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MOHDIII - Unit 2 > Myeloid & Lymphoid Bone Marrow Disorders > Flashcards

Myeloid & Lymphoid Bone Marrow Disorders Flashcards

1
Q

Normal marrow cellularity (cell to fat ratio)

A

100-age: 100-22=78 (aka as you age will get increasing fat percentage)

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2
Q

Two granulocyte pools in blood

A
  • circulating granulocyte pool (CGP): what you’ll get a count on
  • marginal granulocyte pool (MGP): adherent to vessel walls
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3
Q

Neutropenia

A
  • reduction in number of neutrophils

- agranulocytosis: marked neutropenia (

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4
Q

Neutropenia pathogenesis

A
  • inadequate granulopoiesis (aplastic anemia)
  • ineffective granulopoiesis (B12 def, MDS)
  • accelerated removal or destruction (infection or immune)
  • replacement of marrow by tumor
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5
Q

Neutropenia clinical presentation

A
  • infections: lung, urinary tract, mouth ulcers

- bacteria may grow massively in colony-like formation

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6
Q

Neutrophilia causes

A
  • Reactive & Neoplastic
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7
Q

Reactive neutrophilia

A
  • demargination (neutrophils released from vessel enotheliumMGP): epinephrine release, acute stress exercise
  • mobilization of maturation-storage compartment: steroids, infection, inflammation
  • increased production: chronic infection, inflammation, GCSF
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8
Q

Neoplastic neutrophilia

A
  • myeloproliferative neoplasms
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9
Q

Neutrophilia blood smear

A
  • increased neutrophils
  • left shift
  • toxic changes (infection): toxic granulation, cytoplasmic vacuoles, dohle body**light grey/blue bleb in cytoplasm
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10
Q

Leukemoid reaction

A
  • extreme leukocytosis (50,000/uL)
  • physiologic response to stress or infection
  • may resemble leukemia
  • increased immature cells seen
  • *reactive process, excludes cancer(CML)**
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11
Q

Leukemia

A
  • malignant neoplasms of hematopoetic cells, diffuse replacement of bone marrow by neoplastic cells
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12
Q

Leukemia classification

A
  • cell lineage (myeloid vs. lymphoid)
  • maturity (blasts vs. differentiated cells)
  • chronicity (acute vs. chronic): based on clinical presentation
  • acute=blasts, chronic=differentiated*
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13
Q

Most common leukemia

A

Acute myeloid leukemia

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14
Q

Most common child leukemia

A

Acute lymphoblastic leukemia

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15
Q

Acute myeloid leukemia

A
  • neoplasm of multipotent myeloid stem cells characterized by accumulation of myelobasts in bone marrow & blood at least 20%
  • block in differentiation of leukemic stem cells
  • replacement & suppression of normal hematopoetic precursors
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16
Q

AML lineage

A
  • may arise from any myeloid lineage: monocytic, erythroid, megakaryocytic
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17
Q

AML flow cytometry antigens

A
  • CD13, CD33, CD117
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18
Q

Morphology of AML

A
  • auer rods

- myeloperoxidase stain is positive (blue sand appearance)

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19
Q

AML types

A
  • promyelocytic
  • myelomonocytic
  • megakaryblastic
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20
Q

Acute promyelocytic leukemia

A
  • abnormal promyelocytes w/ multiple auer rods (faggot cells)
  • t(15,17)
  • medical emergency
  • risk of DIC
  • initial treatment with ATRA (all trans retinoic acid)
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21
Q

Acute myelomonocytic leukemia blood smear

A
  • increased cytoplasm in immature cells
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22
Q

Acute megakaryoblastic leukemia blood smear

A
  • cytoplasm of mature cells is smudged (looks broken up)
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23
Q

Chromosomal abnormalities in AML

A
  • t(15,17) in acute promyelocytic leukemia
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24
Q

