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Clinical Pathology > Bone Marrow Disorders > Flashcards

Bone Marrow Disorders Flashcards

1
Q

What are 4 CBC indications of where bone marrow collection is helpful?

A
  1. persistent cytopenia/cytosis - neutropenia, thrombocytopenia, pancytopenia, non-regenerative anemia
  2. rubricytosis (nucleated RBCs)
  3. suspected neoplasia or monoclonal gammopathy
  4. leukemia
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2
Q

What 4 clinical situations is it important to collect bone marrow samples?

A
  1. fever of unknown origin to look for underlying inflammation or neoplasia
  2. rule out osteomyelitis
  3. staging lymphoma and mast cell turmors
  4. monitoring chemotherapy response
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3
Q

Where can bone marrow samples be collected in different species?

A

DOGS, CATS: trochanteric fossa, humerus, ilium

HORSES, CATTLE, CAMELIDS: ilium, ribs, sternum

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4
Q

What materials are needed for bone marrow sampling? What is done to collected samples?

A

bone marrow biopsy needle (16-22 gauge) and a 12 cc syringe

  • collected into EDTA tube
  • PREFERABLY: make slide —> air dry, Wright’s stain
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5
Q

What bone marrow samples are used for cytology and histopathology?

A

CYTOLOGY = aspirate, avoid diluting with blood

HISTOPATHOLOGY = core biopsy placed in formalin

(avoid transporting/shipping samples together)

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6
Q

Bone marrow sampling:

A
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7
Q

Bone marrow sampling:

A
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8
Q

How are bone marrow films prepared?

A

squash or pull technique

  • place a drop of bone marrow sample toward the frosted edge of the slide
  • spread the suspension by placing a second slide over the sample perpendicular to the slide with the sample and pull them apart
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9
Q

In what 2 situations is it contraindicated to sample bone marrow?

A
  1. bleeding disorders
  2. if there is a way to achieve a diagnosis with less invasive tests, like CBC and blood smear
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10
Q

How is bone marrow cellularity evaluated?

A

overall percentage of hematopoietic cellularity compared to percentage of adipose

  • inadequate cellularity with increased adipose tissue
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11
Q

What is the myeloid:erythroid ratio? What is the normal ratio?

A

number of granulocytes compared to nucleated erythrocytes

1:1 to 3:1

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12
Q

Where is stored iron found in the bone marrow? When do they become depleted?

A

within macrophages

before the development of anemia or microcytic, hypochromic RBCs

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13
Q

What area is best for evaluating iron storage in the bone marrow?

A

bone marrow spicules —> where macrophages are usually located

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14
Q

Erythroid maturation:

A

healthy = more erythrocytes than immature stages

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15
Q

Myeloid maturation:

A

segmented granulocytes should outnumber myeloblasts

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16
Q

What is important to include with a sample for bone marrow interpretation?

A

recent CBC within 24 hours from collection

  • allows for blood film evaluation simultaneously
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17
Q

What are the best uses for cytology and histopathology biopsy samples of bone marrow?

A

CYTOLOGY = cell morphology

HP = quatitive cellularity of bone marrow to reveal myelofibrosis, architecture patterns and focal lesions

(recommended to do both along with CBC for a case)

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18
Q

What is decreased cellularity within the bone marrow? What will aspirates in these cases look like?

A

severe decrease in all hematopoietic cells in marrow, leading to marrow aplasia, anemia, and pancytopenia

consists of fat with stromal cells, like macrophages, dendritic cells, fibroblasts, mast cells, lymphocytes, and plasma cells

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19
Q

What are 6 possible causes of pancytopenia in the bone marrow?

A
  1. drugs
  2. hormones (estrogen)
  3. infectious agents (Ehrlichia canis)
  4. radiation
  5. immune-mediated
  6. idiopathic
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20
Q

What are 3 causes of an increased M:E ratio?

A
  1. erythroid hypoplasia/aplasia
  2. granulocytic hyperplasia
  3. granulocytic leukemia

(>3:1)

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21
Q

What are 3 causes of a decreased M:E ratio?

A
  1. regenerative anemia
  2. erythroid leukemia
  3. lack of neutrophil production

(<1:1)

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22
Q

What are 5 other cells possibly seen in a bone marrow sample?

