Term
| What percentage cellularity is considered hypercellular in an adult animal? |
|
Definition
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|
Term
| What percentage cellularity is considered hyporcellular in an adult animal? |
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Definition
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Term
| What is the proposed mechanism of aplastic pancytopenia in dogs? |
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Definition
| T lymphocyte mediated immune reaction against hematopoietic stem cells. Cytokines may also induce apoptosis of hematopoietic stem cells. |
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Term
| What drugs have been associated with generalized bone marrow hypoplasia in dogs and cats? |
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Definition
| estrogen, phenylbutazone (also a horse), TMS, albendazole/fenbendazole, grisofulvin, azathioprine, chemotherapy, radiation |
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Term
| What toxins have been associated with generalized bone marrow hypoplasia in cattle? |
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Definition
bracken fern
trichloroethylene-extracted soybean meal |
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Term
| What infectious agents in dogs have been associated with generalized marrow hypoplasia? |
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Definition
| canine parvovirus, chronic ehrlichia canis infection |
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Term
| What drugs may incite aplastic pancytopenia in offspring of mares or cows treated while pregnant? |
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Definition
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Term
| What special stain can help to positively identify gelatinous transformation of the bone marrow? |
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Definition
| Alcian blue, the material is composed of mucopolysaccharides, predominantly hyaluronic acid |
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Term
| Which cytokine is most specifically implicated in cases of myelofibrosis following marrow injury (e.g. inflammation, necrosis, neoplasia, vascular lesion)? |
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Definition
| TGF-beta (which is produced by a number of cells including megakaryocytes and platelets) |
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Term
| In which species has congenital myelofibrosis been reported? |
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Definition
goats
*concurrent megakaryocyte hyperplasia and dysplasia |
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Term
| Which hematopoietic cell line is often increased or normal in animals with myelofibrosis? |
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Definition
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Term
| What concurrent disease is most often observed in animals with pancytopenia and myelofibrosis? |
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Definition
| Concurrent myeloid neoplasia |
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Term
| What is the difference between osteosclerosis and hyperostosis? |
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Definition
Osteosclerosis = widening of trabecular bone
hyperostosis = widening of cortical bone
*both arise from appositional growth of osseous tissue at endosteal and/or periosteal surfaces. IF extensive can lead to osteopetrosis --> medullary space filling with bone and displacing hematopoietic tissue |
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Term
| What peripheral hematologic manifestation is most often observed associated with osteopetrosis? |
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Definition
mild to severe nonregenerative anemia
**confirmation of osteopetrosis typically is done with diagnostic imaging as changes in the thickness of bone in core biopsy samples may reflect sample technique rather than disease |
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Term
| What virus is associated with osteoporosis in calves? |
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Definition
BVD virus
**can also be inherited in angus calves, but typically are aborted late in gestation |
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Term
| What inherited disorder in dogs has been associated with osteosclerosis (thickening of trabecular bone) and myelofibrosis? |
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Definition
pyruvate kinase deficiency
*the anemia is regenerative (b/c PK deficiency --> decreased RBC ATP production --> decreased RBC lifespan) but as sclerosis and fibrosis develops the regenerative response is progressively blunted |
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Term
| What are some features on bone marrow evaluation consistent with appropriate regnerative response to blood loss or hemolysis in a horse? |
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Definition
decreased G:E ratio (<0.5) with a normal to hypercellular marrow
bone marrow reticulocyte counts >5% |
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Term
| What vaccine has rarely been associated with erythroid hypoplasia in dogs? |
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Definition
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Term
| What pattern of hematologic abnormalities is observed in EARLY estrogen toxicity? |
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Definition
Erythroid and megakaryocytic APLASIA
neutrophil HYPERPLASIA |
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Term
| Describe the mechanism of selective erythroid hypoplasia/aplasia in cats with FeLV subtype C infection? |
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Definition
| The cell surface receptor for FeLV-C is FLVCR, which is also a heme exporter. When FeLV-C binds to this receptor on rubriblasts it inhibits heme export --> cell death |
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Term
| What drugs are associated with dysplastic features (esp. nuclear lobulation/pyknosis/fragmentation) in the erythroid lineage? |
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Definition
drugs that interfere with DNA synthesis (e.g. azathioprine, hydroxyurea, cytosine arabinoside)
alkylating agents (cyclophosphamide)
folate anatagonists (methotrexate)
plant alkaloids (vincristine) |
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Term
| What is a nuclear feature of megaloblastic erythroid cells? |
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Definition
chromatin is in finer strands with abundant parachromatin resulting in a pronounced patchy chromatin pattern.
**They are also larger than normal with abundant cytoplasm and nuclear cytoplasmic asynchrony |
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Term
| How long does it take after a stimulus until neutrophil hyperplasia is prominent enough in the bone marrow to increased the G:E ratio? |
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Definition
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Term
| What other cell lines may be increased in the bone marrow of dogs with essential thrombocythemia? |
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Definition
| eosinophils and basophils |
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Term
| Which drugs may be associated with selective neutrophilic hypoplasia in cats? |
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Definition
azathioprine (can also cause selective erythroid hypoplasia, dyserythropoisis or generalized hypoplasia)
doxorubicin, griseofulvin (esp. if concurrent FIV infection), methimazole, lithium carbonate |
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Term
| What conditions are associated with cyclic hematopoiesis in dogs? in cats? |
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Definition
Inherited cyclic hematapoiesis in dogs (gray collies)- when early peripheral neutropenia bone marrow neutrophil hypoplasia with few myeloblasts and prograns -> over the next few days maturative stages increase until the G:E ratio is high and peripheral neutrophils are WRI or increased. Also there is concurrent erythroid hyperplasia when there is granulocytic hypoplasia
FeLV in cats |
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Term
| What conditions are most commonly associated with dysgranulopoeisis? |
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Definition
| AML and MDS (often associated with FeLV +/-FIV in cats) |
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Term
| Maturation arrest in both the erythroid and granulocytic lines have been reported in dogs treated with which antibiotic? |
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Definition
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Term
| In which species has congenital megakaryocyte hypoplasia/aplasia been reported? |
|
Definition
horses
*also concurrent severe neutrophilic hypoplasia/aplasia |
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Term
| What forms of AML are associated with bone marrow monocytoid hyperplasia? |
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Definition
AML-M4 (acute myelomonocytic)- increased myeloblasts and monoblasts
AML-M5 (acute monocytic)- only increased monoblasts |
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Term
| What criteria must be met to diagnose an animal with hemophagocytic syndrome? |
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Definition
pan or bicytopenia
increased benign appearing macs in the bone marrow (at least 2% of all nucleated cells)
Presence of phagocytize immature RBC and/or leukocytes
*hemophagocytic syndrome may be secondary to immune mediated disease, infectious agents and hematapoietic neoplasia. |
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Term
| What stain can be used to distinguish fibrin from edema and/or necrotic debris in bone marrow core biopsies? |
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Definition
| Frazier-Lundrum can be used to identify fibrin |
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Term
| What disorders have been associated with fibrinous inflammation in the bone marrow (appreciated on core bx)? |
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Definition
DIC and systemic vasculitis
**Frazier-Lundrum stain can help distinguish fibrin from edema and/or necrosis on core biopsies |
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Term
| What infectious agents have been associated with increased lymphocytes and plasma cells in the bone marrow (dogs and cats)? |
|
Definition
dogs- E. canis, leishmania
cats- FIP
**increased lymphs and plasma cells can also be seen in immune mediated disorders (primary and secondary) |
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Term
| What are the two main differentials for granulomatous inflammation in the bone marrow? |
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Definition
fungal sepsis
mycobacterium sp. |
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Term
| What antibodys can be used to identify megakaryoblasts via ICC? |
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Definition
CD41 (GpIIb)/CD61 (GpIIIa) [PLT to fibrinogen]
vWF
CD62P (P selectin)
+/-CD34 |
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Term
| What is the most common phenotype of ALL in cats? |
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Definition
| T lymphocytes, usually associated with concurrent FeLV (or less likely FIV) infection |
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Term
| What is the most common phenotype of CLL in dogs and cats? |
|
Definition
T lymphocyte
**in dog's they're typically granular, CD8+ T lymphs, cats are more often CD4+ T lymphs |
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Term
| What antibody is most often implicated in monoclonal gammopathy secondary to B lymphocyte CLL in dogs? |
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Definition
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Term
| In dogs with lymphoma infiltrating the bone marrow, what region is most likely to have the highest concentration of neoplastic lymphocytes? |
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Definition
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Term
| How is the biologic behavior of plasma cell tumors unique in cats? |
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Definition
Cats are likely to have widely metastatic lesions regardless of whether the plasma cell tumor originates from the bone marrow (multiple myeloma) or other location (cutaneous or non-cutaneous extramedullary plasmacytoma). Also the more atypical the plasma cells appear the more aggressive the biologic behavior (vs. dogs were myeloma (and is typically a more aggressive disease) tends to appear better differentiated than extramedullary plasmacytoma).
Myeloma: Usually have liver and spleen involvement at the time of diagnosis. Lytic bone lesions may be present, but not as common in cats as in dogs.
*cats with plasma cell neoplasia are typically negative for feLV/FIV |
|
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Term
| What antibody isotope is most commonly implicated in paraproteinemia associated with plasma cell neoplasia (in dogs and cats)? |
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Definition
Typically IgG
IgA is also possible. |
|
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Term
| Describe the clinical features of primary (Waldenstrom) macroglobulinemia in dogs? |
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Definition
Macroglobilinemia is essentially and IgM monoclonal gammopathy.
It's associated with a lymphoplasmacytic neoplasm that infiltrates the bone marrow +/- other lymphoid tissues (spleen, LN) and liver. BM aspirates may be hypocellular but cores are hypercellular and diffusely infiltrated by neoplastic lymphocytes, plasma cells and plasmacytoid lymphocytes. |
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Term
| What percentage of bone marrow cells must be dysplastic before the term myelodysplasia is used? What percentage of blasts may be present? |
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Definition
>10% dysplastic cells
<20% blasts |
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|
Term
| In what species has MDS been proven to be a clonal disorder? |
|
Definition
cats
*regardless of the species, transformation of MDS to AML is a risk in all affected individuals |
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Term
| Which cell line is often increased in bone marrow aspirates/cores from cats with MDS? |
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Definition
|
|
Term
| What category of MDS has a G:E <1? |
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Definition
| MDS with erythroid predominance (MDS-Er) |
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Term
| How is MDS with refractory cytopenias (MDS-RC) distinguished from MDS with excess blasts (MDS-EB)? |
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Definition
MDS-RC has < 5% myeloblasts
MDS-EB has 5-19% myeloblasts
*both have G:E >1 (as opposed to MDS-Er) |
|
|
Term
| Which type of acute myeloid leukemia is most often associated with increased numbers of eosinophil and/or basophil precursors in cats? |
|
Definition
AML-M2, Myeloblastic leukemia with maturation
20-80% of non-erythroid cells are myeloblasts, at least 10% of non-erythroid cells are differentiating granulocytes (including eo and baso) |
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Term
| Which type of acute myeloid leukemia has not been reported in animals? |
|
Definition
AML-M3 promyelocytic leukemia
Prograns predominate and have atypical nuclear morphology (e.g. folded, reniform, bilobed) |
|
|
Term
| In which type of acute myeloid leukemia is leukopenia more commonly observed in affected cats? |
|
Definition
AML-M2 myeloblastic with maturation (20-89% of non-erythroid cells are myeloblasts, at least 10% of non-erythroid cells are differentiating granulocytic)
