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  1. 1. Lymphomas and Multiple Myeloma<br />Elizabeth Bunting, MS, PA-C<br />Clinical Medicine I<br />April 8, 2011<br />
  2. 2. Objectives<br />For each of the following disorders, describe the pathophysiology, clinical presentation, significant historical and physical examination findings, diagnostic work-up, management, and prognosis:<br />Hodgkin’s disease<br />Non-Hodgkin’s lymphoma<br />Multiple myeloma<br />
  3. 3.
  4. 4. B-cell Transformation <br />
  5. 5. Lymphoma<br />Non-Hodgkin’s disease<br />All others<br />Present at multiple sites in peripheral nodal groups <br />Non contiguous spread to other nodal groups<br />Hodgkin’s disease (HD)<br />Reed-Sternberg cells<br />Nontenderlymphadenopathy along central axis<br />Contiguous spread to other nodal groups<br />
  6. 6. Disease Classification<br />Hodgkin’s<br />Lymphocyte predominate<br />Nodular sclerosing<br />Mixed cellularity<br />Lymphocyte depleted <br />Prognosis dependent on stage and presence of ‘B symptoms’<br />Non-Hodgkin’s<br />Mature or immature<br />B-cell or T-cell<br />Mature cell  less aggressive, disseminate earlier<br />Immature cell more aggressive, disseminate later<br />
  7. 7. Hodgkin’s Disease<br />Essentials of diagnosis<br />Painless lymphadenopathy<br />+/- constitutional symptoms<br />Pathologic diagnosis by lymph node biopsy (Reed-Sternberg cells)<br />
  8. 8. Hodgkin’s Disease<br />Epidemiology<br />Bimodal peak <br />20’s<br />50’s<br />Signs and symptoms<br />Most patients present with a painless mass, usually in the neck<br />Constitutional symptoms include fever, weight loss, night sweats<br />
  9. 9. Hodgkin’s Disease<br />Signs and symptoms<br />Generalized pruritus<br />Pain in an involved lymph node after EtOH ingestion<br />Usually arises within a single lymph node area and spreads contiguously<br />Late in the course, there may be widespread hematogenous dissemination<br />
  10. 10. Hodgkin’s Disease<br />Subtypes<br />Lymphocyte predominance<br />Nodular sclerosis<br />Mixed cellularity<br />Lymphocyte depletion<br />Differential diagnosis<br />Other lymphomas<br />Reactive lymph nodes due to infections or drug reactions<br />
  11. 11. Ann Arbor Staging for Hodgkin’s Disease<br />Category A: patients are asymptomatic<br />Category B: fever, night sweats, weight loss>10% of original body weight<br />
  12. 12. Hodgkin’s Disease<br />Treatment<br />For stage IA and IIA  radiation therapy +/- limited chemotherapy<br />For stage IIIB or IV  combination chemotherapy with ABVD or newer regimen<br /> (ABVD = Adriamycin (doxorubicin), bleomycin, vincristine, and dacarbazine)<br />
  13. 13. Hodgkin’s Disease<br />Prognosis<br />Stage IA or IIA<br />Excellent prognosis<br />10 year survival rate > 80%<br />Stage IIIB or IV<br />5 year survival rate is 50-60%<br />Poorer prognosis for increased age, bulky disease, mixed cellularity<br />
  14. 14. Non-Hodgkin’s Lymphomas<br />General information<br />Heterogeneous group of cancers of lymphocytes<br />Vary in clinical presentation and course<br />Classification is controversial<br />Best-studied pathology is Burkitt’s lymphoma, which has a translocation of chromosomes 8 and 14<br />
  15. 15. Common Non-Hodgkin’s Lymphoma Subtypes<br />Common Adult <br />Follicular lymphoma<br />Small lymphocytic lymphoma<br />Diffuse large B-cell lymphoma<br />Adult T-cell lymphoma<br />Common Childhood and Adolescent<br />Lymphoblastic lymphoma<br />Burkitt’s lymphoma<br />
  16. 16. WHO Classification of Non-Hodgkin’s Lymphomas<br />Precursor B<br />B cell lymphoblastic lymphoma<br />Mature B<br />Diffuse large B cell lymphoma<br />Mediastinal large B cell lymphoma<br />Follicular lymphoma<br />Small lymphocytic lymphoma<br />Lymphoplasmacytic lymphoma<br />
  17. 17. WHO Classification of Non-Hodgkin’s Lymphomas<br />Mature B<br />Mantle cell lymphoma<br />Burkitt’s lymphoma<br />Marginal zone lymphoma<br />MALT type<br />Nodal<br />Splenic<br />Mucosal tissue associated<br />
