Pathology of the Hematopoietic System Pt 1 Flashcards

1
Q

What are the primary lymphoid organs?

A

Thymus
Bursa
Peyers patches
Bone Marrow

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2
Q

What are the secondary lymphoid organs?

A

Tonsils
Spleen
Lymph nodes
Peyers patches
Bone Marrow

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3
Q

What occurs in the primary lymphoid organs?

A

Lymphocyte development

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4
Q

What occurs in the secondary lymphoid organs?

A

Lymphocyte antigen response site

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5
Q

What are the sources of lymphocytes and how that changes as time goes on?

A

Yolk Sac -> fetal liver -> bone marrow

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6
Q

What is the routes of lymphocytes from development to antigen response?

A

Source ( yolk, fetal liver, bone marrow ) -> Primary lymphoid organs -> secondary lymphoid organs

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7
Q

Where does hematopoiesis occur? Is that the same throughout life? What changes as the animal ages? What bones in adults?

A
  • The composition of the marrow changes with age.
  • Hematopoiesis occurs throughout flat and long bones.
  • Hematopoietic tissue (red marrow) regresses and is replaced with nonhematopoietic tissue, mainly fat (yellow marrow).
  • In adults, hematopoiesis occurs primarily in the pelvis, sternum, ribs, vertebrae, and proximal humerus and femur.
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8
Q
A
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9
Q

What is erythropoiesis? What stimulates it?

A
  • Erythropoietin (Epo) regulates production of RBCs
  • Release of Epo stimulated by hypoxia
  • Other stimulators: ILs, CSFs, hormones
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10
Q

What is the stages of RBC development?

A
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11
Q

What are myeloid cells?

A

Granulocytic and monocytic cells are referred to collectively as myeloid cells.

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12
Q

What is the function of neutrophils and monocyte derived macrophages?

A

Neutrophils and monocyte-derived macrophages: phagocytosis and microbicidal activity

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13
Q

What is the function of eosinophils and basophils?

A
  • Eosinophils and basophils: parasiticidal activity, allergic reactions
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14
Q

What is the function of macrophages?

A

Macrophages: antigen processing and presentation, and cytokine production

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15
Q

What are the stimulators of granulopoiesis and monocytopoiesis?

A
  • Stimulators of granulopoiesis and monocytopoiesis
  • Interleukins (ILs)
  • Granulocyte colony-stimulating factor (G-CSF) and GM (granulocyte-macrophage)-CSF
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16
Q

What regulates thrombopoiesis? What is another name for this?

A
  • Thrombopoietin (Tpo), synthesized primarily in the liver, regulates thrombopoiesis.
  • Megakaryopoiesis
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17
Q

What are the stages of megakaryopoiesis?

A
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18
Q

What other cells can be found in the bone marrow?

A
  • Lymphocytes (1-10%)
  • Plasma cells (<1%)
  • Stromal cells: reticular cells, adventitial cells, adipocytes * Osteoblasts, osteoclasts
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19
Q

When should you submit bone marrow aspirates/ core biopsies? What should you submit at the same time?

A

When?
* Any abnormal hematology finding such as:
* Unexplained cytopenias (any non-regenerative anemia)
* Maturation defects or morphologic abnormalities in blood cells * Potential myeloproliferative/ lymphoproliferative disease
* Potential malignancies metastatic to the bone marrow
- Must submit a concurrent CBC!

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20
Q

How do you obtain bone marrow aspirates and core biopsies?

A

How?
* Located in multiple sites but responds as a single tissue
* Samples can be taken from any bone with red marrow:
* Proximal femur, iliac crest, proximal humerus of dogs and cats * Sternum of horses
* Proximal rib of cattle
* Aspirates and core biopsies

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21
Q

What is the diagnostic occurring in this image?

A

bone marrow aspirates and core biopsies

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22
Q

What is the importance of bone marrow aspirates/ smears?

A
  • Interpreted by clinical pathologists
    Important for:
  • Cellular morphology and maturation
  • Erythroid to myeloid ratio (M:E ratio)
  • Primary or metastatic neoplasia
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23
Q

What is the importance of bone marrow core biopsies?

A
  • Interpreted by anatomic pathologists
    Important for:
  • Ratio of fat to hematopoietic cells
  • Erythroid to myeloid ratio (M:E ratio)
  • Adequacy of iron
  • Stromal elements (e.g. for myelofibrosis)
  • Primary or metastatic neoplasia
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24
Q

What diagnostic is seen here?

A

Bone marrow aspirate/smears

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25
Q

What diagnostic is seen here?

A

Bone Marrow Core biopsy

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26
Q

What is this image of?

A

histopath of bone marrow core biopsy

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27
Q

What does each color represent in this image?

A

Teal: polychromatophilic rubricytes
Purple: Metarubricyte
Pink: Progranulocyte
Orange: Rubriblasts
Green: Mature Neutrophil

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28
Q

What is the normal myeloid/ erythroid ratio?

A

~ 3: 1
How can you tell if you have an abnormal ratio if there is too many erythroid cells vs. too few myeloid cells.
THIS IS WHERE CBC IS IMPORTANT.

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29
Q

Is this cats bone marrow core biopsy normal?

A
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30
Q

What are the possible bone marrow patterns that can be seen?

A

Bone marrow patterns
* Hyperplasia
* Hypoplasia
* Myelitis/Necrosis
* Dysplasia/Neoplasia
* Myelofibrosis

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31
Q

What is important to note about hyperplasticity of bone marrow cells?

A
  • One or multiple cell lines may be hyperplastic
    depending on the stimulus
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32
Q

What are the stimuli for Erythroid Hyperplasia and Megakaryocytic Hyperplasia?

A
  • Erythroid hyperplasia ➝ response to anemia
  • Megakaryocytic hyperplasia ➝ response to ↓
    platelets
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33
Q

What is the stimuli for the different cells in myeloid hyperplasia?

A
  • Myeloid hyperplasia (monocytic/granulocytic cell
    lines)
  • Neutrophilia ➝ bacterial infections, tissue necrosis
  • Eosinophilia ➝ parasites, hypersensitivities
  • Monocytosis ➝ chronic infections, specific agents
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34
Q

What is the pathogenesis of hyperplasia of cells in the marrow?

A
  • Pathogenesis:
  • ↓cell numbers in blood caused by increased
    peripheral demand; or adequate numbers of hypofunctional cells in peripheral blood  lead to ↑cell production in the marrow in response to poietins and interleukins.
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35
Q

What is occurring in this image?

A
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36
Q

What is bone marrow hypoplasia/ atrophy? What can be seen with this? What is the sequel dependent on?

A
  • Decreased proliferative activity * Usually characterized by increase in yellow marrow * Often accompanies marrow degeneration. * Sequel will depend on cell line(s) affected
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37
Q

What are some examples of bone marrow hypoplasia/ atrophy?

A
  • Anemia of chronic disease or inflammation
  • Immune-mediated
  • Cytotoxic or drug-induced
  • Infection: Parvovirus, FeLV, FIV
  • Endocrine-induced
  • Iron deficiency
  • Renal failure (EPO decreased)
  • Malnutrition
  • Inherited disorders
  • Idiopathic

FELV, FIV, Parvo -> can infect proginator cells and affect the ability to regenerate these cells.

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38
Q

What can you see in this image?How would you describe the gross lesion? What is the likely cause?

A
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39
Q

What is myelitis and bone marrow necrosis? What are some common cause?

A

Inflammation
* Neutrophilic, granulomatous or pyogranulomatous
Necrosis:
* Neoplasia
* Infections
* Sepsis
* Drugs
* Toxins
* Radiation

40
Q

What can be seen in this image?

A
41
Q

What is myelodysplastic syndrome? What is it characterized by? What does it usually precede? What is an example of a condition that can cause this?

A

Myelodysplastic syndrome (MDS)
* A group of clonal myeloid proliferative disorders with ineffective hematopoiesis in the bone marrow
* Characterized by ineffective hematopoiesis
* Can precede acute myeloid leukemia
* Typically there is a peripheral cytopenia of one or more cell lines and concomitant marrow hypercellularity.
* FeLV infection
* alot of cells in bone marrow undergo apoptosis very quickly so you still see peripheral cytopenia.

42
Q

What is myelofibrosis?

A
  • Inappropriate fibroblast proliferation of the medullary spaces with replacement of hematopoietic tissue.
  • Due to bone marrow injury with cytokine dysregulation
  • Cytopenia
43
Q

What is occuring in this image?

A

myelofibrosis

44
Q

What are the categories of hemopoietic neoplasias?

A
45
Q

What are the subcategories of lymph-proliferative disease?

A
46
Q

What are the subcategories of myeloproliferative disease?

A
47
Q

What are leukemias?

A
48
Q

What are the types of acute leukemias?

A
  • Acute myeloid
  • Acute undifferentiated or mixed phenotype
  • Acute lymphoid
49
Q

What are the types of chronic leukemias?

A
  • Chronic myeloid
  • Chronic Lymphoid
50
Q

What is likely occurring in this dog?

A
51
Q

What is lymphoma? What are the causes? What are they classified by under the World Health Organization ?

A
  • One of the most common malignant neoplasms in
    domestic animals. * Can be idiopathic (sporadic) or due to viral infections:
    mice (M u LV ), cats (FeLV) and cattle (BLV).
  • Current WHO classification of canine lymphomas
  • Histological Pattern, Nuclear size (compared to RBC), Mitotic Rate per 400x HPF, Immunophenotype.
52
Q

What is the histological patterns of lymphoma?

A

nodular or diffuse

53
Q

What is the nuclear sizes of lymphoma compared to RBCs?

A

Small
Intermediate
Large

54
Q

What is the mitotic rate per 400x HPF for lymphoma?

A
55
Q

What are the immunophenotypes for lymphoma?

A

B Cell
T Cell

56
Q

What is the IHC looking for for T cell lymphoma?

A

CD3

57
Q

What is the IHC looking for for B cell lymphoma?

A

B cells: CD20, Pax5, CD79a

58
Q

What is PAAR used for in terms of immunophenotyping for lymphoma?

A
59
Q
A
60
Q

What are the clinical signs of lymphoma?

A

Clinical signs of lymphoma
* Non-specific clinical signs: weight loss and anorexia
* Enlargement of multiple lymph node
* Other signs depend on anatomic location:
* Retrobulbar lymph nodes➝ exophthalmos
* Thymus ➝ dyspnea, esophageal obstruction
* Alimentary ➝ diarrhea, obstruction or melena

61
Q

What are gross lesions seen of lymphoma in animals?

A
62
Q

What is seen in this image?

A
63
Q

What is seen in this image?

A
64
Q

What is seen in this image?

A
65
Q

What is seen in these cytologies?

A
66
Q

What is canine lymphoma? What animals does it typically effect? What is the typical type of lymphoma seen? What is the typical grade seen? What other changes can be seen ?

A
67
Q

What percent of dogs with lymphoma have multicentric lymphoma?

A

85%

68
Q

What causes hypercalcemia of malignancy?

A
  • Hypercalcemia of malignancy is
    occasionally seen in dogs with
    lymphoma → secretion of PTHrP
69
Q

What is feline lymphoma? Which kind is more frequent? What is the order of type of feline lymphoma from most to least frequently Seen?

A
  • Most common malignant neoplasm of cats * Alimentary > multicentric > thymic > miscellaneous forms
70
Q

What viral association is seen for feline lymphoma?

A
  • Association with feline leukemia virus (FeLV):
  • 10 -20 % of cats with lymphoma are FeLV+
  • FeLV is associated with mediastinal and multicentric T cell lymphoma
  • Young cats!
71
Q

What is commonly seen in cats with lymphoma?

A
  • Leukemia and bone marrow involvement are common
72
Q

What is the order of most to least common types of lymphoma in cats?

A
  • Alimentary > multicentric > thymic > miscellaneous forms
73
Q

What is seen in this image?

A

Thymic lymphoma in cats

74
Q

What is gastrointestinal lymphoma? What are the types? Who is each more common in?

A

Enteropathy-associated T cell lymphoma (EATL) * Type 1 (large cell) – most common in dogs
* Type 2 (small cell) – most common in cats
* Arises from the diffuse MALT of the small intestine
* Median survival time of 29 months
* Difficulty in diagnosis, especially in endoscopic samples
* IHC and PARR

75
Q

What is seen in these images?

A

you can see alot of lymphocytes packed in the villi and the mucosa. This is indicative of enteropathic t cell type 2 lymphoma.

76
Q

What is bovine lymphoma? What are the types?

A

BLV associated lymphoma (enzootic bovine leukosis)
and
Non BLV lymphoma (sporadic form) most often T cell lymphoma

77
Q

What is BLV associated lymphoma? What percent of cows with BLV develop lymphoma? What are typical areas in the body affected? What age does it most frequently occur in?

A
78
Q

What is non blv lymphoma? What are the types and when do they typically occur?

A
79
Q

What is the likely causes of the lesions seen in these images?

A
80
Q

What can be seen in this image of a cow?

A

Cutaneous lymphoma in a cow

81
Q

What is multiple myeloma? What is the pathogenesis of this?

A
  • Malignant tumor of plasma cell origin
    arising in the bone marrow
  • Neoplastic (clonal) plasma cells secrete
    immunoglobulin leading to hypergammaglobulinemia
82
Q

What is the specific diagnostic criteria for multiple myeloma?

A
  • Specific diagnostic criteria
  • Neoplastic plasma cells in the bone marrow
  • Lytic bone lesions
  • Presence of clonal immunoglobulin
    paraproteins in the serum (monoclonal
    gammopathy) or urine (Bence-Jones protein)
83
Q

What is the gross pathological lesions seen with multiple myeloma?

A
  • Gross: Pale pink to dark red gelatinous masses replace bone marrow – typically multiple masses
84
Q

What can see histologically with multiple myelomas?

A

Sheets of neoplastic plasma cells

85
Q

What is a likely diagnosis based on these images?

A
86
Q

What percentage of cows with BLV develop lymphoma?

A
  • Approximately 1-5% of BLV-infected cattle develop B cell leukemia/lymphoma.
87
Q

What is seen in this image being indicated by the green arrows?

A

Neoplastic lymphocytes

88
Q

What are the 2 most important diagnostics for lymphoma?

A

IHC and PARR

89
Q

What is PARR used for when diagnosing lymphoma?

A

We use this to see if the t cell or be cell receptors to see if the populations are clonal -> neoplastic
or
polyclonal -> multiple different cell types -> inflammatory

you would not want to give chemo to a dog with inflammatory issues.

90
Q

What is indicated with the orange lines? The green lines?

A
91
Q

What is seen in this image? What does each colored arrow represent?

A
92
Q

What is important to remember when considering a leukemia diagnosis?

A
93
Q

What is this teal arrow pointing to?

A

Megakaryocyte

94
Q

Where is erythropoietin produced? What disease process can affect it and why?

A
  • Epo is produced in the kidney (especially in the peritubular interstitial cells) and liver.
  • Ckd - effects the cells -> thus decrease of epo production.
95
Q

What can be seen in a blood smear, in regards to the red blood cells, that can indicate pathology is occuring?

A

Presence of polychromatophils and metarubricyte in blood smears usually indicate some kind of pathology is going on, this is not normal.

96
Q

What cell does neutrophil, eosinophils, and basophils all derive from? monocytes?

A

Myeloblasts
monoblasts

97
Q

What types of lymphoma are of high suspicion for a cat with FELV?

A

Cats that have FELV you typically see mediastinal and multi-centric T cell lymphoma and its in young cats.