Pathology of the Blood PDF

PATHOLOGY OF THE BLOOD White blood cell (WBC) disorder 1 Malek Ahmed Telegram : Mapatho  Objective 1. Non neoplastic WBC disorder 2. Neoplastic WBCs Disorder 3. Acute leukemia White blood c...

PATHOLOGY OF THE BLOOD White blood cell (WBC) disorder 1 Malek Ahmed Telegram : Mapatho  Objective 1. Non neoplastic WBC disorder 2. Neoplastic WBCs Disorder 3. Acute leukemia White blood cells  White blood cells Peripheral blood smear, showing normal blood leukocytes morphology  White blood cells Bone marrow aspirate showing normal maturation sequence of granulocytic cells *note the nucleus getting smaller White blood cells  Non-neoplastic WBC disorder Whole blood after centrifugation  Non-neoplastic WBC disorder WBC Terminology Leukocytosis Leukopenia Neutrophilia: Eosinophilia: Neutropenia: Lymphopenia: Neutrophil Eosinophil Basophilia: Lymphocytosis: Monocytosis: Lymphocyte Neutrophil count > 7.0 × count > 0.5 × (> 0.1 × 109/L) (> 3.5 × 109/L) (> 1.0 × 109/L) count < 2 × 109/ count < 1.5 × 109/L 109/L 109/L Leukocytosis: increase in the total Leukopenia: decrease in the total white blood cell (WBC) count above the upper limit of WBC count below the normal (> 11 × 109/L). lower limit of normal (< 4 × 109/L)  Non-neoplastic WBC disorder Terminology Leukocytosis: is an increase in the total white blood cell (WBC) count above the upper limit of normal (> 11 × 109/L). Neutrophilia: Neutrophil count > 7.0 × 109/L Eosinophilia: Eosinophil count > 0.5 × 109/L Basophilia: > 0.1 × 109/L Lymphocytosis: > 3.5 × 109/L Normal leukocyte count 4x109 to 11x109 Monocytosis: > 1.0 × 10 /L 9  Non-neoplastic WBC disorder Terminology Leukopenia: is a decrease in the total WBC count below the lower limit of normal (< 4 × 109/L). Neutropenia: Neutrophil count < 2 × 109/L Lymphopenia: Lymphocyte count < 1.5 × 109/L Non-neoplastic WBC disorder Non-neoplastic WBC disorder  Non-neoplastic WBC disorder Neutrophilia Acute bacterial infections (pyogenic bacteria>> can cause abscess) Myocardial infarction, burns Uremia, eclampsia, acidosis, gout Neoplasms of all types Acute hemorrhage or hemolysis Treatment with myeloid growth factors (G-CSF, GM-CSF): - Filgrastim (Neupogen) Both given for cancer patients - Lenograstim (Granocyte) if they have neutropenia However they can cause neutrophilia  Non-neoplastic WBC disorder Eosinophilia Allergic disorders Drug sensitivity ‫اإلصابة‬ Parasitic infestations (e.g. hydatid cyst) Collagen vascular disorders (e.g. SLE , Rheumatoid Arthritis , vasculitis) Certain malignancies (e.g. ALL ,Lymphoma) Myeloproliferative neoplasms Treatment with GM-CSF  Non-neoplastic WBC disorder Basophilia Neoplastic: Often seen in chronic myeloid leukemia. Reactive: seen in Ulcerative colitis, Myxoedema, Smallpox or chickenpox infections.  Non-neoplastic WBC disorder Monocytosis Chronic bacterial infections (e.g., tuberculosis, bacterial endocarditis, syphilis) Malaria Collagen vascular diseases Hodgkin disease, AML Certain chronic myeloproliferative neoplasms Inflammatory bowel diseases  Non-neoplastic WBC disorder Lymphocytosis Infections: - Acute: infectious mononucleosis (EBV),rubella, mumps, infectious hepatitis, CMV, HIV, herpes, B. pertussis - Chronic: typhoid fever, syphilis, healing TB, toxoplasmosis Neoplastic: - Chronic lymphoid leukemias - Acute lymphoblastic leukemia - Non Hodgkin Lymphoma (some) Thyrotoxicosis  Non-neoplastic WBC disorder Neutropenia :is a reduction below normal of the number of neutrophils in peripheral blood. Inadequate or ineffective granulopoiesis: - Generalized marrow failure as in aplastic anemia - Isolated neutropenia: Congenital, Racial or familial,Cyclical neutropenia (3-4 weeks periodicity) Accelerated removal or destruction of neutrophils: - Acquired: drug-induced, immune mediated - Infections: bacterial>>Not pyogenic (typhoid, miliary tuberculosis), viral (hepatitis, influenza, HIV), fungal - Hypersplenism Altered distribution: as in stress and certain drugs  Non-neoplastic WBC disorder Lymphopenia is a reduction below normal of the number of lymphocytes in peripheral blood. 