10..lymphoma final year

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10..lymphoma final year

  1. 1. LYMPHOMA Professor Dr. Rafi Ahmed Ghori Department of Medicine LUMHS Jamshoro
  2. 2. OVERVIEW• Concepts, classification, lymphogenesis• Epidemiology• Clinical presentation• Diagnosis• Staging• Three important types of lymphoma
  3. 3. EPIDEMIOLOGY AND AETIOLOGY OF HODGKINLYMPHOMAIncidence• Approximately 4 new cases/100 000 population / yearSex Ratio• Slight male excess (1.5:1)Age•Median age 31 years; first peak at 20-35 years and second at50-70 yearsAetiology• Unknown. More common in patients from well-educatedbackground and small families. Three time more likely with apast history of infectious mononucleosis but no casual link toEpstein-Barr virus infection proven
  4. 4. EPIDEMIOLOGY OF LYMPHOMAS• 5th most frequently diagnosed cancer overall for both males and females• Males > females• Incidence • NHL increasing over time (Stage III or IV at Diagnosis) • Hodgkin lymphoma stable
  5. 5. RISK FACTORS FOR NHL• Immunosuppression or immunodeficiency• Connective tissue disease• Family history of lymphoma• Infectious agents• Ionizing radiation
  6. 6. WHO PATHOLOGICAL CLASSIFICATION ANDINCIDENCE OF HODGKIN LYMPHOMA (HL)Type Histology IncidenceNodular Lymphocytepredominent HLClassical HL Nodular sclerosing 70% Mixed Cellularity 20% Lymphocyte-rich 5% Lymphocyte-depleted Rare
  7. 7. CLINICAL STAGES OF HODGKIN LYMPHOMA(ANN ARBOR CLASSIFICATION)Stage DefinitionI Involvement of a single lymph node region (I) or extralymphatic site (IA E)II Involvement of two or more lymph node regions (II) or an extralymphatic site and lymph node regions or the same side of (above or below) the diaphragm (IIE)III Involvement of lymph node regions on both sides of the diaphragm with (IIIE) or without (III) localised extralymphatic involvement or involvement of the spleen (IIIS) or both (IIISE)IV Diffuse involvement of one or more extralymphatic tissues, e.g. liver or bone marrowA No systemic symptomsB Weight loss, drenching sweatsThe lymphatic structure are defined as the lymph nodes, spleen,thymus, Waldeyer’s ring, appendix and Payer’s patches
  8. 8. STAGING OF LYMPHOMA Stage I Stage II Stage III Stage IV A: absence of B symptoms B: fever, night sweats, weight loss
  9. 9. THE CHALLENGE OF LYMPHOMA CLASSIFICATIONBiologically rational Clinically useful classification classificationDiseases that have distinct Diseases that have distinct • morphology • clinical features • immunophenotype • natural history • genetic features • prognosis • clinical features • treatment
  10. 10. LYMPHOMA CLASSIFICATION (BASED ON 2001 WHO)• B-cell neoplasms 70% • Precursor B-cell neoplasms • Mature B-cell neoplasms • B-cell proliferations of uncertain malignant potential• T-cell & NK-cell neoplasms 30% • Precursor T-cell neoplasms • Mature T-cell and NK-cell neoplasms • T-cell proliferation of uncertain malignant potential
  11. 11. LYMPHOMA CLASSIFICATION (BASED ON 2001 WHO)• Hodgkin lymphoma 95% • Classical Hodgkin lymphomas • NS 70% (nodular scl.) • MC 20% (mixed cell.) • LR 5% (lympho.rich) • LD RARE (lympho.dep.) • Nodular lymphocyte predominant Hodgkin lymphoma 5%
  12. 12. A PRACTICAL WAY TO THINK OF LYMPHOMA Category Survival of Curability To treat or untreated not to treat patientsNon- Indolent Years Generally GenerallyHodgkin not curable defer Rx iflymphoma asymptomatic Aggressive Months Curable in Treat some Very Weeks Curable in Treat aggressive someHodgkin All types Variable – Curable in Treatlymphoma months to most years
  13. 13. MECHANISMS OF LYMPHOMAGENESIS• Genetic alterations• Infection• Antigen stimulation• Immunosuppression
  14. 14. 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
  15. 15. OTHER COMPLICATIONS OF LYMPHOMA• Bone marrow failure (infiltration)• CNS infiltration• Immune hemolysis or thrombocytopenia• Compression of structures (eg spinal cord, ureters) by bulky disease• Pleural/pericardial effusions, ascites
  16. 16. 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
  17. 17. THREE TYPES OF LYMPHOMA WORTH KNOWING ABOUT• Follicular lymphoma• Diffuse large B-cell lymphoma• Hodgkin lymphoma
  18. 18. NON-HODGKIN LYMPHOMA INCIDENCEDiffuselarge B-cell Follicularlymphoma lymphoma Other NHL
  19. 19. 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
  20. 20. • Defer treatment if asymptomatic (“watch- and-wait”)• Several chemotherapy options if symptomatic• Median survival: years• Although considered “indolent”, morbidity and mortality can be considerable• Transformation to aggressive lymphoma can occur
  21. 21. 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%
  22. 22. HODGKIN LYMPHOMA Thomas Hodgkin (1798-1866)
  23. 23. 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
  24. 24. REED-STERNBERG cell
  25. 25. RS CELL AND VARIANTSclassic RS cell lacunar cell popcorn cell (mixed cellularity) (nodular sclerosis) (lymphocyte predominance)
  26. 26. Reed-Sternberg cell The Scream, 1893 Edvard Munch
  27. 27. A POSSIBLE MODEL OF PATHOGENESIS transforming loss of apoptosis event(s) EBV? cytokinesgerminal centre RS cell inflammatory B cell response
  28. 28. HODGKIN LYMPHOMA HISTOLOGIC SUBTYPES• Classical Hodgkin lymphoma • Nodular sclerosis (most common subtype) • Mixed cellularity • Lymphocyte-rich • Lymphocyte depleted
  29. 29. EPIDEMIOLOGY• Less frequent than non-Hodgkin lymphoma• overall M>F• Peak incidence in 3rd decade
  30. 30. ASSOCIATED (ETIOLOGICAL?) FACTORS• EBV infection• Smaller family size• Higher socio-economic status• Caucasian > non-caucasian• Possible genetic predisposition• Other: HIV? occupation? herbicides?
  31. 31. CLINICAL MANIFESTATIONS:• Lymphadenopathy• Contiguous spread• Extranodal sites relatively uncommon except in advanced disease• “B” symptoms
  32. 32. TREATMENT AND PROGNOSISStage Treatment Failure-free Overall 5 survival year survival I,II ABVD x 4 70-80% 80-90% & radiationIII,IV ABVD x 6 60-70% 70-80%
  33. 33. 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
  34. 34. Case• 25 year old woman• Persistent dry cough• Fever, NS, weight loss x 3 months• Left cervical lymphadenopathy (2 cm)• Left supraclavicular node (2 cm)• No splenomegaly
  35. 35. W.P. at presentation
  36. 36. CASE: DIFFERENTIAL DIAGNOSIS• Lymphoma • Hodgkin • Non-HodgkinLlung cancer• Other neoplasms: thyroid, germ cell• Non-neoplastic causes less likely • Sarcoid, TB, ...
  37. 37. WHAT NEXT?• Needle aspirate of LN: a few necrotic cells• Needle biopsy of LN: admixture of B- and T- lymphocytes. A few atypical cells.
  38. 38. CASE: LYMPH NODE BIOPSY
  39. 39. CASE: LYMPH NODE BIOPSY
  40. 40. CASE: LYMPH NODE BIOPSY
  41. 41. CASE: STAGING INVESTIGATIONS• CT chest/abdo/pelvis• Bone marrow• Gallium scan• Blood work: normal
  42. 42. STAGING INVESTIGATIONS• Bone marrow normal• CT scan: L supraclavicular adenopathy; large mediastinal mass; R hilum; no disease below diaphragm• Gallium avid
  43. 43. What is her diagnosis and stage?• Nodular sclerosis HD• Stage IIB• With bulky mediastinal mass
  44. 44. CASE: TREATMENT• Discussion with patient• Treatment with ABVD x 6 cycles • Constitutional symptoms gone after 1st cycle• Bulky mediastinal mass is a special situation that merits additional radiation after chemotherapy
  45. 45. CASE: POST-ABVD• Response to chemo, but residual mediastinal/hilar mass• Repeat gallium scan negative, suggesting that residual mass may just be fibrotic tissue• Proceed with radiotherapy as originally planned
  46. 46. CASE: POST-RADIOTHERAPY• Serial CT scans did not show progression• patient remains in remission
  47. 47. Therapeutic guideline for Hodgkin LymphomaIndications for radiotherapy• Stage I disease• Stage IIA disease with three or fewer areas involved• After chemotherapy to sites where there was originally bulkdisease• To lesion causing serious pressure problemsIndication for chemotherapy• All patients with B symptoms• Stage II disease with more than three areas involved• Stage III and IV disease
  48. 48. THE ChIVPP REGIMEN FORHODGKIN LYMPHOMADrug DoseChlorambucil 6 mg/m2 (up to 10 mg total) days 1-14 orallyVinblastine 6 mg/m2 (up to 10mg total) days 1 and 8 i.v.Procarbazine 100 mg/m2 days 1-14 orallyPrednisolone 40 mg/m2 days 1-14 orally

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