Hematopoiesis and WBC Disorders - SRS Flashcards

1
Q

What is the definition of leukemia?

A

Term coined by Virchow to indicate a malignancy which greatly increases the “Leuko” fraction of the blood, but now also includes aleukemic leukemias

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2
Q

What is a lymphoma?

A

Solid tumors derived from lymphoid tissue that primarily involve lymph nodes and peripheral organs

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3
Q

What does the category “granulocyte” include? 3

A
  1. Neutrophils
  2. Eosinophils
  3. basophils
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4
Q

Myeloid disorders (leukemias) involve the precursors of what cell types? 4

A
  1. Erythroid
  2. granulocytic
  3. monocytic
  4. megakaryocytes
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5
Q

What are the “so called” myeloid cells?

A

Granulocytes and monocytes only

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6
Q

As far as Lymph node involvement is concerned, how are low grade and high grade non-hodgkin lymphomas different?

A
  • Low grade: Tend to involve multiple nodes (“matted” nodes)
  • High grade: Tend to involve a single node, localized group of nodes or extranodal site
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7
Q

What is the appearance and feel of lymphoma nodes?

A

Fleshy tan and rubbery firm

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8
Q

What are the two most common stain types for peripheral WBCs?

A

Wright and Giemsa

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9
Q

In adults, where does myelopoiesis nearly exclusively take place?

A

Bone marrow

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10
Q

In what portions of the developing fetus does prenatal hematopoiesis occur?

A
  1. Yolk sac
  2. Liver
  3. spleen
  4. Bone marrow
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11
Q

Identify the seven cells shown here.

A
  1. Band neutrophil
  2. Platelet
  3. Eosinophil
  4. Lymphocyte
  5. Segmented Neutrophil
  6. Monocyte
  7. Basophil
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12
Q

What is a monocyte?

A

Circulating macrophage or histiocyte precursor

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13
Q

Guess what?

A

Chicken butt.

Also, some small lymphocytes, small RBCs (spherocytes) and a smudge cell. Smudge cell is probably from an incompetent lab tech, or is just some schmutz.

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14
Q

A bone marrow aspirate is best for?

A

Illustrating cytology and enumeration of cells

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15
Q

What is a needle core biopsy best for?

A

Assess cellularity and architecture

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16
Q

What stain should be used on air dried thin smears of blood?

A

Romanovsky

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17
Q

How is the “manual WBC differential” performed?

A

Light microscopic examination of a “wright stained” peripheral blood smear and counting 100 white cells.

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18
Q

What is hyper-segmentation?

A

PMNs with 5 or more lobes

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19
Q

If you see a PMN with 5 or more lobes, what are three situations which can give rise to this type of hyper-segmentation?

A
  1. megaloblastic anemias
  2. myeloproliferative disorders
  3. chemotherapy
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20
Q

What would you call the increased and prominent azurophilic (primary) granules and cytoplastic vacuoles seen with infections?

A

Toxic granulation and vacuolization

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21
Q

What is a left shift?

A

Absolute increase in neutrophils with an increase in bands +/- metamyelocytes or myelocytes- seen in infections and leukemias

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22
Q

What are these cells?

What is the arrow pointing to?

What else is visible in these cells?

A

Neutrophils, arrow is pointing to Döhle bodies, blue cytoplasmic patches of dilated endoplasmic reticulum

Also see toxic granulations, coarse purple cytoplasmic granules

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23
Q

The relative change in one type of WBC expressed as a % of overall # of WBCs usually doesn’t mean much. What does matter?

A

What matters for each WBC type is the “absolute’ count or % of total multiplied by the total WBC count; e.g.,

Absolute Neutrophil Count = % Neutrophils X total WBC count

Absolute neutrophils = 46% X 10,000 cell/microliter

= 4,600 neutrophils/uL

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24
Q

What are the normal white cell ranges in adults?

A

4.8-10.8

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25
Q

What are the normal granulocytes (%) in adults?

A

40-70

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26
Q

Nl neutrophils in adults? ((×103/μL)

A

1.4-6.5

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27
Q

nl lymphocytes in adults? (×103/μL)

A

1.2-3.4

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28
Q

nl monocytes in adults? (×103/μL)

A

0.1 - 0.6

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29
Q

nl eosinophils in adults? (×103/μL)

A

0 - 0.5

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30
Q

nl basophils in adults? (×103/μL)

A

0 - 0.2

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31
Q

nl red cells in adult males and female respectively?

