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Lymphoma

Lymphoma. ALL. CLL. Lymphomas. MM. Neutrophils. AML. Myeloproliferative disorders. Myeloid progenitor. Eosinophils. Hematopoietic stem cell. Basophils. Monocytes. Platelets. Red cells. na ï ve. germinal center. B-lymphocytes. Plasma cells. Lymphoid progenitor. T-lymphocytes.

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Lymphoma

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  1. Lymphoma

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

  3. CLL MM ALL DLBCL, FL, HL B-cell development memory B-cell germinal center B-cell stem cell mature naive B-cell lymphoid progenitor progenitor-B pre-B immature B-cell plasma cell Bone marrow Lymphoid tissue

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

  5. Mechanisms of lymphomagenesis • Genetic alterations • Infection • Antigen stimulation • Immunosuppression

  6. Epidemiology of lymphomas • 5th most frequently diagnosed cancer in both sexes • males > females • incidence • NHL increasing • Hodgkin lymphoma stable

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

  8. 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

  9. 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

  10. 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

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

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

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

  14. 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

  15. 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

  16. 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%

  17. Hodgkin lymphoma

  18. Classical Hodgkin Lymphoma

  19. 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

  20. Reed-Sternberg cell

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

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

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

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

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

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

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