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_MS2 HemeOnc > 8/11- Leukocytes: Benign Leukocyte Disorders > Flashcards

8/11- Leukocytes: Benign Leukocyte Disorders Flashcards

1
Q

What are 3 causes of eosinophilia?

A

?

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2
Q

What are 3 causes of benign neutrophilic leukocytosis?

A

?

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3
Q

Which of the following cells would be considered granulocytes: A. Neutrophils B. Lymphocyte C. Eosinophil D. Basophil E. Monocyte

A

A, C, D

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4
Q

Which of the following neutrophil functions is effective in chronic granulomatous disease?

A. Chemotaxis

B. Migration

C. Phagocytosis

D. Intracellular killing

A

?

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5
Q

Name four common causes of neutropenia

A

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6
Q

Name three characteristics of neutrophilic leukemoid reaction

A

?

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7
Q

The leukocytosis seen in peripheral blood of pts with infectious mononucleosis are composed largely of which of the following:

A. B cells

B. T cells

C. Monocytes

D. Neutrophils

E. Eosinophils

A

?

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8
Q

Where do granulocytes originate? Mature?

A

Granulocytes (BEN) grow up and mature in the bone marrow

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9
Q

What is this?

A

Neutrophil

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10
Q

Morphologic characteristics of neutrophils?

  • Size
  • Nucleus
  • Chromatin
  • Nucleoli
  • Cytoplasm
A
  • 10-15 um
  • Segmented nucleus with 2-5 lobes (connected by filaments)
  • Clumped chromatin
  • No nucleoli
  • Pale pink cytoplasm with many specific (pink to lilac) granules
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11
Q

What kind of granules do neutrophils contain?

A

Contain primary (general to granulocytes) and secondary (specific) granules

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12
Q

When do primary granules form? What do they contain?

A

Primary granules form at promyelocyte stage

Contain:

- Myeloperoxidase

- Lysozyme

- Elastase

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13
Q

When do secondary (specific) granules form? What do they contain?

A

Myelocyte and metamyelocyte stages

Contain:

- Lactoferrin

- Lysozyme

- Collagenase

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14
Q

What are the main roles of neutrophils?

A
  • Important roles in response to infection and acute inflammation

Specific jobs:

  • Chemotaxis
  • Phagocytosis
  • Killing of microorganisms
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15
Q

What is this?

A

Eosinophil

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16
Q

Morphologic characteristics of eosinophils?

  • Size
  • Nucleus
  • Chromatin
  • Nucleoli
  • Cytoplasm
A
  • 10-15 um
  • Segmented nucleus with 2-3 lobes (connected by a thin filament)
  • Dense and compact chromatin
  • No nucleoli
  • Cytoplasm filled by uniform, coarse spherical orange-red refractile granules
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17
Q

What kind of granules do eosinophils contain?

A

Also have 2 types of granules (electron dense, crystalloid containing)

Both contain:

  • Peroxidase
  • Major basic protein
  • Histamine
  • Collagenase
  • Acid phosphatase
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18
Q

Functions of eosinophils?

A

Shared functions with neutrophils:

  • Chemotaxis
  • Phagocytosis
  • Killing of microorganisms

Special abilities:

  • Killer (effector) cells in antibody-dependent damage to parasites
  • Allergic responses to foreign bodies (like catheters)
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19
Q

What is this?

A

Basophil

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20
Q

Morphologic characteristics of basophils?

  • Size
  • Nucleus
  • Chromatin
  • Nucleoli
  • Cytoplasm
A
  • 10-15 um
  • Segmented nucleus, often obscured by granules
  • Clumped chromatin
  • No nucleoli
  • Cytoplasm is filled with coarse, dense, dark granules
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21
Q

What granules do basophils contain?

A
  • Histamine
  • Heparin
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22
Q

Functions of basophils?

A

Along with mast cells, basophils play important roles in immediate-type hypersensitivity reactions

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23
Q

Morphologic characteristics of monocytes?

