malignant lymphomas by fatin al-sayes md, msc, frcpath associate professor, & consultant...
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Malignant Lymphomas
by Fatin Al-SayesMD, MSc, FRCPath
Associate Professor, & ConsultantHaematologist
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Malignant LymphomasHodgkin’s Lymphoma (HL) Described Originally in 1832
by Sir Thomas Hodgkin’s Less common than non-Hodgkin lymphoma The incidence of HL is bimodal Unknown etiology Viral factors may play a causal role
EB Virus HIV Cont’n
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Malignant Lymphomas
Clustering of cases in a single household ? Other environmental factors ±genetic
predisposition play a significant role in the pathogenesis of the disease.
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Superficial Lymphadenopathy Lymph nodes are non tender Rubbery in Consistency Firm, discrete
Constitutional Fever > (38ºC) Drenching night sweats Loss of more than 10% of usual weight
Clinical features
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Clinical features :cont
Hepatomegaly Splenomegaly (50%) pf the patients Mediastinal involvement in 6- 10% Sings due to infections or anemia.
Enlarged retroperitoneal lymph nodes may be associated with pressure symptoms.e.g. obstruction of the ureters.
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Other Constitutional Symptoms Pruritus Alcohol-induced pain in areas of
disease involvement
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Diagnosis: Laboratory Tests Abnormalities in the peripheral blood
Normochromic, normocytic anemia Neutrophilia in 1/3 of patients Eosinophilia monocytosis and lymphopenia Thrombocytosis during early disease, &
thrombocytopenia with advanced disease.
Cont’n
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High acute phase reactant useful in monitoring disease progress e.g. ESR C- reactive protein Ferritin Plasma viscosity
Liver function test abnormalities
Cont’n
Continuation Diagnosis Laboratory Tests
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Lymph node biopsy Diagnosis is by tissue biopsy The Reed - sternberg cell, the neoplastic cell in a
reactive background
Rye Classification Lymphocyte predominant Nodular Sclorosis Mixed Cellularity Lymphocyte depleted
Continuation Diagnosis Laboratory Tests
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Stage-1: involvement of a single lymph node region
Stage-2: involvement of 2 or more lymph node regions on the same side of the diaphragm.
Stage-3: involvement of lymph node regions on both sides of the diaphragm.
Cont’n
Staging of the diseaseAnn arbor staging system
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Stage-4: Diffuse or disseminated involvement
Each stage is further subdivided intoA: Absence of B symptoms
B: Presence of B symptoms
E: Involvement of an extra nodal sites
X: Bulky disease > 10cm in any single dimension
Continuation of Staging of the disease Ann arbor staging system
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CT Scan of chest, abdomen and pelvis ± neck
Gallium Scan Bone marrow biopsy in advanced
disease is usually positive
?? Liver biopsy
???? laparotomy
Continuation of Staging of the disease Ann arbor staging system
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Early stage (HL) Radio-therapy Combined modality treatment
Advanced Stage (HL) Chemotherapy “ ABVD” 6 – 8 cycles
Relaped Cases Salvage chemotherapy Autologus bone marrow transplantation
Treatment
Continuation of Staging of the disease Ann arbor staging system
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5- years survival rate are for stage “1+2” 85% 5-Years survival rate are for stage “3+4”60%
Curative Disease
Continuation of Staging of the disease Ann arbor staging system
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Mostly of B- lymphocyte origin The incidence of this disorder is increasing at an
annual rate of 4% for men and 3% for women Viruses
HTLV-1 EB HIV ? Hep-C Virus
Cont’n
Non-Hodgkin’s Lymphomas (NHL)
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Cytogenetics and Oncogenes Burkett's Lymphoma ~ MYC
t (8:14), t (8:22), t( 2:8) Immuno Suppression e.g.
Coeliac Disease Dermatitis herpetiform
Autoimmune diseases ~ NHL frequency
Continuation of Non-Hodgkin’s Lymphomas (NHL)
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Peripheral Lymhadenopathy Abdominal or mediastinal masses C.N.S.or bone marrow involvement Waldeyer’s rings 15-30 % Constitutional symptoms e.g. fever,night sweat,
and weight loss Anemia, neutropenia, & thrombocytopenia Involvement of other organs e.g. skin, brain,
testes, etc.
