Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathology > Leukemia II > Flashcards

Leukemia II Flashcards

1
Q

Chronic Lymphocytic
Leukemia/Small Cell Lymphoma
(CLL/SLL)

• Epidemiology

A

– Most common leukemia of adults in the Western World
• In contrast SLL accounts for only 4% of NHLs

– Twice as frequent in males as in females

– Typically occurs >50 yrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

CLL/SLL

A
  • Morphologically, phenotypically, and genotypically indistinguishable from small lymphocytic lymphoma (overlaps with SLL)
  • Leukemia differs from lymphoma:
    – In the degree of peripheral blood lymphocytosis
  • Most cases are of B cell origin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

CLL/SLL

A

• If the peripheral blood lymphocyte count exceeds 5,000 cells/μL

– Diagnosed with CLL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

CLL/SLL: Immunophenotype and
Genetics

A
  • Express pan B cell markers
    – CD19, CD20, and CD 23
  • CD5, a T cell marker
  • Low level Sig
  • A small monoclonal Ig “spike” is present in the blood of some patients
  • Most common chromosomal abnormalities
    – Trisomy 12q, deletions of chromosomes 11q, 13q14, and 17p
  • Chromosomal translocation are rare
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

CLL/SLL: Morphology

A
  • Small round lymphocytes with scant cytoplasm with round to slightly irregular nuclei
  • Smudge cells
  • Diffuse effacement of lymph node architecture
  • Bone marrow is almost always involved
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

CLL/SLL: Laboratory

A 
• WBC: usually elevated 
– lymphocytosis

• Hypogammaglobulinemia

• Increased susceptibility to infection

• May have autoantibodies to RBC or platelets
– Coombs test may be positive
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

CLL/SLL: Clinical Presentation

• Often asymptomatic

A
  • Symptoms, when present are often nonspecific
    – Fatigue, weight loss, and anorexia
  • Generalized lymphadenopathy and hepatosplenomegaly
  • Course and prognosis depend on stage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

CLL/SLL: Prognosis

• Median survival time ~4 to 6 years

A

• Prognosis correlates with size of the total lymphocyte pool and the presence of anemia or thrombocytopenia

• Trisomy 12 and deletions of 11q or 17p23
—worse prognosis

• CD38—worse prognosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

CLL: Prognosis

A
  • May transform to a more aggressive lymphocytic neoplasm

* Prolymphocytic transformation (most commonly) or Richter Syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

CLL: Prognosis

A
  • Due to hypogammaglobulinemia, increased incidence of bacterial infections
  • Infection is a common cause of death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Prolymphocytic Transformation

A 
• Occurs in 15 – 30% of patients with CLL/SLL
• Marked elevation of lymphocyte count 
– 10 – 50% prolymphocytes

• Increased splenomegaly

• Poor response to therapy

• Less than 1 year survival
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

CLL: Richter Syndrome

A
  • Diffuse large B cell lymphoma
    • Seen in ~10% of patients
    • Rapid onset of fever, abdominal pain
  • Progressive lymphadenopathy
    • Poor response to therapy
    • Survival less than 1 year
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Chronic Lymphocytic Disorders

A

Chronic Lymphocytic Leukemia

Hairy Cell Leukemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Hairy Cell Leukemia

• Rare disorder

A

• middle age males

  • M:F =4:1
  • Caucasians

• ~2% of all leukemias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Hairy Cell Leukemia:

Pathogenesis

A

• ~90% have activating point mutations in the serine/threonine kinase BRAF

– Positioned immediately downstream from RAS in the MAP kinase signaling cascade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Hairy Cell Leukemia: Morphology and Immunotyping

A
  • Bcell neoplasm
  • Cells have fine hair-like projections visible in routine blood smears and in phase contrast microscopy
  • Neoplastic cells demonstrate the presence of tartrate resistant acid phosphatase
  • Express pan B-cell markers CD19 and CD20
  • Monocyte associated antigen CD11c and CD103
  • Surface IgH (usually IgG and either κ or λ)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Hairy Cell Leukemia: Clinical Features

A

• Symptomatology results from tissue infiltration
– Splenomegaly: often massive
– Hepatomegaly: less common and not as marked
– Lymphadenopathy: rare
– Pancytopenia: resulting from marrow failure and splenic sequestration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Hairy Cell Leukemia: Prognosis

A
  • Indolent course
  • Especially sensitive to certain chemotherapeutic regimens
  • Long term remissions
    – May relapse after 5 or more years, but generally respond well with re-treatment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Chronic Myeloproliferative Disorders

A

Chronic Myelogenous Leukemia

Polycythemia Vera

Essential Thrombocytosis

Primary Myelofibrosis (Myelofibrosis with Myeloid Metaplasia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Myeloproliferative Disorders

A
  • Have a common pathogenic feature
  • The presence of mutated, constitutively activated tyrosine kinases or other acquired aberrations in signaling pathways that lead to growth factor independence
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Myeloproliferative Disorders
• Common features:

