Lymphoma: What You Need to Know. Richard van der Jagt MD, FRCPC
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1 Lymphoma: What You Need to Know Richard van der Jagt MD, FRCPC
2 Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma
3 Conceptualizing lymphoma neoplasms of lymphoid origin, typically causing lymphadenopathy leukemia vs lymphoma lymphomas as clonal expansions of cells at certain developmental stages
4 ALL CLL Lymphomas MM naïve Lymphoid progenitor B-lymphocytes T-lymphocytes Plasma cells Hematopoietic stem cell Myeloid progenitor AML Myeloproliferative disorders Neutrophils Eosinophils Basophils Monocytes Platelets Red cells
5 B-cell development stem cell lymphoid progenitor progenitor-b ALL pre-b immature B-cell CLL mature naive B-cell germinal center B-cell DLBCL, FL, HL memory B-cell MM plasma cell
6 Classification Biologically rational classification Diseases that have distinct morphology immunophenotype genetic features clinical features Clinically useful classification Diseases that have distinct clinical features natural history prognosis treatment
7 Lymphoma classification (2001 WHO) B-cell neoplasms precursor mature T-cell & NK-cell neoplasms precursor mature Hodgkin lymphoma Non- Hodgkin Lymphomas
8 A practical way to think of lymphoma Category Survival of untreated patients Curability To treat or not to treat Non- Hodgkin lymphoma Indolent Years Generally not curable Aggressive Months Curable in some Generally defer Rx if asymptomatic Treat Very aggressive Weeks Curable in some Treat Hodgkin lymphoma All types Variable months to years Curable in most Treat
9 Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression
10 Epidemiology of lymphomas 5 th most frequently diagnosed cancer in both sexes males > females incidence NHL increasing Hodgkin lymphoma stable
11 Incidence of lymphomas in comparison with other cancers in Canada age adjusted incidence/100,000/yr Year lung colorectal breast NHL Hodgkin lymphoma
12 Age distribution of new NHL cases in Canada 100 Incidence/100,000/annum Age (years)
13 Age distribution of new Hodgkin lymphoma cases in Canada 6 incidence/100,000/annum Age (years)
14 Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation
15 Variable Clinical manifestations 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
16 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
17 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
18 Staging of lymphoma Stage I Stage II Stage III Stage IV A: absence of B symptoms B: fever, night sweats, weight loss
19 Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma
20 Relative frequencies of different lymphomas Non-Hodgkin Lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL ~85% of NHL are B-lineage
21 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
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
23 BR vs CHOP-R
24 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 Overall survival R-CHOP. 8.4 years (95% CI: 5.4-not reached) in the R- CHOP arm (P <.0001).
25
26 Hodgkin lymphoma Thomas Hodgkin ( )
27 Classical Hodgkin Lymphoma
28 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
29 Reed-Sternberg cell
30 RS cell and variants classic RS cell lacunar cell popcorn cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance)
31 A possible model of pathogenesis transforming event(s) EBV? loss of apoptosis germinal centre B cell RS cell cytokines inflammatory response
32 Hodgkin lymphoma Histologic subtypes Classical Hodgkin lymphoma nodular sclerosis (most common subtype) mixed cellularity lymphocyte-rich lymphocyte depleted
33 Epidemiology less frequent than non-hodgkin lymphoma overall M>F peak incidence in 3rd decade
34 Associated (etiological?) factors EBV infection smaller family size higher socio-economic status caucasian > non-caucasian possible genetic predisposition other: HIV? occupation? herbicides?
35 Clinical manifestations: lymphadenopathy contiguous spread extranodal sites relatively uncommon except in advanced disease B symptoms
36 Treatment and Prognosis Stage Treatment Failurefree survival Overall 12 year survival I,II ABVD x 6 87% 94% III,IV ABVD x 6 86% 92%
37 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
38 Lymphoma Summary Many different diseases in many disguises Each case different based on type, stage, prognostic score, genetic differences, susceptibility to rx Many pts live long periods with good quality life
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