A
  1. plasma cells
  2. lymphocytes
  3. macrophages
  4. mast cells (rare)
  5. osteoblasts and osteoclasts
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23
Q

What does an increase (>15%-20%) in plasma cells in a bone marrow sample indicate?

A

plasma cell myeloma or multiple myeloma if infectious disease is ruled out

24
Q

Bone marrow, presence of abnormal cells:

A

ARROW = RBC precursor with a larger nucleus than normal

ARROWHEAD = mitotic figures, increased erythroid mitoses

25
Q

What 4 microorganisms commonly affect bone marrow?

A
  1. Histoplasma capsulatum
  2. Toxoplasma gondii
  3. Leishmania donovani
  4. Babesia (RBC parasite)
26
Q

Histoplasma capsulaum:

A
  • endemic in North and Central America
  • clinical manifestations vary from pulmonary disease to disseminated multi-organ involvement
  • seen in MACROPHAGES
27
Q

How are bone marrow interpretations done?

A

interpret cytologic findings, M:E ration, and overall marrow cellularity within the context of CBC findings

28
Q

What does Ehrlichia canis cause? What are the 6 most frequently reported clinical signs?

A

canine monocytic ehrlichiosis

  1. lethargy
  2. anorexia
  3. fever
  4. lymphadenomegaly
  5. splenomegaly
  6. hemorrhages (petechiae, ecchymoses, epistaxis)
29
Q

What are 2 phases of canine monocytic ehrlichiosis? What makes it a “silent killer?”

A
  1. ACUTE/SUBCLINICAL - lasts months to years
  2. CHRONIC - not all dogs reach this phase, assumed to be associated with susceptibility and breed disposition

produces severe pancytopenia caused by bone marrow suppression in the chronic stage that may not be reversible by the time of diagnosis

30
Q

How does Ehrlichia canis cause persistent thrombocytopenia? What does this result in?

A

produces anti-platelet antibodies —> increased consumption and decreased half-life with splenic sequestration

increased numbers of large regenerative platelets

31
Q

How does Ehrlichia canis cause pancytopenia?

A

destroys bone marrow cells

32
Q

Where does primary bone marrow neoplasia arise form? What are the 3 results?

A

hematopoietic stem cells or later stages

  1. accumulate —> chronic disease
  2. proliferate and die —> myelodysplastic syndrome
  3. proliferate and overtake —> acute leukemia
33
Q

Where do hematopoietic neoplasms arise from? What are the 2 types?

A

bone marrow, lymph nodes, spleen, or thymus

  1. lymphoid
  2. myeloid
34
Q

What is the difference between lymphoma and leukemia?

A

LYMPHOMA = solid tumor of neoplastic lymphocytes located outside of the bone marrow

LEUKEMIA = neoplastic cells of any type in the blood and/or bone marrow

35
Q

What is lymphoid leukemia? Leukemic phase of lymphoma?

A

neoplastic lymphocytes in the blood and/or bone marrow

lymphoma previously diagnosed in other organs (lymph nodes) and has spread to blood and bone marrow - stage V lymphoma

36
Q

What is most often seen on CBC in leukemia?

A
  • very high total WBC count +/- neutrophils and lymphocytes depending on the cell of origin
  • concurrent anemia and thrombocytopenia (bicytopenia)
37
Q

How does acute and chronic leukemia compare?

A

ACUTE = predominance of immature/undifferentiated cells in the bone marrow rapidly within weeks to months; most common in younger animals

CHRONIC = predominance of mature/differentiated cells in the bone marrow slowly within months to years; more common in older animals

38
Q

When is it common for cats to develop acute lymphocytic leukemia?

A

FeLV or FIV infection

39
Q

What are myeloid neoplasms? What are 3 common types?

A

proliferation of one or more non-lymphoid marrow cell lines (granulocytes, monocytes, erythrocytes, megakaryocytes)

  1. myelodysplastic syndrome
  2. acute myeloid leukemia
  3. chronic myeloid neoplasms (myeloproliferative)
40
Q

What results from myelodysplastic syndrome and acute myeloid leukemia? How are they diagnosed?

A

hypercellular bone marrow with cytopenia or leukocytosis in the peripheral blood

MDS = bone marrow blast count <20%
AML = bone marrow blast count >20%

41
Q

Chronic myeloid neoplasms are very rare in veterinary medicine. What 2 things are they categorized by?

