Malignant Disorders of White Bloods PDF

Chapter 11 Malignant Disorders of White Bloods Dr. Tashea S. Hilliard, Associate Professor Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.  Learning Objectives 1) Describe how the various types of leuke...

Chapter 11 Malignant Disorders of White Bloods Dr. Tashea S. Hilliard, Associate Professor Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.  Learning Objectives 1) Describe how the various types of leukemia, lymphoma, and plasma cell myelomas differ based on the type of malignant transformation. 2) Describe how the clinical presentations, prognosis, and management of types of acute and chronic leukemia differ. 3) Explain why malignant disorders of white blood cells are commonly associated with bone marrow depression. 4) Describe how Hodgkin disease is clinically and histologically differentiated from other types of lymphoma. 5) Describe the purpose and process of staging procedures for lymphomas. 6) Identify the clinical and laboratory findings that would suggest a diagnosis of plasma cell myeloma. Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Malignant Disorders of White Blood Cells Leukemia, lymphoma, and plasma cell myeloma (multiple myeloma)—common neoplastic disorders of the bone marrow and lymphoid tissues Leukemias—circulating tumors that are disseminated from the beginning of the disease process; primarily involve blood and bone marrow Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Malignant Disorders of White Blood Cells (Cont.) Lymphoma—tends to localize in lymph tissues; is often disseminated to other sites at diagnosis Plasma cell myeloma—malignant transformation of B-cell plasma cells; likes to form localized tumors in bony structures Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Classification of Hematologic Neoplasms Categories based on the cell type of the neoplasm rather than its location in the body Myeloid lineage: red cells, platelets, monocytes, and granulocytes Lymphoid lineage: B cells, T cells, and natural killer (NK) cells Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Classification of Hematologic Neoplasms (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Etiology of Myeloid and Lymphoid Neoplasms Exact cause of hematologic neoplasms is unknown; basic mechanisms involves cell mutation that disrupts growth control and differentiation pathways Viruses Radiation exposure Chemical exposure (slight) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Diagnosis of Hematologic Neoplasms Most common clinical manifestations Leukopenia: lymphadenopathy, joint swelling and pain, weight loss, anorexia, hepatomegaly, splenomegaly Anemia: pallor, fatigue, malaise, shortness of breath, decreased activity tolerance Thrombocytopenia: a platelet count below 20,000 cells/μl, petechiae, easy bruising, bleeding gums, occult hematuria, retinal hemorrhages Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Diagnosis of Hematologic Neoplasms (Cont.) Neutropenia: absolute neutrophil count 20% blasts Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Acute Myeloid Leukemia (Cont.) Pathogenesis and Clinical Manifestations Subtypes identified by the stage at which development stops FAB system commonly used for classification Most common type of AML: acute granulocytic leukemia; often used interchangeably with AML Cells have large segmented nucleus and fine chromatin Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Acute Myeloid Leukemia (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Acute Myeloid Leukemia (Cont.) Pathogenesis and Clinical Manifestations If cytogenic class not apparent, the classified according to morphologic characteristics Presentation very similar to ALL; difficult to tell apart by only clinical findings Bone pain, anemia, thrombocytopenia, increased infection susceptibility Common infection sites: skin, GI, GU, and respiratory tracts Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Acute Myeloid Leukemia (Cont.) Pathogenesis and Clinical Manifestations Abrupt onset of symptoms Prognosis worse for AML than ALL: 40 years; median age 65 years; men > women Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Plasma Cell Myeloma (Multiple Myeloma) (Cont.) Pathogenesis and Clinical Manifestations Abnormalities in chromosome structure/number commonly found Malignant plasma cells belong to single clone Produce excessive identical monoclonal antibodies Accumulate in the bloodstream Detected by serum protein electrophoresis Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.  Plasma Cell Myeloma (Multiple Myeloma) (Cont.) Pathogenesis and Clinical Manifestations Large amount of one type of antibody; forms a characteristic spike Bence Jones protein: malignant plasma cells produce light-chain antibody fragments that accumulate in blood and urine Helps confirm diagnosis Can accumulate in kidneys and damage them Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.  Plasma Cell Myeloma (Multiple Myeloma) (Cont.) Pathogenesis and Clinical Manifestations Malignant plasma cells tend to accumulate in bone; pathologic fractures common Bone destruction releases calcium into bloodstream—hypercalcemia Most clinical manifestation caused by bone/renal damage Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Plasma Cell Myeloma (Multiple Myeloma) (Cont.) Pathogenesis and Clinical Manifestations Diagnosis based on: Monoclonal antibody peak Presence of Bence Jones protein Hypercalcemia Evidence of bone lesions Bone marrow biopsy confirms diagnosis Plasma cells occupy 30%-95% of bone marrow; minimum of 10%-15% for diagnosis Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Plasma Cell Myeloma (Multiple Myeloma) (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Plasma Cell Myeloma (Multiple Myeloma) (Cont.) Pathogenesis and Clinical Manifestations Onset: slow, insidious Monoclonal gammopathy of undetermined significance (MGUS): premalignant stage apparent in some individuals with excess production of monoclonal antibodies but no bone lesions or Bence Jones protein in urine 25% progress to malignant disease Remain asymptomatic until fairly advanced; may last for many years after malignancy; frequent infections only indication Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Plasma Cell Myeloma (Multiple Myeloma) (Cont.) Pathogenesis and Clinical Manifestations Diagnosis with routine examination during asymptomatic phase Protein in urine High serum calcium levels First symptom usually bone pain Bone marrow depression indicators Anemia Recurrent infections Bleeding tendencies Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Plasma Cell Myeloma (Multiple Myeloma) (Cont.) Pathogenesis and Clinical Manifestations Renal insufficiency: 50% with multiple myeloma Resulting from combination of factors including hyperproteinemia, Bence Jones protein, hypercalcemia, hyperuricemia Culminates with end-stage renal disease Bone involvement consistent feature X-rays show “honeycomb” appearance in ribs, spine, skull, and pelvis; pathologic fractures Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Plasma Cell Myeloma (Multiple Myeloma) (Cont.) Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Plasma Cell Myeloma (Multiple Myeloma) (Cont.) Prognosis and Treatment Antineoplastic agents: induce/maintain remission in plasma cell proliferation Best chemotherapy regimen not yet determined High-dose chemo followed by allogenic BMT becoming more common Autologous stem cell transplantation considered initial optimal therapy Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Plasma Cell Myeloma (Multiple Myeloma) (Cont.) Prognosis and Treatment Autologous stem cell transplant optimal initial therapy Pharmacologic management for renal dysfunction Chronic bone pain—common problem Narcotic/non-narcotic pain relievers Localized application of radiation to bone lesions Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.  Hodgkin Disease Represents about 30% of malignant lymphoma Occurs across life span; half of cases between ages 20 and 40 years Higher incidence in males; also have worse prognosis Overall 5-year survival rate for all stages treated Hodgkin disease: 85% Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Pathogenesis and Clinical Manifestations Malignant disorder of the lymph nodes Characterized by Reed–Sternberg cells Originate from B cells in germinal centers of lymph nodes Malignant but grow/spread in predictable way; sets HD apart from other lymphomas Usually metastasizes along contiguous lymphatic pathways Hodgkin Disease (Cont.) Copyright © 2019, Elsevier Inc. All rights reserved. 52 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Pathogenesis and Clinical Manifestations Epstein–Barr virus frequently found in genome of transformed Reed–Sternberg cells; may be important in pathogenesis of HD Usually present in single node or localized node chain Inflammatory cells accumulate within lymph node; Reed–Sternberg cells constitute around 2% of cells tumor Hodgkin Disease (Cont.) Copyright © 2019, Elsevier Inc. All rights reserved. 53 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Pathogenesis and Clinical Manifestations Two types Rare lymphocyte predominance type (5%) Classical type (cHD) (95%) Can be divided into four subtypes according to relative number of reactive cells in tumor Histologic pattern does not seem to predict prognosis Stage is more relevant. Hodgkin Disease (Cont.) Copyright © 2019, Elsevier Inc. All rights reserved. 