Hematopoietic Neoplasia Ch 3 D&P

Question 1

common lab findings in equine lymphoma?

Answer 1

Systemic inflammation with hyperfibrinogenemia, hypoalbuminemia, hyperglobulinemia, and ventral edema, with multicentric lymphoma.
IHMA with positive Coombs test / direct antiglobulin
Gammopathy is frequent in multicentric lymphoma.

Question 2

What is the role of BLV in bovine lymphoma and lymphocytosis?

Answer 2

most lymphoma or lymphoid leukemia in cattle is due to this.
It results in persistent lymphocytosis of mature, non neoplastic B cells in approx 30% of cattle; BUT fewer than 5% of cows with persistent lymphocytosis develop lymphoma. (so just cause you have lymphocytosis doesn’t mean you have lymphoma).
Persistent lymphocytosis precedes the development of lymphoma by several years in the majority of BLV infected cattle.

Question 3

What is the most common anatomic presentation of lymphoma in cattle?

Answer 3

Multiventric (enzootic) lymphoma, older cattle. ie enlargement of superficial or abdominal LNs progressing to heart, GI tract, uterus, kidney, and other organs (HARVESKUL)

Question 4

What is the phenotype in bovine lymphoma and what markers do the cells express?

Answer 4

Mature B cells expressing MHC II, CD5, surface IgM.

Question 5

Does non BLV associated lymphoma occur in cattle, what are the forms if so?

Answer 5

Yes, but sporadic,
Multicentric lymphoma in calves;
Sporadic mediastinal lymphoma in yearlings
Sporadic cutaneous lymphoma in young cattle

Question 6

Any lab findings in bovine lymphoma?

Answer 6

WBC count highly variable, leukemic blood profile may occur and morphologically abnormal lymphocytes may be seen whether persistent lymphocytosis present or not.
Anemia in cattle uncommon cause of the long WBC lifespan.

Question 7

What are the basic characteristics of Acute lymphocytic leukemia? (ie Age, where it arrises from, clinical course, commonality)

Answer 7

Arises from undiff’d lymphocytes in the marrow
Uncommon compared to lymphoma
May occur at any age and has a very short clinical course.
Now uncommon in cats d/t vaccination

Question 8

What are the laboratory characteristics of ALL (cytology and hemogram)?

Answer 8

Cyto: Lymphocytes are medium to large with round to slightly indented nucleus, dispersed chromatin, one to multiple nucleoli and a thin rim of dark blue cytoplasm (aka blast cells).
Hemogram variable but severe cytopenia is typical - its due to myelophthisis and may be severe and progressive.
Neoplastic lymphocytes may only be in bone marrow or may be circulating in variable numbers.

Question 9

What is the cell phenotype in ALL and what are the cell markers expressed?

Answer 9

Most cases are of B cell origin and CD34 is expressed by undiff’d lymphoid and myeloid precursor celsl. CD34 confirms ALL but DOES NOT ID the lineage of the neoplastic cells (B, T and NK cell have all been reported).
PARR for clonality would probably be better than blood smear examination.

Question 10

What are the ddx for ALL?

Answer 10

Other acute leukemias like acute myelocytic or monocytic leukemia; if they are B cell most would express CD79a or CD21, or CD3 of T cell.
Advanced, ie Leukemic lymphoma and diff’d by solid tissue mass which would be present in lymphoma before leukemic stage and in leukemia it would be in the blood before it infiltrates organs.
ALL and stage V lymphoma may be hard to diff at the end but ALL is not associated with the formation of solid tissue masses.

Question 11

What are the basic characteristics of CLL (ie the cells, animal age, organ involvement)?

Answer 11

Relatively diff’d lymphocytes that home to secondary lymphoid organs such as the spleen.
Older animals usually dogs.
May last months to years, ie protracted.
Splenomegaly pronounced at time of dx but marrow involved only gradually (contrast with ALL).
Develoment of lymphadenopathy may mimic small cell lymphoma.

Question 12

What are the lab and cyto features of CLL?

Answer 12

Resemble benign small lymphocytes and counts range from 10,000 - 100,000.
Fine pink - purple cytoplasmic granules, corresponding to T cell origin (DON”T confuse them wtih large granular lymphocytes, which would have large granules and would be associated with a bad lymphoma with larger uglier cells, like the one that cats get in the GI tract, ie BLUF if you see small granules in lymphocytes that in are increased in the blood its probably CLL, big granules in bigger more pleomorphic cells its bad lymphoma.)
Anemia is usually mild. Bone marrow involevement may occur late, in contrast to ALL where its early, and you may then get myelophthisis. May also have thrombocytopenia and neutropenia (which may cause complications whereas in ALL they just die fast).