A

Men: 4.3 - 5.0 (×106/μL)

Women: 3.5-5.0 (×106/μL)

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32
Q

nl platelets in adults? (×103/μL)

A

150 - 450

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33
Q

What is the lifespan of a neutrophil (granulocyte) in peripheral blood?

A

1 - 48 hours

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34
Q

What percent of mature PMN’s circulate in the intravascular pool?

A

less than 5%

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35
Q

What is the lifespan of an eosinophil in peripheral blood?

A

1 - 48 hours (average 8 hrs)

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36
Q

What is the typical lifespan of a B-cell in peripheral blood?

A

Hours to days

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37
Q

What is the lifespan of T-cells in peripheral blood?

A

Days to years

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38
Q

What are two causes of neutrophilic leukocytosis?

A
  1. acute bacterial infections, particularly those by pyogenic organisms
  2. sterile inflammation, example = tissue necrosis d/t MI or burns
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39
Q

What are four causes (broad) or eosinophilic leukocytosis? 4 bold, 6 total

A
  1. Allergic disorders (asthma, hay fever)
  2. helminthic parasitic infestations
  3. drug reactions
  4. autoimmune disorders
  5. vasculitides
  6. Hodgkin and some NHL’s
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40
Q

Basophilic leukocytosis (basophilia) is rare, and often indicates what disease is occuring?

A

A myeloproliferative disease (e.g. chronic myeloid leukemia)

41
Q

Monocytosis can be caused by what 6 things?

A
  1. Chronic infections
  2. bacterial endocarditis
  3. rickettiosis
  4. malaria
  5. autoimmune disorders
  6. inflammatory bowel disease
42
Q

Lymphocytosis accompanies monocytosis in many disorders associated with what three things?

A
  1. chronic immunological stimulation
  2. viral infections
  3. bordatella pertussis infection
43
Q

What are three broad causes of increased leukocyte production in the marrow?

A
  1. Chronic infection or inflammation
  2. paraneoplastic
  3. myeloproliferative disorders
44
Q

What are three things that cuase increased release of leukocytes from marrow stores?

A
  1. Endotoxemia
  2. infection
  3. hypoxia
45
Q

What are two things that cause decreased margination of leukocytes?

A
  1. exercise
  2. catecholamines
46
Q

What is one thing that causes decreased extravasation of leukocytes into tissues?

A

Glucocorticoids

47
Q

Neutrophils and their precursors are distributed in five pools… Sampling of the peripheral blood assesses only the circulating pool!!! What are the five pools?

A
  1. Precursor pool
  2. storage pool
  3. marginating pool
  4. circulating pool
  5. tissue pool
48
Q

What is a leukamoid reaction? What is it not?

A

A marked elevation in white cell count - usually greater than 20k/uL

Though it simulates chronic myelogenous leukemia, it is not.

49
Q

How do you tell the difference between the leukamoid reaction and chronic myelogenous leukemia?

A
  • Leukamoid reaction: Leukocyte alkaline phosphatase score elevated
  • Chronic Myelogenous leukemia: Low alkaline phosphatase score
50
Q

A leukoerythroblastic reaction will have the presence of immature granulocytes and erythroid precursors in the blood. What are some examples of conditions this is commonly seen in?

A
  1. severe hemolytic anemia
  2. bone marrow infiltration by:
    1. metastatic tumor
    2. granulomas
    3. infiltrative process (fibrosis)
  3. chronic myeloproliferative neoplasms
    1. particularly myelofibrosis
51
Q

What is the critical value for neutropenia (granulocytopenia)?

A

absolute count < 500/µL or < 0.5 x 109/L (<1000/uL clinically worrisome)

52
Q

The lower a patients neutrophil count, the higher the risk of infection. What is the most common cause of acquired neutropenia?

What is the most common cause of clinically significant neutropenias?

A
  1. Infections
  2. Drugs - agranulocytosis, severe neutropenia
53
Q

Neutropenia pathogenisis typically includes what two general causes?

A

Decreased or ineffective production

Accelerated removal or destruction

54
Q

Neutropenia d/t decreased or ineffective production may be d/t inherited or acquired causes. Give examples of each.

A

Inherited - severe congenital neutropenia - Kostmann syndrome

Acquired - aplastic anemia, myelodysplastic syndrome, nutritional deficiencies

55
Q

What are some examples of neurtopenia that involve accelerated removal or destruction?