A

– Increased proliferative drive in the bone marrow

– Homing of the neoplastic stem cells to secondary hematopoietic organs (extramedullary hematopoiesis)

– Variable transformation to a spent phase characterized by marrow fibrosis and peripheral blood cytopenias

– Variable transformation to acute leukemias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Chronic Myelogenous Leukemia

A

CML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

CML: Epidemiology

A
  • Primarily a disease of adults (25 – 60)

* Peak incidence in the fourth and fifth decades

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

CML: Pathogenesis and Genetics

• Etiologyisunknown

A
  • Arises by neoplastic transformation and clonal expansion of pluripotent stem cell
    – Granulocytic precursors are the dominant cell line involved, all hematopoietic lineages can be involved
  • Associated with the presence of a distinctive chromosomal abnormality—the Philadelphia chromosome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Philadelphia Chromosome

t(9;22) present in 90% (Ph1)

A

The BCR-cABL fusion gene results in production of a fusion protein with tyrosine kinase activity

Ph1 negative CML have rearrangements of BCR-cABL

– Normal myeloid progenitors depend on signals generated by growth factors and their receptors for growth and survival

– Growth factor dependence of CML progenitors is greatly decreased by signals generated by BCR- cABL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Nomenclature

A
  • BCR-ABL
    • BCR-cABL
    • t(9;22)
    • Philadelphia Chromosome

* Ph1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

CML: Pathogenesis

A
  • The cell of origin is a pluripotent hematopoietic stem cell
  • For unknown reasons, BCR-ABL preferentially drives the proliferation of granulocytic and megakaryocytic progenitors
  • It also causes the abnormal release of immature granulocytic forms from the marrow into the peripheral blood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

CML: Laboratory Findings

A

• PeripheralBlood
– Anemia and thrombocytosis
– Leukocytosis : markedly increased, often exceeding
100,000 cells/mm3
– Blasts usually make up

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

CML: Laboratory Findings

A

• BoneMarrow

– Markedly hypercellular with granulocytic proliferation
– M:E ratio increased 10 to 20 fold
– Decreased normoblasts

30
Q

CML: Clinical Features

• Onset slow, insidious

A

• Symptoms non specific
• Extreme splenomegaly (dragging sensation in abdomen)
• Fatigue malaise exercise intolerance, fever, sweating, weight loss, anorexia
• Mild to moderate anemia

31
Q

CML: Course

A

• Slow progression

• Drugs which target BCR-AB

– Treatment with BCR-ABL inhibitors results in sustained hematologic remissions in > 90% of patients
– Do not get rid of the CML stem cell
– Now have resistance to 1st generation BCR- ABL inhibitors

• nowhave2ndand3rdgenerationinhibitors

32
Q

CML: Course

A
  • Terminal Phases:
    – Accelerated phase (subacute transformation)
  • Progressive splenomegaly, refractory to therapy, increased anemia, additional chromosomal abnormalities
    – Blast crisis
  • Increased blasts in bone marrow and peripheral blood (myeloid or lymphoid)
  • 50% occur without going through accelerated phase

• 30% have cells resembling precursor B-cells

33
Q

Leukocyte Alkaline Phos (LAP)

In CML

A

Decreased or absent

34
Q

Leukocyte Alkaline Phos (LAP)

In leukamoid

A

increased

35
Q

Basophilia

In CML

A

present

36
Q

Basophilia

In leukamoid

A

absent

37
Q

Thrombocytosis

In CML

A

Present

38
Q

Thrombocytosis

In leukamoid

A

Absent

39
Q

Toxic Granulation

In CML

A

Absent

40
Q

Toxic Granulation

In leukamoid

A

Present

41
Q

anemia

In CML

A

Present

42
Q

anemia

In leukamoid

A

Absent

43
Q

Ph1

In CML

A

Present

44
Q

Ph1

In leukamoid

A

Absent

45
Q

CML: Prognosis

A
  • Targeted therapy
    – Inhibitors of the BCR-cABL tyrosine kinase induce complete remission in a high fraction of patients
  • Allogenic bone marrow transplant
46
Q

PCV: Epidemiology

A
  • Late middle age (median age of onset 60 yrs)

* M>F

47
Q

PCV: Pathophysiology

A
  • Panmyelosis with erythroid percursors dominant
    – Absolute increase in red cell mass (RBC 6 – 12million/μL)
    – Hematocrit 60% or greater
    – Granulocytosis (as high as 50,000/ μL)
    – Thrombocytosis
    – Basophilia
  • Erythropoietin decreased
48
Q

PCV: Genetics

A

• Strongly associated with activating mutations in JAK2
– A tyrosine kinase that acts in the signaling pathways downstream from the erythropoietin receptor
– Participates in the JAK/ STAT pathway
– Lies downstream from multiple hematopoietic growth factor receptors, including erythropoietin

49
Q

PCV: Genetics

A

• The transformed progenitor cells have markedly decreased requirements for erythropoietin and other hematopoietic growth factors
– Due to constitutive JAK2 signaling

50
Q

PCV: Morphology

A
  • Hypercellular marrow with some residual fat
  • Increase in red cell progenitors is subtle
    – Can be increase in granulocytic and megakaryocytic progenitors as well
  • In the spent phase
    – Late in the course
    – Extensive marrow fibrosis
    – Increased extramedullary hematopoiesis (spleen and liver)
51
Q

PCV: Clinical Presentation

A

• Uncommon: 1-3 per 100,000 per year

  • Insidious onset
  • Late middle age
52
Q

PCV: Clinical Presentation

A

• Symptoms due to increased red cell mass and hematocrit
– Increased viscosity
– Vascular stasis
– Thrombotic tendency
– Hemorrhagic diathisis

53
Q

PVC: Clinical Presentation

A

• Headache
• Dizziness
• GI symptoms
• Cyanosis
• Hypertension
• Thrombotic complications

54
Q

PCV: Prognosis and Treatment

A
  • Treatment: phlebotomy
  • Can enter a spent phase
    – `with clinical and anatomic features of primary myelofibrosis
    • May develop terminal AML (~1%)
55
Q

Primary Myelofibrosis (Myelofibrosis with Myeloid Metaplasia)

A

• Definition: A chronic progressive panmylosis with:
– Bone marrow fibrosis
– Splenomegaly with extramedullary hematopoiesis
– Leukoerythroblastic anemia

56
Q

Primary Myelofibrosis: Epidemiology

A

• Uncommon in individuals younger than 60 years

57
Q

Primary Myelofibrosis: Genetics

A

• Activating JAK2 mutations are present in 50 -60%
• Activating MPL mutations in an additional 1-5%
• Most of the remaining cases have calreticulin that is hypothesized to give incrased JAK-STAT signaling

58
Q

Myelofibrosis: Laboratory

A

• Moderate to severe normochromic normocytic anemia
• Marked poikilocytosis
• Nucleated RBC
• Teardrop shaped erythrocytes
• Basophilic stippling
• WBC: increased, decreased, or normal

59
Q

Myelofibrosis: Marrow Findings

A
  • Hypocellular marrow with dense fibrosis
  • Marrow fibrosis appears to be the result of inappropriate release of PDGF and TFG-β from neoplastic megakaryocytes
    – This causes deposition of collagen by non- neoplastic fibroblasts
  • Extramedullary hematopoiesis
60
Q

Primary Myelofibrosis: Clinical Course

A

• Comes to attention because of anemia or splenomegaly
• Fatigue, night sweats, and weight loss
• Left upper quadrant fullness (splenomegaly)
• Secondary gout

61
Q

Primary Myelofibrosis: Treatment

A

• Difficult to treat
• Variable course
• Median survival 4 to 5 years
• In 5 – 20% of cases, transformation to AML

62
Q

Essential Thrombocytosis: Genetics

A

• Often associated with activating point mutations in JAK2 (501%) or MPL (5 – 10%)

– MPL is a receptor tyrosine kinase that is normally activated by thrombopoietin

– Most fo the remaining cases have mutations in calreticulin (a protein with several described functions in the endoplasmic reticulum and cytoplasm

63
Q

Essential Thrombocytosis: Genetics

A

• Progenitors are therefore thrombopoietin independent
• The JAK2 mutation is the same as seen in PCV
– Unclear as to why some patients get PCV and others get ET
– ? Iron deficiency

64
Q

Essential Thromocytosis: Clinical Presentation

A

• Elevated platelet counts
– PCV and primary myelofibrosis are ruled out due to absence of:
• Polycythemia
• Marrow fibrosis

65
Q

ET: Laboratory Findings

• Platelets> 1x 1012/L

A

• Abnormal and giant platelets

  • Neutrophilic leukocytosis
  • Marrow
    – Megakaryocytic markedly hyperplasic
    – Bone marrow cellularity overall is only mildly
    increasee
    – Features of other MPDs are absent
66
Q

ET: Clinical Course

A
  • Bleeding, thrombosis
  • Splenomegaly (50%)
  • Can transform into AML
  • Can transform into another myeloproliferative disorder
67
Q

ET: Clinical Course

A

• Indolent, with a long asymptomatic period

  • Median survival time 12-15 years
  • Erythromelalgia
    – A throbbing, burning of the hands and feet caused by occlusion of small arterioles by platelet aggregates
68
Q

Myelodysplastic Syndromes

A

• A group of clonal stem cell disorders characterized by maturation defects resulting in ineffective hematopoiesis and an increased risk of developing AML

• Arises in two settings:
– Idiopathic
– Therapy related

69
Q

Myelodysplastic Syndromes

A
  • Idiopathic
    – > 50 years of age – Insidious

* Therapy Related
– Complication of previous genotoxic drug or radiation therapy

70
Q

Myelodysplastic Syndromes

A
  • All forms can transform to AML
  • Presents with weakness, infections, and hemorrhages
  • Pancytopenia
  • Median survival 9 - 29 months

Pathology (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions