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Slide 1 - Lymphoma David Lee MD, FRCPC
Slide 2 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma
Slide 3 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages
Slide 4 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center
Slide 5 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell
Slide 6 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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
Slide 7 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas
Slide 8 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma
Slide 9 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression
Slide 10 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable
Slide 11 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada
Slide 12 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada
Slide 13 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada
Slide 14 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation
Slide 15 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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
Slide 16 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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
Slide 17 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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
Slide 18 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss
Slide 19 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma
Slide 20 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage
Slide 21 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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
Slide 22 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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
Slide 23 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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%
Slide 24 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866)
Slide 25 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma
Slide 26 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma 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
Slide 27 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma 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 Reed-Sternberg cell
Slide 28 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma 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 Reed-Sternberg cell RS cell and variants popcorn cell lacunar cell classic RS cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance)
Slide 29 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma 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 Reed-Sternberg cell RS cell and variants popcorn cell lacunar cell classic RS cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance) A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV? cytokines
Slide 30 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma 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 Reed-Sternberg cell RS cell and variants popcorn cell lacunar cell classic RS cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance) A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV? cytokines Hodgkin lymphoma Histologic subtypes Classical Hodgkin lymphoma nodular sclerosis (most common subtype) mixed cellularity lymphocyte-rich lymphocyte depleted
Slide 31 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma 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 Reed-Sternberg cell RS cell and variants popcorn cell lacunar cell classic RS cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance) A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV? cytokines Hodgkin lymphoma Histologic subtypes Classical Hodgkin lymphoma nodular sclerosis (most common subtype) mixed cellularity lymphocyte-rich lymphocyte depleted Epidemiology less frequent than non-Hodgkin lymphoma overall M>F peak incidence in 3rd decade
Slide 32 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma 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 Reed-Sternberg cell RS cell and variants popcorn cell lacunar cell classic RS cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance) A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV? cytokines Hodgkin lymphoma Histologic subtypes Classical Hodgkin lymphoma nodular sclerosis (most common subtype) mixed cellularity lymphocyte-rich lymphocyte depleted Epidemiology less frequent than non-Hodgkin lymphoma overall M>F peak incidence in 3rd decade Associated (etiological?) factors EBV infection smaller family size higher socio-economic status caucasian > non-caucasian possible genetic predisposition other: HIV? occupation? herbicides?
Slide 33 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma 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 Reed-Sternberg cell RS cell and variants popcorn cell lacunar cell classic RS cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance) A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV? cytokines Hodgkin lymphoma Histologic subtypes Classical Hodgkin lymphoma nodular sclerosis (most common subtype) mixed cellularity lymphocyte-rich lymphocyte depleted Epidemiology less frequent than non-Hodgkin lymphoma overall M>F peak incidence in 3rd decade Associated (etiological?) factors EBV infection smaller family size higher socio-economic status caucasian > non-caucasian possible genetic predisposition other: HIV? occupation? herbicides? Clinical manifestations: lymphadenopathy contiguous spread extranodal sites relatively uncommon except in advanced disease “B” symptoms
Slide 34 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma 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 Reed-Sternberg cell RS cell and variants popcorn cell lacunar cell classic RS cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance) A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV? cytokines Hodgkin lymphoma Histologic subtypes Classical Hodgkin lymphoma nodular sclerosis (most common subtype) mixed cellularity lymphocyte-rich lymphocyte depleted Epidemiology less frequent than non-Hodgkin lymphoma overall M>F peak incidence in 3rd decade Associated (etiological?) factors EBV infection smaller family size higher socio-economic status caucasian > non-caucasian possible genetic predisposition other: HIV? occupation? herbicides? Clinical manifestations: lymphadenopathy contiguous spread extranodal sites relatively uncommon except in advanced disease “B” symptoms Treatment and Prognosis
Slide 35 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma 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 Reed-Sternberg cell RS cell and variants popcorn cell lacunar cell classic RS cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance) A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV? cytokines Hodgkin lymphoma Histologic subtypes Classical Hodgkin lymphoma nodular sclerosis (most common subtype) mixed cellularity lymphocyte-rich lymphocyte depleted Epidemiology less frequent than non-Hodgkin lymphoma overall M>F peak incidence in 3rd decade Associated (etiological?) factors EBV infection smaller family size higher socio-economic status caucasian > non-caucasian possible genetic predisposition other: HIV? occupation? herbicides? Clinical manifestations: lymphadenopathy contiguous spread extranodal sites relatively uncommon except in advanced disease “B” symptoms Treatment and Prognosis 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
Slide 36 - Lymphoma David Lee MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell Bone marrow Lymphoid tissue memory B-cell plasma cell germinal center B-cell mature naive B-cell 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 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas A practical way to think of lymphoma Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression Epidemiology of lymphomas 5th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable Incidence of lymphomas in comparison with other cancers in Canada Age distribution of new NHL cases in Canada Age distribution of new Hodgkin lymphoma cases in Canada Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation 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 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 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 Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage 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 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 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% Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma 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 Reed-Sternberg cell RS cell and variants popcorn cell lacunar cell classic RS cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance) A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV? cytokines Hodgkin lymphoma Histologic subtypes Classical Hodgkin lymphoma nodular sclerosis (most common subtype) mixed cellularity lymphocyte-rich lymphocyte depleted Epidemiology less frequent than non-Hodgkin lymphoma overall M>F peak incidence in 3rd decade Associated (etiological?) factors EBV infection smaller family size higher socio-economic status caucasian > non-caucasian possible genetic predisposition other: HIV? occupation? herbicides? Clinical manifestations: lymphadenopathy contiguous spread extranodal sites relatively uncommon except in advanced disease “B” symptoms Treatment and Prognosis 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 Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma