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I & I Part I > Myeloid Neoplasms > Flashcards

Myeloid Neoplasms Flashcards

1
Q

Myeloid Neoplasms

A
  • The myeloid neoplasms are a heterogeneous group of malignant neoplasms that arise from a hematopoietic progenitor cell.
  • Three broad categories of myeloid neoplasms differ in clinical features, prognosis, bone marrow (BM) and peripheral blood findings.
  • MDS (chronic)
  • MPN (chronic)
  • AML
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2
Q

Myelodysplastic Syndrome (MDS)

A
  • Myelo = bone marrow
  • Dysplasia = disordered maturation, abnormal development
  • Characterized by ineffective hematopoiesis

-Impaired division, maturation and production of hematopoeitic cells —> Cytopenia (s)

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3
Q

Myelodysplastic Syndromes (MDS) - Who

A
  • Risk increases with age (mean: 70Y); rare in children
  • Onset earlier than 50 yrs is unusual, with the exception of treatment related MDS
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4
Q

Myelodysplastic Syndromes (MDS) - Symptoms/Clinical Features

A

Many patients are discovered incidentally on routine CBC

  • Symptoms from anemia; less commonly, infection or easy bruising/bleeding
  • Organomegaly and lymphadenopathy, fever (unless coexistent infection), weight loss are uncommon
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5
Q

Myelodysplastic Syndromes (MDS) - Pathogenesis

A
  • Most cases are idiopathic
  • May occur de novo or after chemotherapy and/or radiation therapy (therapy-related)
  • Chemical exposure implicated in some patients

-Benzene, tobacco, solvents, pesticides

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6
Q

Myelodysplastic Syndromes (MDS) - Diagnosis

A
  • Anemia is almost always present (usually normocytic or macrocytic)
  • What do you expect the reticulocyte count to be?
  • Neutropenia and thrombocytopenia less common; rare without anemia
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7
Q

Myelodysplastic Syndromes (MDS) - Categorization

A
  • Number of cytopenias and number of lineages showing dysplasia
  • Percentage of myeloblasts in bone marrow and peripheral blood
  • Percentage of ring sideroblasts

—> Classification drives prognosis and treatment

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8
Q

Myelodysplastic Syndromes (MDS) - Morphology

A
  • Bone marrow is often hypercellular
  • Erythroid precursors: ring sideroblasts, nuclear budding, multinucleation (Image 1)
  • Neutrophils: decreased granules (Image 2), decreased nuclear segmentation (Pelger Huet change) – can also see in blood
  • Megakaryocytes: Small, decreased nuclear lobes (Image 3)
  • Myeloblasts may be increased, by definition are <20%
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9
Q

Myelodysplastic Syndromes (MDS) - Genetics

A
  • Play a major role in determining prognosis
  • Characterized by deletions (5q, 7q, 20q) and monosomies (5,7)
  • Translocations are exceedingly rare
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10
Q

Myelodysplastic Syndromes (MDS) - Prognosis

A

•Prognosis based on:

  • # bone marrow blasts
  • Karyotype
  • # Cytopenias
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11
Q

Myelodysplastic Syndromes (MDS) has a risk of transforming to…

A

…acute myeloid leukemia

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12
Q

Myeloproliferative Neoplasms (MPN)

A

•Clonal stem cell disorders

  • Proliferation of one or more of the myeloid lineages and differentiation beyond the blast stage
  • increase in mature cells in the blood (“cytosis”)

•May involve multiple lineages, but usually one lineage predominates

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13
Q

Myeloproliferative Neoplasms (MPN)

A
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14
Q

Myeloproliferative Neoplasms (MPN) - Who

A

•Most common in middle age and elderly persons

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15
Q

Myeloproliferative Neoplasms (MPN) - Symptoms

A

•Most patients have splenomegaly

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16
Q

Myeloproliferative Neoplasms (MPN) - Pathogenesis

A

•Mutation (JAK2) or translocation (BCR/ABL) results in TYROSINE KINASE with increased activity –> constitutively active –> growth factor independent proliferation

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17
Q

Myeloproliferative Neoplasms (MPN) - Natural History

A
  • Transformation to acute myeloid leukemia
  • Termination in marrow failure or fibrosis (ET, PV, PMF)
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18
Q

Myeloproliferative Neoplasms (MPN) - CML Clinical Features

A
  • May be asymptomatic (1/3)
  • Fatigue, weight loss, night sweats, abdominal fullness - splenomegaly!
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19
Q

Myeloproliferative Neoplasms (MPN) - CML CBC

A
  • Neutrophilic leukocytosis with leftshift to immaturity
  • Absolute basophilia and/or eosinophilia
  • Variable platelet count

-Can be very high (>1 million)

**Rule out causes of reactive leukocytosis and thrombocytosis

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20
Q

Myeloproliferative Neoplasms (MPN) - CML vs. Reactive Neutrophilia

A

myeloblast –> promyleocyte –> myelocyte –> metamyelocyyte –> banded neutrophil –> mature neutrophil –> mature neutrophil in circulation

