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Lymphoma David Lee MD, FRCPC
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Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma
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Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages
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ALLMMCLLLymphomas Hematopoietic stem cell Neutrophils Eosinophils Basophils Monocytes Platelets Red cells Myeloid progenitor Myeloproliferative disorders AML Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve
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B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell memory B-cell plasma cell DLBCL, FL, HL ALL CLL MM germinalcenterB-cell mature naive B-cell
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Clinically useful classification Diseases that have distinct clinical features natural history prognosis treatment Biologically rational classification Diseases that have distinct morphology immunophenotype genetic features clinical features Classification
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Lymphoma classification (2001 WHO) B-cell neoplasms –precursor –mature T-cell & NK-cell neoplasms –precursor –mature Hodgkin lymphoma Non- Hodgkin Lymphomas
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A practical way to think of lymphoma CategorySurvival of untreated patients CurabilityTo treat or not to treat Non- Hodgkin lymphoma IndolentYearsGenerally not curable Generally defer Rx if asymptomatic AggressiveMonthsCurable in some Treat Very aggressive WeeksCurable in some Treat Hodgkin lymphoma All typesVariable – months to years Curable in most Treat
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Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression
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Epidemiology of lymphomas 5 th most frequently diagnosed cancer in both sexes males > females incidence –NHL increasing –Hodgkin lymphoma stable
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Incidence of lymphomas in comparison with other cancers in Canada
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Age distribution of new NHL cases in Canada
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Age distribution of new Hodgkin lymphoma cases in Canada
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Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation
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Clinical manifestations Variable severity: asymptomatic to extremely ill time course: evolution over weeks, months, or years Systemic manifestations fever, night sweats, weight loss, anorexia, pruritis Local manifestations lymphadenopathy, splenomegaly most common any tissue potentially can be infiltrated
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Other complications of lymphoma bone marrow failure (infiltration) CNS infiltration immune hemolysis or thrombocytopenia compression of structures (eg spinal cord, ureters) pleural/pericardial effusions, ascites
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Diagnosis requires an adequate biopsy Diagnosis should be biopsy-proven before treatment is initiated Need enough tissue to assess cells and architecture –open bx vs core needle bx vs FNA
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Stage IStage IIStage IIIStage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss
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Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma
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Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage
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Follicular lymphoma most common type of “indolent” lymphoma usually widespread at presentation often asymptomatic not curable (some exceptions) associated with BCL-2 gene rearrangement [t(14;18)] cell of origin: germinal center B-cell
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defer treatment if asymptomatic (“watch-and-wait”) several chemotherapy options if symptomatic median survival: years despite “indolent” label, morbidity and mortality can be considerable transformation to aggressive lymphoma can occur
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Diffuse large B-cell lymphoma most common type of “aggressive” lymphoma usually symptomatic extranodal involvement is common cell of origin: germinal center B-cell treatment should be offered curable in ~ 40%
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Hodgkin lymphoma Thomas Hodgkin (1798-1866)
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Classical Hodgkin Lymphoma
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Hodgkin lymphoma cell of origin: germinal centre B-cell Reed-Sternberg cells (or RS variants) in the affected tissues most cells in affected lymph node are polyclonal reactive lymphoid cells, not neoplastic cells
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Reed-Sternberg cell
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RS cell and variants popcorn celllacunar cellclassic RS cell (mixed cellularity)(nodular sclerosis) (lymphocyte predominance)
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A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV? cytokines
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Hodgkin lymphoma Histologic subtypes Classical Hodgkin lymphoma –nodular sclerosis (most common subtype) –mixed cellularity –lymphocyte-rich –lymphocyte depleted
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Epidemiology less frequent than non-Hodgkin lymphoma overall M>F peak incidence in 3rd decade
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Associated (etiological?) factors EBV infection smaller family size higher socio-economic status caucasian > non-caucasian possible genetic predisposition other: HIV? occupation? herbicides?
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Clinical manifestations: lymphadenopathy contiguous spread extranodal sites relatively uncommon except in advanced disease “B” symptoms
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Treatment and Prognosis StageTreatmentFailure- free survival Overall 5 year survival I,IIABVD x 4 & radiation 70-80%80-90% III,IVABVD x 660-70%70-80%
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Long term complications of treatment infertility –MOPP > ABVD; males > females –sperm banking should be discussed –premature menopause secondary malignancy –skin, AML, lung, MDS, NHL, thyroid, breast... cardiac disease
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Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma
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