Clinical features of AML

A
  • mainly disease of adults, 20% of childhood leukemias
  • acute onset of symptoms: fatigue-anemia, infections-neutropenia, bleeding-thrombocytopenia
  • presents w/ leukocytosis, or pancytopenia
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25
AML monocytic differentiation clinical features
- infiltration of gums, skin, CNS more common
26
Prognosis of AML
- 60-80% of patients reach initial remission | - relapse is common: better survival rate for
27
Acute lymphoblastic leukemia
- malignant neoplasm or lymphoid stem cells - bone marrow: accumulation of lymphoblasts - blood smear: increased blasts, anemia, thrombocytopenia
28
ALL clinical features
- most common cancer in children 1-7 - fatigue, infections, bleeding, BONE PAIN, hepatoslenomegaly - most patients achieve complete remission and 85% of children cured - 40% cure rate in adults
29
Classification of ALL
- myeloperoxidase stain is negative | - flo cytometry determine lineage: most are precursor B cells
30
Immunophenotype of ALL
- B lineage: CD19/79a/22 | - markers of immaturity: TdT, CD34
31
Cytogenetic abnormalities in B-ALL
- favorable: high hyperdiploid (>50), t(12;21) TEL-AML1 | - unfavorable: hypodiploid, t(9;22) BCR-ABL, 11q23 rearrangements
32
Take home points - Acute leukemias
- present w/ proliferation of BLASTS - lineage determined by flow cytometry, auer rods & MPO stain also contribute - prognosis determined by age & cytogenetics
33
Chronic myeloid leukemia
- increased neutrophils & granulocytic precursors; BASOPHILIA - 15% of leukemias in adults, RARE in children - median age: 55 - lethargy, fatigue, weight loss - may have splenomegaly
34
Morphology of CML
- leukocytosis in peripheral blood - left shift - hypercellular bone marrow w/ increased myeloid:erythroid ratio
35
Cytogenetics in CML
- t(9;22): BCR/ABL
36
Prognosis of CML
- pre imatinib: 5 years | - currently: normal life expectancy
37
Imatinib
- drug for CML | - binds to ATP binding site on tyrosine kinase (BCR/ABL) blocking it
38
Chronic lymphocytic leukemia
- B cell neoplasms which express mature B cell antigens - monotypic kappa or lambda light chains - apperantly express ****CD5**** (CD5 not normally expressed on B cells)
39
Clinical - CLL
- leukemia of patients >60 years old - more common in males - generalized lymphadenopathy in 50-60% of patients * **can also be called small lymphocytic lymphoma***
40
Blood smear - CLL
- smudge cell (no difference b/w cytoplasm & nucleus, purple blob)
41
Bone marrow - CLL
- Nodular: nodules of neoplastic cells - Interstitial: neoplastic cells instead of normal cells - Diffuse: no fate all neoplastic cells * **high power, small round lymphocytes***
42
Myelodysplastic syndromes (MDS)
- clonal myeloid stem cell disorders, with increased risk of transformation to AML (MDS20%) - dypoiesis: abnormal morphologic features in maturing cells
43
Clincal features - MDS
- elderly patients - 50% present w/ infections, hemorrhage, & fatigue - 50% asymptomatic
44
Prognosis - MDS
- 1/3 progress to AML: difficult to treat | - depends on blast percentage, cytogenic abnormalities, degree of cyopenias, age
45
WHO classification of MDS
- number of blasts in blood smear & bone marrow - cytologic features: ring sideroblasts, dypoiesis in 1, 2, or all 3 cell lines - cytogenic abnormalities
46
Morphology of MDS
- pancytopenia w/ dyspoietic featurs of RBCs, granulocytes, platelets - may have increased myeloblasts (
47
Blood smear - MDS
- normal RBCs & hypochromic microcytic RBCs - hypersegmented neutrophils, hypolobate, hypogranular - ring sideroblasts: iron (purple) granules surrounding nucleus
48
Bone marrow - MDS
hypercellular bone marrow, ineffective hematopoiesis
49
Cytogenetics of MDS
- trisomies and deletions are common - specific translocations are uncommon - have prognostic significance
50
Chronic myeloproliferative neoplasms (MPN)
- increased number of differentiated granulocytes, RBCs, or platelets - types: CML, polycythemia vera, essential thrombocytopenia, primary melofibrosis
51
Mutation in JAK2 (V617F)
- seen in most patients w/ polycythemia vera | - half of patients w/ essential thrombocytopenia or primary myelofibrosis
52
Essential thrombocytopenia
- thrombocytosis and increased megakaryocytes in bone marrow - platelet counts are high - thrombosis OR hemorrhage - splenomegaly in 50% of patients
53
Essential thrombocytopenia features and prognosis
- adult disease (50-50 years) - long survival - rarely transforms to AML or myelofibrosis
54
Bone marrow - ET
- increased large platelets | - large atypical megakaryocyte (deer antler nucleus)
55
Primary myeloribrosis
- proliferation of megakaryocytes & granuloctyes in BM | - associated w/ deposition of fibrous CT and extramedullary hematopoiesis
56
Primary myelofibrosis - features & prognosis
- middle age & elderly - progressive development of SPLENOMEGALY - median survival 3 years - 5-20% progress to acute leukemia
57
Blood smear - primary myelofibrosis
- anemia w/ TEAR DROP RBCs - leukoerythroblastic reaction: immature myeloid cells and nucleated RBCs ***can also be seen in high stress person aka newborn***
58
Bone marrow - primary myelofibrosis
- cellular stage: hypercellular marrow w/ increased neutrophils and cluster of large atypical megakaryocytes - fibrotic stage: HYPOcellular marrow, increased fibrosis, intrasinusoidal hematopoiesis
59
Plasma cell neoplasms
- clonal proliferation of differentiated B cells | - secrete monoclonal immunoglobulin call M-protein (monoclonal protein)
60
Plasma cell neoplasms - types
- monoclonal gammopathy of undertermined significance (MGUS) - plasmacytoma - plasma cell myeloma
61
Plasma cell neoplasms - labs
- serum protein electrophoresis: shows large increase in one immunogloulin - immunofixation electrophoresis: characterizes type of immunoglobulin
62
MGUS
- small increase in monoclonal protein WITHOUT overt disease - 3% of people over 70 - usually identified incidentally - 25% progress to disease (plasma cell myeloma) over 20 years
63
Plasmacytoma (solitary myeloma)
- solitary bone lesion or extraosseous lesion - common sites: lung, pharynx, nasal sinuses - MUST do bone marrow biopsy to diagnose (should not have any bone marrow involvement) - treatment: local radiation
64
Plasma cell myeloma
- originates in bone marrow, involvement of skeleton as well | - monoclonal serum (IgG, IgA) and/or urine light chain protein
65
Plasma cell myeloma - symptomatic
- end organ damage - hyperCalcemia, Renal insufficiency, Anemia, Bony lytic lesions (CRAB) - recurrent infections
66
Plasma cell myeloma - asymptomatic
- significant M-protein in serum (>30g/dL) - significant bone marrow involvement (>10%) - NO END ORGAN DAMAGE
67
Blood smear - plasma cell myeloma
- rouleaux (RBCs stuck together)
68
Plasma cell myeloma - prognosis & therapy
- treatment minimizes end organ effects: not curative - new agents (immune modulators & proteasome inhibitors) and autologous stem cell transplant increased survival from 2 years a decade ago to >8 years today - prognosis: cytogenic abnormalities, LDH, age performance status
69
Normal myeloid to erythroid ratio
3:1

MOHDIII - Unit 2 (23 decks)

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