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Lymphomas Ismail M. Siala
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Objectives: The types of lymphoma. Clinical Presentation of lymphomas
Diagnosis of lymphomas Investigations of lymphomas. Staging of lymphomas Treatment options of Lymphomas.
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Definition Lymphomas Neoplasms of lymphoid tissues
Typically causes lymphadenopathy.
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Epidemiology of lymphomas
A common cancer 5th most frequently diagnosed cancer Males > Females
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Classification of Lymphomas
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Lymph Node Bone Marrow Bx Other Tissue
Routine microscopic examination Immunological examination
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Reed-Sternberg Cell Large malignant lymphoid cell Bi-nucleated
B-cell origin Present in small numbers Surrounded by reactive T-cells, plasma cells and eosinophils.
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Based on the pathological findings:
Reed Sternberg Cell The pathology report Based on the pathological findings: Hodgkin lymphoma Non Hodgkin lymphoma Hodgkin Lymphoma Non-Hodgkin Lymphoma
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Hodgkin’s Lymphoma Thomas Hodgkin ( )
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Hodgkin Lymphoma All are B-Cells
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Hodgkin Lymphoma = Reed-Sternberg cell
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Epidemiology Sex > : 1.5 1
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Epidemiology Age A bimodal peaks: the 3rd and the 6th decades.
a bimodal age-incidence curve
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Epidemiology Aetiology
Unknown Well-educated background Small families. Past history of infectious mononucleosis, no proven link to EB virus yet.
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Clinical Features Symptoms
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Clinical Features of Hodgkin Lymphoma Symptoms
Painless Neck Swelling
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Large Mediastinal Mass Nodular Sclerosing disease
Dry Cough Large Mediastinal Mass Nodular Sclerosing disease Breathlessness
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Clinical Features of Hodgkin Lymphoma Systemic Symptoms
Weight loss Sweating Itching Fever
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Clinical Features Physical Signs
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Lymphadenopathy Painless, Rubbery
Usually at neck and supraclavicular areas 10% sub-diaphragmatic
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Sites of LN involvment in HL
Peripheral LN Cervical, supraclavicular and axillary LN (70%) Generalized lymphadenopathy is not typical in HL Thorax Anterior mediastinum in NS HL Others, Rare: Lung Pleural effusion Pericardial effusion SVC obstruction Abdomen Hepatosplenomegaly. Retroperitoneal LN.
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Differential Diagnosis of Lymph-adenopathy
Infections Autoimmune disorders Haematological Lymphomas Leukemias AIDS Metastases Benign
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Hepatosplenomegaly Could be because of: Disease infiltration.
Reactive ( no infiltration).
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Spread to other LN groups
CONTIGUOUS SPREAD From one LN to the next.
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Extranodal Disease Rare Extranodal Disease: Bone Brain Skin
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Investigations of HL
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Hodgkin lymphoma Treatment depends on: Histological Subtype
Clinical Stage
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Investigations of HL Confirm the Diagnosis Histological Subtype
Staging Hodgkin Lymphoma Lymph Node Biopsy Biopsy from other tissues Blood Tests Radiology Other biopsies
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Lymph Node Biopsy Taking the biopsy?
Surgical excision Percutaneous needle biopsy under radiological guidance
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Hodgkin lymphoma - Histological subtypes The WHO classification
Nodular lymphocyte predominant HL (5%) Slow growing Localized Rarely Fatal Classical Hodgkin lymphoma (95%) nodular sclerosing young, F>M mixed cellularity Elderly lymphocyte-rich Men lymphocyte depleted ?NHL
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Investigations of HL Confirm the Diagnosis Histological Subtype
Staging Hodgkin Lymphoma Lymph Node Biopsy Biopsy from other tissues Blood Tests Radiology Other biopsies
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Blood Investigations
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Complete blood count ESR, may be raised May be Normal
Normochromic, normocytic anaemia Lymphopenia ( A bad sign) Eosinophilia Neutrophilia ESR, may be raised
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Renal function tests, need to be normal before Rx.
Liver function tests May be Normal Abnormal With infiltraion or without infiltraion Obstructive pattern enlarged LN at porta hepatis. Renal function tests, need to be normal before Rx. Serum LDH Reflect level of tumor bulk and turnover Not of great significance in HL
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Radiological Investigations
Blood Investigations Radiological Investigations
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Chest X-Ray
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Abdominal Ultrasound Evaluation of the abdomen and retroperitoneum Lymph Nodes Liver, Spleen, Kidneys
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CT-Scan of Chest, Abdomen and Pelvis
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Radiological Investigations
Blood Investigations Radiological Investigations Bone Marrow Biopsy
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Bone Marrow biopsy Indications
1- Hodgkin Lymphoma when bone marrow involvement is suspected abnormal full blood count advanced stage of the disease. 2-ALL cases of Non Hodgkin Lymphoma.
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Staging of lymphoma Ann Arbor classification
Stage I Stage II Stage III Stage IV
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Bulky Disease Mediastinal mass >⅓ of
the maximum transverse diameter of the chest Presence of nodal mass with a maximal dimension > 10cm
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LYMPHOMA STAGING “B” symptoms Stage A No B symptoms
Unexplained Fever > 38oC Unexplained Weight loss > 10% body weight within the preceding 6 months. Drenching night sweets Stage A No B symptoms Stage B any one of the B symptoms
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Stages of Lymphoma I A I B II A II B III A IV A IV B
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Management of Hodgkin Lymphoma
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HODGKIN`S LYMPHOMA MANAGEMENT
INTENTION OF TREATMENT IS CURE With appropriate treatment: 90% of Stage IA are cured 70% of other stages are cured
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Hodgkin lymphoma Treatment depends on: Histological Subtype
Clinical Stage
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+ Involved Field Radiotherapy (IFRT)
Treatment of HL Stage I-II Stage III-IV Radiotherapy ONLY Chemotherapy (ABVD) 8 courses Stage IA-IIA Nodular Lymphocyte Predominant HL Radiotherapy ONLY FOR: Chemotherapy (ABVD) 2-6 courses + Involved Field Radiotherapy (IFRT) 1- Bulky disease 2- Residual disease
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ADRIAMYCIN(DOXORUBICIN)
ABVD A ADRIAMYCIN(DOXORUBICIN) B BLEOMYCIN V VINBLASTINE D DACARBAZINE Give day 1 & 15 every 4 weeks
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Long term complications of treatment
Infertility sperm banking should be discussed premature menopause secondary malignancy skin, AML, lung, MDS, NHL, thyroid, breast... cardiac disease
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Non-Hodgkin Lymphoma
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Epidemiology Sex >
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Age distribution of new NHL cases
Median Age: yrs
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Etiology of NHL Infection: Immunodeficiency:
Viral Infections: EBV Burkitt Human Herpes virus 8 HTLV Chronic H.pylori infection gastric lymphoma Immunodeficiency: AIDS Organ transplant Previous treatment for HL chemo or radiotherapy Chromosomal, T(14:18) in follicular lymphoma
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Intermediate/High grade NHL
Low grade NHL Intermediate/High grade NHL Small cell size Round or cleaved nuclei Low mitotic rate Larger cell size Prominent nucleoli Higher mitotic rate Indolent/ non aggressive NHL Low proliferation rate Late symptoms Indolent course – uncurable with conventional therapy Aggressive NHL High proliferation rate Rapidly produce symptoms Fatal if untreated
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Non-Hodgkin lymphoma Incidence
Diffuse large B-cell lymphoma (High Grade) Follicular Lymphoma (Low Grade) 85% of NHL Other NHL
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Clinical Features Symptoms
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Clinical Features of NHL Symptoms
Painless Swelling Neck Axilla Groins
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Clinical Features of NHL Systemic Symptoms
Weight loss Sweating Itching Fever
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Clinical Features Physical Signs
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Lymphadenopathy
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Hepatosplenomegaly If present indicates; Disease infiltration.
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Spread to other LN groups
SKIPPY SPREAD
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Specially in T-Cell Lymphoma
Extranodal Disease Extranodal Disease: Bone Marrow: Low Grade> High Grade Gut Thyroid Lung Testis Brain Skin Bone , rare More Common in nhl Specially in T-Cell Lymphoma
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Compression Syndromes
Intestinal Obstrucion Ascites SVC obstrucion Spinal Cord Compression More Common in NHL
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NHL vs. HL Clinical Features
Extent at presentation Localized Disseminated Spread to LN Contingous Skippy Extra-nodal Disease Rare More common Obstruction Syndromes Less Common
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Staging of lymphoma Cotswolds Staging classification
Stage I Stage II Stage III Stage IV
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LYMPHOMA STAGING “B” symptoms Stage A No B symptoms
Unexplained Fever > 38oC Unexplained Weight loss > 10% body weight within the preceding 6 months. Drenching night sweets Stage A No B symptoms Stage B any one of the B symptoms
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Investigations of NHL
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As in Hodgkin Lymphoma Hematological examinatons:
Complete blood count Liver function tests Renal function tests Serum LDH Reflect level of tumor bulk and turnover Particularly of relevance in aggressive NHL Radiological examinatons
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3-Bone Marrow biopsy Indications of bone marrow biopsy:
1- Hodgkin Lymphoma when bone marrow involvement is suspected abnormal full blood count advanced stage of the disease. 2-ALL cases of Non Hodgkin Lymphoma.
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As in Hodgkin Lymphoma PLUS
Immunophenotyping of surface antigens: B-Cell or T-Cell Immunoglobulin Levels, some NHL cause raised IgG or IgM levels. Serum Uric Acid Raised in high grade NHL renal failure if not treated. HIV testing, If relevant to clinical condition..
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Non Hodgkin lymphoma Treatment depends on: Grade ( Low or High)
Clinical Stage
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Treatment of Low Grade NHL
Indications for treatment Systemic Symptoms Rapid nodal growth Bone Marrow involvment. Compression Syndromes Observation and Follow up Active Treatment Stage I-II Radiotherapy Palliative Radiotherapy for: SVC obstruction Spinal Cord Compression Pain Stage III-IV Chemotherapy Single agent (Chlarambucil, Fludarabine) Or; Combination chemotherapy (CVP) Rituximab (Monoclonal Antibody) for CD-20 positive follicular lymphoma
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Treatment of high Grade NHL Chemotherapy (CHOP) 3 cycles
Stage I-II – Non Bulky Chemotherapy (CHOP) 3 cycles AND Radiotherapy Stage I-II – Bulky Stage III-IV Chemotherapy (CHOP) 6-8 cycles Chemotherapy (CHOP) + Rituximab For CD20 + Diffuse large B Cell lymphoma Radiotherapy to area of bulky disease Relapsed Disease Autologus Stem Cell Transplantation
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Repeat cycle every 3 weeks
CHOP C CYCLOPHOSPHAMIDE H DOXORUBICIN O VINCRISTINE (Oncovin) P PREDNISOLONE Repeat cycle every 3 weeks
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Rituximab Monoclonal Antibody Against CD20 antigen.
Can be combined with other chemotherapy Used for Diffuse Large B cell Lymphoma Follicular Lymphoma that is CD20 positive
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Gastric MALToma Low grade histology Related to H.pylori infection
Surgery is not routinely performed. Treatment: Treat H.pylori infection Chemotherapy if; Large cell component Deeply penetrating Metastatic Relapsing
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Thank you all for your attention
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Classification of NHL The working formulation (1982)
Clinical behaviour + histopathological features Not incorporated the origin of the cell ( B or T) Missing a large variaty of new clinicopathological entities. The WHO/REAL classification (1993) Incorporates immunophenotypes Differentiate between cells of T or B origin Recognizes seversal less common entities
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The International Prognostic Index (IPI) for NHL
Five independent prognostic factors 1- age older than 60 years 2- higher stage (III or IV) 3- More than one extranodal site involvement 4- lower performance status ( ECOG>1) 5- elevated serum LDH 0-1 5 yr survival is 73% 4-5 5 yr survival is 26%
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A practical way to think of lymphoma
HL NHL Incidence 4: /yr 12: /yr Reed-Sternberg cells Present Absent Cell Type B-cell B-cell(70%), T-cell(30%) Sex Males>Females Medial Age 31 yrs 65-70 yrs LN enlragement Usually supradiaphragmatic Any where Spread pattern Contiguous Skipped Extranodal involvement Less common More common Determinants of treatment Stage (I,II,III,IV) B symptoms Grade (Low/High) Stage(I,II,III,IV)
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A practical way to think of lymphoma
Category Survival of untreated patients Curability To treat or not to treat Non-Hodgkin lymphoma Indolent Low Grade Years Generally not curable Generally defer Rx if asymptomatic Aggressive High Grade Weeks Months Curable in some Treat Hodgkin lymphoma All types Variable – months to years Curable in most
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Modes of Spread of Lymphoma
Hodgkin Lymphoma Almost always originate in a LN Contiguous spread Extranodal disease to bone, brain or skin is rare. Non Hodgkin Lymphoma Usually widespread at presentation Skippy spread Extranodal involvement is more common than in HL Bone marrow, GIT, Thyroid, Lung, Skin , testis, Brain and Bone.
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