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3. Sys Path > CO4 Hemolymphatic > Flashcards

CO4 Hemolymphatic Flashcards

1
Q

Indications for assessing the bone marrow:

A

unexplained changes in the peripheral blood such as:
* persistent anemia without apparent cause
* pancytopenia
* abnormal cells in circulation (blast cells, mast cells, rubricytes, epithelial cells)
* suspected infection of the bone marrow (histoplasmosis, ehrlichiosis, etc.)
* persistent thrombocytopenia or neutropenia without apparent cause
* assessment for primary neoplasia of the bone marrow (leukemia, lymphoma, multiple
myeloma) or metastatic neoplasia (mast cell tumor, carcinoma)

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2
Q

how do we make a cytological preparation of bone marrow?

A

Cytological preparations of bone marrow are prepared by “drilling” a special needle into the marrow and then vigorously aspirating the marrow into a syringe (marrow looks like “thick” blood) and preparing thin “feather-edge” smears.

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3
Q

how can we biopsy bone marrow?

A

bone marrow can be biopsied by “cutting” a cylinder of bone and marrow cells with a special trephine needle, fixation of the core, and examination of sections that have been stained.

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4
Q

what method of bone marrow sampling is better - cytological or biopsy?

A

Each method yields important information, and ideally both should be combined.

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5
Q

what does the pathologist need to interpret bone marrow findings?

A

In order to interpret bone marrow findings the pathologist always needs to know the peripheral blood picture! So, provide blood for a concurrent CBC or at least the most recent numerical results if you are submitting bone marrow samples.

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6
Q

expected findings in bone marrow and blood for
- regenerative anemia

A

Marrow - Increased numbers of erythroid precursors, decreased myeloid:erythroid (M:E) ratio, normal megakaryocytes.
- Blood – many polychromatophilic erythrocytes

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7
Q

expected findings in bone marrow for

  • hemolytic anemia
  • timeline?
A

Depending on the length of time that hemolysis has occurred, there may be increased red cell activity. To see an increase in the generation of rubricytes in the bone marrow requires at least 3 days of anemia.

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8
Q

expected findings in bone marrow for
- thrombocytopenia

A
  • If there is immune destruction of platelets, usually the number of megakaryocytes are markedly increased in the bone marrow.
    If thrombocytopenia is secondary to leukemia, neoplastic cells may be obvious in the bone marrow.
  • If the animal has thrombocytopenia due to excessive consumption, there may be an increase in megakaryocytes if this is a chronic process.
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9
Q

expected findings in bone marrow for
- pancytopenia
Causes of pancytopenia?

A
  • lack of hematopoietic cells. - Only a framework of fibrocytes and adipocytes is present
    <><>
    Pancytopenia can be due to many causes:
  • viral – feline leukemia virus
  • Ehrlichia spp. infection
  • Idiopathic or autoimmune such as aplastic anemia
  • Effect of chemotherapy or radiation
  • Leukemia
  • Estrogen toxicity in dogs, bracken fern toxicity in cattle
  • Myelofibrosis
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10
Q

expected findings in bone marrow for
- iron deficiency anemia

A

The bone marrow lacks stainable iron, and erythropoiesis may be increased with a relative “right shift” consisting of many metarubricytes

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11
Q

expected findings in bone marrow and blood for
- acute leukemia

A

There typically is pancytopenia or bicytopenia in the peripheral blood, with a variable number of neoplastic cells in the blood and bone marrow.

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12
Q

expected findings in bone marrow and blood for
- chronic leukemia

A

There typically are more neoplastic cells in circulation than in acute leukemia, the neoplastic cells still look fairly “normal”, and the degree of anemia, neutropenia or thrombocytopenia is not as severe.

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13
Q

expected findings in bone marrow for
- multiple myeloma

A

Malignant plasma cells accumulate focally in the bone marrow and secrete an abnormal immunoglobulin (paraprotein, monoclonal protein) as well as osteolytic factors. Aspirates from the lytic lesions consist of plasma cells.