A
  • Immunologic disorders
  • Splenomegaly
  • Severe infections, such as overwhelming bacterial infection
56
Q

Peripheral blood eosinophilia may be relative or absolute. What are the criteria for each?

A

Relative Eosinophilia: >3% total wbc differential count

Absolute Eosinophilia: Total Eosinophils >0.5 x 109/L

57
Q

Absolute eosinophilia is further divided into what three categories?

What are the criteria for each category?

A

Mild Eosinophilia 0.35-0.90 x 109/L
Moderate Eosinophilia 1.00-5.00 x 109/L
Marked Eosinophilia >5.00 x 109/L

58
Q

What are the majority of circulating Lymphocytes?

A

> 80% are T cells

59
Q

What causes acute infectious mononucleosis?

A

Epstein Barr virus (EBV)

60
Q

What are four characteristic findings in acute infectious mononucleosis?

A
  1. Severe fatigue
  2. Sore throat
  3. Lymphadenopathy
  4. Lymphocytosis due to variant forms (Downey cells)
61
Q

What cells does EBV infect?

A

B cells

62
Q

EBV infects B cells via glycoprotein binding of CD21/CR2 (C3d complement receptor). May present asymptomatically in kids or with sore throat, fever, febrile rash and lymphadenopathy.

Hepatitis, anemia, thrombocytopenia, splenomegaly.

There is a subsequent B and T cell response. What cells soon predominate in tissues and blood?

A
  • Cytotoxic/supressor CD8+ T cells and CD 16+ NK cells soon predominate in tissues and blood destroying infected B cells
63
Q

What does this describe?

  • sensitive fairly specific heterophile antibody test positive in 1-2 weeks in 85% (Serum absorbed with guinea pig kidney still binds horse erythrocytes)
A

Monospot test

64
Q

What will be identified in heterophile negative EBV cases?

A

Epstein Barr virus antibodies to capsid antigen

65
Q

Identify the two cells shown here.

A

Left: normal small lymphocyte with a compact nucleus filling the entire cytoplasm

Right: atypical T lymphocyte on the right has abundant cytoplasm and a large nucleus with fine chromatin. EBV infected patient

66
Q

Identify these cells

A

Atypical lymphocytes - larger with more cytoplasm, nucleoli in nuclei. Cytoplasm indented by surrounding RBC’s

Atypical lymphocytes often associated with infectious mononucleosis

67
Q

Absolute lymphocytopenia is detected by automated hematology. How do we examine morphology?

A

Microscopic examination

68
Q

What would you do to test an absolute lymphocytopenia with hemogram abnormality?

A

bone marrow aspirate and biopsy

69
Q

If you have a patient with absolute lymphocytopenia and a suspected immune deficiency what four testing options are best?

A
  1. Flow cytometry immunophenotyping
  2. Serum protein concentration
  3. Serum protein electrophoresis
  4. Quantitative serum immunoglobulins
70
Q

What are some common causes of lymphocytopenia?

A
  1. Chemotherapy or irradiation therapy
  2. Cortisone “Steroid” therapy
  3. Administration of erythropoietin
  4. Pregnancy
  5. Various diseases
71
Q

What are some “various diseases” associated with lymphocytopenia?

A
  1. AIDS
  2. Hodgkin’s disease
  3. Idiopathic or acquired aplastic anemia
  4. Acute bacterial infection
  5. Cancer stomach, ovary and breast
  6. Systemic lupus erythematosus
  7. Occasionally viral infections
72
Q

Lymph node architecture includes a mantle zone and a germinal center. What are the three zones of the germinal center?

A
  1. Dark Zone
  2. Basal Light zone
  3. apical light zone
73
Q

In what zone does the following happen?

“Proliferation of B cells and somatic hypermutation”

A

Dark Zone

74
Q

In what zone of the germinal center does the following take place?

“Generation of memory cells and plasma cell precursors and class switching”

A

Apical light zone

75
Q

In what zone of the germinal center does the following take place?

“Positive selection for binding to antigen on follicular dendritic cells”

A

Basal Light zone

76
Q

In what zone will you find follicular dendritic cells?

A

Basal light zone

77
Q

Identify the areas indicated by the boxes.

What cells are found inside the area demarcated by the black circle?

A

Upper right = cortex

lower left = medulla, with cords and sinus

“circle” = paracortex T-cells

78
Q

Identify as many of the indicated structures as possible!