  18. 18. WHO Classification of Non-Hodgkin’s Lymphomas<br />Precursor T<br />T cell lymphoblastic lymphoma<br />Mature T<br />Anaplastic T cell lymphoma<br />Peripheral T cell lymphoma<br />
  19. 19. Non-Hodgkin’s Lymphomas<br />Signs and symptoms<br />Indolent lymphomas<br />Painless lymphadenopathy<br />May be isolated or widespread<br />Retroperitoneum, mesentery, pelvis<br />Usually disseminated at the time of diagnosis<br />Frequent bone marrow involvement<br />Fever, weight loss, night sweats<br />Burkitt’s lymphoma – usually have abdominal pain or fullness<br />
  20. 20. Non-Hodgkin’s Lymphomas<br />Laboratory findings<br />Peripheral smear usually normal<br />Bone marrow shows paratrabecular lymphoid aggregates<br />If meninges involved, there may be malignant cells in the CSF<br />CXR may show mediastinal mass<br />Serums LDH is a useful prognostic marker<br />
  21. 21. Non-Hodgkin’s Lymphomas<br />Laboratory findings<br />Diagnosis made by tissue biopsy<br />FNA may be suspicious, but node biopsy is required for definitive diagnosis and staging<br />
  22. 22. Non-Hodgkin’s Disease<br />Treatment<br />Limited disease (1 abnormal lymph node)<br />Localized radiation <br />Treat for cure<br />Indolent disseminated disease<br />No clear consensus on treatment<br />Rituximab +/- chemotherapy<br />Allogeneic transplant<br />
  23. 23. Non-Hodgkin’s Disease<br />Treatment<br />Intermediate grade lymphomas<br />Treat for cure<br />Chemotherapy (R-CHOP) +/- radiation<br />Advanced disease<br />Chemotherapy with R-CHOP<br />Autologous stem cell transplant<br />Burkitt’s lymphoma – intensive chemotherapy specifically tailored for Burkitt’s<br />
  24. 24. Non-Hodgkin’s Disease<br />Prognosis<br />Median survival rate 6-8 years, but improving<br />Poor prognostic factors<br />Age > 60 years<br />Elevated serum LDH<br />Stage III or IV disease<br />0-1 risk factors = 80% response rate to chemo<br />2 risk factors = 70% response<br />
  25. 25. Multiple Myeloma<br />Essentials of diagnosis<br />Bone pain, often in the back<br />Monoclonal paraprotein found by serum and urine protein electrophoresis<br />Replacement of bone marrow by malignant plasma cells<br />General considerations<br />Malignancy of plasma cells<br />Malignant cells can cause tumors (plasmacytomas) that can compress the spinal cord<br />
  26. 26. Multiple Myeloma<br />General considerations<br />Replacement of bone marrow  anemia  bone marrow failure<br />Paraproteins (IgG or IgA) may cause hyperviscosity<br />Immunoglobulins can lead to renal failure or be deposited in tissues as amyloid<br />Patients are especially prone to infections with encapsulated organisms (Strep pneumoniae, Hib)<br />Epidemiology<br />Mean age = 65 years<br />
  27. 27. Multiple Myeloma<br />Signs and symptoms<br />Most common presenting complaints are anemia, bone pain and infection<br />Bone pain usually in back or ribs or due to pathologic fracture<br />Renal failure<br />Spinal cord compression<br />Hyperviscosity (mucosal bleeding, vertigo, nausea, visual disturbance, changes in mental status)<br />
  28. 28. Multiple Myeloma<br />Signs and symptoms<br />Incidental lab findings<br />Hypercalcemia<br />Proteinuria<br />Increased sed rate<br />Amyloidosis<br />Pallor<br />Bone tenderness<br />Soft tissue masses<br />
  29. 29. Multiple Myeloma<br />Signs and symptoms<br />Signs of spinal cord compression/neuropathy<br />Enlarged tongue<br />CHF<br />Hepatomegaly<br />Fever only with infection<br />
  30. 30. Multiple Myeloma<br />Laboratory findings<br />Anemia with normal RBC morphology<br />Rouleau formation is common<br />Hallmark = paraprotein on serum protein electrophoresis (SPEP)<br />Bone marrow infiltrated by plasma cells (20% to 100%)<br />Lytic lesions seen on xrays (axial skeleton)<br />
  31. 31. RouleauFormation of RBCs<br />
