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Objectives: The types of lymphoma. Clinical Presentation of lymphomas Diagnosis of lymphomas Investigations of lymphomas. Staging of lymphomas Treatment.

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Presentation on theme: "Objectives: The types of lymphoma. Clinical Presentation of lymphomas Diagnosis of lymphomas Investigations of lymphomas. Staging of lymphomas Treatment."— Presentation transcript:

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2 Objectives: The types of lymphoma. Clinical Presentation of lymphomas Diagnosis of lymphomas Investigations of lymphomas. Staging of lymphomas Treatment options of Lymphomas.

3 Lymphomas Definition Neoplasms of lymphoid tissues Typically causes lymphadenopathy.

4 Epidemiology of lymphomas A common cancer A common cancer 5 th most frequently diagnosed cancer MF M ales > F emales

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6 Routine microscopic examination Immunological examination Routine microscopic examination Immunological examination

7 Large malignant lymphoid cell Bi-nucleated B-cell origin Present in small numbers Surrounded by reactive T-cells, plasma cells and eosinophils.

8 The pathology report Hodgkin Lymphoma Non-Hodgkin Lymphoma Reed Sternberg Cell Based on the pathological findings: Hodgkin lymphoma Non Hodgkin lymphoma

9 Hodgkin ’ s Lymphoma

10 Hodgkin Lymphoma All are B-Cells

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12 Sex Epidemiology Sex 1.51 :

13 Age Epidemiology Age A bimodal peaks: A bimodal peaks: the 3 rd and the 6 th decades. 20s >50s a bimodal age-incidence curve

14 Aetiology Epidemiology Aetiology Unknown Unknown Well-educated background Small families. Past history of infectious mononucleosis, no proven link to EB virus yet.

15 Clinical Features Symptoms

16 Symptoms Clinical Features of Hodgkin Lymphoma Symptoms Painless Neck Swelling

17 Nodular Sclerosing disease Large Mediastinal Mass Nodular Sclerosing disease

18  Weight loss  Sweating  Itching  Fever  Weight loss  Sweating  Itching  Fever Systemic Symptoms Clinical Features of Hodgkin Lymphoma Systemic Symptoms

19 Clinical Features Physical Signs

20 Painless, Rubbery Usually at neck and supraclavicular areas 10% sub-diaphragmatic

21 Sites of LN involvment in HL Peripheral LN Peripheral LN Cervical, supraclavicular and axillary LN (70%) Generalized lymphadenopathy is not typical in HL Thorax Thorax Anterior mediastinum in NS HL Others, Rare: Lung Pleural effusion Pericardial effusion SVC obstruction Abdomen Abdomen Hepatosplenomegaly. Retroperitoneal LN.

22 InfectionsInfections Autoimmune disorders HaematologicalLymphomasLeukemiasHaematologicalLymphomasLeukemias MetastasesMetastases AIDSAIDS BenignBenign

23 Could be because of: Disease infiltration. Disease infiltration. Reactive ( Reactive ( no infiltration).

24 CONTIGUOUS SPREAD From one LN to the next.

25 Rare Extranodal Disease:  Bone  Brain  Skin

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28 Investigations of HL Confirm the Diagnosis Histological Subtype Confirm the Diagnosis Histological Subtype Lymph Node Biopsy Biopsy from other tissues Lymph Node Biopsy Biopsy from other tissues Staging Hodgkin Lymphoma Staging Blood Tests Radiology Other biopsies Blood Tests Radiology Other biopsies

29 Taking the biopsy? Lymph Node Biopsy Taking the biopsy? Surgical excision Percutaneous needle biopsy under radiological guidance

30 Hodgkin lymphoma - Histological subtypes The WHO classification Nodular lymphocyte predominant HL (5%) Nodular lymphocyte predominant HL (5%) Slow growing Localized Rarely Fatal Classical Hodgkin lymphoma (95%) Classical Hodgkin lymphoma (95%) nodular sclerosing young, F>M mixed cellularityElderly lymphocyte-richMen lymphocyte depleted?NHL Nodular lymphocyte predominant HL (5%) Nodular lymphocyte predominant HL (5%) Slow growing Localized Rarely Fatal Classical Hodgkin lymphoma (95%) Classical Hodgkin lymphoma (95%) nodular sclerosing young, F>M mixed cellularityElderly lymphocyte-richMen lymphocyte depleted?NHL

31 Investigations of HL Confirm the Diagnosis Histological Subtype Confirm the Diagnosis Histological Subtype Lymph Node Biopsy Biopsy from other tissues Lymph Node Biopsy Biopsy from other tissues Staging Hodgkin Lymphoma Staging Blood Tests Radiology Other biopsies Blood Tests Radiology Other biopsies

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33  Complete blood count  May be Normal  Normochromic, normocytic anaemia  Lymphopenia ( A bad sign)  Eosinophilia  Neutrophilia  ESR, may be raised

34  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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40 Indications Hodgkin Lymphoma when bone marrow involvement is suspected 1- Hodgkin Lymphoma when bone marrow involvement is suspected abnormal full blood countabnormal full blood count advanced stage of the diseaseadvanced stage of the disease. 2-ALL cases of Non Hodgkin Lymphoma.

41 Stage IStage IIStage IIIStage IV

42 Bulky Disease > 1. Mediastinal mass > ⅓ of the maximum transverse diameter of the chest > 2. Presence of nodal mass with a maximal dimension > 10cm

43 “B”symptoms Unexplained Fever > 38 o C 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 LYMPHOMA STAGING

44 I AI B II AII B III A IV AIV B

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46 INTENTION OF TREATMENT ISCURE With appropriate treatment: 90% of Stage IA are cured 70% of other stages are cured

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48 Stage IA-IIA Nodular Lymphocyte Predominant HL Chemotherapy (ABVD) 2-6 courses + Involved Field Radiotherapy (IFRT) Chemotherapy (ABVD) 2-6 courses + Involved Field Radiotherapy (IFRT) 1- Bulky disease 2- Residual disease 1- Bulky disease 2- Residual disease Chemotherapy (ABVD) 8 coursesChemotherapy Radiotherapy ONLY

49 ADRIAMYCIN (DOXORUBICIN) BLEOMYCIN VINBLASTINE DACARBAZINE

50 Long term complications of treatment

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52 Non-Hodgkin Lymphoma

53 Sex Epidemiology Sex

54 Age distribution of new NHL cases Median Age: yrs

55 Etiology of NHL Infection: 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

56 NHL Low grade NHL Intermediate/High grade NHL Small cell size Round or cleaved nuclei Low mitotic rate Small cell size Round or cleaved nuclei Low mitotic rate Larger cell size Prominent nucleoli Higher 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 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 Aggressive NHL High proliferation rate Rapidly produce symptoms Fatal if untreated

57 Non-Hodgkin lymphoma Incidence Diffuse large B-cell lymphoma (High Grade) Follicular Lymphoma (Low Grade) Other NHL

58 Clinical Features Symptoms

59 Symptoms Clinical Features of NHL Symptoms Painless Swelling Neck Neck Axilla Axilla Groins Groins Painless Swelling Neck Neck Axilla Axilla Groins Groins

60  Weight loss  Sweating  Itching  Fever  Weight loss  Sweating  Itching  Fever Systemic Symptoms Clinical Features of NHL Systemic Symptoms

61 Clinical Features Physical Signs

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63 If present indicates; If present indicates; Disease infiltration. Disease infiltration.

64 SKIPPY SPREAD

65 Extranodal Disease:  Bone Marrow: Low Grade> High Grade  Gut  Thyroid  Lung  Testis  Brain  Skin  Bone, rare

66  Intestinal Obstrucion  Ascites  SVC obstrucion  Spinal Cord Compression More Common in NHL

67 NHL vs. HL Clinical Features HLNHL Extent at presentation LocalizedDisseminated Spread to LN ContingousSkippy Extra-nodal Disease Rare More common Obstruction Syndromes Less Common More common

68 Stage IStage IIStage IIIStage IV Staging of lymphoma Cotswolds Staging classification

69 “B”symptoms Unexplained Fever > 38 o C 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 LYMPHOMA STAGING

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71 1. 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 2. Radiological examinatons

72 3-Bone Marrow biopsy Indications of bone marrow biopsy: Hodgkin Lymphoma when bone marrow involvement is suspected abnormal full blood count advanced stage of the disease. ALL cases of Non Hodgkin Lymphoma. 2-ALL cases of Non Hodgkin Lymphoma.

73  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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75 Indications for treatment Systemic Symptoms Rapid nodal growth Bone Marrow involvment. Compression Syndromes Indications for treatment Systemic Symptoms Rapid nodal growth Bone Marrow involvment. Compression Syndromes Radiotherapy Radiotherapy Chemotherapy (Chlarambucil, Fludarabine)Single agent (Chlarambucil, Fludarabine) (CVP)Or; Combination chemotherapy (CVP) Rituximab (Monoclonal Antibody) for CD-20 positive follicular lymphomaRituximab (Monoclonal Antibody) for CD-20 positive follicular lymphomaChemotherapy (Chlarambucil, Fludarabine)Single agent (Chlarambucil, Fludarabine) (CVP)Or; Combination chemotherapy (CVP) Rituximab (Monoclonal Antibody) for CD-20 positive follicular lymphomaRituximab (Monoclonal Antibody) for CD-20 positive follicular lymphoma Observation and Follow up Palliative Radiotherapy for: SVC obstruction Spinal Cord Compression Pain Palliative Radiotherapy for: SVC obstruction Spinal Cord Compression Pain Active Treatment

76 Chemotherapy (CHOP) 3 cycles Chemotherapy (CHOP) 3 cycles Chemotherapy (CHOP) 6-8 cycles Chemotherapy (CHOP) + Rituximab For CD20 + Diffuse large B Cell lymphoma Chemotherapy (CHOP) + Rituximab For CD20 + Diffuse large B Cell lymphoma AND Radiotherapy AND Radiotherapy Radiotherapy to area of bulky disease Radiotherapy to area of bulky disease Autologus Stem Cell Transplantation

77 CYCLOPHOSPHAMIDEDOXORUBICIN VINCRISTINE (Oncovin) PREDNISOLONE

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79 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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82 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

83 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%

84 HLNHLIncidence4: /yr12: /yr Reed-Sternberg cells PresentAbsent Cell Type B-cellB-cell(70%), T-cell(30%) SexMales>Females Medial Age 31 yrs65-70 yrs LN enlragement Usually supradiaphragmatic Any where Spread pattern ContiguousSkipped Extranodal involvement Less commonMore common Determinants of treatment Stage (I,II,III,IV) B symptoms Grade (Low/High) Stage(I,II,III,IV)

85 CategorySurvival of untreated patients CurabilityTo treat or not to treat Non- Hodgkin lymphoma Indolent Low Grade YearsGenerally not curable Generally defer Rx if asymptomatic Aggressive High Grade Weeks Months Curable in some Treat Hodgkin lymphoma All typesVariable – months to years Curable in most Treat

86 Modes of Spread of Lymphoma Hodgkin Lymphoma originate in a LN Almost always originate in a LN Contiguous spread Contiguous spread Extranodal disease to bone, brain or skin is rare.


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