A

Capsule

  1. Subcapsular sinus
  2. Monocytoid B cells
    • IgG or IgM+. IgD-, BCL2-

Secondary Follicle

  1. Germinal Center (BCL2-)
  2. B-blast (small noncleaved)
    • sIgM+, transient
  3. Centroblast (large noncleaved)
    • sIg-, persistent
  4. Centrocyte (small/large cleaved)
    • sIgG+, persistent

Mantle Zone (mostly naïve)

Marginal Zone

  1. IgM+, IgD- (memory cell)

Interfolliclar region/sinuses

Primary Follicle (naïve B-cells)

  1. IgM+,IgD+,CD5-/+,BCL2+
79
Q

Painless enlargement of a lymph node or group of nodes is known as?

A

Lymphadenopathy

80
Q

What is the most likely cause of lymphadenopathy?

A

Infection, particularly viral and in children

81
Q

Although most lymphadenopathy is d/t infection, some areas of nodal enlargement are of greater concern. What are these special case nodes?

A

Supraclavicular and axillary lymph node enlargement is of greater concern

82
Q

If you see a lymph node that is greater than 4cm (in diameter I assume) it is most likely what?

A

Malignant

83
Q

What do you see here?

A

Hilar adenopathy

84
Q

What is the major cause of adenopathy in patients older than 60?

A

Metastatic carcinoma

85
Q

What does this describe?

“Swollen Edematous Tender (painful) lymph node with distended capsule”

A

Lymphadenitis

86
Q

The most common nodal groups associated with lymphadenitis are the cervical and mesenteric. What is lymphadenitis typically associated with?

A

Acute bacterial infection of a localized body site, affecting the local nodes draining the site.

87
Q

What does this describe?

Enlarged but painless; capsule is proportionally enlarged. Nodes are palpable (> 2cm).

A

Chronic nonspecific lymphadenitis

88
Q

What are the three patterns of chronic nonspecific lymphadenitis?

A

Stimulates B-cell populations = Follicular hyperplasia

Stimulates T-cell populations = paracortical hyperplasia

Prominence of Lymphatic sinusoids = Sinus histiocytosis

89
Q

Chronic nonspecific lymphadenitis may have a pattern of follicular hyperplasia with expansion of the germinal centers with an increase in what cell types?

What are three specific causes?

A
  1. Tingible (huh?) body macrophages
  2. Causes…
    1. HIV
    2. Toxoplasmosis
    3. Rheumatoid arthritis
90
Q

When a chronic nonspecific lymphadenitis occurs with paracortical hyperplasia there is expansion of T-cell rich paracortical regions. What are four examples of causes for this?

A
  1. Infectious mono
  2. Acute viral infections
  3. following vaccinations
  4. reactions to Dilantin
91
Q

Chronic nonspecific lymphadenitis may present with sinus histiocytosis, describe this as best you can.

A

Hyperplasia of macrophages lining sinuses, for instance in axillary nodes draining a region of breast cancer

92
Q

What happens at each of the three indicated sites?

A
  1. Follicles - B cell transformation/proliferation
  2. Paracortex - T cell transformation/proliferation
  3. Sinuses - Histiocyte recruitment
93
Q

What happens in the indicated portion of this lymph node?

A

Follice: B cell transformation and proliferation

94
Q

What does this immunohistochemistry stain for B CD20 reveal?

A

Follicular hyperplasia (reactive hyperplasia)

95
Q

What happens in the area indicated?

A

Paracortex: T cell transformation and proliferation

96
Q

What does this stain for CD3 reveal?

A

Diffuse paracortical hyperplasia (reactive hyperplasia subtype)

97
Q

This high power view of the dark zone shows several mitotic figures and numerous macrophages containing phagocytosed apoptotic cells. What are these phagocytosed apoptotic cells called?

A

Tingible bodies

98
Q

A patient comes to you with the lesions shown in the picture. History reveals that they had been scratched by a cat, splinter or thorn or any combination of the three prior to their appearance.

What organism caused this?

A

Bartonella henslae - causes cat scratch disease

99
Q

Cat scratch disease is typically a self limited lymphadenitis of the neck and head and occurs commonly in kids. It rarely presents with encephalitis, osteomyelitis or thrombocytopenia.

What leasions do you initially see on microscopy?

Later?

A

Initially sarcoid-like granulomas

Later stellate necrotizing granulomas