BASI Pathology Review WBC Disorders 2024 PDF

BASI Pathology review WBC disorders 2024 Leukocytes: white blood cells in the peripheral blood; manufactured predominantly in the bone marrow (and other blood-forming organs). A single pleuripotent stem gives rise t...

BASI Pathology review WBC disorders 2024 Leukocytes: white blood cells in the peripheral blood; manufactured predominantly in the bone marrow (and other blood-forming organs). A single pleuripotent stem gives rise to two multipotent stem cells the myeloid precursor and the lymphoid precursor Leukopenia is defined as decreased white blood cells (WBCs) in the blood; two types, granulocytopenia and lymphocytopenia Granulocytopenia (neutropenia; agranulocytosis) Causes: Drug/alcohol effect on bone marrow may cause isolated neutropenia Neutropenia may be part of pancytopenia- decreased neutrophils, RBCs (anemia) and platelets (thrombocytopenia). Pancytopenia is due to : Acute leukemia (total WBCs may be increased or decreased); malignant cells replace normal Aplastic anemia : absence of all bone marrow precursors due to stem cell death Myelodysplasia/myelodysplastic syndromes: defective DNA due to mutations Megaloblastic anemia—B12/folate deficiency leads lack of DNA production Autoimmune destruction: systemic lupus erythematosus and other Symptoms of neutropenia: Infection, fever, agranulocytic angina—ulcerating, necrotizing lesions of the gingiva and floor of mouth Lymphocytopenia- lymphopenia (common cause of leukopenia in children) Causes: Malnutrition- marasmus, Kwashiorkor, anorexia nervosa Congenital immune deficiencies such as DiGeorge syndrome (absent thymus) HIV-AIDS Radiation Corticosteroids Some severe infections, especially disseminated TB; serious COVID-19 (poor prognosis) Leukocytosis Increased WBCs in the blood, two major types Neutrophilia; granulocytosis Causes: Pyogenic infections, Staphylococcus, Streptococcus, and others Sterile inflammation: trauma, myocardial infarction Chronic myelogenous leukemia and polycythemia vera (myeloproliferative disorders) Lymphocytosis causes Viral infections- with atypical lymphocytes: Infectious mononucleosis (EBV); CMV, viral hepatitis Chronic lymphocytic leukemia Eosinophilia Causes: Asthma, Allergies and Parasites Leukemias: Compare/contrast acute lymphocytic leukemia with acute myelocytic leukemia: Acute Lymphoblastic / Acute myeloblastic / Lymphocytic ALL myelocytic / myelogenous AML Symptoms Fatigue (anemia); bleeding / Fatigue (anemia); bleeding / bruising (low platelets); fever- bruising (low platelets); fever- infection (low neutrophils) infection (low neutrophils Age, peak Most < 15yrs; peak age 4 Any age; Median age 50 Labs Anemia; thrombocytopenia; Anemia, thrombocytopenia; WBCs : lymphoblasts present WBC myeloblasts; Auer rods acute TDT+ TDT negative blasts 14minB cell type CD10 CD19+ - most amyelo Subtypes Acute myelocytic (M0-M7) cases T cell type CD2: mediastinal mass Cure Remission 90%; 2/3+ cured Chemotherapy cure less likely Bone marrow transplant cures Compare/contrast chronic lymphocytic leukemia with chronic myelogenous leukemia CLL CNL Chronic lymphocytic leukemia Chronic myelogenous leukemia Age Adults, usually >50; median 60 Any; peak 25-60 years old Most common adult leukemia Clinical Initially asymptomatic Fatigue; symptoms of Mild enlargement of lymph splenomegaly: early satiety; nodes, liver, spleen in half dragging sensation LUQ (small lymphocytic lymphoma). Visual disturbance due to Later: fatigue, weight loss, sluggish retinal blood flow. infections or autoimmune Fever, night sweats (hyper- hematologic disease metabolic) Labs, general Lymphocytosis of “mature”- Neutrophilia with immature appearing small uniform forms (myelocytes, meta- lymphs; smudge cells myelocytes, bands) eosinophils Other findings are late increased; anemia; hypercellur marrow with no increased blasts Specific labs TCI CD profile; B cell most common Philadelphia chromosome, t(9;22); (bcr;abl); leukocyte alkaline phosphatase score low Clinical Two prognostic groups: Median survival with palliative Indolent, median survival of yrs; treatment: 3 years Aggressive form with 2-3year Death from accelerated phase survival. Both progress to more or blast crisis aggressive leukemia; lymphoma ᵗÉIh.am EIiaimenntkk'imontianxman  af Treatment Therapy directed at lineage- Tyrosine kinase inhibitors; bone specific CD, eg anti CD20; marrow transplant may result Palliative in cure What type of neoplasm and what clinical features characterize hairy cell leukemia? Rare B-cell leukemia of middle aged-men; circulating “hairy” type cells, splenomegaly, pancytopenia; indolent (slowly progressive); responds to therapy What are the features of myelodysplastic syndromes? Pancytopenia - reduced neutrophils, RBCs and platelets, due to genetic abnormality of stem cell; anemia does not respond to treatment people rare inyounger Risk for acute myelogenous leukemia AML mostly older WBCs and platelets are morphologically abnormal and are dysfunctional: risk for bleeding; infections Poor prognosis with median survival 9-29 months Define myeloproliferative disorders. List common features; pathogenesis; types. (Acute = acute myelocytic leukemia) Chronic: All exhibit increased hematopoiesis (bone marrow hypercellularity) and splenomegaly; risk for transformation to acute myelocytic leukemia Arise due to clonal genetic abnormality of a myeloid progenitor cell Chronic types Chronic myelogenous leukemia (most common, see previous) Polycythemia vera (see below) (primary myelofibrosis and essential thrombocythemia—will not be covered) What is the dominant defect of polycythemia vera? Clinical features? Clonal; mutation in JAK 2 gene that causes proliferation of predominantly red blood cells-RBCs erythropoietin Éponifient (polycythemia) but also platelets and neutrophils independentof Absolute polycythemia with low erythropoietin Symptoms mostly related to sluggish blood flow: plethoric complexion, hypertension, headache; increased risk of thrombosis/bleeding Splenomegaly, usually massive. END