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14
Q

what does it mean that leukemias are clonal disorders?

A

they arise from single or very few neoplastic cells that proliferate.

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15
Q

what cells can give rise to leukemia

A

Virtually any hematopoietic cell with ability to divide can give rise to leukemia. Thus, we see eosinophilic, neutrophilic, lymphocytic, megakaryocytic, erythrocytic, etc. leukemias.

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16
Q

animal leukemia treatment and prognosis?

A

In animals, we have limited experience with treatment of leukemia, and we don’t know the prognosis in many cases.

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17
Q

typical disease course of acute leukemia?
- oblood observations? types?

A

Acute leukemias tend to have a rapid disease course, and are fatal in most cases within weeks to months.

<><><><>

Acute leukemia: undifferentiated cells, marked cytopenia, sick animal, often rapidly progressive and fatal disease
* myeloid or lymphoid acute leukemia (AML and ALL)

18
Q

chronic leukemia disease course?
- blood observations?

A
  • some chronic leukemias can be indolent, in that they gradually “crowd out” normal hematopoietic tissue (myelophthisis), or gradually enlarge the spleen, but they do not kill the patient for months to years. In these cases, secondary complications such as immunosuppression due to lack of production of normal immune cells, or lack of normally functioning neutrophils or platelets, are more of a concern.
    <><>
    Chronic leukemias often expand well beyond the marrow cavity, and “grow” in other organs of the hemolymphatic system such as the spleen, the lymph nodes, and in the liver sinusoids.
    <><>
    <><>
    Chronic leukemia (rare): large number of fairly “normal” looking cells in blood, slow progression, organ infiltration
  • Chronic neutrophilic leukemia, chronic lymphocytic leukemia, etc.
19
Q

why do we sometimes see a change in the phenotype of leukemias?

A

Genetic markers used in the diagnosis of human leukemia show that often many cell lines carry the same gene change although one cell line predominates in the bone marrow or blood. This feature explains why we sometimes see a change in the phenotype of leukemia.

20
Q

myelofibrosis is found mostly in what animals? what is it? how does it arise?

A
  • Myelofibrosis is a condition observed mainly in dogs.
  • The bone marrow cavity becomes gradually “overgrown” by fibrocytes that produce collagen. This results in myelophthisis (“crowding out”) of the hematopoietic cells.
  • This condition occurs in animals subsequent to chronic bone marrow stimulation such as chronic hemolytic anemia, it may accompany chronic leukemias, and may occur for unknown reasons (idiopathic).
  • Excessive proliferation of fibrocytes is likely the result of aberrant cytokine production.
    <><>
    <><>
  • overgrowth of bone marrow cavity by fibroblasts
  • excess production of collagen
  • cause: aberrant cytokine production by chronically stimulated bone marrow cells, leukemia, or idiopathic
  • cannot aspirate the bone marrow, diagnosis dependent on biopsy
21
Q

sample required to diagnose myelofibrosis

A

In myelofibrosis the bone marrow is difficult or impossible to aspirate, and a biopsy is necessary for diagnosis.

22
Q

myelofibrosis treatment

A

Treatment is directed at the primary cause, or, if no cause has been established, consists of immunosuppression.

23
Q

How is leukemia diagnosed?

A

There are usually changes in the peripheral blood that are suspicious for leukemia such as persistent non-regenerative anemia, neutropenia, thrombocytopenia, or abnormal cells. In these cases a bone marrow examination is necessary to confirm the leukemia.

24
Q

Can the type of leukemia always be determined?

A

No. In particular acute leukemias frequently consist of poorly differentiated blast cells that cannot be classified as granulocytic or monocytic or lymphocytic precursors by morphologic appearance. Immunophenotyping and cytochemical reactivity may be helpful.
<><>
Acute vs MDS vs chronic = yes; type of acute leukemia = only with additional tests

25
Q

Is it important to determine the type of leukemia?

