Chapter 13 Lymphoproliferative Disorders and Related Plasma Cell Disorders Lymphoproliferative Disorders Lymphoproliferative disorders Clonal malignant proliferation of B and T lymphocytes Primarily affect the elderly Chronic Progress slowly with aging process Most related to compromised immune systems Diagnosed with flow cytometry and chromosomal Chronic Lymphocytic Leukemia Caused by clonal proliferation of B lymphocytes May be caused by chromosomal abnormalities Small lymphocytes accumulate in the spleen lymph nodes and bone marrow and can spill out into peripheral circulation Chronic Lymphocytic Leukemia CLL Presenting symptoms Fatigue Pallor Weight loss White counts are exaggerated with many 100 000 109 L M E ratio 10 20 1 Disease Progression in CLL Peripheral smear shows exclusively small lymphocytes intermixed with few lymphoblasts Smudge cells may be present Pieces of lymphocyte chromatin on smear Cell membrane ruptures and do not see all components look squashed Disease Progression in CLL CLL may lead to Splenomegaly Lymphadenopathy Anemia Thrombocytopenia Neutropenia Altered immune function Autoimmune hemolytic anemia Immunologic Function in CLL and Treatment Options Apoptosis programmed cell death RAI staging system In 80 of CLL an antiapoptosis gene is present BCL2 so dysfunctional B cells live Common hypogammaglobinemia Treatment options Irradiation Drugs Alkylating agents ex hydroxyurea Monoclonal antibodies is specific to the antigen produced by the body Allogenic stem cell transplant has a little more complications Hairy Cell Leukemia Rare B cell malignancy Key morphology hairy cell Fragile mononuclear cell Hair like projections of the cytoplasm Spongy appearance of chromatin Diagnosis with cytochemical stain tartrate resistant acid phosphatase Hairy Cell Leukemia Symptoms Thrombocytopenia Pancytopenia Massive spleen Bleeding Infection Anemia Dry tap Bone marrow becomes filled with fibrotic material and marrow cannot be aspirated Treatment Therapeutic splenectomy Sezary Syndrome T cell lymphoma with mycosis fungoides A cutaneous manifestation Skin biopsies reveal an infiltration of lymphocytes Spleen bone marrow and lymph nodes may become affected Sezary cells in peripheral blood Large cells 8 20 m Ovoid nucleus May be mistaken for monocytes Prolymphocytic Leukemia Variant of chronic lymphocytic leukemia Rare disorder Majority of circulating prolymphocytes Have more abundant cytoplasm than mature lymphocytes Severe symptoms Splenic enlargement Liver involvement Escalating white counts Hodgkin s Lymphoma Usually single cervical lymph node becomes firm to the touch and does not disappear Symptoms of hypermetabolism Low grade fever Weight loss Diagnosis based on lymph node biopsy Presence of Reed Sternberg cell Large Multinucleated Resembles owl s eye May involve liver spleen and bone marrow Non Hodgkin s Lymphomas May present as painless cervical lymph node involvement Lymphoma cells may be seen in peripheral smear Diagnosis based on histological types of lymphocytic cells Non Hodgkin s Lymphomas Treatment includes radiation and chemotherapy Disease may spread Gastrointestinal Respiratory Skin Liver Spleen Normal Plasma Cell Normal plasma cells Evolve from B lymphocyte Medium sized cell Have an eccentric nucleus Have well defined Golgi apparatus Cytoplasm has distinct sea blue cornflower color Chromatin organized in a pinwheel structure Normal Plasma Cell Make immunoglobulins 5 types of immunoglobulins IgG IgM IgD IgE IgA Each immunoglobulin has 4 polypeptide chains 2 H chains heavy chains Gamma alpha mu epsilon and delta 2 L chains light chains Kappa and lambda Normal Plasma Cell Immunoglobulins are assessed qualitatively and quantitatively Immunoelectrophoresis separates immunoglobulins by using antibodies directed against each fraction and run through a gel medium with an electric field Multiple Myeloma Disorder of plasma cells Accumulation of plasma cells in bone marrow and other locations Occurs at older age Multiple Myeloma May be caused by environmental and occupational factors Exposure to atomic radiation Work involving organic solvents Toxins within the textile industry Occupations with exposure to chemicals pesticides or herbicides May also be caused by chromosome abnormalities Pathophysiology in Multiple Myeloma Follow three distinct pathways Acceleration of plasma cells in the bone marrow Activation of bone resorption factors or osteoclasts Production of an abnormal monoclonal protein Pathophysiology in Multiple Myeloma Acceleration of plasma cells in the bone marrow Caused by cytokine IL 6 May develop colorless inclusions called Russell bodies or other crystalline inclusions Flame cells may be seen in IgA myeloma Deep pink cytoplasm Pathophysiology in Multiple Myeloma Acceleration of plasma cells in the bone marrow cont Overcrowding of bone marrow with plasma cells causes Anemia Thrombocytopenia Neutropenia May seed to other areas in the body as plasmacytomas Liver Spleen Gastrointestinal tract Nasal cavity Pathophysiology in Multiple Myeloma Activation of bone resorption factors or osteoclasts Increased osteoclast activity Inevitable bone loss Serum calcium increased May lead to kidney failure or kidney stones Pathophysiology in Multiple Myeloma Production of an abnormal monoclonal protein Monoclonal gammopathy Purposeless proliferation of one particular antibody Rouleaux formation Nonspecific binding of red cells Looks like stack of coins Caused by red cells circulating in abnormal proteins Causes falsely decreased red counts Falsely increased MCV and MCHC ESR usually elevated due to increased settling Bence Jones protein found in urine of patients with multiple myeloma Precipitates out when heated Symptoms of Multiple Myeloma Symptoms Fatigue due to anemia Excessive thirst urination due to excess calcium Nausea due to excess calcium Bone pain back and ribs due to plasma cell acceleration Bone fractures due to calcium leeching from bones into circulation Unexpected infections due to compromised immunity Weakness and numbness in the legs due to vertebrae compression Symptoms of Multiple Myeloma Screening CBC Possible bone marrow Urinalysis Protein panel Serum protein electrophoresis Serum beta microglobulin Prognosis and Treatment in Multiple Myeloma Some patients may show punched out lesions on initial radiography Chemotherapy and radiation may relieve some bone pain Plasma Cell Leukemia Plasma cell leukemia is a complication of multiple myeloma in