1. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 28 Disorders of White Blood Cells and Lymphoid Tissues

2. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Formed Elements of Blood Red blood cells Platelets (megakaryocytes) Granulocytes (i.e., neutrophils, eosinophils, and basophils) Monocyte and macrophage lineage –Both are derived from the myeloid stem cell in the bone marrow and circulate in the blood Lymphocytes –T lymphocytes (T cells) and B lymphocytes (B cells) originate in the bone marrow and migrate between the blood and the lymph

3. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Hematopoietic Tissue Myeloid tissue –Bone marrow Lymphoid tissue –Nodes –Thymus –Spleen

4. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Hematopoiesis White blood cells are formed partially in the bone marrow and partially in the lymph system. –They are formed from hematopoietic stem cells that differentiate into committed progenitor cells. –These in turn develop into the myelocytic and lymphocytic lineages needed to form white blood cells. RBCs and platelets are formed in the marrow and released into circulation.

5. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Growth and Reproduction of White Blood Cells The growth and reproduction of different stem cells are controlled by multiple hematopoietic growth factors or inducers. The life span of WBCs is relatively short; constant renewal is necessary to maintain normal blood levels. Conditions that decrease availability of stem cells or hematopoietic growth factors produce a decrease in WBCs.

6. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Diseases of Deficient Blood Cell Production Leukopenia deficiency of leukocytes –Neutropenia –Granulocytopenia Aplastic anemia –Anemia, thrombocytopenia, and agranulocytosis

7. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Causes of Neutropenia Accelerated removal Drug-induced granulocytopenia Periodic or cyclic neutropenia Neoplasms involving bone marrow Idiopathic neutropenia occurring in the absence of other disease or provoking influence Felty syndrome

8. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Signs and Symptoms of Neutropenia Initially, those of bacterial or fungal infections –Malaise –Chills –Fever –Extreme weakness and fatigue Reduced white blood cell count

9. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question The suffix –penia refers to a _____________ in number. –A. increase –B. stasis –C. decrease

10. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer C. decrease Rationale: In hematology neutropenia, granulocytopenia and others refer to decreased circulating cells.

11. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Infectious Mononucleosis Definition –Self-limited lymphoproliferative disorder Causes and Characteristics –Caused by the B-lymphocytotropic EBV, a member of the herpes virus family; transmitted in saliva –Characterized by fever, generalized lymphadenopathy, sore throat, and the appearance in the blood of atypical lymphocytes and several antibodies –Highest incidence in adolescents and young adults –Treatment is symptomatic and supportive.

12. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Neoplastic Disorder of Hematopoietic and Lymphoid Origin Represent the most important of the white cell disorders Include somewhat overlapping categories –Lymphomas (Hodgkin disease and non-Hodgkin lymphoma) –Leukemia –Plasma cell dyscrasias (multiple myeloma)

13. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Clinical Features of Neoplasms Largely determined by –Their site of origin –The progenitor cell from which they originated –The molecular events involved in their transformation into a malignant neoplasm Chromosomal aberrations – Deletions – Polyploidy – Translocations – Hyperploidy – Inversions

14. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Which of the following is NOT a chromosomal aberration? –A. Deletions –B. Polyploidy –C. Translocations –D. Regression –E. Hyperploidy

15. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer D. Regression Rationale: Regression is not a type of chromosomal change.

16. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Hodgkin Disease and Non-Hodgkin Disease Hodgkin Disease –Lymphoma arises in a single node or chain of nodes. –Reed-Sternberg cells are present. Non-Hodgkin disease –Lymphoma originates at extranodal sites and spreads to anatomically contiguous nodes. –Reed-Sternberg cells are not present. Reed-Sternberg cells are derived from B lymphocytes.

17. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Symptoms of Hodgkin Disease Stage A –Lack constitutional symptoms Stage B (40% of persons with Hodgkin disease) –Significant weight loss, fevers, pruritus or night sweats Advanced Stages –Fatigue and anemia –Liver, lungs, digestive tract, and CNS may be involved.

18. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Categories of Non-Hodgkin Lymphomas Low-grade lymphomas –Predominantly B-cell tumors Intermediate-grade lymphomas –Include B-cell and some T-cell lymphomas High-grade lymphomas –Largely immunoblastic (B cell), lymphoblastic (T cell), Burkitt, and non-Burkitt lymphomas

19. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Diagnosis of Hodgkin Disease Reed-Sternberg cell present in a biopsy specimen of lymph node tissue Computed tomography (CT) scans of the chest and abdomen to assess for involvement of mediastinal, abdominal and pelvic lymph nodes A bipedal lymphangiogram to detect structural changes in the lymph nodes too small to visualize on CT scan A positron emission tomography (PET) imaging A bilateral bone marrow biopsy may be performed if disease is disseminated.

20. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Staging of Non-Hodgkin Lymphomas Disease Bone marrow biopsy Blood studies Chest and abdominal CT scans Nuclear medicine studies Cytologic examination of the cerebrospinal fluid

21. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Treatment for Hodgkin and NHL Depends on the histologic type, stage of the disease, and clinical status of the person Types –Radiation –Combination chemotherapy –For NHL only Adjuvant radiation therapy Monoclonal antibodies

22. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Leukemias Definition –Malignant neoplasms arising from the transformation of a single blood cell line derived from hematopoietic stem cells Classification according to cell lineage –Lymphocytic (lymphocytes) –Myelocytic (granulocytes, monocytes)

23. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Chronic Leukemias Definition –Malignancies involving the proliferation of well- differentiated myeloid and lymphoid cells Types of chronic leukemia –Chronic lymphocytic leukemia (CLL) –Chronic myelogenous leukemia (CML)

24. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Classification of Leukemia Types Acute lymphocytic (lymphoblastic) leukemia (ALL) Chronic lymphocytic leukemia (CLL) –Both involve immature lymphocytes and their progenitors in the bone marrow, the spleen, lymph nodes, CNS, and other tissue. Acute myelogenous (myeloblastic) leukemia (AML) Chronic myelogenous leukemia (CML) –Both involve the pluripotent myeloid stem cells in bone marrow and interfere with the maturation of all blood cells.

25. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Goals of Treatment for CML A hematological response characterized by normalized blood counts A cytogenetic response demonstrated by the reduction or elimination of the Ph chromosome from the bone marrow A molecular response confirmed by the elimination of the BCR-ABL fusion protein

26. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Criteria for Remission of ALL and AML Less than 5% blasts in the bone marrow Normal peripheral blood counts Absence of cytogenetic abnormalities Return to pre-illness performance status

27. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Factors Affecting the Likelihood of Achieving Remission Age (most significant prognostic variable) Type of leukemia Stage of the disease at time of presentation

28. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Leukemic Cells Are immature and poorly differentiated Proliferate rapidly and have a long life span Do not function normally Interfere with the maturation of normal blood cells Circulate in the blood stem Cross the blood–brain barrier Infiltrate many body organs

29. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Warning Signs Complications of Acute Leukemia Signs –Fatigue –Pallor –Weight loss –Repeated infections –Easy bruising –Nosebleeds –Other types of hemorrhage Complications –Leukostasis –Tumor lysis syndrome –Hyperuricemia –Blast crisis

30. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Multiple Myeloma Definition –A plasma cell dyscrasia characterized by expansion of a single clone of immunoglobulin-producing plasma cells and a resultant increase in serum levels of a single monoclonal immunoglobulin or its fragments Main sites involved –The bones and bone marrow –Proliferation and activation of osteoclasts that lead to bone resorption and destruction –Pathologic fractures –Hypercalcemia