  • Size
  • Nucleus
  • Chromatin
  • Nucleoli
  • Cytoplasm
A
  • 12-20 um (larger than granulocytes)
  • Round to oval, indented nucleus
  • Chromatin is slightly clumped, rope-like
  • No nucleoli
  • Cytoplasm is gray-blue with scattered vacuoles
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24
Q

Where do monocytes grow up and mature?

A
  • Grow up in bone marrow
  • Circulate in blood and mature into macrophages/histiocytes in the tissues
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25
Q

What is this?

A

Monocyte

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26
Q

What enzymes are contained within monocytes?

A
  • Collagenase
  • Elastase
  • Coagulation system proteins
  • Hydrolytic enzymes
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27
Q

Roles of monocytes?

A
  • Phagocytose particulate material and kill microorganisms (like neutrophils)

Unique functions:

  • Chronic inflammatory response
  • Present antigen to T cells
  • Destroy old RBCs in the bone marrow, spleen, and liver
  • Produce cytokines important in hematopoiesis

(Growth factors such as G-CSF, M-CSF)

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28
Q

What is this?

A

Lymphocyte

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29
Q

What are the main types of lymphocytes?

A
  • B cells
  • T cells
  • NK cells
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30
Q

Where do lymphocytes originate/mature?

A
  • Originate in bone marrow
  • B cells mature in bone marrow
  • T cells mature in thymus
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31
Q

Morphologic characteristics of lymphocytes?

  • Size
  • Nucleus
  • Chromatin
  • Nucleoli
  • Cytoplasm
A
  • 7-15 um (roughly same size as RBC)
  • Round, oval, occ notched nucleus
  • Diffusely dense/coarse chromatin
  • Not visible nucleoli
  • Cytoplasm is scant to moderate, pale to dark (reactive lymphocytes have more cytoplasm)
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32
Q

Functions of lymphocytes

A
  • Chronic inflammatory response (T, B, NK)
  • Humor immunity (B cells, plasma cells)

T cells have different types:

  • T helper (CD4) recognize antigen and stimulate B cells
  • T suppressor/cytotoxic (CD8) regulate other lymphocytes and kill tumor cells or virus-infected cells
33
Q

Where are lymphocytes found after maturity?

A
  • Lymph nodes and other lymphoid tissues (spleen, thymus)
  • Circulate as part of immune surveillance (T more than B)
34
Q

How WBC are analyzed in lab

A
  • Total number
  • Differential (how many of each type)
35
Q

What are some quantitative WBC disorders?

How are they expressed?

A

Too many

- Leukocytosis

- Lymphocytosis

Too few:

- Neutropenia

- Leukopenia

Expressed as either % of total or absolute number (no/volume)

Can also describe in terms of a relative or absolute increase

36
Q

What are some qualitative WBC disorders?

A

Function- not working well

Morphology

  • Nuclear or cytoplasmic changes
  • May or may not work well
  • more than one cell lineage may be affected
37
Q

Inherited WBC disorders?

A

(think syndromes with people’s names)

  • Pelger-Huet anomaly
  • Fanconi anemia
  • Chediak-Higashi
38
Q

Acquired WBC disorders?

A
  • Result of some external stimuli: infection, stress, drugs, immune
39
Q

Reactive WBC disorders? Benign or malignant?

A

Reactive (benign):

  • Infection
  • Congenital (inherited)
  • Drugs
  • Immune
40
Q

Neoplastic WBC disorders?

A
  • Leukemias
  • Lymphomas
  • Myeloproliferative disorders (neoplasms)
  • Myelodysplastic syndromes
41
Q

Describe relative vs. absolute increases in WBCs in terms of numbers/percentages.

Which is more important?

A

Relative increase

  • Overall WBC NOT high but percentage is higher than normal

Absolute increase

  • WBC is high, but percentage is normal
  • WBC is normal/high and percentage is high

Absolute counts are more significant

42
Q

What are leukemoid reactions?

