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148 Cards in this Set

  • Front
  • Back
hyperplasia vs neoplasia
hyperplasia
- proliferation of cells in response to a stimuli
- remove the stimuli and it goes back to normal

neoplasia
- proliferation of cells after cessation of stimuli
- benign
- malignant (characerized by invasion/ metastasis)
define hemaatopoietic neoplasia
neoplasia of hematopoietic cell origin
define cancer
malignant neoplasia

characterized by invasion or metastasis
define leukemia
malignant neoplasm arising from hematopoietic cells in the bone marrow (or spleen)

spleen is also a hematopoietic organ and a lymphoid organ, not just a bag of red cells

typically with significant #s of neoplastic cells in circulation
“Leukemia” is also sometimes used to describe any condition in which neoplastic cells are present in circulation
define lymphoma
(aka malignant lymphoma, lymphosarcoma) – malignant solid tissue neoplasm arising in lymphoid tissue(s) outside the bone marrow (neoplasm of lymphocytes)
normal hematopoietic differentiation
lymphoid vs myeloid neoplasia
Lymphoid neoplasia
- Lymphoid (lymphocytic) leukemias
- Lymphomas
- Plasma cell tumors (secrete immunoglobulins)


Myeloid neoplasia
- Myeloid (myelogenous) leukemias
- Myelodysplastic syndromes
- Other myeloid neoplasms
lymphoma
It is not one dz, it is a spectrum of diseases


Many different forms, depending on:
- Anatomic location
- Cell type (B v. T v. NK)
- Cellular morphology (sometimes small or sometimes big)
- Histologic pattern
- Stage (how disseminated it is in terms of anatomic location)
- Biologic behavior
- Response to therapy
how do you dx lymphoma
Diagnosis usually based on FNA cytology +/or biopsy and histopathology


Dx typically followed by clinical staging (how advanced is the disease?) and immunophenotyping (ID of cell type using antibodies)
histopath vs cytology
Histopath
- Chunk of tissue
- Tissue architecture is intact



Cytology
- Sample lesion
- Fast, cheap, good cell morphology
- No architecture (can be limiting)
- Not limiting in lymphoma
laboratory abnormalities assoc with lymphoma
Laboratory abnormalities are variable

Hematology – nonregenerative anemia is common

Chemistry – some forms of LSA are associated with hypercalcemia
left = high grade lymphoma
- more aggressive
- Big not well differented cells
- More aggressive
- Higher mitotic rate (notice mitotic figure)


right = low grade lymphoma
- less aggressive
- Smaller cells
- Lower mitotic rate
- Less biologic aggressive behavior
high grade lymphoma

notice mitotic figure/
lower cytoplasm : nucleus
what is leukemia
malignant neoplasm arising from hematopoietic cells in the bone marrow (or spleen) typically with significant numbers of neoplastic cells in circulation
basic classification of leukemias (what cells they arise from)
lymphoid or myeloid

chronic or acute

lymphoid leukemias
- B or T cell origin

myeloid leukemias
- erythroid
- granulocytic
- monocytic
- megakaryocytic
what is a blast crisis
when a chronic leukemia transforms into a more acute form (some additional mutation)
Lymphoid vs Myeloid neoplasia *what cancers are included in each*
lymphoid
- lymphomas
- lymphocytic leukemias
- plasma cell tumors

Myeoloid neoplasia
- myeloid leukemias
- myelodysplastic syndromes
- other myeloid neoplasms
what is lymphoma

what variables affect the form?

how do you dx
malignant solid tissue lymphoid neoplasm arising in lymphoid tissue(s) outside the bone marrow

variables include
- anatomic distribution
- immunophenotype (B or T vs. non B or T)
- cellular morphology
- histologic pattern
- stage
- biologic behavior
- response to therapy

initial dx
- aspiration cytology +/or biopsy/ histopath
- followed by clinical staging and immunophenotyping
what laboratory values are assoc with lymphoma
hematology and chemisty are variable
what underlying factors are associated with lymphoma
cats
- FeLk

cattle
- BLV
- persistent lymphocytosis
- lymphoid neoplasia
with _____ leukemias, the cell of origin is easy to identify.