Question 13

What is the most common phenotype of CLL?

Answer 13

Most are T cell origin, CD8+ but B cell CLL has been reported with monoclonal gammopathy.

Question 14

DDx for CLL?

Answer 14

Physiologic lymphocytosis of excited cats.
Dogs with Addisons disease infrequently have lymphocytosis.
Infectious dz like RMSF, anaplasmosis, ehrlichiosis, some lymphs would appear reactive.

Question 15

What are the basic characteristics of large granular lymphocyte lymphoma / leukemia (ie where the arrise, phenotype, spp affected, prognosis)?

Answer 15

LGLs arise from bone marrow and home to epithelial sites, primarily in the intestine. LGL lymphoma arrises in the SI and involves abdominal LNs and liver.
Most are T cells, express receptor CD3 and CD8, some maybe NK cells.
Uncommon but a distinct entity and reported in cats esp, horses, dogs in older animals.
Presenting signs usually anorexia and vomiting with increased proportion of LGL cells on blood smears.
High grade malignancy with rapid course.

Question 16

Cyto and lab findings with large granular lymphocyte lymphoma / leukemia?

Answer 16

Variable in size and cells ahve chinky ping to magenta cytoplasmic granules and variable to pleomorphic nuclei that may resemble myeloid cells, look for lymphoglandular bodies in the smear too.
Absolute lymphocyte counts very high.
Mild anemia and neutropenia.

Question 17

Ddx for large granular lymphocytic leukemia / lymphoma?

Answer 17

T cell origin CLL in the dog (but these are small lymphocytes and originate in the spleen red pulp and NOT associated with intestinal tumors)
Dogs with anaplasmosis may have reactive lymphocytosis and cells have small cytoplasmic granules.

Question 18

Where are solitary plasma cell tumors in cats usually seen, whats the behavior?

Answer 18

Bone or skin and may be locally invasive.

Question 19

Where do plasma cell myelomas / multiple myeloma come from and what do they produce? What is the hallmark of multiple myeloma?

Answer 19

Clonal neoplasm of plasma cells that comes fromt eh marrow and is associated with monoclonal gammopathy and possibly osteolysis in dogs at least.
Can produce IgG, A or M. (production of IgM may cause hyperviscosity).
Note synthesis of normal Ig may be suppressed so they may be predisposed to infection.
Hallmark = Hyperproteinemia with hyperglobulinemia and monoclonal gammopathy.

Question 20

Ddx for monoclonal gammopathy?

Answer 20

Multiple myeloma, FIP in cats (apparently, I didn’t know this), Anaplasmosis/Ehrlichiosis

Question 21

Diagnostic criteria for Mulitple myeloma?

Answer 21

Two of the Four:
Rad evidence of osteolysis
Large clusters of plasma cells in the marrow
Monoclonal gammopathy (beta or gamma region)
Bence Jones proteinuria (free Ig light chains detected by electrophoresis)

Question 22

What exactly is Bence Jones proteins?

Answer 22

THIS IS SOMETHING THAT OCCURS SEPERATE FROM THE GAMMOPATHY IN THIS CONDITION.
Free Ig light chains smaller than albumin and freely pass glomerulus. Greater concentration in urine than serum and “light chain dz” does not result in monoclonal gammopathy on serum protein electrophoresis.
NOTE intact Ig molecules don’t pass the glomerular filter unless glomerular damage is present.
Light chains DO NOT react with protien indicator pad on urine dipsticks so you must use another method to detect (like electrophoresis on the urine).

Question 23

What are the marrow cytology and hematology characteristics of multiple myeloma?

Answer 23

Neoplastic plasma cells indistinguisable from benign plasma cells.
Greater than 15-20% plasma cells in the bone marrow is highly suggestive of myeloma.
Plasma cell leukemia is rare.
Anemia common due to myelophthisis or shortened lifespan due to coating by paraprotein followed by phagocytosis.
Paraprotein may also complex with platelets and clotting factors and mess up fxn so may see bleeding.

Question 24

Other lab findings in multiple myeloma on chemistry?