  • What cells involved
  • WBC levels
A
  • Reactive (benign, not neoplastic) increase in WBC count (leukocytosis)
  • Usually refers to granulocytes (typ neutrophils, but may be eos)
  • Immature forms of 1+ cell lines in the peripheral blood (left shift)
  • May resemble a form of leukemia, but is due to some other cause
    • Usually WBCs > 20-30,000/mm3*
    • May be between 50-100,000/mm3*
    • Very rarely > 100,000/mm3*
43
Q

What are some causes of neutrophilia?

A

Reactive:

  • Infections (bacterial)
  • Inflammation/necrosis
  • Drugs, hormones, toxins (e.g. steroids, Cushing’s)
  • Strong physical/emotional stimuli (trauma)

Neoplastic:

  • Myeloproliferative neoplasms
44
Q

What are some causes of eosinophilia?

  • Associated with what cytokine?
A
  • Associated with IL-5

Reactive causes:

  • Infections (parasites, fungal)
  • Allergy
  • Drugs
  • Collagen vascular diseases
  • Addison’s disease

Neoplastic:

  • Myeloproliferative neoplasms
  • Some T cell lymphomas/leukemias
45
Q

What are some causes of basophilia?

A
  • Rare
  • Usually associated with a myeloproliferative neoplasm (Chronic myelogenous leukemia, CML)
46
Q

What are some causes of moncytosis?

A

Reactive:

  • Neutropenia
  • Collagen vascular diseases
  • Immune disorders
  • infections (viral, TB, syphilis, bacterial endocaditis)

Neoplastic

  • Myeloproliferative neoplasms
  • Leukemias
47
Q

What are some causes of lymphocytosis?

  • Associated with what cytokine?
A
  • Associated with IL-7

Reactive:

  • Infections (viral, pertussis, TB, rickettsial)
  • Infectious mononucleosis (EBV, CMV)
  • Autoimmune disorders
  • Drugs

Neoplastic:

  • Lymphomas/leukemias
48
Q

Case)

  • 14 yo female with fever, sore throat, malaise, cervical lymphadenopathy

CBC:

  • WBC = 18.1 K
  • Hct = 45%
  • Plts = 305K
  • Differential: 35% neutrophils, 58% lymphocytes, 12% monocytes

Differential diagnosis?

A
  • Pt has lymphocytosis

DDx:

Reactive

  • Lymphocytic leukemoid reaction- infectious mononucleosis

Neoplastic: leukemia

  • Acute lymphoblastic leukemia
  • Chronic lymphocytic leukemia
49
Q

What would be seen on PBS with these possible causes of lymphocytosis:

  • Lymphocytic leukemoid reaction- infectious mono:
  • Acute lympohblastic leukemia:
  • Chronic lymphocytic leukemia:
A
  • Lymphocytic leukemoid reaction- infectious mono: reactive lymphocytes
  • Acute lympohblastic leukemia: blasts
  • Chronic lymphocytic leukemia: mature neoplastic B lymphocytes
50
Q

What does this show? Details?

What does it suggest in terms of our previous DDx?

A

Reactive (“atypical”) lymphocytes

  • Large
  • Low N/C ratio (lots of cytoplasm)
  • +/- coarse chromatin, nucleoli
  • Heterogenous population

This is infectious mononucleosis

(pt then had positive Monospot test and EBV serologies)

51
Q

What are the clinical features and lab date of infectious mononucleosis?

A

Clinical features:

  • Adolescents and young adults
  • Fever, tonsillitis
  • Cervical adenopathy
  • Mild hepatitis, moderate splenomegaly

Lab data:

  • Mono-spot test: heterophil anti-sheep RBC Abs
  • EBV titers: IgM, IgG
  • Absolute lymphocytosis with atypical lymphs
  • May see WBC as high as 80E9 C/L
52
Q

What is neutropenia (defined/levels)/

A
  • Blood absolute neutrophil count less than 2 standard deviations below the normal population mean
  • Absolute neutrophil count (ANC) < 1000 is worrisome; ANC < 500 is most serious
53
Q

Consequences of neutropenia?