**often increased eo and baso precursors in cats |
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Term
| What are the most common types of acute myeloid leukemia in dogs? What peripheral blood findings are typical? |
|
Definition
AML-M4 (myelomonocytic)
AML-M5 (monocytic)
Typically associated with a prominent monocytosis
**M4 and M5 are also the most common type of AML reported in horses, although rare in general |
|
|
Term
| Is thrombocytosis or thrombocytopenia more common in animals with AML-M7 (megakaryoblastic)? |
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Definition
| thrombocytopenia is more common but thrombocytosis has been reported |
|
|
Term
| What are the most common types of acute myeloid leukemia in cats? |
|
Definition
AML-M1 (myeloblastic)
AML-M2 (myeloblastic with maturation) |
|
|
Term
| What chromosomal abnormality has been reported in dogs with CML? |
|
Definition
| BCR-ABL (Raleigh chromosome) |
|
|
Term
| What are the most frequent sites of primary tumors that metastasize to bone? |
|
Definition
|
|
Term
| What is the morphologic distinction between progranulocytes and type III myeloblasts? |
|
Definition
Progranulocytes don't have a distinct nucleolus but type II myeloblasts do (myeloblasts also tend to have more basophilic cytoplasm)
**both have numerous magenta primary granules |
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Term
|
Definition
| Free cell nucleus from metarubricytes |
|
|
Term
| What percentage of bone marrow reticulocytes is suggestive of regenerative anemia in a horse? |
|
Definition
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|
Term
| Which species may have a higher proportion of eosinophilic cells in their bone marrow in health? |
|
Definition
|
|
Term
| Which species may have a higher proportion of eosinophilic cells in their bone marrow in health? |
|
Definition
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|
Term
| Which species may have a higher proportion of eosinophilic cells in their bone marrow in health? |
|
Definition
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Term
| What non-hemic disorders have been associated with increased small lymphocytes in the bone marrow of cats? |
|
Definition
thymoma
cholangiohepatitis
(cats can have up to 20% small lymphs in bone marrow in health) |
|
|
Term
| What is the effect of age on the amount of stainable iron in the bone marrow? |
|
Definition
Increased iron accumulates with age (especially apparent in horses)
**caveat, cats don't have stainable bone marrow iron in health regardless of the age. The presence of iron in the bone marrow of cats is suggestive of MDS, hemolytic anemia, or post-transfusion |
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|
Term
| How does the presence of collagen (type I, via trichrome) vs. reticulin (via silver stain) relate to prognosis in cases of fibrosis within the bone marrow? |
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Definition
The presence of type I collage is associated with more severe disease and a worse prognosis
The presence of reticulin has no correlation with disease severity and can be observed with a variety of benign and malignant disease processes |
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Term
| Describe the innervation of the bone marrow and potential role of the sympathetic nervous system on the bone marrow? |
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Definition
Most innervation enters associated with arteries, arterioles and capillaries (more fibers associated with larger vessels)
Efferent sympathetic and sensory nerves are also present.
The sympathetic nervous system may contribute to regulation of hematopoiesis, stem cell trafficking and immune function |
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Term
| What are the two stem cell niches that have been described in the bone marrow? How does stem cell activity vary between locations? |
|
Definition
endosteal niche (trabecular bone)- influenced by osteoblast activity, promotes HSC quiescence and transmarrow migration
vascular niche (venous sinus)- promotes HSC expansion and egress into circulation |
|
|
Term
| What role does c-Kit play with regards to hematopoietic stem cells? |
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Definition
| c-Kit (a transmembrane tyrosine kinase receptor) binds stem cell factor/steel factor and is important in maintenance, proliferation, and differentiation of hematopoietic stem cells (so you know...like everything) |
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|
Term
| What transcription factors regulate stem cell pluripotency and undifferentiation? |
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Definition
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