Pathology of the Hematopoietic System - Part 1 Flashcards

1
Q
A

All of these organs are composed of hematopoietic cells
H cells like lymphocytes and ly –> originate from stem cells (original source = yolk sac).
T cell = replicate in thymus
B cell = replicate in bursa.
Primary = organs that regulate development of lymphocytes
Secondary = where lymphocytes respond to antigens

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2
Q

The composition of the marrow changes with ____.

A

age

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3
Q

Hematopoiesis occurs throughout ___ and ____ bones.

A

flat, long

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4
Q

Hematopoietic tissue ( ____ marrow) ______ and is _______ with ________ tissue, mainly ___ (_____ marrow)

A

red, regresses, replaced, nonhematopoietic, fat, yellow

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5
Q

In adults, hematopoiesis occurs primarily in the?

A

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

This is why when we biopsy, we go to these body parts.

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6
Q
A

Calf, neonate, normal active
bone marrow
When animal is just born, bone marrow is very active.
Color = age

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7
Q
A

Normal bone marrow,
2-month-old calf.
With time, bone marrow is less active.

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8
Q
A

Stem cells differentiate into either lymphocytes or other cells such as myeloid cells, granulocytes, etc. erythrocytes, etc.

Tissue = cells that migrate into tissue and initiate immune response.

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9
Q

Erythropoietin (Epo) regulates production of ____.

A

RBCs
Produced in the kidney and liver, especially in the peritubular epithelial ? cells.

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10
Q

Release of Epo stimulated by ______.

A

hypoxia

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11
Q

Other stimulators of Erythropoiesis: ?

A

ILs, Colony stimulating factors (CSFs), hormones

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12
Q

Label accordingly

A

Nuclei lost at Metano
If see metano or poly in blood smear –> some type of pathology occurring

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13
Q

________ and ______ cells are referred to collectively as myeloid cells.

A

Granulocytic, monocytic
Main purpose of mylopoeisis is to develop B cells so that –> tissue –> attack microbes (main function = host defense).

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14
Q

The functions of Granulopoiesis and monocytopoiesis are:
1. Neutrophils and monocyte-derived macrophages: _______ and _______ activity
2. _______ and _______: parasiticidal activity, allergic
reactions
3. ______: antigen processing and presentation, and cytokine production

A

phagocytosis, microbicidal, Eosinophils, basophils, Macrophages

MQs are also responsible for microbials such as fungi, protozol –> granulomatous inflammation.

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15
Q

List the stimulators of granulopoiesis and monocytopoiesis:

A
  1. Interleukins (ILs)
  2. Granulocyte colony-stimulating factor (G-CSF) and GM
    (granulocyte-macrophage)-CSF
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16
Q

Thrombopoietin (Tpo), synthesized primarily in the ______, regulates _______.

A

liver, thrombopoiesis

Mega = multilobulated nuclei and the cytoplasm will eventually break down and then eventually become platelets.

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17
Q

Other cells in bone marrow include?

A
  • Lymphocytes (1-10%)
  • Plasma cells (<1%)
  • Stromal cells: reticular cells, adventitial cells, adipocytes
  • Osteoblasts, osteoclasts
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18
Q

What samples would you collect from your patient?

A

Bone marrow
aspirates and core biopsies
Always want to do them together because they have different functions and show you different things.

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19
Q

When do you do bone marrow aspirate or core biopsies?
* Any abnormal hematology finding such as:
* Unexplained cytopenias (any non-regenerative anemia)
* Maturation defects or morphologic abnormalities in blood cells
* Potential myeloproliferative (myeloid proliferation)/ lymphoproliferative
(leukemia) disease (suspect neoplasias)
* Potential malignancies metastatic to the bone marrow
Always submit a concurrent CBC to interpret findings in bone marrow (periphery versus site of origin).

A
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20
Q

You collect bone marrow aspirates and core biopsies from any bone with ____ marrow:
* (3) in dogs and cats
* ______ of horses
* Proximal rib of ____

A

red, Proximal femur, iliac crest, proximal humerus, Sternum, cattle

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21
Q

Bone marrow is located in _____ sites but responds as a ____ tissue

A

multiple, single

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22
Q
A

Diagnostics – bone marrow
aspirates and core biopsies

locate site
sterilize
needle for bone marrow
take out piece of marrow
put on glass slide
can also smear
put into formalin fixative agent

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23
Q

Bone marrow aspirate/smears are
interpreted by clinical pathologists and are important for:
1. Cellular _____ and ______
2. _____ to _____ ratio (M:E ratio) in both cytology and biopsy.
3. _____ or ______ neoplasia

A

morphology, maturation, Erythroid, myeloid, Primary, metastatic

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24
Q

Bone marrow core biopsies are interpreted by anatomic pathologists and are important for examining the:
1. Ratio of ___ to _______ cells
2. _____ to _____ ratio (M:E ratio)
3. Adequacy of ____ (difference of storage of iron differs between species)
4. _____ elements (e.g. for myelofibrosis = scarring of bone marrow; loss fo cells –> scarring)
5. _____ or _____ neoplasia

A

fat, hematopoietic, Erythroid, myeloid, iron, Stromal, Primary, metastatic

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25
Q
A

Smear ?

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26
Q
A

Core biopsy
Short, cylinderal biopsy
Bone on bottom
purple dots?
Evaluate amount of fat and hematopoietic cells

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27
Q
A

Bone marrow aspirate on cytology
RB - erythroid origin; eosinophillic cytoplasm
PG - granulated cytoplasm; count these to get ratio.

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28
Q
A

Bone marrow core biopsy
Young cat, bone marrow, H&E - Normal
Myeloid/ Erythroid ratio (~3:1)

Megakaryocyte in top right. not counted in ME ratio.
Clear = fat lobules

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29
Q

List the typical bone marrow patterns:

A
  • Hyperplasia
  • Hypoplasia
  • Myelitis/Necrosis
  • Dysplasia/Neoplasia
  • Myelofibrosis
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30
Q

In bone marrow patterns, one or multiple cell lines may be _______
depending on the stimulus.

A

hyperplastic

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31
Q

Erythroid hyperplasia ➝ ?

A

response to anemia
BM pushes RBC out as fast as possible; takes time; see erythroid cells in anemia?

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32
Q

Megakaryocytic hyperplasia ➝ ?

A

response to ↓
platelets

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33
Q

Myeloid hyperplasia (monocytic/granulocytic cell
lines)
* Neutrophilia ➝ ?
* Eosinophilia ➝ ?
* Monocytosis ➝ ?

A

bacterial infections, tissue necrosis
parasites, hypersensitivities
chronic infections, specific agents

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34
Q

The pathogenesis of bone marrow patterns is described as a ____ in cell ______ in blood caused by ______
peripheral demand; or adequate numbers of ______ cells in peripheral blood -> lead to
___ cell production in the marrow in response to _____ and ______.

A

↓, numbers, increased, hypofunctional, ↑, poietins, interleukins

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35
Q
A

Bone marrow hyperplasia
Gross finding: Red marrow replacing yellow marrow
(fat) at metaphysis and endosteal surface of diaphysis.

Adult horse – bone marrow hyperplasia secondary to EIA (Equine infectious anemia; retrovirus; initially when infected peripheral demand due to anemia so BM is working hard to push RBC out –> hyperplasia).

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36
Q

Bone marrow hypoplasia/atrophy is defined as ________ proliferative activity and is characterized by an ______ in yellow marrow

A

decreased, increase

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37
Q

Bone marrow hypoplasia/atrophy often accompanies

A

marrow degeneration

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38
Q

Bone marrow hypoplasia/atrophy sequel will depend on ?

A

cell line(s) affected

39
Q

List 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
40
Q

Bone marrow atrophy is a result of ____ atrophy of ___

A

serous, fat

41
Q
A

serous atrophy; hypoplasia atrophy of entire marrow; not uncommon to see in emaciated animals.
Gross lesion: Gelatinous transformation of fat within the
marrow. Due to cachexia (malnutrition)

42
Q

Myelitis/bone marrow necrosis results in ?

A
  • Inflammation: Neutrophilic, granulomatous or pyogranulomatous
  • Necrosis
43
Q

Myelitis/bone marrow necrosis is caused by?

A
  • Neoplasia
  • Infections
  • Sepsis
  • Drugs
  • Toxins
  • Radiation
44
Q
A

Bone marrow inflammation
Septic osteomyelitis, foal
Suppurative osteomyelitis is usually the result of bacterial infections

Neutrophilic inflammation; replaces bone marrow and cortical infection due to bacterial infection.

45
Q

Myelodysplastic syndrome (MDS) is a ______ condition caused by a group of clonal _____ proliferative disorders with ineffective ______ in the bone marrow.

A

neoplastic, myeloid, hematopoiesis

46
Q

Myelodysplastic syndrome (MDS) is characterized by _______ _______.

A

ineffective hematopoiesis,

47
Q

Myelodysplastic syndrome (MDS) you will see peripheral cytopenia (cells have undergone apoptosis?) of one or more cell lines and concomitant marrow hypercellularity.
* FeLV infection - myloproliferative disorder of bone marrow –> cytopenia.

A

acute myeloid leukemia

48
Q

Myelofibrosis is an inappropriate ________ proliferation of the _______
spaces with replacement of ________ tissue.
* Due to bone marrow _____ with _______ dysregulation
* _______

A

fibroblast, medullary, hematopoietic, cytokine, Cytopenia (as a result of myleofibrosis).

49
Q
A

Myelofibrosis

50
Q
A

Primary hemato divided into lymph and myelo, which are further divided into?

51
Q

Leukemias are ________ hematopoietic neoplasms that originate in
the ________ _______. They typically have significant numbers of ______ cells in the ____.
* ________ or ______
* _____ or ______

A

Malignant, bone marrow, neoplastic, blood, Lymphocytic, myeloid, Acute, chronic

Many subtypes of leukemia.

52
Q
A

Acute myeloid leukemia in a dog
Blood smear
neutrophils are weird looking because neoplastic. (right)
Left = neoplastic myeloid cells.

53
Q
A

Acute myeloid leukemia in a dog
Bone marrow biopsy

54
Q

Lymphoma is one of the most ________ malignant neoplasms in ______ animals

A

common, domestic

55
Q

Lymphoma can be ________ (sporadic) or due to ___ infections: (3)

A

idiopathic, viral, mice (MuLV), cats (FeLV) and cattle (BLV).

56
Q

Current WHO classification of canine lymphomas

A

Decide grade based on mitotic count.
Last box = prognostic indicator.

57
Q

Immunophenotyping for lymphoma
1. T cells: _____ marker
2. B cells: ______,_______,______ marker

A

CD3, CD20, Pax5, CD79a

58
Q
A

CD3 stain. Cutaneous T-cell lymphoma (epitheliotropic) in a dog

59
Q

PCR for antigen receptor rearrangement (PARR)
* ______ assay
* Differentiate between ______ vs. _______
* Isolating ____ from cells suspected to be neoplastic
→ PCR primers directed at the ______ regions of
__-cell receptor or _______ receptor (___ cells)
→ single-sized PCR product (_______) vs multiple
PCR products (______)

A

Clonality, lymphoma, inflammatory, DNA, conserved, T, immunoglobulin, B, neoplastic, reactive

60
Q
A

Isolate DNA from cells
Conserve region is where we do PCR on
amplify regions –>
Polyclonal = inflammation
Clonal = neoplasia

61
Q

Clinical signs of lymphoma

A
  • Non-specific clinical signs: weight loss and anorexia
  • Enlargement of multiple lymph node
  • Other clinical signs depend on anatomic location:
  • Retrobulbar lymph nodes➝ exophthalmos
  • Thymus ➝ dyspnea, esophageal obstruction
  • Alimentary ➝ diarrhea, obstruction or melena
62
Q
A

Gross lesions of lymphoma
Organomegaly: diffuse
organ enlargemen

63
Q
A

Gross lesions of lymphoma
Multiple tan-white to pink
nodules within organ

64
Q
A

Gross lesions of lymphoma
Thickening of walls of
tubular organs

65
Q
A

Follicular lymphoma in a dog

66
Q

Canine lymphoma is the most ______ canine hematopoietic neoplasia.

A

common

67
Q

Canine lymphoma usually affects _____ aged to _____ animals. 85 % have _____ lymphoma.

A

middle, older, multicentric

68
Q

In cases of canine lymphoma, ______ _____ involvement is common and they are usually?

A

lymph node, medium to high grade

69
Q

In cases of canine lymphoma, _____ are usually normal.

A

leukograms

70
Q

In cases of canine lymphoma, there is no known _____ association.

A

viral

71
Q

In cases of canine lymphoma, ________ of malignancy is
occasionally seen in ____ with
lymphoma → secretion of _____.

A

Hypercalcemia, dogs, PTHrP

72
Q
A

Canine lymphoma

73
Q

Feline lymphoma is the most _____ malignant neoplasm of cats
* Alimentary > multicentric > thymic > miscellaneous forms
* ______ and _____ ____ involvement are common
* Association with ?:
* __ - ___% of cats with lymphoma are ______
* FeLV is associated with _______ and _____ __ cell lymphoma
* Young cats!

A

common, Leukemia, bone marrow, feline leukemia virus (FeLV), 10, 20, FeLV+, mediastinal, multicentric, T

Can also be sporadic

Intestinal lymphoma is not associated with FeLV

74
Q

In cases of feline lymphoma, ________ and ______ _______ involvement are common.

A

leukemia, bone marrow

75
Q

Feline lymphoma is associated with ?:
* ___ - ____% of cats with lymphoma are _____.

A

feline leukemia virus (FeLV), 10, 20, FeLV+

76
Q
A

Feline lymphoma
Thymic lymphoma in a cat

77
Q

Gastrointestinal lymphoma
Enteropathy-associated T cell lymphoma (EATL)
* Type 1 (_____ cell) – most common in ____
* Type 2 (_____ cell) – most common in _____
* Arises from the diffuse ______ of the _____ ______
* Median survival time of ____ ______.
* Difficulty in ______, especially in _______ samples
*____ and ____

A

large, dogs, small, cats, MALT, small intestine, 29 months, diagnosis, endoscopic, IHC, PARR

78
Q
A

Enteropathy-associated T-cell lymphoma type 2 in cats.

CD3 on bottom right

79
Q

Bovine lymphoma
* _____-associated lymphoma (?):
* Polyclonal B lymphocyte lymphocytosis in about ___% of cattle.
* Approximately __-___% of BLV-infected cattle develop ___ cell leukemia/lymphoma.
* Superficial/abdominal LN, retrobulbar, abomasum, heart,
uterus, spleen, kidney.
* Peak incidence 6-8 years old.
* Non-BLV lymphoma (sporadic form): most often T
cell lymphoma
* Calf/juvenile form: fetuses and calves (3-6 months)
* Thymic form: beef cattle <2 years
* Cutaneous form: young cattle 2-3 years

A

BLV, Enzootic bovine leukosis, 30, 1-5, B

80
Q

Bovine lymphoma –> Superficial/abdominal LN, retrobulbar, abomasum, heart, uterus, spleen, kidney.

A
81
Q

Bovine lymphoma has a peak incidence __-___ years old.

A

6-8

82
Q

Non-BLV lymphoma (sporadic form): most often ___
cell lymphoma

A

T

83
Q

Calf/juvenile form: ______ and ______ (__-__ months)

A

fetuses, calves, 3-6

84
Q

______ form: beef cattle <___ years

A

Thymic, 2

85
Q

Cutaneous form: young ______ __-__ years.

A

cattle, 2-3

86
Q
A

Enzootic bovine leukosis

87
Q
A

Cutaneous lymphoma in a cow

88
Q

Multiple myeloma is a _______ tumor of _____ cell origin
arising in the _____ _______.

A

malignant, plasma, bone marrow

89
Q

Multiple myeloma is a _____ (clonal) _____ cells secrete ________ leading to ____________.

A

neoplastic, plasma, immunoglobulin, hypergammaglobulinemia

90
Q

The specific diagnostic criteria of Multiple myeloma are
1. _______ plasma cells in the bone marrow
2. ___ bone lesions
3. Presence of _____ _____ paraproteins in the serum (monoclonal gammopathy) or ___ (____-__ protein)

A

Neoplastic, Lytic, clonal immunoglobulin, urine, Bence-Jones

91
Q
A

Monoclonal gammopathy
in a dog

92
Q
A

Multiple myeloma
* Gross: Pale pink to dark red gelatinous masses replace
bone marrow – typically multiple masses

93
Q
A

Multiple myeloma
Histology: Sheets of neoplastic plasma cells.