A

Increased risk of bacterial or fungal infections

  • Risk inversely proportional to degree of neutropenia
  • Chronic gradual process less dangerous than acute drop in counts Ulceration of oral cavity
  • Also skin, GI, GU tract Symptoms related to infection
  • Fever, chills, malaise
54
Q

Pathogenesis behind neutropenia?

A

Production problem

  • Reduced or ineffective production in the bone marrow
  • Congenital or acquired

Accelerated removal from the circulation

  • Immune – antibody mediated
  • Splenic sequestration
  • Increased utilization – overwhelming infection
55
Q

Causes of neutropenia?

A

Inherited:

  • Congenital neutropenic syndromes
  • Cyclic neutropenia Reactive:
  • Nutritional deficiencies (B12, folate)
  • Drugs
  • Severe infections
  • Autoimmune

Neoplastic:

  • Acute leukemia
  • Myelodysplastic syndrome
  • Large granular lymphocyte (LGL) leukemia
  • Tumor (or other infiltrative process) in the bone marrow
56
Q

What is the mechanism behind drugs causing neutropenia?

A

Marrow suppression as expected side effect: drugs directly toxic to marrow

  • Chemotherapy agents (antimetabolites, alkylating agents) Idiosyncratic reactions
  • Marrow or granulocyte suppression
  • Immunologically mediated
57
Q

What are some characteristics of congenital neutropenias?

A
  • Rare inherited syndromes (e.g. Kostmann Syndrome or agranulocytosis: AR, elastase mutation)
  • May be primary problem or just one of many features of another syndrome
  • Usually present in infancy or childhood
58
Q

How should neutropenia be managed in acute and chronic situations?

A

Acute (often have signs of fever or infection)

  • Supportive measures
  • CBC, blood cultures (fluids, broad spectrum antibiotics)
  • Consider bone marrow exam if etiology not apparent

Chronic (often asymptomatic)

  • Serial CBCs to determine if chronic or cyclic
  • Morphologic examination of blood and bone marrow
  • Test for immune rheumatological or nutritional causes [Whether acute or chronic, some etiologies will respond to G-CSF therapy]
59
Q

Causes of leukopenia?

A

Monocytopenia

  • Aplastic anemia
  • Hairy cell leukemia

Lymphopenia

  • HIV
  • Immune deficiency
  • Infections
  • Drugs (immune suppressive agents)
  • Autoimmune diseases
  • Malnutrition
60
Q

What are some broad characteristics of qualitative WBC changes?

A
  • May be inherited or acquired

Inherited:

  • Usually part of a syndrome
  • May or may not affect WBC function
  • Some associated with increased infections (Chediak Higashi)

Acquired:

  • Much more common than inherited
  • May be reactive or neoplastic
  • Reactive: infecitons, trauma, pregnancy, drugs
  • Neoplastic: myelodysplasia, myeloproliferative neoplasms, acute myelogenous leukemia
61
Q

What are some toxic changes of WBCs?

A
  • Toxic granulation
  • Dohle bodies
  • Vacuoles in cytoplsam
  • Leukocytosis (sometimes leukopenia)
  • “left shift”- circulating bands and immature myeloid precursors in addition to mature granulocytes
62
Q

What is this? Describe

A

Dohle bodies (a toxic change)

  • Rounded, oval, or rod-shaped pale grayish-blue inclusions in neutrophil ctoplasm (1-5 um long)
  • Represents stacks of RER or denatured aggregates of free ribosomes
63
Q

Dohle bodies are associated with what conditions?

A
  • Normal pregnancy
  • infections
  • Pts with various neoplasms
  • Severe burns
  • Trauma
  • G-CSF therapy
  • Kwashiorker
64
Q

What is this?

A

Toxic granulation (a toxic change)

  • Fine or coarse reddish-violet granules scattered throughout neutrophil cytoplasm
  • Primary (azurophilic) granules
  • Result from altered maturation of neutrophil granules
65
Q

Toxic granulation is associated with what conditions?