1. Congenital immunodeficiency diseases 2. Acquired: Advanced HIV infection, miliary TB Treatment with corticosteroids and other immunosuppressive therapy Advanced Hodgkin disease  Quiz Which one of the following infections is associated with neutrophilia A-Acute pyogenic infections B-Infectious mononucleosis C-Hepatitis A D-Brucellosis E-Tuberculosis  Case scenario A 40-year-old man presented with Weakness and Sore throat for one week duration. Physical examination: Pale Petechial Rash on his legs. His Throat was red and inflamed. Cervical and axillary lymph nodes enlargement. Splenomegaly What Laboratory Investigations should be performed? What is your differential diagnosis? Acute leukemia  Acute leukemia Definition: ‫)الخاليا‬ ‫( هي عادةً تحول خبيث ناتج عن استنساخ عدواني يشمل الخاليا الجذعية املكونة للدم أو السالئف املبكرة‬AL) ‫اللوكيميا الحادة‬ ‫ وتتميز بالتكاثر غير املنضبط للخاليا األرومية في نخاع العظم مع تسربها إلى الدم املحيطي وتغلغل متغير في األعضاء‬،(‫األرومية‬.‫األخرى‬ AL (Acute Leukemia ) is usually an aggressive clonal malignant transformation involving the hematopoietic stem cells or early progenitors (blasts) and characterized by uncontrolled proliferation of blast cells in the BM with spillage into the peripheral blood and variable infiltration ‫تَسَلُّل‬ of other organs. There are two major types of AL; 1. Acute lymphoblastic leukemia (ALL) 2. Acute myeloblastic leukemia (AML)  Acute leukemia Clinical Features: AL occurs at any age, and could be classified accordingly into: 1. Childhood AL which is usually lymphoblastic (ALL) 2. Adult AL which is usually myeloblastic (AML). Acute leukemia  Acute leukemia The common symptoms & signs at presentation are mainly attributed to: 1. Bone marrow failure. 2. Organ and Tissue Infiltration by the leukemic cell 1. BONE MARROW FAILURE: A. ANEMIA: Pallor, weakness, fatigue, lethargy, dyspnea on exertion, angina and palpitation.  Acute leukemia B. NEUTROPENIA: Fever and infections due to reduced immunity, especially: Skin infection Respiratory infection  Acute leukemia C. THROMBOCYTOPENIA: Bleeding manifestations into the skin: Petechia Ecchymosis  Acute leukemia 2. Organ and Tissue Infiltration by the leukemic cells: Splenomegaly..Hepatomegaly..Bone pain..Arthralgia.. A. Cervical lymphadenopathy; B. Facial palsy; C. Tongue infiltration; D. Gum infiltration; E. Ocular infiltration; F. Ant. chamber infiltration  Acute leukemia Diagnosis of AL require Presence of blast in the Presence of specific recurrent (leukemia- bone morrow or associated) cytogenetic peripheral or molecular genetic blood abnormalities More Less than 20% than 20%  Acute leukemia Blood Film findings: a. RBCs: anemia is almost always present. b. WBCs total count may be: - Normal - High count - Low count Neutropenia is common c. Platelets: decreased in most cases. Cutoff point is 20% of blast cells in BM Bone marrow aspirate findings: BMA is necessary to confirm the diagnosis (especially when low counts).  Acute leukemia Classification: It is based on: 1. Morphology of blasts. 2. Cytochemistry. 3. Immunophenotyping. 4. Genetic analysis. There are two major types of AL: ❖Acute Lymphoid Leukemia (ALL) ❖Acute Myeloid Leukemia (AML)  Acute leukemia 1-Morphology in AL ALL VS AML morphology Lymphoblast Myeloblast -One or two nucleoli -Multiple nucleoli -Coarse and clumped chromatin -Finer chromatin -Less cytoplasm -More cytoplasm -No AUER rods -May contain granules or AUER rods  Acute leukemia Acute lymphoblastic leukemia. The nuclei of lymphoblasts have somewhat coarse and rather clumped chromatin and one or two nucleoli.  Acute leukemia Granules Nu cle ol i AUER rods Acute myeloblastic leukemia. Myeloblasts tend to have finer chromatin with multiple nucleoli and more cytoplasm, which contain granules or Auer rod.  Acute leukemia 2-Cytochemistry in AL ALL positive only for PAS Acid phosphate  Quiz Which of the following stains is(are) positive for Lymphoblasts A. Sudan Black B. B. Periodic Acid Schiff. C. Myeloperoxidase. D. Acid phosphatase. E. Non-specific Esterase.  Acute leukemia 3-Immunophenotyping in AL Immunophenotyping (IPT) can be determined by flowcytometry or immunohistochemistry. It is very useful in typing and subtyping of AL. -CD79a is the most specific marker for B-cells -CD3 is the most specific marker for T-cells. -Anti-myeloperoxidase (MPO) is the most specific myeloid marker.  Acute leukemia 4-Genetic analysis in AL -ALL: the most common karyotypic abnormalities in B-cell ALL (with good prognosis) is hyperploidy (>50 chromosomes/cell), which is associated with t(12:21). Poor outcomes are observed with 11q23 and the Philadelphia (Ph+) chromosome. AML: good outcome correlates with t(8:21) & t(15:17). Conversely, poor outcome correlates with Ph+, and t(6:9)  Quiz Which of the following markers is the most specific for myeloblasts: A.CD3 B.CD79a C.MPO Acute leukemia Philadelphia chromosome  Acute leukemia Genetic analysis in AL Good prognosis Bad prognosis ALL hyperploidy (>50 11q23 and the chromosomes/cell), Philadelphia (Ph+) which is associated chromosome. with t(12:21). AML t(8:21) & t(15:17). Philadelphia (Ph+), and t(6:9) Philadelphia chromosome has bad prognosis in both AML and ALL  Back to the case scenario What Laboratory Investigations should be performed? 1-Complete Blood Count (CBC) 2-Blood Film  Back to the case scenario 1-CBC  Back to the case scenario 2-Blood film and/or bone morrow aspirate Blood film; Leukemia Blasts showing no evidence of maturation.  Back to the case scenario Differential Diagnosis : ALL  Quiz Which of the following hematological findings is not seen in acute leukemia? A-Normochromic normocytic anemia B-Thrombocytopenia in most cases C-Blood film shows variable numbers of blasts D-BM usually shows infiltration with 10% leukemic blasts  Quiz Which of the following features is consistent with myeloblasts morphology A-The nuclei have somewhat coarse and clumped chromatin B-Presence of two or more nucleoli C-Rather high nucleocytoplasmic ratio D-Agranular cytoplasm E-Small-size blasts  Case scenario A 22 year old female presented with 3 week history of fever and bone pain. Her physical exam revealed cervical lymphadenopathy and multiple bleeding spots.Her blood counts revealed many blasts in the peripheral blood.The best test to differentiate whether she is a case of acute lymphoblastic leukemia or acute myeloid leukemia is: A-the presence of Philadelphia chromosome B-the presence of splenomegaly on ultrasound of abdomen C-immunophenotyping of blast cells D-the count of white blood cells in peripheral blood E-the number of blasts in bone marrow aspirate  Summary Reactive leukocytosis is much more commonly encountered in routine work than neoplastic states. Absolute leukocytes counts are the target for interpretation not their percentages in the PB. Morphology, cytochemistry, IPT and genetic analysis. All these investigations may be required to reach the diagnosis and classify AL. The diagnosis of AL is based on a cutoff point of blast cells (20%) whether in the PB or BM.  Links to my channels 1-Pathology course channel https://t.me/+wOjFm2MEhxBkM2My 2-Medical channel https://t.me/Malekahmed09 3-Lectures Bot https://t.me/PathologyMAbot