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

ALL CLL naïve Lymphomas MM B-lymphocytes Plasma cells T-lymphocytes Lymphoid progenitor AML Hematopoietic stem cell Myeloid progenitor Myeloproliferative disorders Neutrophils Eosinophils Basophils Monocytes Platelets Red cells .

HL ALL pre-B immature B-cell plasma cell .B-cell development stem cell lymphoid progenitor progenitor-B CLL mature naive B-cell germinal center B-cell memory B-cell MM DLBCL. FL.

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 .

Lymphoma classification (2001 WHO) • B-cell neoplasms – precursor – mature NonHodgkin Lymphomas • T-cell & NK-cell neoplasms – precursor – mature • Hodgkin lymphoma .

A practical way to think of lymphoma Category Survival of untreated patients Years Curability To treat or not to treat NonHodgkin lymphoma Indolent Generally not curable Generally defer Rx if asymptomatic Aggressive Months Curable in some Curable in some Curable in most Treat Very aggressive Hodgkin lymphoma All types Weeks Treat Variable – months to years Treat .

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 .

000/yr 70 60 50 40 30 20 10 0 1985 1990 1995 Year NHL Hodgkin lymphoma lung colorectal breast 2000 .Incidence of lymphomas in comparison with other cancers in Canada age adjusted incidence/100.

Incidence/100.000/annum 100 20 40 60 80 0 Age distribution of new NHL cases in Canada Age (years) 0-1 1-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ .

incidence/100.000/annum 0 1 2 3 4 5 6 Age distribution of new Hodgkin lymphoma cases in Canada Age (years) 0-1 1-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ .

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

weight loss. months.Clinical manifestations • Variable • severity: asymptomatic to extremely ill • time course: evolution over weeks. pruritis • Local manifestations • lymphadenopathy. anorexia. night sweats. splenomegaly most common • any tissue potentially can be infiltrated . or years • Systemic manifestations • fever.

ascites .Other complications of lymphoma • • • • bone marrow failure (infiltration) CNS infiltration immune hemolysis or thrombocytopenia compression of structures (eg spinal cord. ureters) • pleural/pericardial effusions.

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 Stage I Stage II Stage III Stage IV A: absence of B symptoms B: fever. weight loss . night sweats.

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

Relative frequencies of different lymphomas Non-Hodgkin Lymphomas Diffuse large B-cell Hodgkin lymphoma NHL Follicular Other NHL ~85% of NHL are B-lineage .

18)] • cell of origin: germinal center B-cell .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.

morbidity and mortality can be considerable • transformation to aggressive lymphoma can occur .• defer treatment if asymptomatic (“watch-and-wait”) • several chemotherapy options if symptomatic • median survival: years • despite “indolent” label.

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 .

not neoplastic cells .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.

Reed-Sternberg cell .

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

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

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 .

II ABVD x 4 & radiation ABVD x 6 III.IV 60-70% 70-80% .Treatment and Prognosis Stage Treatment Failurefree survival 70-80% Overall 5 year survival 80-90% I.

lung. AML.. MDS. breast. • cardiac disease .. males > females – sperm banking should be discussed – premature menopause • secondary malignancy – skin.Long term complications of treatment • infertility – MOPP > ABVD. thyroid. NHL.

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

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