A
  1. bone marrow hyperplasia
  2. high cell counts in peripheral blood
42
Q

What are non-hematopoietic neoplasms? What are the 3 most common types?

A

infiltrative neoplasms that do not arise in the bone marrow and replace bone marrow cells (myelophthisis), leading to cytopenias

  1. multiple myeloma
  2. histiocytic sarcoma
  3. mast cell tumor
43
Q

What 2 metastatic tumors typically affect the bone marrow?

A

carcinomas of epithelial origin

  1. urothelial carcinoma
  2. mammary carcinoma
44
Q

What are 2 types of advanced diagnostic techniques for lymphoma and leukemia?

A
  1. immunophenotyping - immunocytochemistry (ICC) for fresh smears/aspirates from cytology, immunohistochemistry (IHC) for biopsies in formalin from histology, flow cytometry
  2. clonality assays - PCR of antigen receptor rearrangement (PARR)
45
Q

When are ICC and IHC most useful? What do they detect?

A
  • cytology or histology are inconclusive for neoplasia
  • immunophenotyping/classifying lymphoma diagnosed on cytology or histology

antigens on cells by chemical or immunologic reactions

46
Q

What are 3 common targets for ICC and IHC?

A
  1. CD8 cells in canine bone marrow - T-lymphocyte leukemia
  2. CD79a cells in canine bone marrow - B-lymphocyte leukemia
  3. myeloperoxidase (MPO) in feline bone marrow - myeloid leukemia
47
Q

What does immunophenotyping identify?

A

lymphocyte subsets based on the proteins they express on their surface

  • T cells = CD3, CD4 (helper), CD8 (cytotoxic)
  • B cells = CD21, CD19
48
Q

In what 2 situations is flow cytometry best used for immunophenotyping? What is it used to do?

A
  1. previously diagnosed lymphoma on cytology/histology
  2. leukemia, especially acute when morphology is unreliable

differentiates reactive from neoplastic lymphocytes

49
Q

What samples are used for flow cytometry? What cannot be used?

A

live cells in fluid suspension - fresh aspirates or cavitary fluids in saline and serum or whole blood or bone marrow in EDTA

cytology slides

50
Q

How does flow cytometry work?

A

fluid suspension of cells flow past a laser and the direction of light scatter by the cells correlates to cell size and granularity

  • forward scatter = cell size (X axis)
  • side scatter = internal complexity - cell lineage, which correlates with prognosis (Y axis)
51
Q

What are clonality assays (PARR) best used for? In what 3 specific cases is it best used?

A

differentiates reactive lymphocytes from lymphoma when cytology and histopathology is inconclusive (increased clones = neoplasm)

  1. differentiates follicular lymphoms from hyperplastic reactions when there is lack of architectural effacement
  2. characterizes lymphohistiocytic proliferations in feline or canine skin
  3. differentiates feline inflammatory bowel disease from intestinal lymphoma
52
Q

What 5 samples can be used in clonality assays (PARR)?

A
  1. EDTA blood or bone marrow
  2. cavitary fluids and CSF
  3. fresh aspirates in saline
  4. biopsy specimens
  5. cytology slides (stained and unstained)
53
Q

Why must clonality assays (PARR) be used carefully?

A
  • dogs infected with Ehrlichia canis may induce lymphocytosis of granular lymphocytes and cytotoxic T-cell clonality expansion mimicking CLA
  • dogs infected with Borrelia burgdorferi may have clonality expansion of B cells
  • dogs infected with Leishmania may have clonality expansion of T or B cells
54
Q

How should clonality assays (PARR) be used for diagnosis?

A

NEVER USE ALONE - adjunctive and should be interpreted with clinical pathology and diagnostic tests (hemogram, chemistry, bone marrow, aspirates)

55
Q

What are the main 3 samples used to diagnose leukemia? Further advanced tests?

A
  1. blood smear
  2. CBC
  3. bone marrow aspirate AND core biopsy
    - aspirate = cellular morphology and determination of lineage
    - core biopsy = architecture (myelophthisis)

ICC, IHC, flow cytometry, PARR

Clinical Pathology (33 decks)

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