  32. 32. Multiple Myeloma<br />Differential diagnosis<br />Monoclonal gammopathy of unknown significance (MGUS)<br />More common than myeloma<br />Progresses to malignant disease in 25% of cases<br />Reactive polyclonal hypergammaglobulinemia<br />Primary amyloidosis<br />
  33. 33. Multiple Myeloma<br />Treatment<br />Observation for minimal disease<br />Optimal treatment is in flux<br />Previously combination chemotherapy<br />Thalidomide + dexamethasone<br />Velcade (bortezomib)<br />Revlimid (lenalidomide) being investigated<br />Autologous stem cell transplant<br />
  34. 34. Multiple Myeloma<br />Treatment<br />Allogeneic transplantation is potentially curative, but has 40-50% mortality rate<br />Localized radiation for palliation of bone pain<br />Prognosis<br />Median survival rate = 4-6 years<br />Improving with new therapies<br />
  35. 35. ThumbnailEpidemiology<br />Non-Hodgkin’s lymphoma<br />75% of all lymphomas<br />Mean age of onset = 42<br />Risk factors<br />Radiation/benzene exposure<br />EBV, HTLV-1 viral infections<br />Autoimmune disease <br />immunosuppresion<br />Hodgkin’s lymphoma<br />25% of all lymphomas<br />Bimodal distribution:<br />20s and >50s<br />Men>Women<br />Increased with HIV<br />
  36. 36. ThumbnailPathophysiology<br />Non-Hodgkin’s lymphoma<br />Varied translocations affect cellular proliferation of lymphoid cells<br />Hodgkin’s lymphoma<br />Malignant Reed-Sternberg cells recruit inflammatory cells<br />
  37. 37. ThumbnailClinical Presentation<br />Non-Hodgkin’s lymphoma<br />Non-tender, multiple, peripheral nodal groups<br />Non contiguous spread to other nodes<br />Extranodal lymphoid tissue involvement<br />Pruritus<br />B-symptoms<br />Hodgkin’s lymphoma<br />Nontender, single or nodal group<br />Contiguous spread to adjacent nodes along central axis<br />Mediastinal or abdominal LAD<br />Generalized pruritus<br />B-symptoms<br />Clinical anergy<br />
  38. 38. ThumbnailDiagnosis<br />Non-Hodgkin’s lymphoma<br />Lymph node/tissue biopsy<br />Histologic examination<br />Prognosis depends on grade<br />Hodgkin’s lymphoma<br />Reed-Sternberg cells found on node biopsy<br />Prognosis depends on stage<br />
  39. 39. ThumbnailTherapy<br />Non-Hodgkin’s lymphoma<br />Radiation treatment<br />Chemotherapy<br />Immunotherapy<br />Stem cell transplant<br />Hodgkin’s lymphoma<br />Radiation therapy for stages I and II<br />Combination therapy for stages III and IV<br />
  40. 40. Key Points<br />Lymphomas are solid tumors of lymphoid origin<br />HD - Reed-Sternberg cells<br />NHD – all others<br />HD – central axis LAD with contiguous spread<br />NHD – peripheral LAD with non-contiguous spread<br />Plasma cell neoplasms hypersecrete IgM, IgG to produce serum hyperviscosity. <br />
  41. 41. Case Study - HPI<br />TL, a 59 yo female, presents with 5 days of fever and night sweats. She also noted a 20# unexplained weight loss in the last 3 months from her previous weight of 150#. She has had an intermittent cough with mild wheezing when lying on her right side. She has had no sick contacts nor symptoms suggesting infection. PPD negative 1 year ago and no risk factors for TB exposure. <br />PMHx – Hashimoto’s thyroiditis during her 20s, now hypothyroid taking L-thyroxine. No history of smoking or drinking. <br />
  42. 42. Case Study - PE<br />T 38.6C BP 135/75 HR 85 RR 20 SaO2 98%<br />Patient is thin and ill-appearing. Her exam is significant for positional wheezing audible anteriorly on the right middle chest when lying on the right side. Nontender lymphadenopathy consisting of two 2.5 cm rubbery nodules in the left axillary and right inguinal regions. <br />
  43. 43. What Labs/Tests?<br />CBC<br />Chest X-ray<br />
  44. 44. Case Conclusions<br />Biopsies of the left axillary and right inguinal nodes reveal follicular lymphoma. Given that the patient presented with fever, night sweats and weight loss, she was thought to have more advanced disease and combination chemotherapy was initiated. She achieved complete remission, but relapsed in 2 years with histologic changes to diffuse large B-cell lymphoma. <br />
  45. 45. Any Questions??<br />