lymphoma

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Presentation Transcript

Lymphoma : 

Lymphoma David Lee MD, FRCPC

Overview : 

Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma

Conceptualizing 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: 

Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve germinal center

B-cell development : 

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

Classification : 

Classification

Lymphoma classification(2001 WHO) : 

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 : 

A practical way to think of lymphoma

Mechanisms of lymphomagenesis : 

Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression

Epidemiology of lymphomas : 

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 : 

Incidence of lymphomas in comparison with other cancers in Canada

Age distribution of new NHL cases in Canada : 

Age distribution of new NHL cases in Canada

Age distribution of new Hodgkin lymphoma cases in Canada : 

Age distribution of new Hodgkin lymphoma cases in Canada

Risk factors for NHL : 

Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation

Clinical manifestations : 

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 : 

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 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

Staging of lymphoma : 

Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss

Three common lymphomas : 

Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma

Relative frequencies of different lymphomas : 

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 : 

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: 

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 : 

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 : 

Hodgkin lymphoma Thomas Hodgkin (1798-1866)

Slide 25: 

Classical Hodgkin Lymphoma

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 : 

Reed-Sternberg cell

RS cell and variants : 

RS cell and variants popcorn cell lacunar cell classic RS cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance)

A possible model of pathogenesis : 

A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV? cytokines

Hodgkin lymphomaHistologic subtypes : 

Hodgkin lymphomaHistologic subtypes Classical Hodgkin lymphoma nodular sclerosis (most common subtype) mixed cellularity lymphocyte-rich lymphocyte depleted

Epidemiology : 

Epidemiology less frequent than non-Hodgkin lymphoma overall M>F peak incidence in 3rd decade

Associated (etiological?) factors : 

Associated (etiological?) factors EBV infection smaller family size higher socio-economic status caucasian > non-caucasian possible genetic predisposition other: HIV? occupation? herbicides?

Clinical manifestations: : 

Clinical manifestations: lymphadenopathy contiguous spread extranodal sites relatively uncommon except in advanced disease “B” symptoms

Treatment and Prognosis : 

Treatment and Prognosis

Long term complications of treatment : 

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 : 

Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma