Pathology of the Hematopoietic System Flashcards

1
Q

What are the 3 main sources of lymphocytes?

A

yolk sac —> fetal liver —> bone marrow

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2
Q

What is the difference between primary and secondary lymphoid organs?

A

PRIMARY: sites of lymphocyte development
- thymus
- bursa
- Peyer’s patches
- bone marrow

SECONDARY: sites where lymphocytes respond to trapped antigens to launch immune response
- tonsils
- spleen
- lymph nodes
- Peyer’s patches
- bone marrow

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3
Q

How does the composition of bone marrow change with age?

A

YOUNG: active, red marrow

OLD: nonhematopoietic tissue, mainly fat; yellow

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4
Q

Where does hematopoiesis usually occur? In adults specifically?

A

throughout flat and long bones

pelvis, sternum, ribs, vertebrae, and proximal humerus and femur

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5
Q

What are the major 2 events that stem cells undergo during differentiation?

A
  1. hematopoiesis
  2. lymphopoiesis
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6
Q

What is the main regulator of erythropoiesis? When and where is it produced? What are 3 additional stimlators?

A

erythropoietin (Epo) regulated the production of RBCs

during hypoxia in the kidney and liver

  1. ILs
  2. CSFs (colony stimulating factors)
  3. hormones
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7
Q

What are myeloid cells? What is the production of these cells called? Why are these cells produced?

A

granulocytic (granulopoiesis) and monocytic (monocytopoiesis) cells

myelopoiesis - cells that migrate from blood to tissue to induce inflammation in response to microorganisms (host defense)

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8
Q

What are the functions of the cells produced during myelopoiesis (granulopoiesis + monocytopoiesis)?

A

NEUTROPHILS and MONOCYTE-DERIVED MACROPHAGES: phagocytosis and microbicidal activity (bacteria)

EOSINOPHILS and BASOPHILS: parasiticidal activity, allergic reactions

MACROPHAGES: antigen processing and presentation, cytokine production

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9
Q

What are the 3 stimulators of granulopoiesis and monocytopoiesis?

A
  1. ILs
  2. G-CSF (granulocyte colony-stimulating factor)
  3. GM-CSF (granulocyte-macrophage colony-stimulating factor)
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10
Q

What regulates megakaryopoiesis (thrombopoiesis)? Where is it produced?

A

thrombopoietin (Tpo)

liver

(megakaryocyte —> platelet)

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11
Q

What are 4 other cells found in the bone marrow?

A
  1. lymphocytes (1-10%)
  2. plasma cells (<1%)
  3. stromal cells: reticular cells, adventitial cells, adipocytes
  4. osteoblasts/osteoclasts
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12
Q

What 2 diagnostics are used to examine bone marrow? In what 4 situations is this done?

A

bone marrow aspirates and core biopsies

  1. unexplained cytopenias (any non-regenerative anemia0
  2. maturation defects or morphological abnormalities in blood cells
  3. potential myeloproliferative/lymphoproliferative disease
  4. potential malignancies metastatic to bone marrow
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13
Q

What needs to also be submitted with bone marrow aspirated and core biopsies?

A

CBC

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14
Q

Bone marrow is located in multiple sites, but responds as a single tissue. Where are aspirates and core biopsies typically taken from dogs and cats, horses, and cattle?

A

(from any bone with red marrow)

DOGS/CATS: proximal femur, iliac crest, proximal humerus

HORSES: sternum

CATTLE: proximal rib

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15
Q

Bone marrow aspirates and core biopsy:

A
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16
Q

Who interprets bone marrow aspirates/smears? What 3 things are they important for observing?

A

clinical pathologist

  1. cellular morphology and maturation
  2. myeloid to erythroid ratio (M:E)
  3. primary or metastatic neoplasia
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17
Q

Who interprets bone marrow core biopsies? What 5 things are they important for observing?

A

anatomical pathologist

  1. ratio of fat to hematopoietic cells
  2. myeloid to erythroid ratio (M:E)
  3. adequacy of iron
  4. stomal elements (myelofibrosis, scaring)
  5. primary or metastatic neoplasia
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18
Q

Bone marrow aspirate on cytology:

A
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19
Q

What is the normal myeloid-to-erythroid ratio?

A

3:1
(bone marrow core biopsy)

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20
Q

What are the 5 predominant bone marrow patterns?

A
  1. hyperplasia
  2. hypoplasia
  3. myelitis/necrosis
  4. dysplasia/neoplasia
  5. myelofibrosis
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21
Q

How do the 3 types of hyperplastic pattern change depending on the stimulus?

A

ERYTHROID hyperplasia - response to anemia

MEGAKARYOCYTIC hyperplasia - response to low platelets

MYELOID hyperplasia
- neutrophilia - bacterial infections, tissue necrosis
- eosinophilia - parasites, hypersensitivities
- monocytosis - chronic infections, specific agents

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22
Q

What is the pathogenesis behind the bone marrow hyperplasia pattern?

A

decrease in cell numbers in blood caused by increased peripheral demand or the adequate number of hypofunctional cells in peripheral blood leads to increased cell production in the marrow in response to poietins and interleukins

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23
Q

What is the gross finding in bone marrow hyperplasia?

A

red marrow replacing yellow marrow (fat) at metaphysis and endosteal surface of the diaphysis

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24
Q

What is bone marrow hypoplasia/atrophy? What is it characterized by and accompanied by?

A

decreased proliferative activity of the bone marrow

increase in yellow marrow
marrow degeneration

25
Q

What is the most common cause of bone marrow hypoplasia/atrophy? What are some additional causes?

A

anemia of chronic disease of inflammation

  • immune-mediated (attack of progenitor cells)
  • cytotoxic or drug-induced
  • infection: Parvovirus, FeLV, FIV
  • endocrine-induced
  • iron deficiency
  • renal failure (EPO decrease)
  • malnutrition
  • inherited disorder
  • iodiopathic
26
Q

What is the gross lesion associated with bone marrow atrophy? What commonly causes this lesion?

A

serous atrophy of fat leaving behind a yellow gelatinous transformation of fat within the marrow

cachexia

27
Q

What is the root cause of myelitis/bone marrow necrosis? What leads to this?

A

inflammation - neutrophilic, granulomatous, pyogranulomatous

  • neoplasia
  • infections
  • sepsis
  • drugs
  • toxins
  • radiation
28
Q

What is the gross lesion associated with bone marrow necrosis/myelitis?

A

loss of tissue leading to the formation of an area of pale discoloration in the bone marrow

29
Q

What is myelodysplastic syndrome (MDS)? What can it precede?

A

(bone marrow dysplasia/neoplasia)

group of clonal myeloid proliferative disorder with ineffective hematopoiesis in the bone marrow

acute myeloid leukemia

30
Q

How does myelodysplastic syndrome (MDS) affect the bone marrow?

A

peripheral cytopenia of one or more cell lines and concomitant marrow hypercellularity

31
Q

What typically causes myelodysplastic syndrome (MDS) in cats?

A

FeLV infection

32
Q

What is myelofibrosis? What causes this? What is the result?

A

inappropriate fibroblast proliferation of the medullary spaces with replacement of hematopoietic tissue

bone marrow injury with cytokine dysregulation

cytopenia —> scar tissue (fibrosis) replaces hematopoietic tissue

33
Q

What are the main 2 types of primary hematopoietic neoplasia? What are examples of both?

A
  1. lymphoproliferative disease: lymphoma, lymphoid leukemia, multiple myeloma plasma cell tumors
  2. myeloproliferative disease: myeloid leukemia, histiocytic neoplasia, myelodysplastic syndrome, mast cell tumors
34
Q

What is leukemia? What is commonly seen in this situation?

A

malignant hematopoietic neoplasms that originate in the bone marrow

significant number of neoplastic cells in the blood

35
Q

What are the 2 types of leukemia? What must be it be differentiated from to make a diagnosis?

A
  1. lymphocytic
  2. myeloid

lymphoma with a leukemic phase

36
Q

Acute myeloid leukemia in a dog:

A
37
Q

What is one of the most common malignant neoplasms in domestic animals? What are the main 2 causes?

A

lymphoma

  1. idiopathic (sporadic)
  2. due to viral infections: mice (MuLV), cats (FeLV), and cattle (BLV)
38
Q

What is the main way that lymphoma is classified? In what 2 ways is this done?

A

immunophenotype for B-cells and T-cells

  1. immunohistochemistry
  2. PCR for antigen receptor rearrangement (PARR)
39
Q

How are T cells and B cells stained in immunohistochemistry?

A

T cells: CD3

B cells: CD20, Pax5, CD79a

40
Q

What is PCR for antigen receptor rearrangement (PARR) and what does it do?

A

clonality assay to differentiate between lymphoma and inflammation

41
Q

How is PARR done? What do the possible results indicate?

A

DNA is isolated from cells suspected to be neoplastic and PCR primers are directed at the conserved regions of T-cell receptors or immunoglobulin receptors on B-cells

  • single sized PCR product (monoclonal) = neoplastic
  • multiple PCR products (polyclonal) = reactive, inflammation
42
Q

PARR:

A
43
Q

What are the main 2 signs of lymphoma?

A
  1. non-specific clinical signs: weight loss, anorexia
  2. enlargement of multiple lymph nodes
44
Q

How does the placement of the enlarged lymph nodes in lymphoma cause different clinical signs?

A

RETROBULBAR lymph nodes = exopthalmos
THYMUS = dyspnea, esophageal obstruction
ALIMENTARY = diarrhea, obstruction, melena

45
Q

What are 3 common gross lesions of lymphoma?

A
  1. organomegaly: diffuse organ enlargement
  2. multiple tan-white to pink nodules within organs
  3. thickening of walls of tubular organs
46
Q

Follicular lymphoma, dog:

A
47
Q

What aged dogs typically get lymphoma? What kind do most dogs get?

A

middle-aged to older

multicentric lymphoma

48
Q

Is canine lymphoma typically sporadic or viral-induced? What is commonly seen in dogs with lymphoma?

A

sporadic —> no known viral association

hypercalcemia of malignancy due to secretion of PTHrP

49
Q

What is the most common malignant neoplasm of cats? What forms are most common?

A

feline lymphoma

alimentary > multicentric > thymic > miscellaneous

50
Q

What is commonly involved in feline lymphoma? What are 2 very common causes? What aged cats are most affected?

A

leukemia and bone marrow involvement

  1. FeLV
  2. mediastinal and multicentric T cell lymphoma

young cats

51
Q

What is the most common GI lymphoma? What are the 2 types?

A

enteropathy-associated T cell lymphoma (EATL)

  1. TYPE 1 (large cell) - most common in dogs
  2. TYPE 2 (small cell) - most common in cats
52
Q

What does Type 2 enteropathy-associated T cell lymphoma (EATL) arise from? What is the median survival time? How is it diagnosed?

A

from the diffuse MALT of the small intestine

29 months

difficult with endoscopic samples (IHC and PARR)

53
Q

Enteropathy-associated T-cell lymphoma:

A
54
Q

What are the 2 types of bovine lymphoma?

A
  1. BLV-associated lymphoma (enzootic bovine leukosis)
  2. non-BLV lymphoma (sporadic)
55
Q

What inflammatory cells cause BLV-associated lymphoma? What lymph nodes are affected?

A

polyclonal B lymphocyte lymphocytosis —> develop B cell leukemia/lymphoma

  • superficial/abdominal LN
  • retrobulbar LN
  • abomasal LN*
  • heart LN*
  • uterus LN*
  • spleen LN
  • kidney LH
56
Q

What inflammatory cells cause non-BLV lymphoma? What are the 3 forms?

A

T cell lymphoma

  1. calf/juvenile form: fetuses and calves (3-6 months)
  2. thymic form: beef cattle <2 years
  3. cutaneous form: young cattle 2-3 years
57
Q

How does the incidence of BLV-associated lymphoma and non-BLV lymphoma compare?

A

BLV-ASSOCIATED: peak incidence at 6-8 years old

NON-BLV: young cattle

58
Q

Enzootic bovine leukosis gross lesions:

A
59
Q

Cutaneous lymphoma cow:

A