1. MLAB 1415- Hematology Keri Brophy-Martinez Lymphoid Malignancies

2. Introduction Two broad categories  Leukemia A malignant disease of hematopoietic tissue characterized by replacement of normal bone marrow elements with abnormal (neoplastic) blood cells. Abnormal cells are also seen in peripheral blood  Lymphoma Abnormal proliferation of lymphoid cells within the lymphatic tissue or lymph nodes, results in a solid tumor

3. Pathogenesis Acquired genetic factors  Proto-oncogenes  Tumor suppressor genes Inherited genetic factors  Wiskott Aldrich  Ataxia telangiectasia Environmental factors  EBV infection  Helicobacter pylori

4. Classification Factors to consider  Morphological appearance of cells Clonality  Flow cytometry  Chromosome analysis Translocations present?  Molecular analysis  Clinical information & history

5. MATURE B CELL NEOPLASMS

6. Chronic Lymphocytic Leukemia(CLL) General requirements for diagnosis  Peripheral blood and bone marrow lymphocytosis (>5 x 10 9 /L)  Lymphocytes are small with mature appearance Nucleus is round, with block-type chromatin Cytoplasm scarce  Smudge cells common Occur due to the cell’s fragility in making a smear  Prolymphocyte < 10%

7. CLL Blood Picture

8. Chronic Lymphocytic Leukemia Clinical features  Occurs in persons >50 years old  Chronic fatigue, infection Result of bone marrow replacement of normal cells with lymphocytes.  Skin and organ infiltration and enlargement  Median survival is 10 years

9. Chronic Lymphocytic Leukemia Treatment  Usually treatment is not required until lymphocytosis causes other cells to be crowded out resulting in infections.  Treatment depends on the stage at which the disease is diagnosed and is usually for the symptoms, not the disease. Chemotherapy

10. Prolymphocytic Leukemia Aggressive Non-responsive to treatment  Poor prognosis Low incidence rate Origin can be B or T cell

11. Prolymphocytic Blood Picture Punched out nucleolus

12. Hairy cell leukemia (HCL)  Presents in middle age  Affects males7:1 over females  Spleenomegaly  Pancytopenia common Increases opportunity for infections  Bone marrow aspirate can result in a “dry tap” due to marrow fibrosis.  Hairy cell leukemia can be treated with a one-time chemotherapy regimen with a good prognosis of long-term survival.

13. Hairy cell TRAP stain

14. Mature T cell Neoplasms Less common than B cell Lymphoma  ~10% of all lymphomas Occur in extranodal sites

15. Sezary’s syndrome  Leukemic phase of the most common cutaneous T-cell lymphoma, mycosis fungoides.  Lymphadenopathy  Red skin due to disesemination

16. Sezary Cell

17. Hodgkin’s Lymphoma  Cause is unknown, but has been linked to Epstein-Barr virus.  Bimodal distribution Diagnosed between 15 and 35 years of age Over 50 population  Males have higher incidence rates  Lymph node are involved Regional, contiguous sites

18. Hodgkin’s Lymphoma  Characteristic cell is the Reed-Sternberg Found in tissue biopsy Giant size (up to 45µm in diameter) Abundant acidophilic cytoplasm Multinucleated or polylobated nucleus Gigantic nucleoli

19. Hodgkin’s lymphoma Treatment and prognosis  Radiation of localized involvement  Chemotherapy  Combination of above  With early diagnosis, long-term disease-free survival is seen in about 80-90% of cases.

20. Nodular Lymphocyte Predominant Hodgkin’s Lymphoma Cause is unknown at this time. Predisposing factors seem to be chemicals, ionizing radiation and certain viruses. Reed-Sternberg cells are NOT present. B cell origin Widely disseminated, extranodal

21. Burkitt Lymphoma  Three variants Endemic  Common in Africa  Children aged 4-7  Jawbone mass Sporadic  Children & adults  Abdominal mass Immunodeficiency-associated  Rapid growth and tumor cell death results in “starry sky” appearance of the biopsy caused by macrophages cleaning up the dead cells.

22. Plasma Cell Disorders Disorders that do not involve lymph nodes Secrete monoclonal immunoglobulin into the serum and /or urine Disorders Plasma Cell Myeloma Plasmacytoma Monoclonal gammopathy of undetermined significance (MGUS)

23. Plasma Cell Myeloma Overproduction of abnormal plasma cells which are the final stage in the development of B lymphocytes. These cells secrete immunoglobulin, resulting in lytic bone lesions Risk increases with age- rare under 40  Median age 70 years old Suspected cause is chronic stimulation of the immune system from environmental sources.  Ionizing radiation  Viruses

24. Etiology 50% greater risk for men than women Risk increases with age; rare under 40  Median age 65 years old Suspected cause is chronic stimulation of the immune system from environmental sources.  Ionizing radiation  Viruses

25. Features  Increased production of immunoglobulin heavy and light chains (monoclonal gammopathy) Heavy chains: IgG, IgA, IgD, IgE, IgM Light chains: kappa, lambda Most common type of plasma cell myeloma is increased production of IgG.  Bence-Jones protein Light chains spill into the urine and can be detected by lab test Causes kidney damage  Hyperviscosity syndrome Excess immunoglobulin causes viscous blood which sludges and causes fluid congestion.  Normal Immunoglobulin production decreased Results in infections

26. Lab Findings CBC and peripheral smear  Red cells form characteristic rouleaux formation (resemble stacked coins)  Plasma cells may be seen in peripheral blood Bone marrow  Increased number of plasma cells which form “sheets” ESR  Increased - serum protein causes red cells to stick together and fall faster Chemistry studies  Increased BUN and creatinine (kidney tests)  Increased calcium  Increased LDH

27. Plasma Cell Myeloma C: hyperCalcemia R: Renal insufficiency A: Anemia B: lytic Bone lesions

28. Plasma Cell Myeloma Treatment  Chemotherapy  Radiation for localized areas  Bone marrow/stem cell transplant for younger patients  Poor prognosis for individuals that are symptomatic

29. References http://www.itriagehealth.com/wl/disease/burkitt-lymphoma- %28lymph-node-tumor%29#wrapperTop http://www.itriagehealth.com/wl/disease/burkitt-lymphoma- %28lymph-node-tumor%29#wrapperTop http://www.med- ed.virginia.edu/courses/path/innes/wcd/lympleuk.cfm McKenzie, S. B., & Williams, J. L. (2010). Clinical Laboratory Hematology. Upper Saddle River: Pearson Education, Inc.