Intro to White Blood Cell Disorders Flashcards Preview

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Flashcards in Intro to White Blood Cell Disorders Deck (61):

Where are WBCs found?

  • Bone marrow
  • Peripheral blood
  • Lymph nodes, thymus, spleen, tonsils, adenoids, Peyer patches
  • Mucosa-associated lymphoid tissue (MALT)


What is cytoses?

What is cytopenia?

Increased leukocytes

Decreased leukocytes


What is the normal reference range for WBCs?

4000 - 10,000/uL


What is a leukemoid reaction and what cells may be involved?

NOT leukemia

A benign, exaggerated response to infection with an absolute leukocyte count > 50,000

May involve neutrophils, lymphocytes or eosinophils


What are potential causes of a leukemoid reaction?

  • Perforating appendicitis - neutrophils
  • Whooping cough (Bordetella pertussis) - lymphocytes
  • Cutaneous larva migrans - Eosinophils


What is a leukoerythroblastic reaction? 

What can cause it?

Immature bone marrow cells in the peripheral blood

Can be due to a BM infiltrative disease (fibrosis or breast cancer metastasis) or severe BM stress (sepsis or growth factor)


Neutrophilia is defined as an absolute neutrophil greater than ________



What are some causes of neutrophilia?

  • Infection
  • Sterile inflammation with necrosis (acute MI)
  • Drugs (steroids, catecholamines, lithium)
  • Increased production and decreased margination (extravasation)


Neutropenia is an absolute neutrophil count less than ______



What are some possible causes of neutropenia?

  • Chemotherapy
  • Aplastic anemia
  • Immune destruction
  • Septic shock
  • Decreased production and/or increased destruction or margination


Eosinophilia is an absolute eosinophil count greater than _____ and is caused by...(4)


  • Type I hypersensitivity (allergies)
  • Invasive helminths (hookworm) 
  • Hypocortisolism (Addison's disease)
  • Neoplasms (Hodgkin lymphoma)


Basophilia is a basophil count greater than ____ and can be caused by... (2)


  • Chronic myelogenous leukemia (and other chronic myeloproliferative neoplasms)
  • Chronic kidney disease


What do leukemia and lymphoma have in common?

What is the difference?

Both are a proliferation of neoplastic cells

Leukemia: Primarily in BM and PB (peripheral blood)

Lymphoma: Primarily in lymph nodes and extramedullary lymphoid tissue


What four criteria are used to classify Myeloid neoplasms (neoplastic stem cell disorders)

  • Morphology
  • Immunophenotype
  • Genetic features
  • Clinical features


What are the 3 categories of myeloid neoplasms?

  1. Myeloproliferative neoplasms (MPN)
  2. Myelodysplastic syndromes (MDS)
  3. Acute myeloid leukemia (AML)


What are four types of myeloproliferative neoplasms?

  1. Chronic myelogenous leukemia, BCR-ABL positive (CML)
  2. Polycythemia vera (PV)
  3. Primary myelofibrosis (PMF)
  4. Essential thrombocythemia (ET)


MPN is a proliferation of...

One or more of the myeloid lineages

  • Granulocytic
  • Erythroid
  • Megakaryocytic
  • Mast cells


MPN general features

  • Age group:
  • BM appearance:
  • Effect on other organs:
  • Possible complications:

  • Age group: Common in adults (5th - 7th decade)
  • BM appearance: Hypercellular BM with effective hematopoiesis
  • Effect on other organs: Splenomegaly or hepatomegaly
  • Possible complications: Potential for progression - BM fibrosis or acute leukemia


What are the differences between myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS)?

  • MPN: Hypercellular BM with effective hematopoiesis (cytoses, increased PB counts, cell proliferation)
  • MDS: Hypercellular BM with ineffective hematopoies-is (cytopenias, decreased PB counts, cell death)



Chronic myelogenous leukemia (CML)

  • Age group:
  • Cellular mechanism:
  • Genetic defect:
  • Clinical findings:

  • Age group: peak at 40-60 years
  • Cellular mechanism: Neoplastic expansion of pluripotential stem cell
  • Genetic defect: BCR-ABL fusion gene
  • Clinical findings: Hepatosplenomegaly; weight loss, fatigue, weakness, anorexia


What are the laboratory findings in CML?

  • Leukocytosis with immature myeloid cells
  • Basophilia
  • Philadelphia chromosome: t(9;22)
  • BCR-ABL fusion gene
  • Few myeloblasts
  • Thrombocytosis (45-50%) or thrombocytopenia
  • Hypercellular BM (granulocytic hyperplasia)


What are the 3 stages in the course of CML?

  1. Chronic phase (3 years)
  2. Accelerated phase (1 year)
  3. Blast phase = acute leukemia (myeloid or lymphoblastic)


What therapy is done for CML?

  • Allogeneic stem cell transplant
  • BCR-ABL tyrosine inase inhibitors
    • Gleevec
    • Dasatinib
    • Nilotinib


Polycythemia vera (PV)

  • Increase in...
  • Genetic defect:

  • Increase in RBCs, granulocytes and platelets
  • Genetic defect: Janus 2 kinase (JAK2) mutation in virtually all cases


Clinical findings in PV


  • Splenomegaly
  • Thrombotic events (due to hyper viscosity)
  • Gout (increased cell breakdown)
  • Increased histamine (from mast cell sin the skin)
    • Ruddy face, pruritus after bathing, peptic ulcer


What are the laboratory findings in PV?

  • Increased RBC mass (increased hemoglobin)
  • Decreased EPO (dysfunctional Hb feedback loop)
  • Leukocytosis
  • Thrombocytosis
  • Normal oxygen saturation
  • Hypercellular BM with fibrosis (in later stages)


EPO increases in all polycythemias EXCEPT...

Polycythemia vera


With conservative treatment of PV, median survival is greater than ___

Most patients die of _____ or ______

Median survival is greater than 10 years

Most patients die of thrombosis or hemmorhage


Primary myelofibrosis (PMF) involves rapid development of __ _______ and  _______ _______ in the spleen, liver and lymph nodes

BM fibrosis; Extramedulary hematopoiesis (EMH)


What are the clinical findings in PMF? (2)

  • Splenomegaly (with portal hypertension)
  • Splenic infarcts with left sided pleural effusions


Laboratory findings in PMF?


  • BM fibrosis and clusters of atypical megakaryotcytes
  • JAK2 (or MPLmutation in 50%
  • Peripheral blood leukocytosis (early)
  • Normochromic, normocytic anemia
    • Teardrop cells
    • Leukoerythroblastic reaction


What is the median survival of PMF?

3-7 years in fibrotic stage

>10 years in early (prefibrotic) stage


What are the major causes of morbidity and mortality in PMF?

  • BM failure
  • Thromboembolic events
  • Portal hypertension
  • Cardiac failure
  • AML


Essential thrombocythemia involves a proliferation of...



What cellular abnormalities are associated with Essential Thrombocythemia (ET)?

  • Platelet count > 450,000/uL
  • Mild neutrophilic leukocytosis
  • Hypercellular BM with abnormal megakaryocytes


General ET characteristics

  • Clinical findings:
  • Genetic mutation:
  • Median survival:
  • Treatment:

  • Clinical findings: Bleeding, splenomegaly
  • Genetic mutation: JAK2 mutation (50%)
  • Median survival: 12-15 years
  • Treatment: Alkylating agents, lower platelet count


Myelodysplastic syndromes are characterized by... (3)

  • Cytopenias (enhanced degree of apoptosis)
  • Dysplasia (one or more myeloid cell lineages)
  • Ineffective hematopoiesis (myeloblasts < 20%)


What are some laboratory findings in MDS?

  • Cytopenias
  • Leukoerythroblastic reaction
  • Dysplastic features
  • Hypercellular BM
  • Ring sideroblasts
  • Increased myeloblasts


What chromosomal abnormalities are associated with MDS?

Chromosomal abnormalities in 50%

del5q, +8, or del7q


MDS clinical course

  • Age group:
  • Clinical signs:
  • Median survival:
  • Progression to ___ in 30% of cases

  • Age group: elderly (50-80 years)
  • Clinical signs: weakness, infections, hemmorhage
  • Median survival: 9-29 months (t-MDS: 4-8 months)
  • Progression to AML in 30% of cases


What is the treament for MDS?

  • Supportive: blood products, antibiotics, growth factors
  • Hypomethylating agents: not curative
    • Decitabine
    • Azacitidine
  • Allogenetic stem cell transplant


What is the definition of Acute leukemia and what are the two main categories?

Neoplastic proliferation of immature cells (blasts) recapitulatin progenitor cells of the hematopoietic system

  • Myeloblastic (myeloid) - AML
  • Lymphoblastic (lymphoid) - ALL


Compare acute vs. chronic leukemia

  • Acute leukemia
    • Immature cells
    • Untreated natural history of weeks to months
  • Chronic leukemia
    • Mature cells
    • Untreated natural history of months to years



What are some differences between AML and ALL in terms of age group, male/female ratio and incidence?

  • AML
    • Primarily Adults (Median age = 60)
    • M:F = 1:1
    • 3 cases/100,000 pop./year
  • ALL
    • Most common in Children (75% under age 18)
    • M:F = 1.4:1
    • 1.4 cases/100,000 pop./year


What are some cytologic differences in Blasts in AML and ALL?

AML has larger cells, finely dispersed chromatin, granular cytoplasm and auer rods

ALL has smaller (variable) cells, coarse chromatin, no granules and no auer rods


What are the most useful cytochemical stains in identifying AML and ALL?

Myeloperoxidase (MPO): myeloblasts

Non-specific esterase (NSE): monocytic blasts in AMLs with monocytic differentiation


What is the purpose of immunophenotyping in acute leukemia?

  • Distinguishes ALL from AML
  • Distinguishes B-ALL from T-ALL
  • Identifies subtypes
  • Identifies treatment and prognostic group
  • Fingerprint for minimal residual disease assessment


Sorry about this slide but...

What are some examples of lymphoid antigens in...

T lineage:

B lineage:

AND what are some examples of myeloid antigens


Sub lineage associated:

  • T lineage: CD1a, CD2, CD3, CD4, CD5, CD7, CD8
  • B lineage: CD19, CD20, CD22
  • Generic: CD13, CD15, CD33, CD117, MPO
  • Sub lineage associated: CD41 and CD61 (megakaryocytes); CD14 (monocytes)


What are markers of immaturity in immunophenotyping for acute leukemia?

  • CD34 (AML and ALL)
  • TdT (mostly seen in ALL)
  • CD117 (AML)
  • CD1a (restricted to immature T cells)


What is the prognosis in AML?

What is the cellular neoplasm in AML?

  • Poor outcome: long term survival = 25%
  • Systemic neoplasms of myeloid progenitor cells
    • Primarily involves blood and bone marrow


Clinical features of AML?

  • Related to cytopenias - Weakness, fatigue, infections
  • Less common findings - organomegaly, lymphadenopathy
  • Coagulopathy in specific variants


What is the diagnostic criterion for AML?

Greater than 20% myeloid blasts in blood or marrow

Maturation may be towards any one of the myeloid lineages (Granulocytes, monocytes, megakaryocytes, erythroid precursors)


What are the hematologic features of AML?

  • Severe leukopenia to marked leukocytosis
  • Anemia and thrombocytopenia are the norm
  • Maturing/mature cells of all myeloid lineages may be dysplastic


What are the different types of AML?

  • AML with recurrent cytogenetic abnormalities
  • AML with myelodysplasia-associated changes
  • AML and MDS, therapy related
  • AMLy not otherwise categorized


AML with recurrent cytogenetic abnormalities

  • Incidence rate by age group:
  • Prognosis:
  • Antecedent myelodysplastic syndrome?:

  • Incidence rate by age group: flat incidence rate over different age groups
  • Prognosis: generally favorable
  • Antecedent myelodysplastic syndrome?: no


AML with myelodysplasia-associated changes

  • Incidence rate by age group:
  • Prognosis:
  • Antecedent myelodysplastic syndrome?:

  • Incidence rate by age group: Increasing incidence with age
  • Prognosis: Poor
  • Antecedent myelodysplastic syndrome?: likely


What genetic defects in AML are associated with favorable outcomes? unfavorable?

  • Favorable
    • t(8;21): AML1/ETO
    • inv(16): CBFß/MYH11
    • t(15;17): PML/RAR alpha
  • Unfavorable
    • 11q23 (MLL) rearrangements


Describe AML with t(15;17)

  • Acute promyelocytic leukemia
  • Single cells with multiple auer rods (faggot cells)
  • Responds to all-trans retinoic acid (ATRA) - unique to this variant
  • Usually leukopenic


Histiocytic conditions: Langerhans cell histiocytosis

  • Mutations:
  • Appearance on EM:
  • Cluster of differentiation:

  • Mutations: BRAF mutations
  • Appearance on EM: "tennis racket" - Birbeck granules
  • Cluster of differentiation: CD1a, langerin


Histiocytic conditions: Hemophagocytic lymphohistiocytosis

Primary (defect):
Secondary HLH:
Distinguishing feature:

  • Primary (defect): defects in perforin gene
  • Secondary HLH: EBV, lymphomas
  • Distinguishing feature: very high ferritin