54 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Pathogenesis and Clinical Manifestations Clinical manifestations depend on origin site and dissemination stage. Early stages: often asymptomatic Painless lymphadenopathy; possibly with fever, night sweats, pruritus, weight loss, malaise Lymph node enlargement above diaphragm, cervical nodes most common site Hodgkin Disease (Cont.) Copyright © 2019, Elsevier Inc. All rights reserved. 55 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Pathogenesis and Clinical Manifestations Nodes below diaphragm less common primary site Inguinal nodes most common subdiaphragmatic site Disease spreads from site of origin to other lymph nodes/lymphatic tissue, including spleen and bone marrow. Hodgkin Disease (Cont.) Copyright © 2019, Elsevier Inc. All rights reserved. 56 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Prognosis and Treatment Ann Arbor staging system (also used for NHL) Uses presence/absence of certain clinical symptoms AND locations of affected nodes Four stages Four modifying characteristics Hodgkin Disease (Cont.) Copyright © 2019, Elsevier Inc. All rights reserved. 57 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Hodgkin Disease (Cont.) Prognosis and Treatment A: absence of clinical symptoms B: symptoms present at time of staging Loss of more than 10% body weight Unexplained fevers Night sweats CS: based on history, physical examination, noninvasive procedures PS: determined by invasive procedure results Copyright © 2019, Elsevier Inc. All rights reserved. 58 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. Prognosis and Treatment Stage dictates treatment modality. Localized tumors: radiation therapy (most common) Disseminated disease: chemotherapy Hodgkin Disease (Cont.) Copyright © 2019, Elsevier Inc. All rights reserved. 59 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin) Do not have Reed–Sternberg cells Majority arise from lymph nodes, but can originate in any lymphoid tissue 95% occur in older adults Males somewhat higher risk than females Incidence increasing, especially in AIDS populations Most arise from B cells, T cells, or NK cells Copyright © 2019, Elsevier Inc. All rights reserved. 60 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin) (Cont.) Prognosis varies according to type Grouped as indolent or aggressive Indolent: longer survival times Aggressive: disseminated at presentation, generally poor prognosis As a group: spread early and unpredictably when compared to Hodgkin’s Copyright © 2019, Elsevier Inc. All rights reserved. 61 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin) (Cont.) Pathogenesis and Clinical Manifestations Similar to other malignancies Tumor cells derived from single mutant precursor cell and are clonal Viruses suspected in development of some lymphomas (e.g., Burkitt lymphoma and Epstein–Barr virus) 5-year survival rate:75% Copyright © 2019, Elsevier Inc. All rights reserved. 62 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin) (Cont.) Pathogenesis and Clinical Manifestations Most present with advanced (stage III or IV) disease Painless lymphadenopathy, fever, night sweats, weight loss, malaise, pruritus Extranodal involvement occurs early. May present with infiltrative disease of the skin, GI tract, bone, or bone marrow Copyright © 2019, Elsevier Inc. All rights reserved. 63 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin) (Cont.) Pathogenesis and Clinical Manifestations Complications include two serious oncologic emergencies: Superior vena cava obstruction Spinal cord compression Other complications: infection, bone metastasis, joint effusions Staging and classification same as Hodgkin disease Copyright © 2019, Elsevier Inc. All rights reserved. 64 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin) (Cont.) Prognosis and Treatment Therapy effectiveness varies. Stages I and II: favorable outcomes Stages III and IV: less favorable Therapeutic management is determined by clinical stage, histologic type, patient age, and bone marrow integrity at diagnosis. Copyright © 2019, Elsevier Inc. All rights reserved. 65 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc. B-Cell, T-Cell, and NK-Cell Lymphoma (Non-Hodgkin) (Cont.) Prognosis and Treatment Common therapies: Radiation Chemotherapy Tissue-specific therapies: monoclonal antibodies and BMT Copyright © 2019, Elsevier Inc. All rights reserved. 66 Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.