A

Yes, if we wish to eventually better treat and prognosticate leukemias. Identifying the type of an acute leukemia is probably of “academic interest” since they all seem to do poorly. But, without accumulating knowledge about the prevalence and response to therapy of leukemias, we will never know if and how to treat them.
<><>
Yes, since acute, MDS and chronic since have different prognoses

26
Q

Can leukemia occur outside of the bone marrow?

A

Yes. Leukemia is defined as “neoplastic cells in circulation or in hematopoietic tissue”. Some chronic lymphocytic leukemias arise in the spleen, are associated with marked lymphocytosis, but do not involve the bone marrow until late in the disease course. The spleen has tremendous hematopoietic potential, and it is thus not unusual to have primary or secondary leukemia in the spleen.
<><>
The most common leukemia in dogs with CLL, which is predominantly in the spleen.

27
Q

Do leukemias occur in non-domestic animals?

A

Yes. Leukemia has been described in virtually any species of animal. Lymphocytic leukemia is the most common type recognized in birds.

28
Q

Does a very high leukocyte count always imply leukemia?

A

No. Some solid tissue cancers (carcinomas, sarcomas) may aberrantly produce a hematopoietic cytokine such as G-CSF, which can result in tremendous neutrophilia (100 to 200x109/L), but if the primary tumor is removed or treated this leukocytosis quickly resolves. As well, some chronic inflammatory conditions in dogs (for example pyometra) and cats can result in marked leukocytosis (50-100x109/L) that is not leukemia.

29
Q

what do blood samples tell us about neutrophils and lymphocytes based on their life span and distribution in the body?

A
  • Blood samples capture a “snapshot” of neutrophil production – short-lived cells!
  • Blood samples capture a “snapshot” of lymphocyte distribution – long-lived cells, and mostly in tissues and lymphatics.
30
Q

How long does it take to increase erythroid or granulocyte production in the bone marrow?

A

2-3 days, depending on the age of the animal, concurrent illness and nutritional status.

31
Q

How long does it take to produce a “new” neutrophil from an undifferentiated precursor cell into the blood?

A

About 6 days.

32
Q

What is the proportion of granulocyte precursors to erythroid precursors (G:E or M:E ratio) in bone marrow?

A

About 1:1 in dogs and cats, and 1:2 or 1:3 in large animals.

33
Q

Main change in RBC in non-regenerative anemia?

A

Hypochromic (pale) RBC.

34
Q

How would the numerical indices on the CBC be changed for non-regenerative anemia?

A

Low MCHC, low HCT, Hgb, RBC

35
Q

Rubricytosis and abnormal behaviour in a puppy
- possible cause?

A

Lead toxicity

36
Q

Non-regenerative anemia, hyperproteinemia in a dog
- most likely diagnosis?

A

Multiple myeloma
<><>
Multiple myeloma is a cancer that forms in a type of white blood cell called a plasma cell. Healthy plasma cells help fight infections by making proteins called antibodies. Antibodies find and attack germs. In multiple myeloma, cancerous plasma cells build up in bone marrow.

37
Q

Aplastic anemia, pancytopenia (“bone marrow hypoplasia”)
- causes?

A
  1. Infectious – Anaplasma spp., parvovirus, FeLV, EIAV, etc.
  2. Drugs or hormones – estrogen, phenylbutazone, phenobarbital, chemotherapy, trimethoprim sulfadiazine, etc.
  3. Toxins – bracken fern, trichloroethylene, etc.
  4. Idiopathic (autoimmune)
38
Q

Leukemia diagnosis:

A

Abnormal cells in the peripheral blood and/or bone marrow + cytopenia
1. Bone marrow cytology and/or histology
2. Occasionally splenic disease – aspirate/biopsy of spleen

39
Q

Leukemia classification (grading)
- what do we need?

A
  1. Acute, MDS or chronic? Big difference in prognosis
  2. Need specialized tests such as immunophenotyping, cytochemistry
40
Q

what can give very high leukocyte counts other than leukemia?

A

Chronic inflammation, paraneoplastic leukocytosis

3. Sys Path (28 decks)

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