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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
Q

AML monocytic differentiation clinical features

A
  • infiltration of gums, skin, CNS more common
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26
Q

Prognosis of AML

A
  • 60-80% of patients reach initial remission

- relapse is common: better survival rate for

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27
Q

Acute lymphoblastic leukemia

A
  • malignant neoplasm or lymphoid stem cells
  • bone marrow: accumulation of lymphoblasts
  • blood smear: increased blasts, anemia, thrombocytopenia
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28
Q

ALL clinical features

A
  • 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
Q

Classification of ALL

A
  • myeloperoxidase stain is negative

- flo cytometry determine lineage: most are precursor B cells

30
Q

Immunophenotype of ALL

A
  • B lineage: CD19/79a/22

- markers of immaturity: TdT, CD34

31
Q

Cytogenetic abnormalities in B-ALL

A
  • favorable: high hyperdiploid (>50), t(12;21) TEL-AML1

- unfavorable: hypodiploid, t(9;22) BCR-ABL, 11q23 rearrangements

32
Q

Take home points - Acute leukemias

A
  • present w/ proliferation of BLASTS
  • lineage determined by flow cytometry, auer rods & MPO stain also contribute
  • prognosis determined by age & cytogenetics
33
Q

Chronic myeloid leukemia

A
  • increased neutrophils & granulocytic precursors; BASOPHILIA
  • 15% of leukemias in adults, RARE in children
  • median age: 55
  • lethargy, fatigue, weight loss
  • may have splenomegaly
34
Q

Morphology of CML

A
  • leukocytosis in peripheral blood
  • left shift
  • hypercellular bone marrow w/ increased myeloid:erythroid ratio
35
Q

Cytogenetics in CML

A
  • t(9;22): BCR/ABL
36
Q

Prognosis of CML

A
  • pre imatinib: 5 years

- currently: normal life expectancy

37
Q

Imatinib

A
  • drug for CML

- binds to ATP binding site on tyrosine kinase (BCR/ABL) blocking it

38
Q

Chronic lymphocytic leukemia

A
  • 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
Q

Clinical - CLL

A
  • 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
Q

Blood smear - CLL

A
  • smudge cell (no difference b/w cytoplasm & nucleus, purple blob)
41
Q

Bone marrow - CLL

A
  • Nodular: nodules of neoplastic cells
  • Interstitial: neoplastic cells instead of normal cells
  • Diffuse: no fate all neoplastic cells
  • high power, small round lymphocytes*
42
Q

Myelodysplastic syndromes (MDS)

A
  • clonal myeloid stem cell disorders, with increased risk of transformation to AML (MDS20%)
  • dypoiesis: abnormal morphologic features in maturing cells
43
Q

Clincal features - MDS

A
  • elderly patients
  • 50% present w/ infections, hemorrhage, & fatigue
  • 50% asymptomatic
44
Q

Prognosis - MDS

A
  • 1/3 progress to AML: difficult to treat

- depends on blast percentage, cytogenic abnormalities, degree of cyopenias, age

45
Q

WHO classification of MDS

A
  • number of blasts in blood smear & bone marrow
  • cytologic features: ring sideroblasts, dypoiesis in 1, 2, or all 3 cell lines
  • cytogenic abnormalities
46
Q

Morphology of MDS

A
  • pancytopenia w/ dyspoietic featurs of RBCs, granulocytes, platelets
  • may have increased myeloblasts (
47
Q

Blood smear - MDS

A
  • normal RBCs & hypochromic microcytic RBCs
  • hypersegmented neutrophils, hypolobate, hypogranular
  • ring sideroblasts: iron (purple) granules surrounding nucleus
48
Q

Bone marrow - MDS

A

hypercellular bone marrow, ineffective hematopoiesis

49
Q

Cytogenetics of MDS

A
  • trisomies and deletions are common
  • specific translocations are uncommon
  • have prognostic significance
50
Q

Chronic myeloproliferative neoplasms (MPN)

A
  • increased number of differentiated granulocytes, RBCs, or platelets
  • types: CML, polycythemia vera, essential thrombocytopenia, primary melofibrosis
51
Q

Mutation in JAK2 (V617F)

A
  • seen in most patients w/ polycythemia vera

- half of patients w/ essential thrombocytopenia or primary myelofibrosis

52
Q

Essential thrombocytopenia

A
  • thrombocytosis and increased megakaryocytes in bone marrow
  • platelet counts are high
  • thrombosis OR hemorrhage
  • splenomegaly in 50% of patients
53
Q

Essential thrombocytopenia features and prognosis

A
  • adult disease (50-50 years)
  • long survival
  • rarely transforms to AML or myelofibrosis
54
Q

Bone marrow - ET

A
  • increased large platelets

- large atypical megakaryocyte (deer antler nucleus)

55
Q

Primary myeloribrosis

A
  • proliferation of megakaryocytes & granuloctyes in BM

- associated w/ deposition of fibrous CT and extramedullary hematopoiesis

56
Q

Primary myelofibrosis - features & prognosis

A
  • middle age & elderly
  • progressive development of SPLENOMEGALY
  • median survival 3 years
  • 5-20% progress to acute leukemia
57
Q

Blood smear - primary myelofibrosis

A
  • anemia w/ TEAR DROP RBCs
  • leukoerythroblastic reaction: immature myeloid cells and nucleated RBCs can also be seen in high stress person aka newborn
58
Q

Bone marrow - primary myelofibrosis

A
  • cellular stage: hypercellular marrow w/ increased neutrophils and cluster of large atypical megakaryocytes
  • fibrotic stage: HYPOcellular marrow, increased fibrosis, intrasinusoidal hematopoiesis
59
Q

Plasma cell neoplasms

A
  • clonal proliferation of differentiated B cells

- secrete monoclonal immunoglobulin call M-protein (monoclonal protein)

60
Q

Plasma cell neoplasms - types

A
  • monoclonal gammopathy of undertermined significance (MGUS)
  • plasmacytoma
  • plasma cell myeloma
61
Q

Plasma cell neoplasms - labs

A
  • serum protein electrophoresis: shows large increase in one immunogloulin
  • immunofixation electrophoresis: characterizes type of immunoglobulin
62
Q

MGUS

A
  • 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
Q

Plasmacytoma (solitary myeloma)

A
  • 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
Q

Plasma cell myeloma

A
  • originates in bone marrow, involvement of skeleton as well

- monoclonal serum (IgG, IgA) and/or urine light chain protein

65
Q

Plasma cell myeloma - symptomatic

A
  • end organ damage
  • hyperCalcemia, Renal insufficiency, Anemia, Bony lytic lesions (CRAB)
  • recurrent infections
66
Q

Plasma cell myeloma - asymptomatic

A
  • significant M-protein in serum (>30g/dL)
  • significant bone marrow involvement (>10%)
  • NO END ORGAN DAMAGE
67
Q

Blood smear - plasma cell myeloma

A
  • rouleaux (RBCs stuck together)
68
Q

Plasma cell myeloma - prognosis & therapy

A
  • 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
Q

Normal myeloid to erythroid ratio

A

3:1

MOHDIII - Unit 2 (23 decks)

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