Pathology of the Hematopoietic System - Part 1 Flashcards
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
The composition of the marrow changes with ____.
age
Hematopoiesis occurs throughout ___ and ____ bones.
flat, long
Hematopoietic tissue ( ____ marrow) ______ and is _______ with ________ tissue, mainly ___ (_____ marrow)
red, regresses, replaced, nonhematopoietic, fat, yellow
In adults, hematopoiesis occurs primarily in the?
pelvis, sternum, ribs, vertebrae, and proximal humerus and femur.
This is why when we biopsy, we go to these body parts.
Calf, neonate, normal active
bone marrow
When animal is just born, bone marrow is very active.
Color = age
Normal bone marrow,
2-month-old calf.
With time, bone marrow is less active.
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.
Erythropoietin (Epo) regulates production of ____.
RBCs
Produced in the kidney and liver, especially in the peritubular epithelial ? cells.
Release of Epo stimulated by ______.
hypoxia
Other stimulators of Erythropoiesis: ?
ILs, Colony stimulating factors (CSFs), hormones
Label accordingly
Nuclei lost at Metano
If see metano or poly in blood smear –> some type of pathology occurring
________ and ______ cells are referred to collectively as myeloid cells.
Granulocytic, monocytic
Main purpose of mylopoeisis is to develop B cells so that –> tissue –> attack microbes (main function = host defense).
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
phagocytosis, microbicidal, Eosinophils, basophils, Macrophages
MQs are also responsible for microbials such as fungi, protozol –> granulomatous inflammation.
List the stimulators of granulopoiesis and monocytopoiesis:
- Interleukins (ILs)
- Granulocyte colony-stimulating factor (G-CSF) and GM
(granulocyte-macrophage)-CSF
Thrombopoietin (Tpo), synthesized primarily in the ______, regulates _______.
liver, thrombopoiesis
Mega = multilobulated nuclei and the cytoplasm will eventually break down and then eventually become platelets.
Other cells in bone marrow include?
- Lymphocytes (1-10%)
- Plasma cells (<1%)
- Stromal cells: reticular cells, adventitial cells, adipocytes
- Osteoblasts, osteoclasts
What samples would you collect from your patient?
Bone marrow
aspirates and core biopsies
Always want to do them together because they have different functions and show you different things.
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).
You collect bone marrow aspirates and core biopsies from any bone with ____ marrow:
* (3) in dogs and cats
* ______ of horses
* Proximal rib of ____
red, Proximal femur, iliac crest, proximal humerus, Sternum, cattle
Bone marrow is located in _____ sites but responds as a ____ tissue
multiple, single
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
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
morphology, maturation, Erythroid, myeloid, Primary, metastatic
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
fat, hematopoietic, Erythroid, myeloid, iron, Stromal, Primary, metastatic
Smear ?
Core biopsy
Short, cylinderal biopsy
Bone on bottom
purple dots?
Evaluate amount of fat and hematopoietic cells
Bone marrow aspirate on cytology
RB - erythroid origin; eosinophillic cytoplasm
PG - granulated cytoplasm; count these to get ratio.
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
List the typical bone marrow patterns:
- Hyperplasia
- Hypoplasia
- Myelitis/Necrosis
- Dysplasia/Neoplasia
- Myelofibrosis
In bone marrow patterns, one or multiple cell lines may be _______
depending on the stimulus.
hyperplastic
Erythroid hyperplasia ➝ ?
response to anemia
BM pushes RBC out as fast as possible; takes time; see erythroid cells in anemia?
Megakaryocytic hyperplasia ➝ ?
response to ↓
platelets
Myeloid hyperplasia (monocytic/granulocytic cell
lines)
* Neutrophilia ➝ ?
* Eosinophilia ➝ ?
* Monocytosis ➝ ?
bacterial infections, tissue necrosis
parasites, hypersensitivities
chronic infections, specific agents
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 ______.
↓, numbers, increased, hypofunctional, ↑, poietins, interleukins
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).
Bone marrow hypoplasia/atrophy is defined as ________ proliferative activity and is characterized by an ______ in yellow marrow
decreased, increase
Bone marrow hypoplasia/atrophy often accompanies
marrow degeneration
Bone marrow hypoplasia/atrophy sequel will depend on ?
cell line(s) affected
List some examples of Bone marrow hypoplasia/atrophy
- 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
Bone marrow atrophy is a result of ____ atrophy of ___
serous, fat
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)
Myelitis/bone marrow necrosis results in ?
- Inflammation: Neutrophilic, granulomatous or pyogranulomatous
- Necrosis
Myelitis/bone marrow necrosis is caused by?
- Neoplasia
- Infections
- Sepsis
- Drugs
- Toxins
- Radiation
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.
Myelodysplastic syndrome (MDS) is a ______ condition caused by a group of clonal _____ proliferative disorders with ineffective ______ in the bone marrow.
neoplastic, myeloid, hematopoiesis
Myelodysplastic syndrome (MDS) is characterized by _______ _______.
ineffective hematopoiesis,
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.
acute myeloid leukemia
Myelofibrosis is an inappropriate ________ proliferation of the _______
spaces with replacement of ________ tissue.
* Due to bone marrow _____ with _______ dysregulation
* _______
fibroblast, medullary, hematopoietic, cytokine, Cytopenia (as a result of myleofibrosis).
Myelofibrosis
Primary hemato divided into lymph and myelo, which are further divided into?
Leukemias are ________ hematopoietic neoplasms that originate in
the ________ _______. They typically have significant numbers of ______ cells in the ____.
* ________ or ______
* _____ or ______
Malignant, bone marrow, neoplastic, blood, Lymphocytic, myeloid, Acute, chronic
Many subtypes of leukemia.
Acute myeloid leukemia in a dog
Blood smear
neutrophils are weird looking because neoplastic. (right)
Left = neoplastic myeloid cells.
Acute myeloid leukemia in a dog
Bone marrow biopsy
Lymphoma is one of the most ________ malignant neoplasms in ______ animals
common, domestic
Lymphoma can be ________ (sporadic) or due to ___ infections: (3)
idiopathic, viral, mice (MuLV), cats (FeLV) and cattle (BLV).
Current WHO classification of canine lymphomas
Decide grade based on mitotic count.
Last box = prognostic indicator.
Immunophenotyping for lymphoma
1. T cells: _____ marker
2. B cells: ______,_______,______ marker
CD3, CD20, Pax5, CD79a
CD3 stain. Cutaneous T-cell lymphoma (epitheliotropic) in a dog
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 (______)
Clonality, lymphoma, inflammatory, DNA, conserved, T, immunoglobulin, B, neoplastic, reactive
Isolate DNA from cells
Conserve region is where we do PCR on
amplify regions –>
Polyclonal = inflammation
Clonal = neoplasia
Clinical signs of lymphoma
- 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
Gross lesions of lymphoma
Organomegaly: diffuse
organ enlargemen
Gross lesions of lymphoma
Multiple tan-white to pink
nodules within organ
Gross lesions of lymphoma
Thickening of walls of
tubular organs
Follicular lymphoma in a dog
Canine lymphoma is the most ______ canine hematopoietic neoplasia.
common
Canine lymphoma usually affects _____ aged to _____ animals. 85 % have _____ lymphoma.
middle, older, multicentric
In cases of canine lymphoma, ______ _____ involvement is common and they are usually?
lymph node, medium to high grade
In cases of canine lymphoma, _____ are usually normal.
leukograms
In cases of canine lymphoma, there is no known _____ association.
viral
In cases of canine lymphoma, ________ of malignancy is
occasionally seen in ____ with
lymphoma → secretion of _____.
Hypercalcemia, dogs, PTHrP
Canine lymphoma
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!
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
In cases of feline lymphoma, ________ and ______ _______ involvement are common.
leukemia, bone marrow
Feline lymphoma is associated with ?:
* ___ - ____% of cats with lymphoma are _____.
feline leukemia virus (FeLV), 10, 20, FeLV+
Feline lymphoma
Thymic lymphoma in a cat
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 ____
large, dogs, small, cats, MALT, small intestine, 29 months, diagnosis, endoscopic, IHC, PARR
Enteropathy-associated T-cell lymphoma type 2 in cats.
CD3 on bottom right
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
BLV, Enzootic bovine leukosis, 30, 1-5, B
Bovine lymphoma –> Superficial/abdominal LN, retrobulbar, abomasum, heart, uterus, spleen, kidney.
Bovine lymphoma has a peak incidence __-___ years old.
6-8
Non-BLV lymphoma (sporadic form): most often ___
cell lymphoma
T
Calf/juvenile form: ______ and ______ (__-__ months)
fetuses, calves, 3-6
______ form: beef cattle <___ years
Thymic, 2
Cutaneous form: young ______ __-__ years.
cattle, 2-3
Enzootic bovine leukosis
Cutaneous lymphoma in a cow
Multiple myeloma is a _______ tumor of _____ cell origin
arising in the _____ _______.
malignant, plasma, bone marrow
Multiple myeloma is a _____ (clonal) _____ cells secrete ________ leading to ____________.
neoplastic, plasma, immunoglobulin, hypergammaglobulinemia
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)
Neoplastic, Lytic, clonal immunoglobulin, urine, Bence-Jones
Monoclonal gammopathy
in a dog
Multiple myeloma
* Gross: Pale pink to dark red gelatinous masses replace
bone marrow – typically multiple masses
Multiple myeloma
Histology: Sheets of neoplastic plasma cells.