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21
Q

Reactive Neutrophilia

A
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22
Q

Myeloproliferative Neoplasms (MPN) - CML has [] Phases

A

3

1) Chronic Phase
- Initial indolent phase
- Most patients present in this phase
2) Accelerated Phase (AP)
3) Blast Phase (BP)
- Myeloid (70%)
- Lymphoid (30%)

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23
Q

Myeloproliferative Neoplasms (MPN) - CML Morphology

A

•Peripheral blood

-Leukocytosis with shift to immaturity, eosinophilia, basophilia and thrombocytosis

•Bone marrow

  • Hypercellular
  • proliferation of granulocytes and megakaryocytes

•Spleen

-Granulocytic infiltration

24
Q

Myeloproliferative Neoplasms (MPN) - CML Genetic Features

A

• t(9;22)(q34;q11) –> Philadelphia Chromosome

  • BCR/ABL fusion protein
  • Enhanced tyrosine kinase activity
25
Q

Myeloproliferative Neoplasms (MPN) - CML Targeted Therapy

A

•Gleevec

26
Q

Myeloproliferative Neoplasms (MPN) - PV

A

•Clonal stem cell disorder

  • Increased RBC production
  • Increased RBC mass
27
Q

Myeloproliferative Neoplasms (MPN) - PV Symptoms

A

•Major symptoms related to increased RBC mass:

  • Headache
  • Dizziness
  • Visual disturbance
  • Paresthesias
  • Plethora

•Thrombosis: Mesenteric, portal or splenic vein thrombosis and Budd-Chiari syndrome; other sites (CNS, MI, PE/DVT)

28
Q

What is the difference between embolism and thrombosis?

A

Thrombosis is when a blood clot travels through your vascular system and gets stuck. This reduces the flow of blood getting where it needs to go. Embolism, on the other hand, is similar in the fact that it is a blood clot (or foreign body) that gets stuck in your vascular system.

29
Q

Budd-Chiari Syndrome

A

•Interruption or decrease of blood flow out of liver

-Common usage: Thrombosis of the hepatic veins and/or intrahepatic or suprahepatic inferior vena cava

30
Q

Myeloproliferative Neoplasms (MPN) - PV Lab Results

A

• Pre-polycythemic phase

-Borderline to mild erythrocytosis

• Overt polycythemia phase

  • Excess of normochromic, normocytic RBCs
  • Diagnostic criteria:

Male: Hgb >16.5 g/dL (HCT > 49%)

Female: Hgb > 16.0 g/dL (HCT >48%) 

  • thrombocytosis
  • Neutrophilia, sometimes basophilia
  • ↓ serum erythropoietin

“Spent phase”

  • Hemoglobin normalizes and then decreases
  • Cytopenias
31
Q

Myeloproliferative Neoplasms (MPN) - PV Morphology Polycythemic Phase

A
  • Hypercellular marrow
  • Blood: increase in WBCs, RBCs, platelets
32
Q

Myeloproliferative Neoplasms (MPN) - PV Morphology Spent Phase

A
  • Bone marrow fibrosis
  • Blood:

-Leukoerythroblastic reaction

*nRBCs –>

*Left-shifted granulocytes (O)

-Teardrop cells (*)

33
Q

Myeloproliferative Neoplasms (MPN) - PV Associated Tumors

A
  • increased erythropoietin
  • pheochromocytoma
  • renal cell carcinoma
  • HCC
  • hemangioblastoma
  • leiomyoma
34
Q

Myeloproliferative Neoplasms (MPN) - PV Genetics

A

•JAK2 mutation is found in >95% of patients with PV

-Gain of function mutation

•BCR/ABL negative

35
Q

Myeloproliferative Neoplasms (MPN) - ET

A

•Criteria: Sustained thrombocytosis >450,000/uL

36
Q

Myeloproliferative Neoplasms (MPN) - ET Symptoms

A
  • Many (>50%) patients are asymptomatic
  • Progression to fibrosis and significant splenomegaly, as seen in other MPNs, is less common
  • Vascular occlusion
  • Microvascular (TIAs, gangrene)
  • Splenic or hepatic vein thrombosis (Budd-Chiari)
  • Bleeding (bleeding with a high platelet count?? YES!!
  • GI tract, upper airway
  • Qualitative platelet disorder, acquired von Willebrand disease
37
Q

Myeloproliferative Neoplasms (MPN) - ET Diagnosis

A
  • Must exclude causes of reactive thrombocytosis since they are MORE COMMON than ET
  • look for acute phase reactants:
  • ferritin
  • fibrinogen
  • serum amyloid A
  • hepcidin
  • C reactive protein
38
Q

Myeloproliferative Neoplasms (MPN) - ET Morphology

A

• Bone Marrow

– Proliferation of large megakaryocytes

– No significant fibrosis

•Peripheral blood

– Increased platelets, variable in size

– Leukoerythroblastic reaction not typical (no teardrops, nRBCs)

39
Q

Myeloproliferative Neoplasms (MPN) - ET Genetics

A
  • JAK2 mutation in ~50% of patients
  • BCR/ABL negative
40
Q

Myeloproliferative Neoplasms (MPN) - PMF

A

•Characterized by progression from initial prefibrotic phase to a fibrotic phase

41
Q

Myeloproliferative Neoplasms (MPN) - PMF Symptoms

A

•~30% asymptomatic

  • Splenomegaly
  • Thrombocytosis or leukocytosis

•Fatigue, weight loss, fever, bleeding, night sweats

42
Q

Myeloproliferative Neoplasms (MPN) - PMF Morphology Fibrotic Stage

A

•Bone Marrow

  • Extensive fibrosis May lead to a dry tap
  • May be devoid of hematopoietic elements

•Spleen

-Extramedullary hematopoiesis

•Peripheral blood

-Leukoerythroblastosis and teardrops

43
Q

Myeloproliferative Neoplasms (MPN) - Differential diagnosis of leukoerythroblastosis with teardrop cells

A

•Infiltrative disorders of the bone marrow

  • Granulomatous diseases
  • Metastatic malignancy
  • Gaucher disease
  • MPNs
  • Teardrop cells (Dacrocytes) are thought to form as a result of the removal of an inclusion from the cell as it moves through the spleen. This process is referred to as pitting. Since red cells are quite flexible and usually return to their normal shape following pitting, it has been theorized that in this case the membrane may have been stretched too far and thus cannot return to its original shape. The arrows in this image point to several teardrop cells.
44
Q

Myeloproliferative Neoplasms (MPN) - Causes of a dry tap

A

•Severely hypocellular marrow

-aplastic anemia

  • Needle not in marrow space
  • Hypercellular marrow – packed marrow

-Leukemia, lymphoma, other malignancy

Marrow fibrosis

  • Myeloproliferative neoplasms
  • B-cell neoplasm
  • Hairy cell leukemia
  • Metastatic neoplasm
  • Granulomatous inflammation
45
Q

Myeloproliferative Neoplasms (MPN) PMF Genetics

A
  • JAK2 mutation in ~50% of patients
  • BCR/ABL Negative
46
Q

Acute Myeloid Leukemia - AML

A

•Clonal proliferation of myeloid precursors with a reduced capacity to differentiate into mature cells

-Blasts accumulate in marrow, blood and/or other tissues –> Marrow failure and complications related to anemia, thrombocytopenia, and/or neutropenia

•Most cases are of unknown etiology

  • Previous chemotherapy, radiotherapy or other toxin exposure in some patients
  • May be a terminal event in other myeloid neoplasms

*MPNs, MDS

47
Q

Acute Myeloid Leukemia - AML Symptoms

A
  • Weakness/fatigue, infections, bleeding
  • Fever: infection or disease-related
  • Infiltration of skin or gingiva

-Monocytic leukemias

•Localized tissue mass

-Myeloid sarcoma

•DIC in patients with acute promyelocytic leukemia

48
Q

Acute Myeloid Leukemia - AML Morphology

A

•Peripheral blood: Usually anemia, neutropenia and/or thrombocytopneia

-Myeloblasts usually present (leukocytosis)

  • Marrow: ↑ cellularity ← proliferation of immature cells
  • Myeloblasts
  • Delicate nuclear chromatin, prominent nucleoli
  • Scant cytoplasm (high nuclear/cytoplasm ratio)
  • Auer Rods
  • Needle-shaped cytoplasmic structures (Fused granules?)

–> Definitive evidence of myeloid differentiation; not found in normal cells

49
Q

Acute Myeloid Leukemia - AML Diagnostic Criteria

A

•≥20% blasts in the marrow (NL: 2-3%) or blood (NL: 0%)

50
Q

Acute Myeloid Leukemia - AML Subtype: Acute Promyelocytic Leukemia Clinical Presentation

A

•Propensity to abnormal bleeding (disseminated intravascular coagulation, DIC)

-due to release of procoagulant granules

51
Q

Acute Myeloid Leukemia - AML Subtype: Acute Promyelocytic Leukemia Morphology

A

•Hypergranular promyelocytes with numerous Auer rods

52
Q

Acute Myeloid Leukemia - AML Subtype: Acute Promyelocytic Leukemia Genetics

A

•t(15;17) –> PML/RARA fusion protein

53
Q

Acute Myeloid Leukemia - AML Subtype: Acute Promyelocytic Leukemia Treatment

A

•Vitamin A derivative (all-trans retinoic acid, ATRA) + arsenic (yes, arsenic!!) +/- chemo

54
Q

Acute Myeloid Leukemia - AML Subtype: Acute Promyelocytic Leukemia Prognosis

A

•With optimal treatment, prognosis is more favorable than for any other AML subtype

55
Q

Acute Myeloid Leukemia - AML Genetics

A

•AML with recurrent cytogenetic abnormalities

  • Balanced translocations
  • Some have high rate of clinical remission and favorable prognosis

•ALL NEW CASES OF AML SHOULD BE EVALUATED FOR THESE GENETIC ABNORMALITIES

I & I Part I (25 decks)

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