Why is it sometimes difficult to dx.
chronic leukemia
- b/c well differentiated cells

sometims hard to tell if cells are neoplastic or reactive

dx often one of exclusion
______ are characterized high numbers of blasts in the bone marrow

why is it sometimes difficult to dx
acute leukemias (> 20-30% of neucleated cells)

the specific lineage usually cant be determined by routine micro exam b/c poorly differentiated

ID by immunophenotyping and/or cytochemical staining
what is MDS
myelodysplastic syndrome

clonal myeloid proliferation characterized by ineffective hematopoiesis

doesn't meet traditional definition for acute leukemia
- MDS is characterixed by increased apoptosis compared to AML

clasically dx by findings of
- < 20-30% of blasts in bone marrow
- cytopenia of > 1 cell line
- morphological evidence of dyshematopoiesis
how do you differentiate lymphoma from lymphocytic leukemia
how do you differentiate b/w chronic and acute leukemias
where does lymphoma start & where can it spread?

leukemia?
Lymphoma
- start anywhere
- spread to bone marrow/blood

leukemia
- starts in bone marrow/spleen/blood and can spread anywhere
Which leukemia is often characterized by neutropenia, thrombocytopenia, and anemia
acute
which leukemia is often characterized by non-regenerative animea but not pancytopenia
chronic
2 main forms of plasma cell tumors
plasmacytoma
- solid tumors that typically involve skin or mm
- usually benign
- excision normally curative

mult myeloma
- typically arise from bone marrow
- secrete large amts of Ig leading to hyperglobulinemia
- dx based on finding at least 2 of the following
1) markedly increased numbers of plasma cells in bone marrow, esp in aggregates (plasma cells must be at least 30% of nucleated cells in the marrow)
2) monoclonal gammopathy
3) radiographic evidence of osteolysis (osteoclasts support growth of myeloma cells)
4) light chain proteinuria (don't react with dipstick protein indicators, require electrophoresis and immunoprecipitation)
- may also see hypercalcemia, lesions assoc with hyperglobulinemia (hemorrhage due to secondary platelet dysfxn, renal amyloidosis, hyperviscosity syndrome), cytopenias due to high numbers of neoplastic cells in bone marrow
immunophenotyping
use of antibodies to recognize specific molecules expressed on different cell types to determine identity of cell population

immunohistochemistry
immunocytochemistry
flow cytometry
clonality assays
PCR for lymphocyte antigen receptor gene arrangements

exploits the fact that neoplastic cells are monoclonal whereas reactive cells are polyclonal

highly sensitive and specific test

valuabe for dx lymphoid neoplasia

most useful in distinguishing lymphoid neoplasia (lymphoma or lymphocytic leukemia from non-neoplastic lymphoid proliferations
plasma cell neoplasia

Multiple myeloma
– malignancy of plasma cells, usually arises in bone marrow

Plasmacytoma
– solid tumors
- Cutaneous
- Extra-cutaneous (often @ mucous membranes)
- Variable biologic behavior
diagnostic criteria for multiple myeloma
what are some tumors of hematopoietic but not considered hematopoietic neoplasms
Mast cell tumors

Histiocytic tumors
- Macrophages
- Dendritic cells
1. With _____ leukemia, ou will see a high lymphocyte count.


2. With _____ leukemia, where neoplastic cells are blasts, you may get errors b/c machine doesn't know how to count them.
1. chronic

2. acute
Immunophenotyping LSA
mechanisms of dz in the bone marrow
hypoplasia

hyperplasia

dysplasia (messed up somehow making cells look wrong)

aplasia

neoplasia

myelophthisis

infection
indications for bone marrow exam
unexplained cytopenias of one or more of the major hematopoietic lineages
- anemia
- thrombocytopenia
- neutropenia
*help determine the mechanism of cytopenia*


unexplained presence of abnormal cells in circulation
- blasts
- other immature cells (nRBC, immature granulocytes)
- cells of abnormal morphology
- well differentiated cells not normally found in circulation (ex mast cells)
*helps determine mechanism causing presence of abnormal cells*


cancer staging or monitoring
- staging most commonly for lymphoma


reasonable suspicion of neopolasia or infection in bone marrow
- ex mult myeloma (esp in pt with monoclonal gammopathy), tick borne dz, fungal dz
contraindications and complications of bone marrow
main contraindication = unnecessary bx

anesthesia is usually a greater risk than the collection procedure

thrombocytopenia isn't a contraindication

complications rare
- iatrogenic infection
- iatrogenic frx
what do you do with the bone marrow sample
cytology & histopathology

if only 1 choice, cytology is the better choice (esp if highly cellular sample)

cytology
- faster
- less expensive
- excellent cellular morphologic detail
- no tissue architecture
- less reliable measure of marrow cellularity

histopath
- preservation of tissue architecture
- more reliable assessment of marrow cellularity
- slower
- more expensive
- inferior cellular morphologic detail
preferred sites of bone marrow sample collection
crest of ilium

proximal humerus (cats/ small dogs)

trochanteric fossa of femur

sternum, tuber coxae (horses)
bone marrow aspirate sample collection.

what do you need to put in syringe before attaching syringe to needle

how much sample do you need
0.3 ml EDTA

small amt (<0.5 ml) of marrow
marrow cytologic interpretation
microscopic evaluation
- cell #'s, types, morphology
- iron stores
- +/- organisms

need CBC (and preferrably a blood smear from same day as marrow collection) and thorough clinical work-up to fully interpret bone marrow findings
what do you need to interpret bone marrow findings
a concurrent CBC and thorough clinical work up
marrow cytology interpretation

what do you look at under low power?

high power?
low power
- overall cellularity
- megakaryocyte #s
- iron stores
- initial impression of M:E ratio

high power
- detailed evaluation of M:E ratio
- #'s of minor cell populations (lymphocytes, plasma cells, macrophages, +/- others such as mast cells, osteoclasts, neoplastic cells)
- cellular detail (maturation morphology)
- +/- organisms
normal marrow cellularity
age dependent

juvenile = 75%

adult = 25%

remaining non-hematopoietic is mostly fat
how do you assess marrow cellularity (cytologic preparations)
on the basis of unit particles (small chunks of tissue)

how much of the unit particles consist of hematopoietic tissue instead of fat

to a lesser degree on the density of individual hematopoietic cells in the monolayer of the slide
causes of increased marrow cellularity

decreased marrow cellualrity
increased
- hyperplasia of one or more hematopoietic lineages
- neoplasia


decreased
- hypoplasia of one or more hematopoietic lilneages
- fibrosis
what do you look at in marrow cytology for cellular composition
evaluating 3 main marrow hematopoietic lineages (megakaryocytic, erythroid, granulocytic) as well as other cell types normally found in lower #s (lymphocytes, plasma cells, and macrophages)

mature megakaryocytes large with abundant slightly eosinophilic cytoplasm

immature megakaryocytes smaller with less abundant more basophilic cytoplasm
marrow hyperplasia witih increased M:E is
myeloid hyperplasia
marrow hypoplasia with increased M:E is
erythroid hypoplasia
bone marrow exam

What is the M:E ratio
Rough estimate (subjective)

Quantitative assessment
100- v. 500- v. 1000-cell count

The M:E in most normal dogs and cats is apx. 1:1 to 2:1.
causes of increased marrow cellularity
hyperplasia of one or more hematopoietic lineages

neoplasia
causes of decreased marrow cellularity
hypoplasia of one or more hematopoietic lineages

fibrosis
bone marrow exam

what do you look at on low power (4x-10x)
overall cellularity

megakaryocyte numbers

iron stores

inital impression of M:E ratio
bone marrow exam

what do you look at on high power (50x-100x)
detailed evaluation of M:E ratio

numbers of minor cell populations
- lymphocytes
- plasma cells
- macrophages
- +/- others (mast cells, osteoclasts, neoplastic cells)

cellular detail (maturation/ morphology)

+/- organisms
normal marrow cellularity based on age
juvenile = 75% hematopoietic tissue

adult = 25% hematopoietic tissue
bone marrow exam

in cytologic preparations, cellularity is assessed mainly on the basis of
unit particles (small chunks of tissue)

how much of the tissue chunks consist of hematopoietic tissue instead of fat

and to a lesser degree, the density of individual hematopoietic cells in the monolayer of the slide
The M:E in most normal dogs and cats is approximately
1:1 or 2:1
what are the main cell types/ lineages assessed in the marrow evaluation
hematopoietic lineages
- megakaryocytic
- erythroid
- granulocytic

other cell types normally found in lower numbers
- lymphocytes
- plasma cells
- macrophages
What is the M:E in most normal cats
1:1 or 2:1
What is the M:E in most normal dogs?
1:1 or 2:1
bone marrow exam

in cytologic preparations, cellularity is assessed mainly on the basis of
unit particles (small chunks of tissue)

how much of the tissue chunks consist of hematopoietic tissue instead of fat

and to a lesser degree, the density of individual hematopoietic cells in the monolayer of the slide
The M:E in most normal dogs and cats is approximately
1:1 or 2:1
what are the main cell types/ lineages assessed in the marrow evaluation
hematopoietic lineages
- megakaryocytic
- erythroid
- granulocytic

other cell types normally found in lower numbers
- lymphocytes
- plasma cells
- macrophages
What is the M:E in most normal cats
1:1 or 2:1
What is the M:E in most normal dogs?
1:1 or 2:1
bone marrow exam of megakaryocytes
majority are normally very large with abundant, slightly eosinophilic cytoplasm

immature ones are smaller and have less abundant, more basophilic cytoplasm
bone marrow exam of erythroid and granulocytic cell numbers
assessed on the basis of overall marrow cellularity and myeloid:erythroid ratio
bone marrow exam

assessment of maturation of each lineage
complete (maturation through segmented neutrophils and polychromatophilic erythrocytes)


synchronous (normal proportions of early and late stage cells
how much of the population of nucleated cells is normally comprised of lymphocytes?

plasma cells?

macrophages?
lymphocytes: < 5% (dogs) or < 20% (cats)


plasma cells: < 2%


macrophages: < 2%
dysplasia
abnormal morphology
canine bone marrow iron stores
normally has small to moderate amts of hemosiderin

absence of bone marrow hemosiderin in dogs is an abnormality consistent with iron deficiency
feline bone marrow iron stores
normally doesn't have detectable hemosiderin

presence of bone marrow hemosiderin in cats is consistent with iron overload
what organisms can occasionally be detected in the bone marrow
bacteria

rickettsia

fungi

protozoa
indications for bone marrow exam
Unexplained cytopenia(s):
- Anemia
- Thrombocytopenia
- Neutropenia


Unexplained presence of abnormal cells in circulation:
- Blasts
- Other immature cells (e.g., nRBCs, immature granulocytes)
- Cells of abnormal morphology
- Well-differentiated cells not normally found in circulation (e.g., mast cells)

Cancer staging or monitoring
- e.g., Lymphoma


Look for occult disease – especially if there is reasonable suspicion of neoplasia or infection in the bone marrow
- e.g., Multiple myeloma
- High globulins without evidence of infection response can be indicative of multiple myeloma
what is the main contraindication for bone marrow exam
unnecessary bx
interpretation of M:E ratio in context of overall marrow cellularity
Interpretation of bone marrow results for patient with nonregenerative anemia
bone marrow hypoplasia indicates that cytopenia is probably due to
decreased production
bone marrow hyperplasia with unexplained non-regenerative anemia indicates that cytopenia is probably due to
increased destruction (usually immune mediated)
bone marrow maturation arrest indicates that a persistent cytopenia is probably due to
increased destruction (consistent with immune mediated disease of myelodysplastic syndrome)
bone marrow aplasia may occur in one or more lineages and main ddx are
immune mediated dz

toxic insult

infectious dz

idiopathic
bone marrow microscopic interpretation of hypoplasia, hyperplasia, maturation arrest, aplasia
Hypoplasia: cytopenia is due to decreased production

Hyperplasia: cytopenia is due to increased destruction (usually immune-mediated)

Maturation arrest: persistent cytopenia is due to increased destruction (consistent with immune-mediated disease or MDS).


Aplasia may occur in one or more lineages
Ddx include immune-mediated disease, toxic insult, infectious disease, idiopathic
blood types
inherited antigens (alloantigens on RBC)

various RBC membrane proteins

impt in transfusion medicine
transfusion medicine

sensitization
acquired alloantibodies

prior transfusion

pregnancy

certain vaccines
which blood types are impt in dogs
DEA 1.1
what is the ideal canine donor?
DEA 1.1 neg
cat blood types

naturally occurring alloantibodies
Type A
- weak anti-B antibody
- transfuse type A cat with type B blood and get small transfusion rxn


Type B
- strong anti-A antibody
- give small amt of type A blood, and will get life threatening transfusion rxn


Type AB
- not anti-A or anti-B
canine blood types
feline blood types
equine blood types
Have type AB cat, that is anemic and needs trx

1. Have type B blood sitting around, can you give it?

2.What about type A blood?
1. No b/c type B blood has strong anti-A antibody

2. May still have rxn but won't be life threatening
What type of blood should you give a Type AB cat?
type A or B packed, washed RBC
Type B cat given washed packed type A blood
will not stop the blood from being type A so you will still have the host response against the new cells (just not the response from the type A blood)
true or false

a cat with type AB blood is the universal recipient of whole blood
false

it is the universal recipient of A or B packed, washed RBC
will there be a rxn if give type B donor blood to a type AB cat
yes

whole blood of type B, plasma components have strong anti-A antibodies
what equine blood types are the most impt
Aa

Ac

Ca

Qa
do equine blood types have naturally occurring alloantibodies?
rare (Aa and Ac)

poss in Ca

no for Qa
do K9 blood types have naturally occurring alloantibodies
yes
- DEA 3
- DEA 5
- DEA 7

no
- DEA 1.1
- DEA 1.2
- DEA 4
- DEA 6
do feline blood types have naturally occurring alloantibodies
yes
- A has weak anti-B
- B has strong anti-A

no
- AB
true or false

DEA 6 can be associated with NI
false

its prevalance in the US is 100%
cattle blood groups
Cattle have 11 blood groups with over 70 identified factors


Not many of them are clinically significant
clinically most impt blood types
Dogs
- DEA 1.1

Cats
- A
- B
- AB

Horses
- Aa
- Ac
- Ca
- Qa
which blood types are most impt in NI (hint: they are both equine)
Aa & Qa
when do you see NI in dogs, cats, and horses
dog
- DEA 1.1+ pup born to DEA 1.1- bitch
- rare unless prior sensitization


cats
- type A or type AB born to type B queen


horses
- Aa+ foals born to Aa- mare
- Qa+ foals born to Qa- mare
- mule born to a mare bred to a jack
what is the ideal donor for foal in NI crisis
Qa- blood from horse that was never sensitized

or packed, washed RBC from mare

don't give blood from sire
pretransfusion testing
blood typing
- confirm blood type

cross matching
- determine donor-patient compatibility
agglutination testing
can be performed in test tube, on glass slide, or in gel

positive = RBC agglutination

patient RBC and test kit reagents

RBC & plasma from patient and donor
hemolytic testing
positive = RBC hemolysis

some blood typing of cattle, pigs, and camelids has hemolysis as an end point
blood typing for dogs/ cats
card
- test kit reagents contain either antiserum or lectins
- reagent is mixed with patient blood (EDTA)
- look for agglutination

gel
- neg = pellet
- pos = line at the top of the gel
- agglutinated RBC (pos) do not migrate through the gel and form a band at the top of the gel column
- non-agglutinated cells (neg test result) DO migrate through gel and form a button at bottom of the gel column
major cross-match
washed donor RBC + recipient plasma

takes 1-1.5 hrs

if agglutination = don't use
- person doing test must know their shit

can be done in test tube, on slide, with gel kit
major vs minor incompatibility
maj
- not safe to give

minor
- not ideal but could be okay with minor rxn
minor cross match
donor plasma + recipient RBC

look for agglutination
when can you not do a crossmatch
with IMHA
cross matching compatibility
in clinical small animal practice you will perform ______ (blood typing/ cross matching/ both)
blood typing
in small animal clinical practice, what species can get transfusion without typing/ cross-matching
dogs (1 time)

cats need typing and cross-matching prior to transfusion
true or false

a patient could still have an adverse reaction despite typing and cross-matching
true
true or false

i am sick of making clin path flashcards
true
how do animals get sensitized to blood group antigens
transfusion of whole blood or packed RBC

pregnancy (exposure of antigen neg dam to her fetus' antigen pos blood via transplacental hemorrhage)

vaccination with certain vaccines
- ex Anaplasma vaccines that contain RBC membranes
neonatal isoerythrolysis refers to
hemolytic anemia occurring in a neonate that acquired antibodies against its own RBC from its dam (via colostrum ingestion)
pathogenesis of NI
antigen neg dam bred to antigen pos sire

fetus expresses sire's antigen

dam exposed to fetal blood during gestation

dam makes antibodies to antigen she doesn't have

neonate is born

neonate ingests colostrum containing those antibodies

neonate develops hemolytic anemia
NI can occur in
type A and type AB kittens born to type B queens

Type Qa foals born to Type Qa neg mare (or Aa foal to Aa neg mare)

only occurs in puppies born to bitch that was transfused prior to whelping

in cattle occurs only in calves born to a cow that was previously given a RBC membrane containing vaccine
DEA refers to
dog erythrocyte antigen system used to classify canine blood groups
canine blood transfusion med
dogs can develop antibodies against any blood group antigen but only DEA 1.1 is impt

b/c most antigenic and most critical

often positive for mult DEA antigens
where to alloantibodies come from
naturally occurring

acquired (sensitized)
blood groups are impt in
transfusion med

pathogenesis of NI

verify parentage for pedigree records and breeding registries
what is a universal blood donor
individual having minimallly antigenic blood that could (in theory) be given to any individual of the same spp with low risk of adverse effects (O- humans)

universal donors highly desirable
what is a universal recipient
an individual with mult blood group antigens that could (in theory) receive blood from any other individual of the same spp with low risk of adverse effects (type AB+ humans)

these guys lucky
animals having antibodies to a particular blood group antigen may experience an adverse rxn (such as ______) if exposed to that antigen
hemolysis and/or anaphylaxis
which blood type is unable to be tested for (canine)
DEA 6
type AB cats can be considered universal recipients of
type A, B or AB packed RBC

not universal recipients for whole blood ro plasma
in equine what are the most antigenic blood types (most resp for NI)

which are impt in transfusion med
NI
- Aa
- Qa

transfusion med
- Aa
- Ac
- Ca
- Qa
pretransfusion testing is most relevant to _____
RBC

the transfusion of whole blood or packed RBC
goals of pretransfusion testing are
confirm blood type (blood typing)

determine donor and recipient compatibility (cross-matching)
the end point (positive result) of blood typing is

cross matching
endpoint of both is macroscopically visible agglutination of RBCs w/in seconds to minutes after reagents are mixed

no agglutination = neg


in blood typing
- RBC agglutination is caused by interactions b/w patients RBC and test kit reagents (antiserum or lectins that react w/ blood group)


cross matching
- agglutination is caused by antigen-antibody interactions b/w RBC and plasma (or serum)
blood typing is performed using what sample

cross matching?
typing
- EDTA anticoagulated blood

matching
- EDTA blood sample from patient and bag of whole blood or packed RBC from donor
how do you store blood samples for transfusion use
4C
what diseases cause difficulties in blood typing/ crossmatching and why
pt with marked RBC rouleaux (some animals with systemic inflammation)

agglutination due to dz (IMHA)

leavve this to laboratories with specially trained med techs
2 types of commonly used commercially available blood typing test kits in the US
DEA 1.1 antigen (dogs)

type A & B (cats)

in the form of cards and gels
typing cards accurately identify (dogs)
DEA 1.1 +

DEA 1.2 pos may have weak pos rxns (can misclassify as DEA 1.1+)
typing cards accurately ID (cats)
A and B cats

cats that are B or AB should undergo confirmatory testing
gel typing accurately IDs
reliable in dogs and cats
which is better gel or card typing
gel is better b/c
- results easier to interpret
- gel fixes agglutination rxn (so can view over a longer period of time)
- gels can be photocopies and photocopy placed in medical record (thus can be archived)
why do you use cross matching
confirm compatibility

investigate cause of adverse transfusion rxn
what is impt about cross matching
it does not guarantee normal donor RBC survival in recipient and do not complete eliminate risk of adverse transfusion rxn


focuses on RBC so doesn't prevent adverse leukocyte or platelet rxns
know the tranfusion blood components and their indications (whole blood vs packed RBC vs fresh frozen plasma, etc.)