.

6. Subcutaneous panniculitis-like T-celllymphoma.

7. Angioimmunoblastic T-cell lymphoma.

8. Extranodal T-/NK-cell lymphoma, nasaltype.

9. Enteropathy-type intestinal T-celllymphoma.

10. Adult T-cell lymphoma/leukemia (HTLV1+).

11. Anaplastic large cell lymphoma, primarysystemic type.

12. Anaplastic large cell lymphoma, primarycutaneous type.

13. Aggressive NK-cell leukemia.


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Hodgkins lymphoma (Hodgkins disease)

A. Nodular lymphocyte-predominant Hodgkinslymphoma.

B. Classical Hodgkins lymphoma.

1. Nodular sclerosis Hodgkins lymphoma.

2. Lymphocyte-rich classical Hodgkins

lymphoma.

3. Mixed-cellularity Hodgkins lymphoma.

4. Lymphocyte-depleted Hodgkins

lymphoma


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9. PREVENTION

Avoid Repeated Exposure to Certain

Chemicals

Avoid Exposure to HIV

Lymphopoietic System-kbk Blok Hematologi

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