Term
| What ploidy are most megakaryocytic? |
|
Definition
~16N (however they can vary in size and ploidy)
Megakaryocytes develop from endomitotis (nucleus divides repeatedly without cell division) |
|
|
Term
| How many nuclei do promegakaryocytes have? |
|
Definition
|
|
Term
| Which species has the highest G:E ratio? Which has the lowest? |
|
Definition
Cats have the highest (1.63)
Cattle have the lowest (0.71)
but in general around 1 is considered normal |
|
|
Term
| What species can have more bone marrow lymphocytes in health? |
|
Definition
| Cats (up to 20%, while in most other species <5% lymphs is normal) |
|
|
Term
| On average, what percentage of cellularity is associated with bone marrow hypercellularity and bone marrow hypocellularity (keeping in mind the age of the patient)? |
|
Definition
<25% adipose tissue = hypercellular
>75% adipose tissue = hypocellular
if bone marrow spicules are not present but the preparation is highly cellular the bone marrow is likely to be hypercellular. If the bone marrow spicules are not present but the preparation is hypo cellular the sample may be hypocellular, or just poorly representative and core biopsy should be evaluated. |
|
|
Term
| What are the cells in the proliferative granulocyte pool? |
|
Definition
| Myeloblast, progranulocyte, myelocyte |
|
|
Term
| T/F healthy young animals of all species may have absent bone marrow iron stores |
|
Definition
True
**also cats, regardless of age don't have bone marrow iron stores normally, but iron may be present if there is hemolytic or myeloproliferative disease, or following a blood transfusion |
|
|
Term
| How is secondary appropriate erythrocytosis distinguished from secondary inappropriate erythrocytosis? |
|
Definition
If there is persistent hypoxia or increased tissue demand for oxygen the erythrocytosis is appropriate.
If there is inappropriate production of erythropoietin in the absence of tissue hypoxia the erythrocytosis is inappropriate |
|
|
Term
| Describe diagnostic features of immune-mediated anemia at the level of the bone marrow? |
|
Definition
non-regenerative anemia, bone marrow erythroid hyperplasia, phagocytosis of erythroid precursors in the bone marrow +/- positive coombs test
**there may be a maturation arrest with increased numbers of erythroid stages prior to the target cell stage and all more mature forms absent. If very early erythroid cells or erythroid precursors are targeted there may be erythroid hypoplasia or aplasia |
|
|
Term
| Describe bone marrow findings with iron deficiency anemia |
|
Definition
| Erythroid hyperplasia- erythropoiesis is defective, late stage erythroid precursors don't mature properly and are not released into the blood. Reticulocytosis may be present in initial stages, but not enough to meet peripheral demands. When progressed rubricates may be smaller with less hemoglobinized cytoplasm. |
|
|
Term
| In what breeds have inherited abnormalities in cobalamin receptors been associated with ineffective erythropoiesis which may be accompanied by dysplastic changes? |
|
Definition
| Giant schnauzer, beagles, border collies, australian shepherds |
|
|
Term
| What are five underlying etiologies of non-inflammatory, but effective, granulocytic hyperplasia (i.e. bone marrow granulocytic hyperplasia accompanied by peripheral neutrophilic)? |
|
Definition
paraneoplastic
leukocyte adhesion deficiency
G-CSF administration
early phase of estrogen toxicity
cyclic hematapoiesis (grey collies, feLV infected cats) |
|
|
Term
| What conditions are associated with granulocytic hyperplasia and ineffective granulopoesis (i.e. peripheral neutropenia)? |
|
Definition
immune mediate neutropenia (+/- left shift depending on the stage of neutrophil targeted +/- phagocytosis of neutrophils (BM, liver, spleen) <- if early stage granulocytic precursors are targeted there can be granulocytic hypoplasia with left shift and maturation arrest)
drug induced (phenobarbital)- may have been secondary immune mediated
G-CSF deficiency (reported in a Rottweiler)- G-CSF is needed for terminal neutrophil deficiency. In this case there was granulocytic hyperplasia consisting of numerous myeloblasts and programs with few myelocytes or more mature granulocytes) |
|
|
Term
| What mediators stimulate megakaryocytic hyperplasia in response to peripheral thrombocytopenia? |
|
Definition
| thrombopoeitin, stem cell factor, IL-3, GM-CSF |
|
|
Term
| What mediators stimulate eosinopoeisis? |
|
Definition
| IL-5, GM-CSF (released from mast cells, macrophages, and lymphocytes) stimulate eosinopoeisis |
|
|
Term
| What condition in cats is associated with bone marrow eosinophilic hyperplasia, but not necessarily peripheral eosinophilia? |
|
Definition
|
|
Term
| What is the underlying pathogenesis of primary pure red cell aplasia vs. secondary? |
|
Definition
Primary pure red cell aplasia is an immune mediated disorder and can be seen in association with spherocytic hemolytic anemia.
Secondary pure red cell aplasia has been reported following treatment with recombinant human EPO in dogs, cats and horses. Also may be associated with viral infection (FeLV, parvovirus). |
|
|
Term
| What is the expected bone marrow findings with immune mediated hemolytic anemia at the level of the marrow? |
|
Definition
| Erythroid hypoplasia with left shift and maturation arrest (beginning at the targeted stage) |
|
|
Term
| What strain of FeLV causes sever erythroid hypoplasia in neonatal kittens but not in older cats? |
|
Definition
Kawakami-theilen strain
** weaning and adult cats can develop erythroid hypoplasia if infected with other feLV strains |
|
|
Term
| What bone marrow findings are supportive of anemia of chronic disease? |
|
Definition
Increased iron
there may or may not be an appreciative erythroid hypoplasia either because it may be mild, or because concurrent granulocytic hyperplasia makes it challenging to determine if erythroid hypoplasia is relative or absolute
**non-regenerative anemia and the absence of erythroid hyperplasia in the BM supports suppressed erythropoiesis (e.g. anemia of chronic disease) even if erythroid hypoplasia is not evident |
|
|
Term
| What endocrinopathies are associated with selective erythroid hypoplasia (which may be too mild to appreciate on bone marrow evaluation)? |
|
Definition
| hypothyroidism, hypoadrenocorticism, and hypoandrogenism |
|
|
Term
| What drug can induce transient erythroid hypoplasia in dogs and cats? |
|
Definition
chloramphenicol
**there may be concurrent granulocytic and megakaryocytic hypoplasia as well in cats |
|
|
Term
| What infectious agents have been associated with selective granulocytic hypoplasia (+/- generalized marrow hypoplasia) in veterinary species? |
|
Definition
parvovirus (k9, feline)
feLV
toxoplasma
chronic ehrlichiosis |
|
|
Term
| What toxic agents/drugs have been associated with selective granulocytic hypoplasia in veterinary species? |
|
Definition
| bracken fern, chemo drugs, chloramphenicol (cats), estrogen, griseofulvin, phenylbutazone, diphenylhydantoin (an anticonvulsant) |
|
|
Term
| What is the pathogenesis of granulocytic hypoplasia in parvovirus? |
|
Definition
Damage to proliferative pool granulocyte cells
Depletion of storage pool granulocytes due to excessive peripheral demand
endotoxin mediated bone marrow injury |
|
|
Term
| What drugs are associated with selective megakaryocytic hypoplasia? |
|
Definition
| bracken fern (ruminants), chemo drugs, estrogen (dogs_, griseofulvin, meclofenamic acid (NSAID), phenylbutazone, TMS |
|
|
Term
| Which species may have the most bone marrow lymphocytes in health? |
|
Definition
| Cats (up to 20%) vs. all other species should have <5% (usually <1%) |
|
|
Term
| What disease was most commonly associated with bone marrow lymphocytosis (>20%) in cats? |
|
Definition
| pure red cell aplasia and immune mediated anemia |
|
|
Term
| What phenotype of lymphocytes are most commonly observed in CLL in cats? |
|
Definition
T lymphocytes, present in a diffuse infiltrate of the bone marrow
**(as opposed to inflammatory lymphocytosis which lymphocytes are often present in follicles or aggregates) |
|
|
Term
| What is the most typical peripheral manifestation of myelofibrosis in dogs? |
|
Definition
moderate to severe, non-regenerative to poorly regenerative anemia, without other cytopenias
**although, pancytopenia may occur if the myelofibrosis is extensive |
|
|
Term
| What protozoal organism is most likely to incite inflammation in the marrow? |
|
Definition
|
|
Term
| What are the three underlying diseases that can result in myelophthisis (replacement or displacement of hematapoetic elements by abnormal tissue)? |
|
Definition
| neoplasia, myelofibrosis, osteopetrosis |
|
|
Term
| How can you distinguish erythroleukemia/M6-Er from AML? |
|
Definition
erythroleukemia/M6-Er (>50% of all nucleated cells in the BM are erythroid)
for both AML and erythroleukemia >20% of bone marrow cells are blasts |
|
|
Term
| What are the diagnostic criteria for AML with multi-lineage dysplasia? |
|
Definition
>20% blasts, dysplasia in at least 50% of the cells in two or more of the myeloid lineages
**these leukemias arise following myelodysplasia or myeloproliferative disease |
|
|
Term
| What therapies can induce AML and MDS (often months to years after the therapy has been applied)? |
|
Definition
| alkylating agents, radiation, topoisomerase inhibitors (chemo drugs) |
|
|
Term
| What are some dysplastic changes that can be observed in the granulocytic lineages? |
|
Definition
| Cell gigantism, abundance of azurophilic granules (in cells other than programs), polyploidy or hypersegemented neutrophil nuclei or pelter-huet like features |
|
|
Term
| What are some dysplastic changes that can be observed in the erythroid lineage? |
|
Definition
| Multiple nuclei, nuclear fragmentation, megaloblastic appearance (larger), excessive cytoplasm relative to nucleus or nuclear to cytoplasmic maturation asynchrony, abnormal distribution of siderosomes, macrocytic erythrocytes |
|
|
Term
| What are some dysplastic changes that can be observed in the megakaryocyte lineage? |
|
Definition
| hyposegmented nucleus, multiple small nuclei, dwarf megakaryocytic, megaplatelets, platelets or megakaryocytes with abnormal granularity or vacuolation |
|
|
Term
| What five congenital nonneoplastic dyshematapoeisis disorders have been describe in veterinary species? |
|
Definition
1. poodle macrocytosis
2. cobalamin malabsorption in giant schnauzers, border collies, australian shepherds and beagles
3. dyserythropoeisis in english springer spaniels
4. dyserythropoesis and progressive alopecia in polled herford calves
5. macrothrombocytopenia in cavalier king charles spaniels |
|
|
Term
| What non-neoplastic and non-congenital conditions have been associated with acquired secondary MDS in veterinary species? |
|
Definition
Drugs/toxins (lead, chemo drugs, estrogen, cephalosporins, chloramphenicol, phenobarbital, colchicine (anti-inflammatory agent))
Fe deficiency
IMHA/ITP
Inflammatory diseases (FIP, sepsis, pyometra, pancreatitis)
neoplaisa (lymphoma, multiple myeloma) |
|
|
Term
| What are the peripheral blood and bone marrow findings supportive of chronic myelomonocytic leukemia? |
|
Definition
peripheral blood: leukopenia, non-regenerative anemia, atypical hypersegmented monocytoid cells
Bone marrow: hypercellular, <10% blasts, atypical hypersegmented monocytoid cells (as observed in blood +/- lymph nodes).
The disease has a chronic course |
|
|
Term
| What are the features of chronic myeloproliferative diseases? |
|
Definition
chronic, clonal disorders of pluripotent stem cells --> excessive proliferation or accumulation of well differentiated neoplastic cells with for to no microscopic or functional abnormalities
Usually diagnosed by exclusion as clonality tests in myeloid cells are not generally available in veterinary species |
|
|
Term
| What are the four distinct disorders categorized under chronic myeloproliferative disease? |
|
Definition
1. Chronic myelogenous leukemia (aka chronic granulocytic leukemia or chronic myeloid leukemia)- neutrophilia and typically a left shift. Chronic eosinophilic leukemia and chronic basophilic leukemia are variants.
2.Polycythemia vera (aka primary erythrocytosis)
3. Megakaryocyte myelosis (aka essential thrombocythemia)
4. Chronic idiopathic myelofibrosis with extramedullary hematapoeisis (hard to distinguish from secondary myelofibrosis and proof that this is a clonal (aka neoplastic) entity in veterinary species is lacking |
|
|
Term
| Where do acute and chronic leukemia of granular lymphocytes originate? |
|
Definition
|
|
Term
| Describe the cytomorphology, immunophenotype, tissue distribution, and accompanying clfinicopathologic abnormalities associated with hemophagocytic histolytic sarcoma |
|
Definition
Relatively bland appearing macrophages, although may have some more atypia
CD11d
present reliably in the spleen and bone marrow, other tissues may also be involved (e.g. liver, lung)
often associated with regenerative anemia, thrombocytopenia, hypocholesterolemia and hypoalbuminemia |
|
|
Term
| Describe the cytomorphology, immunophenotype, tissue distribution associated with interstitial dendritic cell histolytic sarcoma |
|
Definition
Markedly pleomorphic
CD1c, CD11c
Wide tissue distribution (BM, spleen, lung, liver, LN)
phagocytosis may be observed |
|
|
Term
| What leukocytes (dog and cat) have peroxidase activity? |
|
Definition
| neutrophils, eosinophils (only dogs). +/- monocytes (both) |
|
|
Term
| What leukocytes (dog and cat) have sudan black B activity? |
|
Definition
| neutrophils, eosinophils (dog only), +/- monocytes (both) |
|
|
Term
| What leukocytes (dog and cat) have chloracetate esterase activity? |
|
Definition
| neutrophils, basophils +/- megakaryocytes |
|
|
Term
| What leukocytes (dog and cat) have leukocyte alkaline phosphatase activity? |
|
Definition
| immature neutrophils, +/- eosinophils +/- basophils |
|
|
Term
| What leukocytes (dog and cat) have alpha-napthyl butyl esterase activity? |
|
Definition
| monocytes +/- lymphocytes, +/- megakaryocytes |
|
|
Term
| What cytochemical stain can be performed to identify cells of monocyte lineage? |
|
Definition
| NBE (alpha-napthyl butyrate esterase) |
|
|
Term
| What cytochemical stains can be used to identify canine eosinophils? |
|
Definition
| peroxidase and sudan black b |
|
|
Term
| What cytochemical stains can be used to identify basophils? |
|
Definition
| CAE (chloracetate esterase) +/- leukocyte alkaline phosphatase |
|
|
Term
| Other than MHC class II restricted helper T lymphocytes, what other hemic cell reliably expresses CD4? |
|
Definition
neutrophils
Monocytes, macrophages, and dendritic cells can also express CD4 if they are activated (facilitates antigen presentation) |
|
|
Term
| What CD molecule is specific to macrophages (and T lymphs) in splenic red pulp and bone marrow? |
|
Definition
CD11d
*good for hemophagocytic histolytic sarcoma* |
|
|
Term
| What CD molecule is deficient in irish setters with leukocyte adhesion deficiency? |
|
Definition
| CD18 (a beta-2 integrin subunit) |
|
|
Term
| What immunophenotyping targets can be used to detect megakaryocyte lineage? |
|
Definition
CD41 (alpha-2 integrin of the fibrinogen receptor aka GPIIb)
CD61 (beta-3 integrin of the fibrinogen receptor aka GPIIIa)
vWF |
|
|
Term
| What CD molecule is useful as a marked of non-lymphoid leukemias? |
|
Definition
| CD11b (granulocytes, monocytes, some macrophages) |
|
|
Term
| What phenotype are most canine CLL? |
|
Definition
T lymphocytes
-often granular, usually alpha-beta TCR (even if non-granular) |
|
|
Term
| What phenotype is most common for ALL in dogs (non-granular)? |
|
Definition
|
|
Term
| What pattern of CD molecules supports NK origin? |
|
Definition
CD3-, CD11d+, CD8alpha+
(vs. granular lymphs which are CD3+, CD8alphabeta+, and CD11d+) |
|
|
Term
| What region of immunoglobulin (B lymphs) and TCR (T lymphs) genes encode the antigen binding regions? |
|
Definition
|
|