Answer 24

Hypercalcemia due to osteoclast activating factors and resorption of bone. > may cause nephrcalcinosis due to chronic hypercalcemia and/or renal toxicity of light chains.
Compensatory hypoalbuminemia (d/t increased globulins to offset oncotic pressure)

Question 25

What does "myeloproliferative disorder" refer to?

Answer 25

General term for all leukemias that originate in the bone marrow and involve cells other than lymphocytes.

Question 26

What are the general characteristics of myeloproliferative disorders (in terms of types, blood profilea and tissues involved)?

Answer 26

Leukemic blood profile Classification into acute or chronic leukemia based on percentage of undiff'd blast cells in blood or marrow. Same as with lymphoid leukemia, acute is bad and chronic is slow. Infiltrative dz involves splenic red pulp, sinusoidal and subcapsular areas of LNs, sinusoidal and portal regions of liver and vascular areas of other organs. Leukemic cells generally don't form discrete masses. (except for chloromas in granulocytic leukemia) In acute leukemia hematopoietic marrow is replaced by neoplastic cells. Chronic leukemia > marrow hypercellularity, gradual hepatosplenomealy, mild lymphadenopathy. Myeloprolif dzs are much less common than lymphoproliferative dzs.

Question 27

What are the criteria for making a diganosis of acute myeloid leukemia?

Answer 27

When more than 30% of the nucleated cells in the marrow are blast cells and the total nonerythroid cells comprise more than 50% of the nucleated cell population.

Question 28

What is acute undifferentiated leukemia (AUL)?

Answer 28

A type of acute myeloid leukemia where there are large numbers of blast cells whose lineage cannot be determined. They label with CD34 which IDs undiff'd lymphocytic and myelocytic precursor cells in the marrow.

Question 29

What is acute myeloblastic (granulocytic / neutrophilic) leukemia?

Answer 29

Another type of acute myeloid leukemia where there are two subtypes, myeloblastic leukemia with and without maturation; without maturation includes more than 90% of the nonerythroid cells in the marrow are myeloblasts; in the maturation form, 30-90% of the nonerythroid cells are myeloblasts and basophilic and eosinophilic diff'n may be seen.

Question 30

What are the lab features of acute myeloblastic leukemia?

Answer 30

Neutrophilic blasts are myeloperoxidase positive Alk phos staining may show up in immature orneoplastic neutrophils Leukemic cells express CD34 and the panleukocyte marker CD45a nd possibly neutrophil specific antigen. Leukocyte counts vary and a marrow aspirate is necessary for dx of AML where there is neutropenia and few neoplastic cells in the blood; the marrow should have more than 30% blasts. Nonregen anemia and thrombocytopenia result from myelophthysis.

Question 31

What is myelomonocytic leukemia?

Answer 31

Both neutrophilic and monocytic cell lines affected; IHC with CD14 or MAC 387 IDs monoblastic or monocytic origin.

Question 32

What is monocytic leukemia?

Answer 32

Monocytic lineage, ID'd by CD14 or calprotectin. Marked monocytosis in the blood.

Question 33

What is Erythroleukemia? What sp are affected, how do you ID erythroid precursors? What are the lab features?

Answer 33

Co production of erythroblasts or myeloblasts, ie it has a dual cell lineage., basically its a mix of erythorid precursors and myeloblasts. Its in cats and poultry, esp cats with FeLV. You see dark blue cytoplasmic stanining in erythroid precursors (there are no markers). You see severe anemia, marked metarubricytosis with variable red cell precursors in the blood and no polychoromasia or retics. Severe non regen anemia and leukemia. Acute and chronic forms.

Question 34

What is megakaryocyte leukemia? What are the markers and features?

Answer 34

ie megakaryocytic myelosis More than 30% of nucleated bone marrow cells are megakaryoblasts. Immunoreactivity for VWf or glycoprotein IIb-IIIa may be used for cell ID. Concurrent expression of CD34 IDs cells as megakaryoblasts. Myelofibrosis and inability to aspirate marrow is a feature.

Question 35

What is myelodysplastic syndrome? (hows it defined) | Which spp is affected?

Answer 35

Preleukemic syndrome that evolves into acute leukemia. It means the presence of fewer than 30% blast cells in the marrow, dyserythropoiesis (abnormal RBC morphology) and cytopenia affecting more than one cell line. Mostly in cats (like cats with FeLV) and less in dogs and horses.

Question 36

What are the lab features of myelodysplastic syndrome?

Answer 36

Cytopenia affecting more than one cell line > non regne anemia, neutropenia, thrombocytopenia. Hematologic changes in MDS may include macrocytosis without polychromasia, metarubricytosis, abnormal giant neuts, odd eosinophils, giant platelets etc. Hypercellular bone marrow samples along with a bunch of other matureation abnormalities and giant cells etc. May progress to AML.

Question 37

Myeloproliferative neoplasms category encompasses what group of neoplasms? What is a Blast Crisis?

Answer 37

The chronic myeloid neoplasms, ie all the none AML tumors. ie clonal prolifs of mature and less mature granulocytes, erythrocytes and platelets with gradual (ie chronic) disease progression. Features include marrow hypercellularity, splenomegaly, leukocytosis, erythroytosis or thrombocytosis. Dz of older animals. Txformation into acute myeloid leukemia may occur with a change to mostly undifferentiated cells (ie BLAST CRISIS)

Question 38

What are the subgroups of myeloproliferative neoplasms?

Answer 38

``` Chronic granulocytic leukemia. Chronic eosinophilic leukemia. Chronic basophilic leukemia. Polycythemia vera. Essential thrombocythemia. Chronic myelomonocytic leukemia. Chronic monocytic leukemia. ```

Question 39

What is chronic granulocytic leukemia and what other condition must you diff it from?

Answer 39

Prolif of relatively mature neuts - which distinguishes CGL from AML in marrow aspirates, remember AML has mostly myeloblasts. Moderate to severe neutrophilia with disorderly left shift. CGL must be diff'd from leukemoid inflammatory responses where you see marked neutrophilia with a left shift and a dx of CGL is made by excluding the possibility of inflammation and infection and observing neutrophil morphology. Also there are some paraneoplastic conditions that produce G-CSF like renal carcinoma, fibrosarcoma etc that stimulate neutrophil production resulting in high counts.

Question 40

What is chronic eosinophilic leukemia, what must it be diff'd from and who is it seen in ?

Answer 40

Marked eosinophilia in blood and marrow accompanied by variable eosinophil maturation. Rare but seeen in the cat. Must be diff'd from hypereosinophilic syndrome in cats and rottweiler dogs where mild to moderate blood eosinophilia is accompanied by non specific tissue infiltration by eosinophils.

Question 41

What is chronic basophilic leukemia and what must it be diff'd frranulation.om?

Answer 41

Basophils predominate in blood and marrow? Rare but described in dog and cat. Diff basophilis from Mast cells by the presence of segmented nuclei and less intense granulation. Mast cell granules are more fine and numerous.

Question 42

What is polycythemia vera?

Answer 42

Primary erythrocytosis, ie proliferation of mature RBCs independent of EPO stimulation. (make sure the animal deosn't have a renal carcinoma > EPO prduction). With polycyth vera EPO concentrations should be low.

Question 43

What is essential thrombocythemia?

Answer 43

Rare form of leukemia, may have abnormal giant platelets and intense granulation with numerous megakaryocytes in the marrow.

Question 44

What is chronic myelomonocytic leukemia?

Answer 44

Excess production of neutrophils and monocytes that appear well diff'd or mature. Hepatosplenomegaly is common.

Question 45

What is Chronic monocytic leukemia?

Answer 45

Excess production of monocytes. May see extreme leukocytosis with very high monocyte counts. and they appear well diff'd. Hepatosplenomegaly common.

Question 46

What characterizes mast cell leukemia?r

Answer 46

Circulating mast cells that either appear morphologically normal or have variable ganulation and cell size. May occur as primary hematopoietic neoplasm that arrises int he absence of cutaneous neoplasms in dogs or GI neoplasms in cats. Its rare and must be diff'd solid MCTs with leukemic blood profile and from benigh mastocytemia that can be seen with a number of conditions.

Question 47

What is often seen with splenic mast cell tumors in cats?

Answer 47

Systemic mastocytosis with leukemic blood profile.

Question 48

What is the cell of origin for hemophagocytic histiocytic sarcoma, what does the neoplasm characteristically express, and what are the lab features?

Answer 48

Hits of bone marrow macrophage origin, expresses CD11d (NOT CD1 and NOT CD11c; Note: Histiocytic sarcoma from dendritic cells expresses CD1a, MHCII and CD11c). Lab findings include: Anemia, thrombocytopenia, hypoalbminemia and hypocholesterolemia.