A
  • Severe infections
  • Other inflammatory states
  • Pregnancy
  • Trauma
  • Burns
  • G-CSF therapy
66
Q

What is this?

A

Vacuoles in the cytoplasm (a toxic change)

  • Clear round spaces in cytoplasm
  • Sites of digestion of phagocytized material
  • Occur in many cases of septicemia
67
Q

Vacuoles in the cytoplasm is associated with what conditions?

A
  • Infections
  • Acute alcohol poisoning
  • Carnitine deficiency
  • Kwashiorkor
  • (may be an artifact of prolonged storage in EDTA)
68
Q

What are these?

A

The “toxic changes”

69
Q

What is seen here? When is it seen?

A

Hyposegmentation

- Inherited: Pelger-Huet anomaly

- “Pseudo Pelger-Huet” change: associated with myelodysplasia and AML, drugs, infection (mycoplasma, HIV), rarely in bone marrow transplant pts

70
Q

What is seen here?

A

Hypersegmentation (6 or more nuclear lobes)

71
Q

What does hypersegmentation typically mean?

Associated with what?

A

Usually means megaloblastic myelopoeisis

  • Most unequivocal morphologic finding (may precede RBC changes)
  • Impaired DNA synthesis

Associations:

  • Nutritional deficiencies (B12, folate)
  • Alcoholism
  • Drugs (corticosteroids, folate antagonists)
  • Rarely in renal insufficiency, sepsis, MDS, MPN
72
Q

What are the main duties of the neutrophil?

A
  • Chemotaxis – follow the scent
  • Migration – move out of the blood, into & through the tissues
  • Phagocytosis – bind & ingest the offending agent
  • Killing & digestion of said offending agent (organisms/foreign materials)

**Impairment in 1 or more of these activities results in increased infections**

73
Q

What is chronic granulomatous disease (CGD)?

A

Problem with killing and digestion

  • Defective oxidative respiratory burst (can’t make H2O2- hydrogen peroxide)
  • Affects neutrophils and monocytes
  • Especially catalase positive microorganisms (live happily within neutrophils, safe from Abx: Staph, Aspergillus, Candida)

Body makes granulomas to help fight/contain the bugs it can’t kill

  • Recurrent abscesses, infections

Rare disorder

  • Most cases are X-linked recessive
74
Q

How can CGD be diagnosed?

A

Measuring respiratory burst

75
Q

Treatment for CGD?

A

Only curative measure is bone marrow transplant

Aggressive supportive measures:

  • Cultures & radiographic imaging as soon as infection suspected
  • Drainage of abscesses
  • Prolonged use of antibiotics
76
Q

What is seen here? Describe the condition

A

Pelger-Huet Anomaly

  • Autosomal dominant inheritance
  • Incidence 1 in 5000
  • Marked reduction in number of neutrophil lobes
  • Usually normal neutrophil number & function
  • Heterozygotes – most patients [2 lobes (pince-nez appearance) in 50-75% of their neutrophils]
77
Q

What is seen here? Describe the condition

A

May-Hegglin Anomaly

  • Rare
  • Autosomal dominant inheritance
  • MYH9 disorder
  • Intracytoplasmic inclusions in granulocytes and monocytes (Look like giant Döhle bodies)
  • Giant platelets
78
Q

What is seen here? Describe the condition

A

Chediak-Higashi Syndrome

  • Rare
  • Autosomal recessive
  • Reduced & abnormally large granules (Giant, often round; Red, blue, or greenish-gray)
  • Partial oculocutaneous albinism
  • Recurrent infections
79
Q

What is seen here? Describe the condition

A

Alder-Reilly Anomaly

  • Also known as Alder’s anomaly
  • Autosomal recessive
  • Seen in mucopolysaccharidoses
  • Abnormally course azurophilic granules in neutrophils and sometimes lymphocytes & monocytes

_MS2 HemeOnc (33 decks)

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