Diseases of the Bone Marrow 2

Question 1

estrogen is a major cause of what in dogs?

Answer 1

aplastic anemia

Question 2

what are non-neoplastic causes of lymphocytosis?

Answer 2

• excitement: epinephrine
• ehrlichia canis
• addison’s
• chronic inflammation
• paraneoplastic lymphocytosis
• hyperthyroidism
• age/antigenic stimulation (Cats)

Question 2

what is the cause of persistent lymphocytosis in cattle?

Answer 2

bovine leukosis virus
only small % develop neoplasia

Question 3

how does the WHO classify hematopoietic neoplasia?

Answer 3

• degree of differentiation: acute vs chronic
• cell lineage: B vs T, marrow vs periphery
• genetic abnormalities
• lymphoma vs leukemia based on tissue with the largest tumor burden

Question 3

what is the difference between lymphoma and leukemia?

Answer 3

lymphoma is identified in the lymph nodes
leukemia is identified in the bone marrow

Question 4

what is the antigenic to bone marrow stem cells?

Answer 4

CD34

Question 5

what is myeloproliferative disease?

Answer 5

neoplastic disease originating in the BONE MARROW, unregulated growth of hematopoietic stem cells

Question 6

what is lymphoproliferative disease?

Answer 6

neoplastic disease of LYMPHOCYTES (plasma cells)
includes both lymphoma and leukemia

Question 7

what is a myelodysplastic syndrome?

Answer 7

diverse group of hematologic disorders characterized by INEFFECTIVE/DYSPLASTIC PRODUCTION OF HEMATOPOIETIC CELLS

Question 8

what causes myelodysplastic syndrome?

Answer 8

• Clonal myeloid proliferation with ineffective hematopoiesis in the bone marrow > cytopenia of one or more cell lines.
• dysplasia of myeloid (bone marrow) cells
• less than 20% blasts in the bone marrow

Question 9

what infectious disease is myelodysplastic syndrome commonly associated with?

Answer 9

feline leukemia virus

Question 10

in acute myeloid leukemia, are blast % high or low?

Answer 10

they are very high, whereas normally blast % is low

Question 11

what are the types of acute leukemias?

Answer 11

ALL: acute lymphoid leukemia
AML: acute myeloid leukemia
AUL: acute undifferentiated leukemia

Question 12

what are the features of acute leukemias?

Answer 12

• poorly differentiated
• expression of CD34 antigen by flow cytometry
• aggressive clinical course: median survival time of 9-56 days with treatment
• > 20% blast cells in the barrow or BLOOD
• pancytopenia: anemia, neutropenia, thrombocytopenia
• median age 7-8 but wide range in dogs

Question 13

what antigen is expressed in flow cytometry when evaluating acute leukemia?

Answer 13

CD34

Question 14

what is pancytopenia?

Answer 14

anemia, neutropenia, thrombocytopenia

Question 15

CD34 is expressed in what cells?

Answer 15

hematopoietic stem cells that can become myeloid or lymphoid cells

Question 16

a 2 year-old german shepherd presents with decreased appetite, submandibular lymph node prominence. CBC shows a moderate anemia, thrombocytopenia, and neutropenia, as well as abnormal circulating lymphocytes. you perform flow cytometry on peripheral blood and almost all the cells are large with high complexity, and are expressing CD34. what is your diagnosis?

Answer 16

acute leukemia

Question 17

what is the normal canine lymphocyte range?

Answer 17

1-5,000 lymphs/uL

Question 18

what antigenic marker would B cells express on flow cytometry?

Answer 18

CD21

Question 19

prognostic factors in dogs with B cell chronic lymphocytic leukemia

Answer 19

• Overall median survival time was 300 days (1-1644 days)
• Boxers have a significant shorter survival time (MST 178 days)
• Non-boxers MST = 423 days
• High lymphocyte count >60,000 lymph/uL associated with significantly shorter survival
• Higher Ki-67 (protein marker) associated with a worse survival

Question 20

what breed has a lower survival time with B cell chronic lymphocytic leukemia?

Answer 20

boxers: MST 178
non-boxers: MST 423 days
High lymphocyte count >60,000 lymph/uL associated with significantly shorter survival

Question 21

what clinical finding is diagnostic for chronic lymphocytic leukemia in dogs? (CLL)

Answer 21

5,000 neoplastic cells/uL for diagnosis

Question 22

what are the most common phenotypes of chronic lymphocytic leukemia in dogs?

Answer 22

CD8 lymphocytosis (T cell)
CD21 lymphocytosis (CLL/SLL)- B cell chronic lymphocytic leukemia/small cell lymphocytic lymphoma

Question 23

what clinical findings are seen with CLL in dogs?

Answer 23

- 5,000 neoplastic cells/uL for diagnosis - often incidental lymphocytosis - anemia not uncommon - other cytopenias not usually present, may be well-differentiated cells - flow cytometry can be used to differentiate homogenous from heterogenous lymphoid expansion

Question 24

what is the most common CLL phenotype in cats?

Answer 24

CD4 (T cell) lymphocytosis

Question 25

what are necropsy findings in chronic leukemia? (CLL)

Answer 25

* Splenomegaly (50%) * Anemia (26%) * Lymphadenopathy (50%) * Highly cellular bone marrow

Question 26

what are necropsy findings in acute leukemia?

Answer 26

* Pale mucous membranes * Bone marrow highly cellular but pancytopenia * Splenomegaly * Lymph node involvement * Can infiltrate many organs

Question 27

why is flow cytometry useful for lymphocytosis?

Answer 27

- large # of antigens can be evaluated - distinguishes HOMOGENOUS from HETEROGENOUS expansions when cytology IDs mature cells - identifies aberrant antigen expression (CD34 expression in acute leukemia) - objective measure of size - provides prognostic information

Question 28

T/F: flow cytometry is useful for prognostic information

Answer 28

true

Question 29

what lymphocyte count is associated with significantly shorter survival in dogs with B cell chronic lymphocytic leukemia?

Answer 29

lymphocyte count >60,000 lymph/uL

Question 30

You identify an incidental lymphocytosis in an older dog presenting for a senior wellness exam. The dog has no clinical findings and you are suspecting chronic lymphocytic leukemia. What is a negative prognostic indicator in B cell chronic lymphocytic leukemia?

Answer 30

negative prognostic indicator = associated with more aggressive disease - high lymphocyte count - high Ki-67 - boxer

Question 31

what is multiple myeloma?

Answer 31

tumor of plasma cells arising from the bone marrow

Question 32

what clinical findings are seen with multiple myeloma?

Answer 32

- increased plasma cells in the bone marrow (>20-30%, normally only 10%) - monoclonal gammopathy - osteolysis - light chain proteinuria - hyperglobulinemia: bc plasma cells producing ab - hypercalcemia: from osteolysis - pancytopenia: other cells can't proliferate

Question 33

in serum protein electrophoresis, what is typically the most present protein? what about in multiple myeloma?

Answer 33

normally albumin is most present in multiple myeloma, have high production of immunoglobulin

Question 34

what disease causes anemia in horses?

Answer 34

equine infectious anemia: lentivirus

Question 35

prognosis of EIA

Answer 35

- acute, subacute and chronic forms and can be fatal - disease often subsides within a year, horses are lifelong carriers -

Question 36

what causes EIA?

Answer 36

lentivirus- anemia caused by immune-mediated hemolysis and decreased erythropoiesis (icterus + variable bone marrow response) - bone marrow erythropoiesis or erythroid production depending on stage of disease, hemosiderin laden macrophages, plasma cell hyperplasia

Question 37

what are clinical signs of EIA?

Answer 37

fever, depression, LN enlargement, splenic congestion, icterus, hemolytic crisis: pale with mucosal hemorrhages and dependent edema

Question 38

how is EIA transmitted?

Answer 38

biting flies

Question 39

how is EIA diagnosed?

Answer 39

coggins test

Question 40

with a horse with EIA, why might you see a variable bone marrow response?

Answer 40

there is both immune disease and decreased erythropoiesis, can see regeneration or non-regeneration - anemia caused by immune-mediated hemolysis and decreased erythropoiesis

Question 41

what leads to the EIA symptoms?

Answer 41

macrophage infection of the virus leads to production of pro-inflammatory modulators - fever - thrombocytopenia: bound IgG or IgM > immune mediated destruction of RBCs and thrombocytes - inhibition of erythropoiesis = anemia

Question 42

what disease causes thrombocytopenic hemorrhagic syndrome in cattle?

Answer 42

Bovine viral diarrhea virus: BVDV - type 2 infected animals - impaired thrombopoiesis and compensatory thrombopoiesis - severely thrombocytopenic and neutropenic with multisystemic hemorrhage: GI, spleen, gallbladder, urinary bladder, LNs

Question 43

what disease causes atrophy and necrosis of bone lining and bone marrow cells in dogs?

Answer 43

canine distemper virus - atrophy and necrosis of bone lining and bone marrow cells - may infect erythrocytes, leukocytes, platelets - decreased peripheral neutrophils, lymphocytes, mono, platelets during viremia - thrombocytopenia resulting from membrane immune complex formation

Question 44

what disease disrupts normal hematopoiesis by inducing genetic mutations, infecting hematopoietic cells in cats?

Answer 44

feline leukemia virus - dysmyelopoiesis (dysfunction of production of bone marrow cells) with cytopenias and neoplastic transformation > myelodysplastic syndrome