Clinical FeaturesContinuation of Non-Hodgkin’s Lymphomas (NHL)
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A normocytic, normochromic anemia or autoimmune hemolytic anemia
Leucopenia and thrombocytopenia PBF assessment
Lymphoma Cells Liver function tests abnormalities Elevation of serum creatinine High LDH important for diagnosis & prediction of outcome. Serum uric acid may be elevated especially when the tumor
burden is high. Cont’n
Laboratory FeaturesContinuation of Non-Hodgkin’s Lymphomas (NHL)
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adequate tissue biopsy immunologic analysis, flowcytometry molecular analysis Bone marrow aspiration and trephine
biopsy
Diagnosis
Continuation of Non-Hodgkin’s Lymphomas (NHL)
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International working formulation REAL Classification WHO Classification
Classifications
Continuation of Non-Hodgkin’s Lymphomas (NHL)
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Ann Arbor Staging SystemNHL does not spread by orderly,
anatomic pathways International Prognostic Index
Age ≤60 or >60 years Stage I/II, III, IV Number of extranodal sites Performance status (0, 1 or 2, 3, 4) LDH
Staging
Continuation of Non-Hodgkin’s Lymphomas (NHL)
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Therapy for patients with indolent lymphoma
Early Stages I, II
■ Uncommon Involved fields radiotherapy 2.5-4Gy
Advanced Stages ■ remains controversial ■ vast majority of patients are not cured
■ for a symptomatic patients, deferred therapy with careful observation
■ oral alkylating agent steroid
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■ combination chemotherapy such as CHOP ■ purine nucleoside fludrabine
■ anti-CD20 monoclonal antibody may be considered as first line therapy alone or in conjunction with chemotherapy
■ Intensive therapy with chemotherapy and radiotherapy followed by autologus peripheral stem cell transplantation.
Therapy for patients with indolent lymphoma con
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Continuation of Non-Hodgkin’s Lymphomas (NHL
Diffuse Large – B-cell lymphoma
Early Stages I & II
■ low dose irradiation
■ or low dose irradiation and abbreviated CHOP
Advanced Stages II bulky, III & IV
CHOP-R remain the best available standard therapy
(50-85%) CR
cure rate (25-45%)
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Continuation of Non-Hodgkin’s Lymphomas (NHL
I. Doxorubcin (Adriamycin) ■ Inhibits topoisomerase II, produce force radicals, which
may cause DNA destruction. Side effects: - severe heart failure& cardiomyopathy - impaired cardiac function - myelosuppression
- extravasationlocal tissue necrosisII. Vinrestine (oncovin) vinca alkaloidantimitosis Side effects: - hepatic impairment - neuromuscular dysfunction
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Continuation of Non-Hodgkin’s Lymphomas (NHL
III. Cyclophosphamide (cytoxan)
Alkylating agent
■ Cross linking of DNA which may interfere with
growth of normal and neoplastic cells
Side effects: - myelosuppression
- hemorrhagic cystitis
Iv . Monoclonal antibody Rituximab (375 mg/m2 ) infusion over 4-5 hours
Side effects: - anaphylaxis
- hypotention, chills fever etc.
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Salvage Therapy
Second or third line chemotherapy
Autologous bone marrow transplantation
Continuation of Non-Hodgkin’s Lymphomas (NHL)
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Special Clinical Syndrome MALT Lymphoma
o Helicobacter pylori associated Burkitt’s Lymphoma
o young African childreno jaw lesionso extranodal abdominal involvemento C-Myc Oncogen
Mycosis fungoides and sézarýs syndromeo Cutaneous T-cell lymphomao Psoriasis like lesionso Affection of deeper organs such as lymph node,
spleen, liver, and bone marrow.
Continuation of Non-Hodgkin’s Lymphomas (NHL)
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