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LYMPHOPOIETIC SYSTEM :
thymus, MALT
Lymphocytes : all derived from Bone Marrow stem cells. Thymus : T cells BM : B cells
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 peripheral blood.
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 .
cytoplasm. After activation and clonal expansion in germinal centers, B lymphocytes migrate B cell-dependt medullary cords of lymph nodes Igsecreting plasma cells or exit lymph nodes as memory B lymphocytes.
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 export immunoglobulins.
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 export immunoglobulins.
express neither B nor T cell differentiation antigens. Act as cytotoxic or natural killer cells (NK cells. CD56+, CD3-, and CD8-
LYMPH NODES
Outer cortex and an inner medulla .
B-cell-dependent cortex : Inactive follicles (primary follicles) cohesive
aggregates of small, normal-appearing lymphocytes. Active follicles (secondary follicles) Germinal centers contain large lymphocytes (centroblasts) and small lymphocytes with cleaved nuclei (centrocytes) & scattered macrophages.
lymphadenitis. Follicular Hyperplasia : Hyperplasia of secondary follicles (germinal centers) and plasmacytosis of medullary cords indicate B lymphocyte immunoreactivity nonspecific reactive follicular hyperplasia etiology not known (viral, drug/inflammatory), AIDS.
nonspecific interfollicular hyperplasia viral infections or immunologic reactions mononucleosis, varicella-herpes zoster infection, measles, and cytomegalovirus lymphadenitis, SLE. Mixed Patterns hyperplasia toxoplasmosis, Cat-scratch disease, lymphogranuloma venereum and tularemia
MALIGNANT LYMPHOMA
Non Hodgkin Lymphoma.
Hodgkin Lymphoma.
lymphoproliferative malignancies with differing patterns of behavior 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 Hodgkins lymphoma and has a far greater predilection to disseminate to extra nodal sites. The prognosis depends on the histological type, stage, and treatment.
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 :
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.
infected with
- HTLV-1 - EBV - Helicobacter pylori exposed to certain chemicals - ingredients in pesticides - herbicides - solvents - fertilizers
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
DIAGNOSIS
Physical examination Medical history Biopsy
- excisional - incisional - fine needle aspiration Imaging studies - chest x-ray - computed tomography (CT) scan - PET scan - MRI - Lymphangiogram:
around the lymph system or to other areas. - CBC - Blood chemistry analysis - Lumbar puncture - Bone marrow test
Biopsy
TREATMENT
Chemotherapy
Radiation Therapy Bone Marrow Transplantation
Biological Therapy
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
Radiation Therapy
External beam
Linear accelerator Short burst of x-ray Square-shaped manner Also kill other cell
donor's bone marrow into your vein The new stem cells travel through the bloodstream to your bone cavities. Stem cells are cells that can produce red blood cells, white blood cells, and platelets.
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.
CLASSIFICATION
Morphologic
Immune-Based The Working Formulation
Morphologic Classification
type of involvement
1956 Rappaport Classification Simple, separate more aggressive & less
aggressive
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
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-grade D. 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)
- Nodular histiocytic (NH) - Diffuse lymphocytic, poorly differentiated (DLDP) - Diffuse mixed, lymphocytic and histiocytic (DM) - Diffuse histiocytic (DH)
Hematopathology societies have been collaborating on a new World Health Organization (WHO) classification, which represents an updated version of the REAL system. 3 major categories of lymphoid malignancies based on morphology and cell lineage: - B-cell neoplasms - T-cell/natural killer (NK)-cell neoplasms - Hodgkins lymphoma
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. 2. 3. 4. 5. 6.
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. 2. 3. 4. 5.
7.
8. 9. 10. 11. 12.
B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. B-cell prolymphocytic leukemia. Lymphoplasmacytic lymphoma/immunocytoma. Mantle cell lymphoma. Follicular lymphoma. Extranodal marginal zone B-cell lymphoma of MALT type. Nodal marginal zone B-cell lymphoma ( monocytoid B-cells). Splenic marginal zone lymphoma ( villous lymphocytes). Hairy cell leukemia. Plasmacytoma/plasma cell myeloma. Diffuse large B-cell lymphoma. Burkitt's lymphoma.
6.
7. 8. 9. 10. 11. 12. 13.
T-cell chronic lymphocytic leukemia/prolymphocytic leukemia. T-cell granular lymphocytic leukemia. Mycosis fungoides/Szary syndrome. Peripheral T-cell lymphoma, not otherwise characterized. Hepatosplenic gamma/delta T-cell lymphoma. Subcutaneous panniculitis-like T-cell lymphoma. Angioimmunoblastic T-cell lymphoma. Extranodal T-/NK-cell lymphoma, nasal type. Enteropathy-type intestinal T-cell lymphoma. Adult T-cell lymphoma/leukemia (HTLV 1+). Anaplastic large cell lymphoma, primary systemic type. Anaplastic large cell lymphoma, primary cutaneous type. Aggressive NK-cell leukemia.
Hodgkins lymphoma (Hodgkins disease) A. Nodular lymphocyte-predominant Hodgkins lymphoma. 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
9. PREVENTION
Avoid Repeated Exposure to Certain